Publications

@article{pmid36533539,

title = {Breast cancer risk for women with diabetes and the impact of metformin: A meta-analysis},

author = {Yifan Lu and Ali Hajjar and Vincent L Cryns and Amy Trentham-Dietz and Ronald E Gangnon and Brandy M Heckman-Stoddard and Oguzhan Alagoz},

doi = {10.1002/cam4.5545},

issn = {2045-7634},

year  = {2023},

date = {2023-05-01},

journal = {Cancer Med},

volume = {12},

number = {10},

pages = {11703--11718},

abstract = {BACKGROUND: Diabetes mellitus has been associated with increased breast cancer (BC) risk; however, the magnitude of this effect is uncertain. This study focused on BC risk for women with type 2 diabetes mellitus (T2DM).nnMETHODS: Two separate meta-analyses were conducted (1) to estimate the relative risk (RR) of BC for women with T2DM and (2) to evaluate the risk of BC for women with T2DM associated with the use of metformin, a common diabetes treatment. In addition, subgroup analyses adjusting for obesity as measured by body mass index (BMI) and menopausal status were also performed. Studies were identified via PubMed/Scopus database and manual search through April 2021.nnRESULTS: A total of 30 and 15 studies were included in the first and second meta-analyses, respectively. The summary RR of BC for women with T2DM was 1.15 (95% confidence interval [CI], 1.09-1.21). The subgroup analyses adjusting BMI and adjusting BMI and menopause resulted in a summary RR of 1.22 (95% CI, 1.15-1.30) and 1.20 (95% CI, 1.05-1.36), respectively. For women with T2DM, the summary RR of BC was 0.82 (95% CI, 0.60-1.12) for metformin users compared with nonmetformin users.nnCONCLUSIONS: Women with T2DM were more likely to be diagnosed with BC and this association was strengthened by adjusting for BMI and menopausal status. No statistically significant reduction of BC risk was observed among metformin users.nnIMPACT: These two meta-analyses can inform decision-making for women with type 2 diabetes regarding their use of metformin and the use of screening mammography for early detection of breast cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37142815,

title = {CheckList for EvaluAtion of Radiomics research (CLEAR): a step-by-step reporting guideline for authors and reviewers endorsed by ESR and EuSoMII},

author = {Burak Kocak and Bettina Baessler and Spyridon Bakas and Renato Cuocolo and Andrey Fedorov and Lena Maier-Hein and Nathaniel Mercaldo and Henning M\"{u}ller and Fanny Orlhac and Daniel Pinto Dos Santos and Arnaldo Stanzione and Lorenzo Ugga and Alex Zwanenburg},

doi = {10.1186/s13244-023-01415-8},

issn = {1869-4101},

year  = {2023},

date = {2023-05-01},

journal = {Insights Imaging},

volume = {14},

number = {1},

pages = {75},

abstract = {Even though radiomics can hold great potential for supporting clinical decision-making, its current use is mostly limited to academic research, without applications in routine clinical practice. The workflow of radiomics is complex due to several methodological steps and nuances, which often leads to inadequate reporting and evaluation, and poor reproducibility. Available reporting guidelines and checklists for artificial intelligence and predictive modeling include relevant good practices, but they are not tailored to radiomic research. There is a clear need for a complete radiomics checklist for study planning, manuscript writing, and evaluation during the review process to facilitate the repeatability and reproducibility of studies. We here present a documentation standard for radiomic research that can guide authors and reviewers. Our motivation is to improve the quality and reliability and, in turn, the reproducibility of radiomic research. We name the checklist CLEAR (CheckList for EvaluAtion of Radiomics research), to convey the idea of being more transparent. With its 58 items, the CLEAR checklist should be considered a standardization tool providing the minimum requirements for presenting clinical radiomics research. In addition to a dynamic online version of the checklist, a public repository has also been set up to allow the radiomics community to comment on the checklist items and adapt the checklist for future versions. Prepared and revised by an international group of experts using a modified Delphi method, we hope the CLEAR checklist will serve well as a single and complete scientific documentation tool for authors and reviewers to improve the radiomics literature.},

keywords = {},

pubstate = {published},

tppubtype = {article}

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@article{pmid37128666,

title = {Umbrella review and meta-analysis of reconstructed individual patient data of mortality following conventional endovascular and open surgical repair of infrarenal abdominal aortic aneurysm},

author = {Vladica M Veli\v{c}kovi\'{c} and Daniel Carradice and Jonathan R Boyle and Mohamad Hamady and Trevor Cleveland and Simon Neequaye and Aleksandra Ignjatovi\'{c} and Dragana Bogdanovi\'{c} and Jelena Savovic and Uwe Siebert},

doi = {10.1080/14779072.2023.2207009},

issn = {1744-8344},

year  = {2023},

date = {2023-05-01},

urldate = {2023-05-01},

journal = {Expert Rev Cardiovasc Ther},

volume = {21},

number = {5},

pages = {347-356},

abstract = {OBJECTIVES: This umbrella review aims to quality assess published meta-analyses, conduct a de-novo meta-analysis of the available randomized control trials (RCTs), and test the hypothesis that there is a long-term difference in mortality between OSR and EVAR.nnMETHODS: A systematic search was conducted in MEDLINE and EMBASE's bibliographic databases (June 2022). Data were extracted using standardized extraction forms. The methodological quality of publications was assessed using the ROBIS tool. Data were analyzed with 'one-stage' and 'two-stage' approaches.nnRESULTS: According to two-stage analysis, EVAR has significantly favorable mortality for up to four years (increasing evidence). Subsequently, until the longest available time period, there is no difference between EVAR and OSR; all the results are statistically non-significant.In one stage analysis, the Cox model demonstrated a non-significant (weak evidence) hazard ratio of 1.03 (95% confidence interval [CI]: 0.94-1.12) in favor of OSR. The best-fitting parametric model (generalized gamma), leads to an hazard ratio of 0.97 (95% CI: 0.93-1.01) in favor of EVAR, with the results approaching significance (weak evidence).nnCONCLUSION: The results of this umbrella systematic review and meta-analysis failed to demonstrate any difference in long-term mortality following planned EVAR, compared with OSR of infrarenal AAA.},

keywords = {},

pubstate = {published},

tppubtype = {article}

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@article{pmid36960710,

title = {A Comprehensive Study on the Diagnosis and Management of Noninvasive Follicular Thyroid Neoplasm with Papillary-Like Nuclear Features},

author = {Bayan A Alzumaili and Lauren N Krumeich and Reagan Collins and Timothy Kravchenko and Emad I Ababneh and Adam S Fisch and William C Faquin and Vania Nos\'{e} and Maria Martinez-Lage and Gregory W Randolph and Rajshri M Gartland and Carrie C Lubitz and Peter M Sadow},

doi = {10.1089/thy.2023.0035},

issn = {1557-9077},

year  = {2023},

date = {2023-05-01},

journal = {Thyroid},

volume = {33},

number = {5},

pages = {566--577},

abstract = { Since the noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTPs) was introduced in 2016, most retrospective studies have included cases diagnosed as encapsulated follicular variant of papillary thyroid carcinoma. We investigate a cohort diagnosed with NIFTP at resection.  Retrospective institutional cohort of NIFTP from 2016 to 2022, including clinical, cytological, and molecular data for 319 cases (6.6% of thyroid surgeries, 183 cases as NIFTP-only).  The patient cohort had unifocal or multifocal thyroid nodules. Female:male ratio was 2.7:1, mean age was 52 years and median NIFTP size was 2.1 cm. NIFTP was associated with multiple nodules in 23% patients ( = 73) and 12% of NIFTP were multifocal ( = 39). Fine needle aspiration (FNA) of NIFTP ( = 255) were designated as nondiagnostic = 5%, benign = 13%, atypia of undetermined significance/follicular lesion of undetermined significance (AUS/FLUS) = 49%, follicular neoplasm/suspicious for follicular neoplasm (FN/SFN) = 17%, suspicious for malignancy = 12%, or malignant = 4%. Molecular alterations were identified in 93% ( = 114),  or -like. Thyroid Imaging Reporting and Data System (TI-RADS) score 4 was recorded in 50% of NIFTP, followed by scores 3 and 5 (26% and 20%, respectively). We also investigated the factors associated with extent of surgery. In our NIFTP-only group ( = 183), 66% were identified after hemithyroidectomy (HT) and 34% after total thyroidectomy (TT). On univariate analysis, TT patients demonstrated higher Bethesda category by FNA, more often had aberrant preoperative thyroid function, and/or underwent an FNA of additional nodule(s). With multivariable regression, Bethesda V NIFTP, in the presence of other nodules being evaluated by FNA and aberrant preoperative thyroid function, independently predicts TT. Bethesda II NIFTP correlated significantly with HT. Fifty-two patients (28%) with NIFTP-only had at least one postoperative surveillance ultrasound. In the NIFTP-only cohort, no HT patients had completion thyroidectomy or received postoperative radioactive iodine. No recurrence or metastases were recorded with median follow-up of 35 months (6-76 months;  = 120).  Given this large cohort of NIFTP, including a large subset of isolated NIFTP-only, some with >6 years of follow-up and no tumor recurrences, consensus practical guidelines are needed for adequate postoperative management. Given the American Thyroid Association (ATA) provides guidelines for management of low-risk malignancies, guidance regarding that for borderline/biologically uncertain tumors, including NIFTP, is a reasonable next step.},

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pubstate = {published},

tppubtype = {article}

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@article{pmid37105689,

title = {Monitoring multidimensional aspects of quality of life after cancer immunotherapy: protocol for the international multicentre, observational QUALITOP cohort study},

author = {Petra C Vinke and Marc Combalia and Geertruida H de Bock and Cl\'{e}mence Leyrat and Anne Mea Spanjaart and Stephane Dalle and Maria Gomes da Silva and Aurore Fouda Essongue and Aur\'{e}lie Rabier and Myriam Pannard and Mohammad S Jalali and Amal Elgammal and Mike Papazoglou and Mohand-Said Hacid and Catherine Rioufol and Marie-Jos\'{e} Kersten and Martijn Gh van Oijen and Erick Suazo-Zepeda and Ananya Malhotra and Emmanuel Coquery and Am\'{e}lie Anota and Marie Preau and Mathieu Fauvernier and Elsa Coz and Susana Puig and Delphine Maucort-Boulch},

doi = {10.1136/bmjopen-2022-069090},

issn = {2044-6055},

year  = {2023},

date = {2023-04-27},

urldate = {2023-04-01},

journal = {BMJ Open},

volume = {13},

number = {4},

pages = {e069090},

abstract = {INTRODUCTION: Immunotherapies, such as immune checkpoint inhibitors and chimeric antigen receptor T-cell therapy, have significantly improved the clinical outcomes of various malignancies. However, they also cause immune-related adverse events (irAEs) that can be challenging to predict, prevent and treat. Although they likely interact with health-related quality of life (HRQoL), most existing evidence on this topic has come from clinical trials with eligibility criteria that may not accurately reflect real-world settings. The QUALITOP project will study HRQoL in relation to irAEs and its determinants in a real-world study of patients treated with immunotherapy.nnMETHODS AND ANALYSIS: This international, observational, multicentre study takes place in France, the Netherlands, Portugal and Spain. We aim to include about 1800 adult patients with cancer treated with immunotherapy in a specifically recruited prospective cohort, and to additionally obtain data from historical real-world databases (ie, databiobanks) and medical administrative registries (ie, national cancer registries) in which relevant data regarding other adult patients with cancer treated with immunotherapy has already been stored. In the prospective cohort, clinical health status, HRQoL and psychosocial well-being will be monitored until 18 months after treatment initiation through questionnaires (at baseline and 3, 6, 12 and 18 months thereafter), and by data extraction from electronic patient files. Using advanced statistical methods, including causal inference methods, artificial intelligence algorithms and simulation modelling, we will use data from the QUALITOP cohort to improve the understanding of the complex relationships among treatment regimens, patient characteristics, irAEs and HRQoL.nnETHICS AND DISSEMINATION: All aspects of the QUALITOP project will be conducted in accordance with the Declaration of Helsinki and with ethical approval from a suitable local ethics committee, and all patients will provide signed informed consent. In addition to standard dissemination efforts in the scientific literature, the data and outcomes will contribute to a smart digital platform and medical data lake. These will (1) help increase knowledge about the impact of immunotherapy, (2) facilitate improved interactions between patients, clinicians and the general population and (3) contribute to personalised medicine.nnTRIAL REGISTRATION NUMBER: NCT05626764.},

keywords = {},

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@article{pmid37040087,

title = {Molecular Profiling and Treatment Pattern Differences between Intrahepatic and Extrahepatic Cholangiocarcinoma},

author = {Kristen Spencer and Leontios Pappas and Islam Baiev and Jordan Maurer and Andrea Grace Bocobo and Karen Zhang and Apurva Jain and Anaemy Danner De Armas and Stephanie Reyes and Tri Minh Le and Osama E Rahma and Jennifer Stanton and Thomas T DeLeon and Marc Roth and Mary Linton B Peters and Andrew X Zhu and Jochen K Lennerz and A John Iafrate and Kylie Boyhen and Christine VanCott and Lewis R Roberts and Stacie Lindsey and Nora Horick and Laura Williams Goff and Kabir Mody and Mitesh J Borad and Rachna T Shroff and R Katie Kelley and Milind M Javle and Lipika Goyal},

doi = {10.1093/jnci/djad046},

issn = {1460-2105},

year  = {2023},

date = {2023-04-11},

urldate = {2023-04-01},

journal = {J Natl Cancer Inst},

abstract = {BACKGROUND: Treatment patterns for intrahepatic cholangiocarcinoma (ICC) and extrahepatic cholangiocarcinoma (ECC) differ, but limited studies exist comparing them. This study examines differences in molecular profiling rates and treatment patterns in these populations, focusing on use of adjuvant, liver-directed, targeted, and investigational therapies.nnMETHODS: This multi-center collaboration included patients with ICC or ECC treated at one of eight participating institutions. Retrospective data were collected on risk factors, pathology, treatments, and survival. Comparative statistical tests were two-sided.nnRESULTS: Among 1,039 patients screened, 847 patients met eligibility (ICC = 611, ECC = 236). Patients with ECC were more likely than those with ICC to present with early-stage disease (53.8% vs 28.0%), undergo surgical resection (55.1% vs 29.8%), and receive adjuvant chemoradiation (36.5% vs 4.2%), (all p < 0.00001). However, they were less likely to undergo molecular profiling (50.3% vs 64.3%) or receive liver directed therapy (17.9% vs 35.7%), targeted therapy (4.7% vs 18.9%), and clinical trial therapy (10.6% vs 24.8%), (all p < 0.001). In patients with recurrent ECC after surgery, the molecular profiling rate was 64.5%. Patients with advanced ECC had a shorter median overall survival than those with advanced ICC (11.8 vs 15.1 months, p < 0.001).nnCONCLUSIONS: Patients with advanced ECC have low rates of molecular profiling, possibly in part due to insufficient tissue. They also have low rates of targeted therapy use and clinical trial enrollment. While these rates are higher in advanced ICC, the prognosis for both subtypes of cholangiocarcinoma remains poor, and a pressing need exists for new effective targeted therapies and broader access to clinical trials.},

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pubstate = {published},

tppubtype = {article}

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@article{pmid37020497,

title = {Enumerating contributions of fentanyls and other factors to the unprecedented 2020 rise in opioid overdose deaths: model-based analysis},

author = {Erin J Stringfellow and Tse Yang Lim and Catherine DiGennaro and Zeynep Hasgul and Mohammad S Jalali},

doi = {10.1093/pnasnexus/pgad064},

issn = {2752-6542},

year  = {2023},

date = {2023-04-01},

journal = {PNAS Nexus},

volume = {2},

number = {4},

pages = {pgad064},

abstract = {In 2020, the ongoing US opioid overdose crisis collided with the emerging COVID-19 pandemic. Opioid overdose deaths (OODs) rose an unprecedented 38%, due to a combination of COVID-19 disrupting services essential to people who use drugs, continued increases in fentanyls in the illicit drug supply, and other factors. How much did these factors contribute to increased OODs? We used a validated simulation model of the opioid overdose crisis, SOURCE, to estimate excess OODs in 2020 and the distribution of that excess attributable to various factors. Factors affecting OODs that could have been disrupted by COVID-19, and for which data were available, included opioid prescribing, naloxone distribution, and receipt of medications for opioid use disorder. We also accounted for fentanyls' presence in the heroin supply. We estimated a total of 18,276 potential excess OODs, including 1,792 lives saved due to increases in buprenorphine receipt and naloxone distribution and decreases in opioid prescribing. Critically, growth in fentanyls drove 43% (7,879) of the excess OODs. A further 8% is attributable to first-ever declines in methadone maintenance treatment and extended-released injectable naltrexone treatment, most likely due to COVID-19-related disruptions. In all, 49% of potential excess OODs remain unexplained, at least some of which are likely due to additional COVID-19-related disruptions. While the confluence of various COVID-19-related factors could have been responsible for more than half of excess OODs, fentanyls continued to play a singular role in excess OODs, highlighting the urgency of mitigating their effects on overdoses.},

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tppubtype = {article}

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@article{pmid35060002,

title = {To Prescribe or Not to Prescribe?: Barriers and Motivators for Progressing Along Each Stage of the Buprenorphine Training and Prescribing Path},

author = {Rachel P Winograd and Bridget Coffey and Candice Woolfolk and Claire A Wood and Vinith Ilavarasan and David Liss and Subodh Jain and Erin Stringfellow},

doi = {10.1007/s11414-021-09783-z},

issn = {1556-3308},

year  = {2023},

date = {2023-04-01},

journal = {J Behav Health Serv Res},

volume = {50},

number = {2},

pages = {165--180},

abstract = {This study aimed to identify the strongest barriers and motivators associated with each step toward buprenorphine prescribing (1. obtaining a waiver, 2. beginning to prescribe, and 3. prescribing to more people) among a sample of Missouri-based medical professionals (N = 130). Item weights (number of endorsements times mean rank of the item's importance) were calculated based on their responses. Across groups, lack of access to psychosocial support services, need for higher levels of care, and clinical complexity were strong barriers. Among non-prescribers (n = 57, 46.3%), administrative burden, potential of becoming an addiction clinic, and concern about misuse and diversion were most heavily weighted. Among prescribers (n = 66, 53.7%), patients' inability to afford medications was a barrier across phases. Prominent motivators among all groups were the effectiveness of buprenorphine, improvement in other health outcomes, and a personal interest in treating addiction. Only prescribers reported the presence of institutional support and mentors as significant motivators.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{SchnellInderst2021,

title = {[Testicular Cancer Screening in Men Aged 16 Years and Older: IQWiG ThemenCheck Health Technology Assessment Report on Medical, Economic, Social, Ethical, Legal and Organisational Aspects].},

author = {Petra Schnell-Inderst and Anja Laschkolnig and Georg Marckmann and Daniela Antony and Uwe Siebert and Nikolai M\"{u}hlberger},

url = {https://pubmed.ncbi.nlm.nih.gov/34872119/},

doi = {10.1055/a-1658-0057},

issn = {1439-4421},

year  = {2023},

date = {2023-04-01},

urldate = {2021-12-01},

journal = {Gesundheitswesen (Bundesverband der Arzte des Offentlichen Gesundheitsdienstes (Germany))},

volume = {85},

issue = {4},

pages = {234-241},

abstract = {Testicular cancer occurs mainly in young men between 25 and 45 years and is the most common cancer at this age. Possible testicular cancer early detection measures, clinical palpation and scrotal ultrasound (CUS) or testicular self-examination (TSE) in asymptomatic men aged 16 years and older, could perhaps avoid deaths and aggressive late therapies. Therefore, we investigated whether these measures have an additional benefit compared to the current situation. Ethical, legal, social and organisational aspects were considered as well. The methodology of this review follows IQWiG's "Allgemeine[n] Methoden Version 5.0". In addition, to estimate the theoretically possible benefits and potential harms of screening, a supplementary presentation was used for the benefit assessment based on published data from tumour registries and data on predictive values from diagnostic studies. No intervention studies were identified, therefore evidence-based statements on additional benefit or harm of the studied interventions could not be made. The epidemiological data showed that per 100,000 men participating in screening annually, a maximum of 1.2 advanced tumours and 0.4 deaths would have been preventable. Harm calculations suggest that with CUS of 100,000 men, 1 to 22 unnecessary testicular exposures or removals might be expected, with TSE it would be 2 cases. However, these data on the possible harm of screening are subject to great uncertainty. There are no intervention studies demonstrating that the benefit of testicular cancer screening in men aged 16 years and older outweighs the harm. The maximum possible additional benefit is low and chances of detection and cure are good even without screening. At present, testicular cancer screening cannot be recommended.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36913348,

title = {Incorporating algorithmic uncertainty into a clinical machine deep learning algorithm for urgent head CTs},

author = {Byung C Yoon and Stuart R Pomerantz and Nathaniel D Mercaldo and Swati Goyal and Eric M L'Italien and Michael H Lev and Karen A Buch and Bradley R Buchbinder and John W Chen and John Conklin and Rajiv Gupta and George J Hunter and Shahmir C Kamalian and Hillary R Kelly and Otto Rapalino and Sandra P Rincon and Javier M Romero and Julian He and Pamela W Schaefer and Synho Do and Ramon Gilberto Gonz\'{a}lez},

doi = {10.1371/journal.pone.0281900},

issn = {1932-6203},

year  = {2023},

date = {2023-03-13},

urldate = {2023-01-01},

journal = {PLoS One},

volume = {18},

number = {3},

pages = {e0281900},

abstract = {Machine learning (ML) algorithms to detect critical findings on head CTs may expedite patient management. Most ML algorithms for diagnostic imaging analysis utilize dichotomous classifications to determine whether a specific abnormality is present. However, imaging findings may be indeterminate, and algorithmic inferences may have substantial uncertainty. We incorporated awareness of uncertainty into an ML algorithm that detects intracranial hemorrhage or other urgent intracranial abnormalities and evaluated prospectively identified, 1000 consecutive noncontrast head CTs assigned to Emergency Department Neuroradiology for interpretation. The algorithm classified the scans into high (IC+) and low (IC-) probabilities for intracranial hemorrhage or other urgent abnormalities. All other cases were designated as No Prediction (NP) by the algorithm. The positive predictive value for IC+ cases (N = 103) was 0.91 (CI: 0.84-0.96), and the negative predictive value for IC- cases (N = 729) was 0.94 (0.91-0.96). Admission, neurosurgical intervention, and 30-day mortality rates for IC+ was 75% (63-84), 35% (24-47), and 10% (4-20), compared to 43% (40-47), 4% (3-6), and 3% (2-5) for IC-. There were 168 NP cases, of which 32% had intracranial hemorrhage or other urgent abnormalities, 31% had artifacts and postoperative changes, and 29% had no abnormalities. An ML algorithm incorporating uncertainty classified most head CTs into clinically relevant groups with high predictive values and may help accelerate the management of patients with intracranial hemorrhage or other urgent intracranial abnormalities.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36987566,

title = {Delay in Surgery and Papillary Thyroid Cancer Survival in the United States: a SEER-Medicare Analysis},

author = {Natalia Chaves and Jordan M Broekhuis and Scott C Fligor and Reagan A Collins and Anna M Modest and Sumedh Kaul and Benjamin C James},

doi = {10.1210/clinem/dgad163},

issn = {1945-7197},

year  = {2023},

date = {2023-03-01},

journal = {J Clin Endocrinol Metab},

abstract = {INTRODUCTION: Delays in surgery and their impact on survival in papillary thyroid cancer (PTC) is unclear. We sought to investigate the association between time to surgery and survival in patients with PTC.nnMETHODS: A total of 8,170 Medicare beneficiaries with PTC who underwent thyroidectomy were identified within the SEER-Medicare linked data files between 1999-2018. Disease-specific survival (DSS) and overall survival (OS) were estimated using Kaplan-Meir analysis, and Cox proportional hazards models were specified to estimate the association between time to surgery and survival.nnRESULTS: Among 8,170 patients with PTC, mean age 69.3 (SD+/- 11.4), 89.8% had surgery within the first 90 days, 7.8% had surgery 91-180 days from diagnosis, and 2.4% had surgery after 180 days. Increasing time to surgery was associated with increased mortality for OS in the >180-day group (aHR 1.24, 95% CI 1.01-1.53). Moreover, on stratification by summary stage, those with localized disease in the 91-180-day group increased risk by 25% (aHR 1.25 95%CI 1.05-1.51) and delaying over 180 days increased risk by 61% (aHR 1.61 95%CI 1.19-2.18) in OS. Those with localized disease in the >180-day group had almost four times the estimated rate of DSS mortality (aHR3.51 95%CI 1.68-7.32). When stratified by T stage, those with T2 disease in the >180 days group had double the estimated rate of all-cause mortality (aHR 2.0, 95% CI 1.1-3.3) and almost triple the estimated rate of disease-specific mortality (aHR 2.7, 95% CI 1.05-6.8).nnCONCLUSIONS: Delays in surgery for PTC may impact OS and DSS in localized disease, prior to nodal metastasis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36533415,

title = {Raising the standards of patient-centered outcomes research in myelodysplastic syndromes: Clinical utility and validation of the subscales of the QUALMS from the MDS-RIGHT project},

author = {Fabio Efficace and Karin Koinig and Francesco Cottone and David Bowen and Moshe Mittelman and Kathrin Sommer and Saskia Langemeijer and Dominic Culligan and Kalman Filanovsky and Michael Storck and Alexandra Smith and Corine van Marrewijk and Martin Dugas and Igor Stojkov and Uwe Siebert and Theo de Witte and Reinhard Stauder},

doi = {10.1002/cam4.5487},

issn = {2045-7634},

year  = {2023},

date = {2023-03-01},

urldate = {2022-12-01},

journal = {Cancer Med},

volume = {12},

issue = {6},

pages = {7529-7539},

abstract = {BACKGROUND: Clinical decision-making for patients with myelodysplastic syndromes (MDS) is challenging, and both disease and treatment effects heavily impact health-related quality of life (HRQoL) of these patients. Therefore, disease-specific HRQoL measures can be critical to harness the patient voice in MDS research.



METHODS: We report a prospective international validation study of the Quality of Life in Myelodysplasia Scale (QUALMS) with a main focus on providing information on the psychometric characteristics of its three subscales: physical burden (QUALMS-P), emotional burden (QUALMS-E), and benefit finding (QUALMS-BF). The analysis is based on patients enrolled from three European countries and Israel, participating to the MDS-RIGHT Project. The scale structure and psychometric properties of the QUALMS were assessed.



RESULTS: Overall, 270 patients with a median age of 74 years were analyzed and the majority of them (60.3%) had a low MDS-Comorbidity Index score. Results of the confirmatory factor analysis supported the underlying scale structure of the QUALMS, which, in addition to a total score, includes three subscales: QUALMS-P, QUALMS-E, and the QUALMS-BF. The QUALMS-P exhibited the highest Cronbach's alpha coefficients. Discriminant validity analysis indicated good results with the QUALMS-P and QUALMS-E distinguishing between patients with different performance status, comorbidity, anemia, and transfusion dependency status. No floor and ceiling effects were observed. Responsiveness to change analysis supported the validity of the measure. Patients with a hemoglobin (Hb) level of <11 g/dL at study entry, who subsequently showed an improvement in their Hb levels, also reported a mean score change of 9 and 8 points (scales ranging between 0 and 100) in the expected direction of the QUALMS-E and QUALMS-P, respectively.



CONCLUSIONS: Our study provides additional validation data on the QUALMS from the international MDS-RIGHT Project. The use of this disease-specific HRQoL measure may contribute to raise quality standards of patient-centered outcomes research in MDS.},

keywords = {},

pubstate = {published},

tppubtype = {article}

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@article{pmid36745885,

title = {Risk Model-Based Lung Cancer Screening : A Cost-Effectiveness Analysis},

author = {Iakovos Toumazis and Pianpian Cao and Koen de Nijs and Mehrad Bastani and Vidit Munshi and Mehdi Hemmati and Kevin Ten Haaf and Jihyoun Jeon and Martin Tammem\"{a}gi and G Scott Gazelle and Eric J Feuer and Chung Yin Kong and Rafael Meza and Harry J de Koning and Sylvia K Plevritis and Summer S Han},

doi = {10.7326/M22-2216},

issn = {1539-3704},

year  = {2023},

date = {2023-02-01},

journal = {Ann Intern Med},

abstract = {BACKGROUND: In their 2021 lung cancer screening recommendation update, the U.S. Preventive Services Task Force (USPSTF) evaluated strategies that select people based on their personal lung cancer risk (risk model-based strategies), highlighting the need for further research on the benefits and harms of risk model-based screening.



OBJECTIVE: To evaluate and compare the cost-effectiveness of risk model-based lung cancer screening strategies versus the USPSTF recommendation and to explore optimal risk thresholds.



DESIGN: Comparative modeling analysis.



DATA SOURCES: National Lung Screening Trial; Surveillance, Epidemiology, and End Results program; U.S. Smoking History Generator.



TARGET POPULATION: 1960 U.S. birth cohort.



TIME HORIZON: 45 years.



PERSPECTIVE: U.S. health care sector.



INTERVENTION: Annual low-dose computed tomography in risk model-based strategies that start screening at age 50 or 55 years, stop screening at age 80 years, with 6-year risk thresholds between 0.5% and 2.2% using the PLCOm2012 model.



OUTCOME MEASURES: Incremental cost-effectiveness ratio (ICER) and cost-effectiveness efficiency frontier connecting strategies with the highest health benefit at a given cost.



RESULTS OF BASE-CASE ANALYSIS: Risk model-based screening strategies were more cost-effective than the USPSTF recommendation and exclusively comprised the cost-effectiveness efficiency frontier. Among the strategies on the efficiency frontier, those with a 6-year risk threshold of 1.2% or greater were cost-effective with an ICER less than $100 000 per quality-adjusted life-year (QALY). Specifically, the strategy with a 1.2% risk threshold had an ICER of $94 659 (model range, $72 639 to $156 774), yielding more QALYs for less cost than the USPSTF recommendation, while having a similar level of screening coverage (person ever-screened 21.7% vs. USPSTF's 22.6%).



RESULTS OF SENSITIVITY ANALYSES: Risk model-based strategies were robustly more cost-effective than the 2021 USPSTF recommendation under varying modeling assumptions.



LIMITATION: Risk models were restricted to age, sex, and smoking-related risk predictors.



CONCLUSION: Risk model-based screening is more cost-effective than the USPSTF recommendation, thus warranting further consideration.



PRIMARY FUNDING SOURCE: National Cancer Institute (NCI).},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36746516,

title = {Partial response in non-resectable adenosquamous carcinoma of the pancreas with high tumour mutation burden treated with gemcitabine, nab-paclitaxel and pembrolizumab},

author = {Rodrigo Paredes de la Fuente and James W Doolin and Mary Linton Peters},

doi = {10.1136/bcr-2022-251936},

issn = {1757-790X},

year  = {2023},

date = {2023-02-01},

journal = {BMJ Case Rep},

volume = {16},

number = {2},

abstract = {A previously healthy man in his 60s was diagnosed with a rare histological subtype of pancreatic cancer, adenosquamous carcinoma. After somatic mutation profiling, it was found that the tumour had microsatellite instability status high and a high tumour mutational burden. The patient was started on combination therapy with gemcitabine, nab-paclitaxel and pembrolizumab. Tumour size and biomarkers showed a dramatic response eventually leading to the patient being transitioned to maintenance therapy with pembrolizumab. The patient has demonstrated continued response since the start of the treatment. This is the first report in the literature showing a sustained response in this type of neoplasm that was treated with a checkpoint inhibitor, and thus adds to the evidence supporting universal somatic testing in all pancreatic cancers for a tailored approach to therapy.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36549175,

title = {Cervical cancer geographical burden analyzer: An interactive, open-access tool for understanding geographical disease burden in patients with recurrent or metastatic cervical cancer},

author = {Tara Castellano and Kathleen Moore and Jie Ting and Christina Washington and Yasin Yildiz and Andy Surinach and Kalyani Sonawane and Jagpreet Chhatwal and Turgay Ayer},

doi = {10.1016/j.ygyno.2022.12.004},

issn = {1095-6859},

year  = {2023},

date = {2023-02-01},

urldate = {2022-12-01},

journal = {Gynecol Oncol},

volume = {169},

pages = {113--117},

abstract = {OBJECTIVE: Cervical cancer (CC) disproportionately affects women based on socioeconomic status and racial/ethnic background. There is limited research in quantifying and visualizing whether substantial geographical disparities in the US exist with respect to CC burden, and especially with respect to recurrent or metastatic CC (r/mCC) disease burden. Identifying regions with higher r/mCC burden may help inform effective healthcare resource allocation and navigating patients to appropriate care.



METHODS: We conducted a retrospective analysis of the 2015-2020 MarketScan® Commercial and Supplemental Medicare claims data; r/mCC burden was estimated as the number of patients initiating r/mCC systemic therapy over CC-diagnosed patients for each of the 410 metropolitan statistical areas (MSAs) considered. We developed a public, web-based tool, the Cervical Cancer Geographical Disease Burden Analyzer (Cervical Cancer Geo-Analyzer, http://www.geo-analyzer.org), that allows users to visualize r/mCC burden across MSAs over multiple years.



RESULTS: There was considerable variation in r/mCC burden across MSAs, with a range of 0-83.3%. Burden increased in Boston-Cambridge-Newton, MA (r/mCC to CC ratio: 41% in 2018 to 50% in 2020), and Sacramento-Roseville-Arden-Arcade, CA (33% in 2018 to 50% in 2020). On the other hand, while r/mCC burden remained high, it decreased in Grand Rapids, MI (55% in 2018 to 31% in 2020) and San Francisco-Oakland-Hayward, CA (40% in 2018 to 26% in 2020). There were regions with sparse or no data, suggesting a need for more representative data capture.



CONCLUSION: The Cervical Geo-Analyzer is a tool to visualize areas with high need for CC interventions. It also builds the foundation for further work to understand local risk factors of disease burden, identify populations of interest, characterize health disparities of CC or r/mCC and inform targeted interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37260919b,

title = {Occupational therapy for persons with cognitive impairments},

author = {Petra Schnell-Inderst and Annette Conrads-Frank and Igor Stojkov and Cornelia Krenn and Lisa-Maria Kofler and Uwe Siebert},

doi = {10.3205/000316},

issn = {1612-3174},

year  = {2023},

date = {2023-01-01},

journal = {Ger Med Sci},

volume = {21},

pages = {Doc02},

abstract = {BACKGROUND: Damage to the central nervous system can occur in adulthood, for example, due to stroke, trauma, tumours, or chronic diseases. After damage to the central nervous system, cognitive impairments occur in addition to physical limitations. Occupational therapy is most often prescribed for neurological diagnoses, including stroke and traumatic brain injury.nnMETHODS: The health technology assessment (HTA) report this HTA article is based on investigates the clinical effectiveness, cost-effectiveness, and patient-related, social and ethical aspects of occupational therapy for patients with cognitive impairments compared to no occupational therapy. In addition, the effects of different occupational therapy interventions with and without cognitive components were compared in an explorative overview. Patients with moderate or severe dementia are excluded from the assessment. Systematic overviews, that is, systematic reviews of systematic reviews, were conducted.nnRESULTS: For the evaluation of clinical effectiveness, a total of nine systematic reviews were included. No systematic review was identified for the assessment of costs or cost-effectiveness. Five systematic reviews were included for the assessment of patient and social aspects. For the assessment of clinical effectiveness compared with no occupational therapy, five systematic reviews comprising 20 randomised controlled trials with a total of 1,316 subjects reported small positive effects for the outcomes "global cognitive function" and "activities of daily living" as well as a non-quantified positive effect on the outcomes "health-related quality of life" and "behavioural control". No effect was found for individual components of cognition and measures of perception. The quality of the evidence for all outcomes is low due to a high risk of bias. In the supplementary presentations, no positive effects could be demonstrated on the basis of the available evidence. The quality of this evidence was not assessed. For the assessment of patient and social aspects, five systematic reviews on patients with a stroke or a traumatic brain injury - without specification regarding cognitive deficits or studies with their relatives - were included. It was reported that patients and family caregivers go through different phases of rehabilitation in which the discharge home is a decisive turning point. The discharge home represents a crucial breaking point. Regaining an active, self-determining role is a process that requires therapists to find the right level of support for patients and relatives. For the assessment of ethical aspects, nine documents were included. We identified ethical problem-solving models for occupational therapy and 16 ethical aspects in occupational therapy for cognitive deficits. The central theme of the analysis is the limited autonomy due to the consequences of the disease as well as the resulting tensions with those treating the patient.nnCONCLUSIONS: Based on this systematic overview, it can neither be proven nor excluded with certainty that occupational therapy for cognitive impairment is an effective therapy for adult patients with central nervous system injuries compared to no occupational therapy. There is a lack of randomised trials with sufficient sample size, well-defined interventions, and comparable concomitant therapies in the control groups, but there is also a lack of well-designed observational studies in routine care and health economic studies. The identified systematic reviews on patient and social aspects provide information on the needs of patients after stroke or traumatic brain injury and their relatives, but there is a lack of studies on this aspect in German-speaking countries. For the ethical assessment, in addition to the identified theoretical models for solving ethical conflicts in occupational therapy, more empirical studies on ethical aspects with patients with cognitive deficits and their relatives as well as occupational therapists are needed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid37260919,

title = {Occupational therapy for persons with cognitive impairments},

author = {Petra Schnell-Inderst and Annette Conrads-Frank and Igor Stojkov and Cornelia Krenn and Lisa-Maria Kofler and Uwe Siebert},

doi = {10.3205/000316},

issn = {1612-3174},

year  = {2023},

date = {2023-01-01},

journal = {Ger Med Sci},

volume = {21},

pages = {Doc02},

abstract = {BACKGROUND: Damage to the central nervous system can occur in adulthood, for example, due to stroke, trauma, tumours, or chronic diseases. After damage to the central nervous system, cognitive impairments occur in addition to physical limitations. Occupational therapy is most often prescribed for neurological diagnoses, including stroke and traumatic brain injury.nnMETHODS: The health technology assessment (HTA) report this HTA article is based on investigates the clinical effectiveness, cost-effectiveness, and patient-related, social and ethical aspects of occupational therapy for patients with cognitive impairments compared to no occupational therapy. In addition, the effects of different occupational therapy interventions with and without cognitive components were compared in an explorative overview. Patients with moderate or severe dementia are excluded from the assessment. Systematic overviews, that is, systematic reviews of systematic reviews, were conducted.nnRESULTS: For the evaluation of clinical effectiveness, a total of nine systematic reviews were included. No systematic review was identified for the assessment of costs or cost-effectiveness. Five systematic reviews were included for the assessment of patient and social aspects. For the assessment of clinical effectiveness compared with no occupational therapy, five systematic reviews comprising 20 randomised controlled trials with a total of 1,316 subjects reported small positive effects for the outcomes "global cognitive function" and "activities of daily living" as well as a non-quantified positive effect on the outcomes "health-related quality of life" and "behavioural control". No effect was found for individual components of cognition and measures of perception. The quality of the evidence for all outcomes is low due to a high risk of bias. In the supplementary presentations, no positive effects could be demonstrated on the basis of the available evidence. The quality of this evidence was not assessed. For the assessment of patient and social aspects, five systematic reviews on patients with a stroke or a traumatic brain injury - without specification regarding cognitive deficits or studies with their relatives - were included. It was reported that patients and family caregivers go through different phases of rehabilitation in which the discharge home is a decisive turning point. The discharge home represents a crucial breaking point. Regaining an active, self-determining role is a process that requires therapists to find the right level of support for patients and relatives. For the assessment of ethical aspects, nine documents were included. We identified ethical problem-solving models for occupational therapy and 16 ethical aspects in occupational therapy for cognitive deficits. The central theme of the analysis is the limited autonomy due to the consequences of the disease as well as the resulting tensions with those treating the patient.nnCONCLUSIONS: Based on this systematic overview, it can neither be proven nor excluded with certainty that occupational therapy for cognitive impairment is an effective therapy for adult patients with central nervous system injuries compared to no occupational therapy. There is a lack of randomised trials with sufficient sample size, well-defined interventions, and comparable concomitant therapies in the control groups, but there is also a lack of well-designed observational studies in routine care and health economic studies. The identified systematic reviews on patient and social aspects provide information on the needs of patients after stroke or traumatic brain injury and their relatives, but there is a lack of studies on this aspect in German-speaking countries. For the ethical assessment, in addition to the identified theoretical models for solving ethical conflicts in occupational therapy, more empirical studies on ethical aspects with patients with cognitive deficits and their relatives as well as occupational therapists are needed.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36896035,

title = {Incorporating Well-Being into Mentorship Meetings: A Case Demonstration at Massachusetts General Hospital Department of Surgery a Harvard Medical School Affiliate},

author = {Beth Frates and David Cron and Carrie Cunningham Lubitz and Genevieve Boland and Sunita Srivastava and Richard A Hodin and Antonia E Stephen and Kelsey Carney and Roy Phitayakorn},

doi = {10.1177/15598276221105830},

issn = {1559-8284},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {Am J Lifestyle Med},

volume = {17},

number = {2},

pages = {213--215},

abstract = {Surgeons have been under great pressure during the COVID pandemic. Their careers are filled with fast paced decisions, life and death situations, and long hours at work. The COVID pandemic created more tasks and even new responsibilities at times, but when the operating rooms were closed down, there was less work. The COVID experience invited the opportunity to rethink mentoring in the surgery department at the Massachusetts General Hospital. The leadership experimented with a new style of mentoring which involved a team approach. In addition, they tried something else that was new: adding a lifestyle medicine expert and wellness coach to the mentoring team. The program was tested on 13 early stage surgeons who found the experience to be beneficial, and they commented that they wished they had it even earlier in their careers. Including a non-surgeon who was a lifestyle medicine physician and wellness coach added an element of whole person health that was acceptable to the surgeons and even embraced as the majority of them elected to follow up with one on one coaching after the mentoring meeting. This team mentoring program with senior surgeons and a lifestyle medicine expert is one that can be explored by other departments and other hospitals given its success at the department of surgery at Massachusetts General Hospital.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36350592,

title = {Racial and Ethnic Disparities in Buprenorphine Treatment Duration in the US},

author = {Huiru Dong and Erin J Stringfellow and W Alton Russell and Mohammad S Jalali},

doi = {10.1001/jamapsychiatry.2022.3673},

issn = {2168-6238},

year  = {2023},

date = {2023-01-01},

urldate = {2023-01-01},

journal = {JAMA Psychiatry},

volume = {80},

issue = {1},

pages = {93-95},

abstract = {Buprenorphine is used to treat opioid use disorder (OUD) and reduce overdose risk.1 Duration of buprenorphine treatment is a measure of quality of care; longer retention is associated with superior clinical outcomes. Racial and ethnic minority patients are more likely to discontinue buprenorphine treatment earlier than White patients. To our knowledge, no nationally representative studies have examined buprenorphine treatment duration over time across racial and ethnic groups. This information is needed to close the racial and ethnic gap in treatment retention for OUD.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36210185,

title = {Limited disease progression in endocrine surgery patients with treatment delays due to COVID-19},

author = {Reagan A Collins and Catherine DiGennaro and Toni Beninato and Rajshri M Gartland and Natalia Chaves and Jordan M Broekhuis and Lekha Reddy and Jenna Lee and Angelina Deimiller and Maeve M Alterio and Michael J Campbell and Yeon Joo Lee and Tyler K Khilnani and Latoya A Stewart and Mollie A O'Brien and Miguel Valdivia Y Alvarado and Feibi Zheng and David McAneny and Rachel Liou and Catherine McManus and Sophie Y Dream and Tracy S Wang and Tina W Yen and Amal Alhefdhi and Brendan M Finnerty and Thomas J Fahey and Claire E Graves and Amanda M Laird and Matthew A Nehs and Frederick Thurston Drake and James A Lee and Christopher R McHenry and Benjamin C James and Janice L Pasieka and Jennifer H Kuo and Carrie Cunningham Lubitz},

doi = {10.1016/j.surg.2022.06.043},

issn = {1532-7361},

year  = {2023},

date = {2023-01-01},

journal = {Surgery},

volume = {173},

number = {1},

pages = {93--100},

abstract = {BACKGROUND: The COVID-19 pandemic profoundly impacted the delivery of care and timing of elective surgical procedures. Most endocrine-related operations were considered elective and safe to postpone, providing a unique opportunity to assess clinical outcomes under protracted treatment plans.



METHODS: American Association of Endocrine Surgeon members were surveyed for participation. A Research Electronic Data Capture survey was developed and distributed to 27 institutions to assess the impact of COVID-19-related delays. The information collected included patient demographics, primary diagnosis, resumption of care, and assessment of disease progression by the surgeon.



RESULTS: Twelve out of 27 institutions completed the survey (44.4%). Of 850 patients, 74.8% (636) were female; median age was 56 (interquartile range, 44-66) years. Forty percent (34) of patients had not been seen since their original surgical appointment was delayed; 86.2% (733) of patients had a delay in care with women more likely to have a delay (87.6% vs 82.2% of men, χ = 3.84, P = .05). Median duration of delay was 70 (interquartile range, 42-118) days. Among patients with a delay in care, primary disease site included thyroid (54.2%), parathyroid (37.2%), adrenal (6.5%), and pancreatic/gastrointestinal neuroendocrine tumors (1.3%). In addition, 4.0% (26) of patients experienced disease progression and 4.1% (24) had a change from the initial operative plan. The duration of delay was not associated with disease progression (P = .96) or a change in operative plan (P = .66).



CONCLUSION: Although some patients experienced disease progression during COVID-19 delays to endocrine disease-related care, most patients with follow-up did not. Our analysis indicated that temporary delay may be an acceptable course of action in extreme circumstances for most endocrine-related surgical disease.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36113098,

title = {Cost-Effectiveness and Value-of-Information Analysis Using Machine Learning-Based Metamodeling: A Case of Hepatitis C Treatment},

author = {John Austin McCandlish and Turgay Ayer and Jagpreet Chhatwal},

doi = {10.1177/0272989X221125418},

issn = {1552-681X},

year  = {2023},

date = {2023-01-01},

journal = {Med Decis Making},

volume = {43},

number = {1},

pages = {68--77},

abstract = {BACKGROUND: Metamodels can address some of the limitations of complex simulation models by formulating a mathematical relationship between input parameters and simulation model outcomes. Our objective was to develop and compare the performance of a machine learning (ML)-based metamodel against a conventional metamodeling approach in replicating the findings of a complex simulation model.



METHODS: We constructed 3 ML-based metamodels using random forest, support vector regression, and artificial neural networks and a linear regression-based metamodel from a previously validated microsimulation model of the natural history hepatitis C virus (HCV) consisting of 40 input parameters. Outcomes of interest included societal costs and quality-adjusted life-years (QALYs), the incremental cost-effectiveness (ICER) of HCV treatment versus no treatment, cost-effectiveness analysis curve (CEAC), and expected value of perfect information (EVPI). We evaluated metamodel performance using root mean squared error (RMSE) and Pearson's  on the normalized data.



RESULTS: The  values for the linear regression metamodel for QALYs without treatment, QALYs with treatment, societal cost without treatment, societal cost with treatment, and ICER were 0.92, 0.98, 0.85, 0.92, and 0.60, respectively. The corresponding  values for our ML-based metamodels were 0.96, 0.97, 0.90, 0.95, and 0.49 for support vector regression; 0.99, 0.83, 0.99, 0.99, and 0.82 for artificial neural network; and 0.99, 0.99, 0.99, 0.99, and 0.98 for random forest. Similar trends were observed for RMSE. The CEAC and EVPI curves produced by the random forest metamodel matched the results of the simulation output more closely than the linear regression metamodel.



CONCLUSIONS: ML-based metamodels generally outperformed traditional linear regression metamodels at replicating results from complex simulation models, with random forest metamodels performing best.



HIGHLIGHTS: Decision-analytic models are frequently used by policy makers and other stakeholders to assess the impact of new medical technologies and interventions. However, complex models can impose limitations on conducting probabilistic sensitivity analysis and value-of-information analysis, and may not be suitable for developing online decision-support tools.Metamodels, which accurately formulate a mathematical relationship between input parameters and model outcomes, can replicate complex simulation models and address the above limitation.The machine learning-based random forest model can outperform linear regression in replicating the findings of a complex simulation model. Such a metamodel can be used for conducting cost-effectiveness and value-of-information analyses or developing online decision support tools.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36527244,

title = {A population-based cohort of adult patients with diabetes mellitus in a Western District of Austria: The Diabetes Landeck cohort},

author = {Veronika Haslwanter and Ursula Rochau and Uwe Siebert and Hans-Robert Sch\"{o}nherr and Willi Oberaigner},

doi = {10.1002/edm2.395},

issn = {2398-9238},

year  = {2022},

date = {2022-12-16},

urldate = {2022-12-01},

journal = {Endocrinol Diabetes Metab},

pages = {e395},

abstract = {INTRODUCTION: Diabetes mellitus (DM) has become an important and exacerbating health epidemic, with severe consequences for both patients and health systems. The National Diabetes Strategy of Austria addresses the lack of high-quality data on DM in Austria and the need for developing a national data network. The aims of our study are to establish a cohort including all adult diabetes patients in a district in western Austria, describe the demographic and clinical characteristics of this cohort, and provide an estimation of diabetes prevalence.



METHODS: We recruited a population-based cohort of adult patients with a diagnosis of DM in cooperation with a network of all caregivers. Data collection was based on a case report form, including patient characteristics, clinical parameters and long-term complications.



RESULTS: In total, 1845 patients with DM were recruited and analysed. We observed an overall prevalence of 5.3% [95% CI: 5.0%-5.5%]. For the subsequent main analysis, we included 1755 patients with DM after excluding 90 patients with gestational DM. There were significant differences between genders in the distribution of specific clinical parameters, patient characteristics, and the long-term complications diabetic foot, amputation and cardiovascular disease.



CONCLUSION: To the best of our knowledge, we established the first diabetes cohort study in Austria. Prevalence and the proportion of specific long-term complications were lower when compared to the international context. We assume that the Diabetes Landeck Cohort has reached a high degree of completeness; however, we were not able to identify independent data sources for a valid check of completeness.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36506039,

title = {Factors associated with receipt of second-line recurrent or metastatic cervical cancer treatment in the United States: A retrospective administrative claims analysis},

author = {Kalyani Sonawane and Tara Castellano and Christina Washington and Jie Ting and Andy Surinach and Carol Kirshner and Jagpreet Chhatwal and Turgay Ayer and Kathleen Moore},

doi = {10.1016/j.gore.2022.101101},

issn = {2352-5789},

year  = {2022},

date = {2022-12-13},

urldate = {2022-12-13},

journal = {Gynecol Oncol Rep},

volume = {44},

number = {Suppl 1},

pages = {101121},

abstract = {PURPOSE: Contemporary, real-world data on eligible patients receiving treatment following progression on first-line (1L) recurrent or metastatic cervical cancer (r/mCC) therapy are needed to inform treatment algorithms and identify potential gaps in the r/mCC care continuum.



METHODS: This study estimated the prevalence and predictors of second-line (2L) r/mCC therapy among 1L-treated patients using the 2015-2020 IBM MarketScan® commercial claims database. Women ≥ 18 years diagnosed with cervical cancer and treated with first-line systemic therapies were identified and followed for 12 months from their 1L therapy end date. Women with claims for a new therapy after 60 days but no later than 365 days from the end of 1L treatment were identified as those who progressed and received 2L therapy for r/mCC. Descriptive statistics examined baseline cohort characteristics and multivariable logistic regression model examined the factors associated with receiving 2L treatment.



RESULTS: We identified 384 1L-treated patients with r/mCC with ≥ 12 months of follow-up post-1L treatment. During follow-up, over half (51.0 %) of the 1L-treated r/mCC patients received 2L treatment. Patients from the South and Midwest had a lower likelihood of receiving 2L treatment compared with those living in the Northeast (adjusted odds ratio [aOR] = 0.43; 0.23-0.84) and (aOR = 0.52; 0.28-0.95, respectively). Patients not treated with bevacizumab in 1L were also less likely to receive 2L therapy (aOR = 0.65; 0.43-0.99).



CONCLUSION: Additional research and targeted outreach efforts are needed to understand geography-, population-, or practice-specific barriers impacting access to 2L therapy among patients with r/mCC.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35166973,

title = {Determinants of willingness to pay for health services: a systematic review of contingent valuation studies},

author = {Caroline Steigenberger and Magdalena Flatscher-Thoeni and Uwe Siebert and Andrea M Leiter},

doi = {10.1007/s10198-022-01437-x},

issn = {1618-7601},

year  = {2022},

date = {2022-12-01},

journal = {Eur J Health Econ},

volume = {23},

number = {9},

pages = {1455--1482},

abstract = {INTRODUCTION: Stated preference studies are a valuable tool to elicit respondents' willingness to pay (WTP) for goods or services, especially in situations where no market valuation exists. Contingent valuation (CV) is a widely used approach among stated-preference techniques for eliciting WTP if prices do not exist or do not reflect actual costs, for example, when services are covered by insurance. This review aimed to provide an overview of relevant factors determining WTP for health services to support variable selection.



METHODS: A comprehensive systematic literature search and review of CV studies assessing determinants of WTP for health services was conducted, including 11 electronic databases. Two of the authors made independent decisions on the eligibility of studies. We extracted all determinants used and related p values for the effect sizes (e.g. reported in regression models with WTP for a health service as outcome variable). Determinants were summarised in systematic evidence tables and structured by thematic domains.



RESULTS: We identified 2082 publications, of which 202 full texts were checked for eligibility. We included 62 publications on 61 studies in the review. Across all studies, we identified 22 WTP determinants and other factors from 5 thematic domains: sociodemographic characteristics, perceived threat, perceived benefit, perceived barriers, and other information.



CONCLUSION: Our review provides evidence on 22 relevant determinants of WTP for health services, which may be used for variable selection and as guidance for planning CV surveys. Endogeneity should be carefully considered before interpreting these determinants as causal factors and potential intervention targets.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36252741,

title = {Causal analyses with target trial emulation for real-world evidence removed large self-inflicted biases: Systematic bias assessment of ovarian cancer treatment effectiveness},

author = {Felicitas Kuehne and Marjan Arvandi and Lisa M Hess and Douglas E Faries and Raffaella Matteucci Gothe and Holger Gothe and Julie Beyrer and Alain Gustave Zeimet and Igor Stojkov and Nikolai M\"{u}hlberger and Willi Oberaigner and Christian Marth and Uwe Siebert},

doi = {10.1016/j.jclinepi.2022.10.005},

issn = {1878-5921},

year  = {2022},

date = {2022-12-01},

urldate = {2022-10-01},

journal = {J Clin Epidemiol},

volume = {152},

pages = {269-280},

abstract = {BACKGROUND: Drawing causal conclusions from real-world data (RWD) poses methodological challenges and risk of bias. We aimed to systematically assess the type and impact of potential biases that may occur when analyzing RWD using the case of progressive ovarian cancer.



METHODS: We retrospectively compared overall survival with and without second-line chemotherapy using electronic medical records. Potential biases were determined using directed acyclic graphs. We followed a stepwise analytic approach ranging from crude analysis and multivariable-adjusted Cox model up to a full causal analysis using a marginal-structural-Cox-model (MSCM) with replicates emulating a reference randomized controlled trial. To assess biases, we compared effect estimates (hazard ratios [HRs]) of each approach to the HR of the reference trial.



RESULTS: The reference trial showed a HR for second-line versus delayed-therapy of 1.01 (95% confidence interval [95%CI]: 0.82-1.25). The corresponding HRs from the RWD analysis ranged from 0.51 for simple baseline adjustments to 1.41 (95%CI 1.22-1.64) accounting for immortal time bias with time-varying covariates. Causal trial emulation yielded a HR of 1.12 (95%CI: 0.96-1.28).



CONCLUSIONS: Our study, using ovarian cancer as an example, shows the importance of a thorough causal design and analysis if one is expecting RWD to emulate clinical trial results.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35608673,

title = {Comorbidities and COVID-19 hospitalization, ICU admission and hospital mortality in Austria : A retrospective cohort study},

author = {Lukas Rainer and Florian Bachner and Karin Eglau and Herwig Ostermann and Uwe Siebert and Martin Zuba},

doi = {10.1007/s00508-022-02036-9},

issn = {1613-7671},

year  = {2022},

date = {2022-12-01},

journal = {Wien Klin Wochenschr},

volume = {134},

number = {23-24},

pages = {856--867},

abstract = {BACKGROUND: The protection of vulnerable populations is a central task in managing the Coronavirus disease 2019 (COVID-19) pandemic to avoid severe courses of COVID-19 and the risk of healthcare system capacity being exceeded. To identify factors of vulnerability in Austria, we assessed the impact of comorbidities on COVID-19 hospitalization, intensive care unit (ICU) admission, and hospital mortality.



METHODS: A retrospective cohort study was performed including all patients with COVID-19 in the period February 2020 to December 2021 who had a previous inpatient stay in the period 2015-2019 in Austria. All patients with COVID-19 were matched to population controls on age, sex, and healthcare region. Multiple logistic regression was used to estimate adjusted odds ratios (OR) of included factors with 95% confidence intervals (CI).



RESULTS: Hemiplegia or paraplegia constitutes the highest risk factor for hospitalization (OR 1.61, 95% CI 1.44-1.79), followed by COPD (OR 1.48, 95% CI 1.43-1.53) and diabetes without complications (OR 1.41, 95% CI 1.37-1.46). The highest risk factors for ICU admission are renal diseases (OR 1.76, 95% CI 1.61-1.92), diabetes without complications (OR 1.57, 95% CI 1.46-1.69) and COPD (OR 1.53, 95% CI 1.41-1.66). Hemiplegia or paraplegia, renal disease and COPD constitute the highest risk factors for hospital mortality, with ORs of 1.5. Diabetes without complications constitutes a significantly higher risk factor for women with respect to all three endpoints.



CONCLUSION: We contribute to the literature by identifying sex-specific risk factors. In general, our results are consistent with the literature, particularly regarding diabetes as a risk factor for severe courses of COVID-19. Due to the observational nature of our data, caution is warranted regarding causal interpretation. Our results contribute to the protection of vulnerable populations and may be used for targeting further pharmaceutical interventions.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35467475,

title = {Opioid overdose decedent characteristics during COVID-19},

author = {Gian-Gabriel P Garcia and Erin J Stringfellow and Catherine DiGennaro and Nicole Poellinger and Jaden Wood and Sarah Wakeman and Mohammad S Jalali},

doi = {10.1080/07853890.2022.2067350},

issn = {1365-2060},

year  = {2022},

date = {2022-12-01},

journal = {Ann Med},

volume = {54},

number = {1},

pages = {1081--1088},

abstract = {INTRODUCTION: Alongside the emergence of COVID-19 in the United States, several reports highlighted increasing rates of opioid overdose from preliminary data. Yet, little is known about how state-level opioid overdose death trends and decedent characteristics have evolved using official death records.



METHODS: We requested vital statistics data from 2018-2020 from all 50 states and the District of Columbia, receiving data from 14 states. Accounting for COVID-19, we excluded states without data past March 2020, leaving 11 states for analysis. We defined state-specific analysis periods from March 13 until the latest reliable date in each state's data, then conducted retrospective year-over-year analyses comparing opioid-related overdose death rates, the presence of specific opioids and other psychoactive substances, and decedents' sex, race, and age from 2020 to 2019 and 2019 to 2018 within each state's analysis period. We assessed whether significant changes in 2020 vs. 2019 in opioid overdose deaths were new or continuing trends using joinpoint regression.



RESULTS: We found significant increases in opioid-related overdose death rates in Alaska (55.3%), Colorado (80.2%), Indiana (40.1%), Nevada (50.0%), North Carolina (30.5%), Rhode Island (29.6%), and Virginia (66.4%) - all continuing previous trends. Increases in synthetic opioid-involved overdose deaths were new in Alaska (136.5%), Indiana (27.6%), and Virginia (16.5%), whilst continuing in Colorado (44.4%), Connecticut (3.6%), Nevada (75.0%), and North Carolina (14.6%). We found new increases in male decedents in Indiana (12.0%), and continuing increases in Colorado (15.2%). We also found continuing increases in Black non-Hispanic decedents in Massachusetts (43.9%) and Virginia (33.7%).



CONCLUSION: This research analyzes vital statistics data from 11 states, highlighting new trends in opioid overdose deaths and decedent characteristics across 10 of these states. These findings can inform state-specific public health interventions and highlight the need for timely and comprehensive fatal opioid overdose data, especially amidst concurrent crises such as COVID-19. Key messages:Our results highlight shifts in opioid overdose trends during the COVID-19 pandemic that cannot otherwise be extracted from aggregated or provisional opioid overdose death data such as those published by the Centres for Disease Control and Prevention.Fentanyl and other synthetic opioids continue to drive increases in fatal overdoses, making it difficult to separate these trends from any possible COVID-19-related factors.Black non-Hispanic people are making up an increasing proportion of opioid overdose deaths in some states.State-specific limitations and variations in data-reporting for vital statistics make it challenging to acquire and analyse up-to-date data on opioid-related overdose deaths. More timely and comprehensive data are needed to generate broader insights on the nature of the intersecting opioid and COVID-19 crises.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36436793,

title = {Disability-Adjusted Life Years for Drug Overdose Crisis and COVID-19 Are Comparable During the Two Years of Pandemic in the United States},

author = {Qiushi Chen and Paul M Griffin and Sarah S Kawasaki},

doi = {10.1016/j.jval.2022.11.010},

issn = {1524-4733},

year  = {2022},

date = {2022-11-01},

journal = {Value Health},

abstract = {OBJECTIVES: The drug overdose crisis with shifting patterns from primarily opioid to polysubstance uses and COVID-19 infections are two concurrent public health crises in the United States, affecting the population of sizes in different magnitudes (approximately <10 million for substance use disorder (SUD) and drug overdoses vs. 80 million for COVID-19 within two years of the pandemic). Our objective is to compare the relative scale of disease burden for the two crises within a common framework, which could help inform policymakers with resource allocation and prioritization strategies.



METHODS: We calculated disability-adjusted life years (DALYs) for SUD (including opioids and stimulants) and COVID-19 infections, respectively. We collected estimates for SUD prevalence, overdose deaths, COVID-19 cases and deaths, disability weights, and life expectancy from multiple publicly available sources. We then compared age distributions of estimated DALYs.



RESULTS: We estimated a total burden of 13.83 million DALYs for SUD and drug overdoses and 15.03 million DALYs for COVID-19 in two years since March 2020. COVID-19 burden was dominated by the fatal burden (>95% of total DALYs), whereas SUD burden was attributed to both fatal (53%) and non-fatal burdens (47%). The highest disease burden was among individuals aged 30-39 for SUD (27%) and 50-64 for COVID-19 (31%).



CONCLUSIONS: Despite the smaller size of the affected population, SUD and drug overdoses resulted in comparable disease burden to the COVID-19 pandemic. Additional resources supporting evidence-based interventions in prevention and treatment may be warranted to ameliorate SUD and drug overdoses during both the pandemic and post-pandemic recovery.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36414968,

title = {DNA methylation-based detection and prediction of cervical intraepithelial neoplasia grade 3 and invasive cervical cancer with the WID™-qCIN test},

author = {Chiara Herzog and Karin Sundstr\"{o}m and Allison Jones and Iona Evans and James E Barrett and Jiangrong Wang and Elisa Redl and Lena Schreiberhuber and Laura Costas and Sonia Paytubi and Lukas Dostalek and Michal Zikan and David Cibula and Gaby Sroczynski and Uwe Siebert and Joakim Dillner and Martin Widschwendter},

doi = {10.1186/s13148-022-01353-0},

issn = {1868-7083},

year  = {2022},

date = {2022-11-01},

journal = {Clin Epigenetics},

volume = {14},

number = {1},

pages = {150},

abstract = {BACKGROUND: Cervical screening using primary human papilloma virus (HPV) testing and cytology is being implemented in several countries. Cytology as triage for colposcopy referral suffers from several shortcomings. HPV testing overcomes some of these but lacks specificity in women under 30. Here, we aimed to develop and validate an automatable triage test that is highly sensitive and specific independently of age and sample heterogeneity, and predicts progression to CIN3+ in HPV+ patients.



RESULTS: The WID™-qCIN, assessing three regions in human genes DPP6, RALYL, and GSX1, was validated in both a diagnostic (case-control) and predictive setting (nested case-control), in a total of 761 samples. Using a predefined threshold, the sensitivity of the WID™-qCIN test was 100% and 78% to detect invasive cancer and CIN3, respectively. Sensitivity to detect CIN3+ was 65% and 83% for women < and ≥ 30 years of age. The specificity was 90%. Importantly, the WID™-qCIN test identified 52% of ≥ 30-year-old women with a cytology negative (cyt-) index sample who were diagnosed with CIN3 1-4 years after sample donation.



CONCLUSION: We identified suitable DNAme regions in an epigenome-wide discovery using HPV+ controls and CIN3+ cases and established the WID™-qCIN, a PCR-based DNAme test. The WID™-qCIN test has a high sensitivity and specificity that may outperform conventional cervical triage tests and can in an objective, cheap, and scalable fashion identify most women with and at risk of (pre-)invasive cervical cancer. However, evaluation was limited to case-control settings and future studies will assess performance and generalisability in a randomised controlled trial.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36327437,

title = {Longitudinal Associations of Risk Factors and Hepatocellular Carcinoma in Patients With Cured Hepatitis C Virus Infection},

author = {Jennifer R Kramer and Yumei Cao and Liang Li and Donna Smith and Jagpreet Chhatwal and Hashem B El-Serag and Fasiha Kanwal},

doi = {10.14309/ajg.0000000000001968},

issn = {1572-0241},

year  = {2022},

date = {2022-11-01},

journal = {Am J Gastroenterol},

volume = {117},

number = {11},

pages = {1834--1844},

abstract = {INTRODUCTION: There are limited data on the effect and evolution of risk factors for hepatocellular carcinoma (HCC) in patients with virologically cured hepatitis C virus (HCV) infection.



METHODS: We conducted a retrospective cohort study of patients with HCV who achieved sustained virological response with direct-acting antivirals from 130 Veterans Administration hospitals during 2014-2018, followed through 2021. Cox proportional hazards models were constructed at 3 landmark times (baseline and 12 and 24 months after sustained virological response) to examine associations between demographic, clinical, and behavioral factors and HCC risk, stratified by cirrhosis status.



RESULTS: Among 92,567 patients (32% cirrhosis), 3,247 cases of HCC were diagnosed during a mean follow-up of 2.5 years. In patients with cirrhosis, male sex (hazard ratios [HR]: 1.89, 1.93, and 1.99), cirrhosis duration ≥5 years (HR: 1.71, 1.79, and 1.34), varices (HR: 1.73, 1.60, and 1.56), baseline albumin (HR: 0.48, 0.47, and 0.49), and change in albumin (HR: 0.82 and 0.90) predicted HCC risk at each landmark time. HCV genotype 3, previous treatment, bilirubin, smoking, and race influenced HCC risk at baseline, but their effects attenuated over time. In patients without cirrhosis, diabetes (HR: 1.54, 1.42, and 1.47) and hypertension (HR: 1.59, 1.65, and 1.74) were associated with HCC risk at all landmark times. Changes in fibrosis-4 scores over time were associated with HCC risk both in patients with and without cirrhosis.



DISCUSSION: Risk factors for HCC were different in patients with and without cirrhosis and some also evolved during follow-up. These factors can help with risk stratification and HCC surveillance decisions in patients with cured HCV.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid36229503,

title = {Longitudinal bioluminescence imaging to monitor breast tumor growth and treatment response using the chick chorioallantoic membrane model},

author = {Sumreen Javed and Sepideh Soukhtehzari and Nazarine Fernandes and Karla C Williams},

doi = {10.1038/s41598-022-20854-9},

issn = {2045-2322},

year  = {2022},

date = {2022-10-01},

journal = {Sci Rep},

volume = {12},

number = {1},

pages = {17192},

abstract = {The development of successful treatment regimens for breast cancer requires strong pre-clinical data generated in physiologically relevant pre-clinical models. Here we report the development of the chick embryo chorioallantoic membrane (CAM) model to study tumor growth and angiogenesis using breast cancer cell lines. MDA-MB-231 and MCF7 tumor cell lines were engrafted onto the chick embryo CAM to study tumor growth and treatment response. Tumor growth was evaluated through bioluminescence imaging and a significant increase in tumor size and vascularization was found over a 9-day period. We then evaluated the impact of anti-angiogenic drugs, axitinib and bevacizumab, on tumor growth and angiogenesis. Drug treatment significantly reduced tumor vascularization and size. Overall, our findings demonstrate that the chick embryo CAM is a clinically relevant model to monitor therapeutic response in breast cancer and can be used as a platform for drug screening to evaluate not only gross changes in tumor burden but physiological processes such as angiogenesis.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35999710,

title = {Assessing Bias and Limitations of Clinical Validation Studies of Molecular Diagnostic Tests for Indeterminate Thyroid Nodules: Systematic Review and Meta-Analysis},

author = {Catherine DiGennaro and Vahab Vahdat and Mohammad Jalali and Asmae Toumi and Tina Watson and G Scott Gazelle and Nathaniel Mercaldo and Carrie C Lubitz},

doi = {10.1089/thy.2022.0269},

issn = {1557-9077},

year  = {2022},

date = {2022-10-01},

urldate = {2022-09-26},

journal = {Thyroid},

volume = {32},

issue = {10},

pages = {1144-1157},

abstract = {BACKGROUND: Molecular tests for thyroid nodules with indeterminate fine needle aspiration results are increasingly used in clinical practice; however, true diagnostic summaries of these tests are unknown. A systematic review and meta-analysis were completed to (1) evaluate the accuracy of commercially available molecular tests for malignancy in indeterminate thyroid nodules and (2) quantify biases and limitations in studies which validate those tests.



METHODS: PubMed, EMBASE, and Web of Science were systematically searched through July 2021. English language articles that reported original clinical validation attempts of molecular tests for indeterminate thyroid nodules were included if they reported counts of true negative, true positive, false negative, and false positive results. We performed screening and full text review, followed by assessment of eight common biases and limitations, extraction of diagnostic and histopathological information, and meta-analysis of clinical validity using a bivariate linear mixed-effects model.



RESULTS: 49 studies were included. Meta-analysis of Afirma GEC (n=38 studies) revealed a sensitivity of 0.92 (95% CI: 0.90-0.94), specificity of 0.26 (0.20-0.32), negative likelihood ratio (LR-) of 0.32 (0.23-0.44), positive likelihood ratio (LR+) of 1.24 (1.15-1.35), and AUC of 0.83 (0.74-0.89). Afirma GSC (n=10) had a sensitivity of 0.94 (0.89-0.96), specificity of 0.38 (0.27-0.50), LR- of 0.18 (0.10-0.30), LR+ of 1.52 (1.28-1.87), and AUC of 0.91 (0.62-0.92). ThyroSeq v1 and v2 (n=10) had a sensitivity of 0.86 (0.82-0.90), specificity of 0.74 (0.59-0.85), LR- of 0.19 (0.13-0.26), LR+ of 3.52 (2.08-5.92), and AUC of 0.86 (0.81-0.90). ThyroSeq v3 (n=6) had a sensitivity of 0.92 (0.86-0.95), specificity of 0.41 (0.18-0.69), LR- of 0.24 (0.09-0.62), LR+ of 1.67 (1.09-2.98), and AUC of 0.90 (0.63-0.92). 14% of studies conducted blinded histopathologic review of excised thyroid nodules, and 8% made the decision to go to surgery blind to molecular test results.



CONCLUSIONS: Meta-analyses reveal high diagnostic accuracy of molecular tests for thyroid nodule assessment of malignancy risk; however, these studies are subject to several limitations. Limitations and their potential clinical impacts must be addressed and, when feasible, adjusted for using valid statistical methodologies.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{PETERS2022,

title = {‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬‬Genetic testing to guide screening for pancreatic ductal adenocarcinoma: Results of a microsimulation model},

author = {Mary Linton B. Peters and Andrew Eckel and Anna Lietz and Claudia Seguin and Peter Mueller and Chin Hur and Pari V. Pandharipande},

url = {https://www.sciencedirect.com/science/article/pii/S1424390322001703},

doi = {https://doi.org/10.1016/j.pan.2022.05.003},

issn = {1424-3903},

year  = {2022},

date = {2022-09-22},

urldate = {2022-05-31},

journal = {Pancreatology},

volume = {22},

issue = {6},

pages = {760-769},

abstract = {Background 

First-degree relatives (FDRs) of patients with pancreatic ductal adenocarcinoma (PDAC) have elevated PDAC risk, partially due to germline genetic variants. We evaluated the potential effectiveness of genetic testing to target MRI-based screening among FDRs. 

Methods 

We used a microsimulation model of PDAC, calibrated to Surveillance, Epidemiology, and End Results (SEER) data, to estimate the potential life expectancy (LE) gain of screening for each of the following groups of FDRs: indviduals who test positive for each of eight variants associated with elevated PDAC risk (e.g., BRCA2, CDKN2A); individuals who test negative; and individuals who do not test. Screening was assumed to take place if LE gains were achievable. We simulated multiple screening approaches, defined by starting age and frequency. Sensitivity analysis evaluated changes in results given varying model assumptions. 

Results 

For women, 92% of mutation carriers had projected LE gains from screening for PDAC, if screening strategies (start age, frequency) were optimized. Among carriers, LE gains ranged from 0.1 days (ATM + women screened once at age 70) to 510 days (STK11+ women screened annually from age 40). For men, LE gains were projected for all mutation carriers, ranging from 0.2 days (BRCA1+ men screened once at age 70) to 620 days (STK11+ men screened annually from age 40). For men and women who did not undergo genetic testing, or for whom testing showed no variant, screening yielded small LE benefit (0\textendash2.1 days). 

Conclusions 

Genetic testing of FDRs can inform targeted PDAC screening by identifying which FDRs may benefit.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35945907,

title = {Comparison of a multitarget blood test to ultrasound and alpha-fetoprotein for hepatocellular carcinoma surveillance: Results of a network meta-analysis},

author = {Amit G Singal and Benjamin Haaland and Neehar D Parikh and A Burak Ozbay and Carol Kirshner and Shubham Chakankar and Kyle Porter and Jagpreet Chhatwal and Turgay Ayer},

doi = {10.1002/hep4.2045},

issn = {2471-254X},

year  = {2022},

date = {2022-08-01},

journal = {Hepatol Commun},

abstract = {Ultrasound-based surveillance has suboptimal sensitivity for early detection of hepatocellular carcinoma (HCC) in patients with cirrhosis. There are several emerging alternatives, including a novel multitarget HCC blood test (Mt-HBT). We compared performance of mt-HBT against ultrasound with or without alpha-fetoprotein (AFP) for early HCC detection in patients with cirrhosis. Per the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines, two reviewers searched PubMed, Cochrane, Embase, and clinicaltrials.gov databases from January 1990 through December 2020 to identify studies reporting sensitivity and/or specificity of ultrasound and AFP for overall and early stage HCC detection in patients with cirrhosis. Mt-HBT diagnostic performance was derived from a clinical validation study. A network meta-analysis model was built for comparative assessment, and pooled estimates of sensitivity at a fixed specificity were estimated based on Bayesian binormal receiver operating characteristic models for each modality. Forty-one studies (comprising 62,517 patients with cirrhosis) met inclusion criteria. Ultrasound-alone sensitivity was 51.6% (95% credible interval [CrI], 43.3%-60.5%) for early stage HCC detection, which increased with the addition of AFP to 74.1% (95% CrI, 62.6%-82.4%); however, this was offset by decreased specificity (87.9% vs. 83.9%, respectively). With specificity fixed at 90%, mt-HBT sensitivity for early stage HCC detection was higher than ultrasound alone (18.2%; 95% CrI, 0.2%-37.7%) and similar to ultrasound with AFP (-3.3%; 95% CrI, -22.3%-17.4%). Pairwise posterior probabilities suggested a preference for mt-HBT over ultrasound alone in 97.4% of cases but only 36.3% of cases versus ultrasound with AFP. Conclusion: A blood-based mt-HBT has higher sensitivity than ultrasound alone for early stage HCC detection but similar sensitivity compared to ultrasound and AFP. Mt-HBT could be a comparable alternative to existing methods for HCC surveillance in patients who are at risk.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35880086,

title = {Brief Report: A Blood-Based MicroRNA Complementary Diagnostic Predicts Immunotherapy Efficacy in Advanced-Stage NSCLC With High Programmed Death-Ligand 1 Expression},

author = {Timothy Rajakumar and Rastislav Horos and Paul Kittner and Mustafa Kahraman and Tobias Sikosek and Franziska Hinkfoth and Kaja Tikk and Nathaniel D Mercaldo and Albrecht Stenzinger and Klaus F Rabe and Martin Reck and Michael Thomas and Petros Christopoulos and Bruno R Steinkraus},

doi = {10.1016/j.jtocrr.2022.100369},

issn = {2666-3643},

year  = {2022},

date = {2022-08-01},

urldate = {2022-08-01},

journal = {JTO Clin Res Rep},

volume = {3},

number = {8},

pages = {100369},

abstract = {Introduction: Patients with advanced, non-oncogene-driven NSCLC with high programmed death-ligand 1 (PD-L1) expression are eligible for treatment with immunotherapy. There is, however, an urgent medical need for biomarkers identifying cases that require additional combination with chemotherapy. We previously uncovered a myeloid-based 5-microRNA (5-miRNA) signature that identified responders to immunotherapy in PD-L1 unstratified patients; however, its potential utility in treatment guidance for patients with PD-L1 high tumors remained unclear.



Methods: We trained (n = 68) and validated (n = 56) a 5-miRNA multivariable Cox proportional hazards model predictive of overall survival on small RNA sequencing data of whole blood samples prospectively collected before the commencement of immunotherapy for stage IV NSCLC with PD-L1 tumor proportion score greater than or equal to 50%, treated with PD-1 inhibitor monotherapy (immunotherapy alone [IO]). Specificity was demonstrated in a control cohort treated with immunochemotherapy (ICT) (n = 31).



Results: The revised 5-miRNA risk score (miRisk) stratified IO-treated patients and identified a high-risk group with significantly shorter overall survival (hazard ratio = 5.24, 95% confidence interval: 2.17-12.66,  < 0.001). There was a significant interaction between the miRisk score and type of treatment (IO or ICT,  = 0.036), indicating that the miRisk score may serve as a predictive biomarker for immunotherapy response. Furthermore, the miRisk score could identify a group of high-risk patients who may benefit from treatment with ICT as opposed to IO (hazard ratio = 0.35, 95% confidence interval: 0.15-0.82,  = 0.018).



Conclusions: The miRisk score can distinguish a group of patients with PD-L1 high, stage IV NSCLC likely to benefit from adding chemotherapy to immunotherapy and may support treatment decisions as a blood-based complementary diagnostic.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35870306,

title = {Familial hypercholesterolemia: A systematic review of modeling studies on screening interventions},

author = {Beate Jahn and J\'{u}lia Santamaria and Hans Dieplinger and Christoph J Binder and Christoph Ebenbichler and Sabine Scholl-B\"{u}rgi and Annette Conrads-Frank and Ursula Rochau and Felicitas K\"{u}hne and Igor Stojkov and Jovan Todorovic and Lyndon James and Uwe Siebert},

doi = {10.1016/j.atherosclerosis.2022.06.1011},

issn = {1879-1484},

year  = {2022},

date = {2022-08-01},

urldate = {2022-06-01},

journal = {Atherosclerosis},

volume = {355},

pages = {15--29},

abstract = {BACKGROUND AND AIMS: FH is still underdiagnosed. Cost-effectiveness results of preventive screening strategies vary. We aimed at systematically assessing the benefits, harms and cost effectiveness of screening for familial hypercholesterolemia (FH) and at providing an overview of the main characteristics and methodological approaches of applied decision-analytic models.



METHODS: A systematic literature search was conducted in MEDLINE, EconLit, CRD-databases and the CEA-registry for FH screening starting 2012. Earlier studies were included from a published systematic review. Results were reported in standardized semi-quantitative evidence tables. Costs were converted to current euros. Incremental cost-effectiveness ratios (ICERs) were recalculated according to economic guidelines.



RESULTS: Out of our 211 retrieved studies, eight were included in the review in addition to six studies from an earlier review. Studies were conducted in Europe (UK, The Netherlands, Spain, Poland), USA and Australia evaluating cascade (CS), opportunistic (OS), universal screening (UniS), or combinations using genetic testing, clinical criteria or combinations. Studies evaluating only CS identified strategies with an ICER of up to 37,100 EUR/quality-adjusted life-year (QALY) but some strategies were dominated depending on test combinations. UniS of newborns in combination with CS had an ICER≤15,000 EUR/QALY for sequential cholesterol-genetic screening. In other studies, UniS was dominated by OS/CS.



CONCLUSIONS: Our systematic review demonstrates the values of FH screening and provides an overview of potentially relevant screening strategies to be tested using a decision-analytic model for the respective country or region. Future research is needed on the transferability of results to other countries and modeling spillover effects to newborns.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35660221,

title = {Identifying key risk factors for premature discontinuation of opioid use disorder treatment in the United States: A predictive modeling study},

author = {Celia Stafford and Wesley J Marrero and Rebecca B Naumann and Kristen Hassmiller Lich and Sarah Wakeman and Mohammad S Jalali},

doi = {10.1016/j.drugalcdep.2022.109507},

issn = {1879-0046},

year  = {2022},

date = {2022-08-01},

urldate = {2022-05-01},

journal = {Drug Alcohol Depend},

volume = {237},

pages = {109507},

abstract = {BACKGROUND: Treatment for opioid use disorder (OUD), particularly medication for OUD, is highly effective; however, retention in OUD treatment is a significant challenge. We aimed to identify key risk factors for premature exit from OUD treatment.



METHODS: We analyzed 2,381,902 cross-sectional treatment episodes for individuals in the U.S., discharged between Jan/1/2015 and Dec/31/2019. We developed classification models (Random Forest, Classification and Regression Trees (CART), Bagged CART, and Boosted CART), and analyzed 31 potential risk factors for premature treatment exit, including treatment characteristics, substance use history, socioeconomic status, and demographic characteristics. We stratified our analysis based on length of stay in treatment and service setting. Models were compared using cross-validation and the receiver operating characteristic area under the curve (ROC-AUC).



RESULTS: Random Forest outperformed other methods (ROC-AUC: 74%). The most influential risk factors included characteristics of service setting, geographic region, primary source of payment, and referral source. Race, ethnicity, and sex had far weaker predictive impacts. When stratified by treatment setting and length of stay, employment status and delay (days waited) to enter treatment were among the most influential factors. Their importance increased as treatment duration decreased. Notably, importance of referral source increased as the treatment duration increased. Finally, age and age of first use were important factors for lengths of stay of 2-7 days and in detox treatment settings.



CONCLUSIONS: The key factors of OUD treatment attrition identified in this analysis should be more closely explored (e.g., in causal studies) to inform targeted policies and interventions to improve models of care.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35640366,

title = {Impacts of alcohol and opioid polysubstance use on road safety: Systematic review},

author = {Elizabeth Beaulieu and Rebecca B Naumann and Genevieve Deveaux and Lindsay Wang and Erin J Stringfellow and Kristen Hassmiller Lich and Mohammad S Jalali},

doi = {10.1016/j.aap.2022.106713},

issn = {1879-2057},

year  = {2022},

date = {2022-08-01},

urldate = {2022-05-01},

journal = {Accid Anal Prev},

volume = {173},

pages = {106713},

abstract = {Connections between substance use, impairment, and road safety have been frequently researched. Yet, little is known about how simultaneous use of opioids and alcohol affects road safety outcomes, which is an increasingly critical link within the current landscape of the substance use environment and public health. Lack of this understanding is partly due to testing complications and data limitations. We define polysubstance use here as alcohol and opioids consumed together or within a small-time window such that both are present in the system. This polysubstance use is on the rise and produces greater health risks than when the substances are consumed separately. Given the increasing rate of opioid use, high prevalence of alcohol use, and dangers of polysubstance use, we aim to synthesize literature on the prevalence and impact of this polysubstance on road safety-related outcomes. We performed a systematic review of studies published between 1974 and 2020 that examined opioid and alcohol use exposures and road safety-related outcomes. Out of 644 initial findings, 20 studies were included in this review. Outcomes included motor vehicle crash injuries, deaths, or driver culpability; suspected driving under the influence; and simulated driving performance. Evidence from multiple sources showed a significant rise, approximately 1% to 7%, in the prevalence of opioids among fatally injured drivers in the U.S. from 1995 to 2016. Information published on the simultaneous presence of opioids and alcohol in people involved in crashes was scarce. The limited available findings point toward an overlap where up to 30% of opioid-positive people involved in a crash were also positive for alcohol. Studies also suggest a possibly elevated risk presented by this polysubstance use relative to the substances used alone, though the majority of identified studies did not estimate this association. The synthesized research indicates that alcohol and opioid use is not uncommon and may be increasing among people involved in adverse driving events. More research and better data are needed to improve estimates of association with road traffic-related outcomes, potentially improving substance testing in current surveillance systems or using linked data sets and other novel data sources to improve estimates.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{pmid35537918,

title = {Evaluating disparities in prescribing of naloxone after emergency department treatment of opioid overdose},

author = {Scott G Weiner and Aleta D Carroll and Nicholas M Brisbon and Claudia P Rodriguez and Charles Covahey and Erin J Stringfellow and Catherine DiGennaro and Mohammad S Jalali and Sarah E Wakeman},

doi = {10.1016/j.jsat.2022.108785},

issn = {1873-6483},

year  = {2022},

date = {2022-08-01},

urldate = {2022-04-01},

journal = {J Subst Abuse Treat},

volume = {139},

pages = {108785},

abstract = {INTRODUCTION: Patients who initially survive opioid-related overdose are at high risk for subsequent mortality. Our health system aimed to evaluate the presence of disparities in prescribing naloxone following opioid overdose.



METHODS: This was a retrospective cohort study of patients seen in our health system, which comprises two academic centers and eight community hospitals. Eligible patients had at least one visit to any of our hospital's emergency departments (EDs) with a diagnosis code indicating opioid-related overdose between May 1, 2018, and April 30, 2021. The primary outcome measure was prescription of nasal naloxone after at least one visit for opioid-related overdose during the study period.



RESULTS: The health system had 1348 unique patients who presented 1593 times to at least one of the EDs with opioid overdose. Of included patients, 580 (43.2%) received one or more prescriptions for naloxone. The majority (68.9%, n = 925) were male. For race/ethnicity, 74.5% (1000) were Non-Hispanic White, 8.0% (n = 108) were Non-Hispanic Black, and 13.0% (n = 175) were Hispanic/Latinx. Compared with the reference age group of 16-24 years, only those 65+ were less likely to receive naloxone (adjusted odds ratio [aOR] 0.41, 95% confidence interval [CI] 0.20-0.84). The study found no difference for gender (male aOR 1.23, 95% CI 0.97-1.57 compared to female). Hispanic/Latinx patients were more likely to receive a prescription when compared to Non-Hispanic White patients (aOR 1.72, 95% CI 1.22-2.44), while no difference occurred between Non-Hispanic Black compared to Non-Hispanic White patients (aOR 1.31, 95% CI 0.87-1.98).



CONCLUSIONS: Naloxone prescribing after overdose in our system was suboptimal, with fewer than half of patients with an overdose diagnosis code receiving this lifesaving and evidence-based intervention. Patients who were Hispanic/Latinx were more likely to receive naloxone than other race and ethnicity groups, and patients who were older were less likely to receive it. Health systems need ongoing equity-informed implementation of programs to expand access to naloxone to all patients at risk.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}