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A letter to the editor of the Journal of the American Medical Association reports an error in a study comparing antibiotic treatment for acute sinusitis in children and adolescents. The error occurred in how the study captured the outcome of days with an antibiotic prescription without an outpatient encounter. The correct overall treatment failure risk is 3.1% and the correct serious treatment failure risk is 0.05%. The corrected analysis shows a slightly increased risk with amoxicillin-clavulanate, but the events are still rare, indicating no clinically important difference in treatment failure. The error has been corrected and a correction notice has been published. [Extracted from the article]

This database study examines the association between glucagon-like peptide 1 agonists (eg, semaglutide, liraglutide) used for weight loss and reports of gastrointestinal adverse events. [ABSTRACT FROM AUTHOR]

Importance: Nonrandomized studies using insurance claims databases can be analyzed to produce real-world evidence on the effectiveness of medical products. Given the lack of baseline randomization and measurement issues, concerns exist about whether such studies produce unbiased treatment effect estimates. Objective: To emulate the design of 30 completed and 2 ongoing randomized clinical trials (RCTs) of medications with database studies using observational analogues of the RCT design parameters (population, intervention, comparator, outcome, time [PICOT]) and to quantify agreement in RCT-database study pairs. Design, Setting, and Participants: New-user cohort studies with propensity score matching using 3 US claims databases (Optum Clinformatics, MarketScan, and Medicare). Inclusion-exclusion criteria for each database study were prespecified to emulate the corresponding RCT. RCTs were explicitly selected based on feasibility, including power, key confounders, and end points more likely to be emulated with real-world data. All 32 protocols were registered on ClinicalTrials.gov before conducting analyses. Emulations were conducted from 2017 through 2022. Exposures: Therapies for multiple clinical conditions were included. Main Outcomes and Measures: Database study emulations focused on the primary outcome of the corresponding RCT. Findings of database studies were compared with RCTs using predefined metrics, including Pearson correlation coefficients and binary metrics based on statistical significance agreement, estimate agreement, and standardized difference. Results: In these highly selected RCTs, the overall observed agreement between the RCT and the database emulation results was a Pearson correlation of 0.82 (95% CI, 0.64-0.91), with 75% meeting statistical significance, 66% estimate agreement, and 75% standardized difference agreement. In a post hoc analysis limited to 16 RCTs with closer emulation of trial design and measurements, concordance was higher (Pearson r, 0.93; 95% CI, 0.79-0.97; 94% meeting statistical significance, 88% estimate agreement, 88% standardized difference agreement). Weaker concordance occurred among 16 RCTs for which close emulation of certain design elements that define the research question (PICOT) with data from insurance claims was not possible (Pearson r, 0.53; 95% CI, 0.00-0.83; 56% meeting statistical significance, 50% estimate agreement, 69% standardized difference agreement). Conclusions and Relevance: Real-world evidence studies can reach similar conclusions as RCTs when design and measurements can be closely emulated, but this may be difficult to achieve. Concordance in results varied depending on the agreement metric. Emulation differences, chance, and residual confounding can contribute to divergence in results and are difficult to disentangle. This study uses results from randomized clinical trials as a reference to learn whether similar clinical conclusions could be drawn had the RCT protocol been translated and implemented as a database study protocol. Key Points: Question: Are database studies that are explicitly designed to emulate past and ongoing randomized clinical trials (RCTs) of medications able to generate similar causal conclusions? Findings: In this highly selected, nonrepresentative sample, real-world evidence studies generally reached similar conclusions as RCTs (Pearson correlation r, 0.82; 75% statistical significance agreement, 66% estimate agreement, 75% standardized difference agreement). In a post hoc, exploratory stratified analysis, agreement was higher in RCT-database pairs classified as having closer emulation of the RCT design. Meaning: Selected database studies can complement RCT evidence to enhance understanding of how medications work in clinical practice. Emulation differences, chance, and residual confounding can contribute to divergence in results and are difficult to disentangle. [ABSTRACT FROM AUTHOR]

This study uses data from the US Centers for Disease Control and Prevention Wide-ranging Online Data for Epidemiologic Research database to assess 20-year trends in drug overdose fatalities among older adults in the US. [ABSTRACT FROM AUTHOR]

This study uses data from an all-payer database of prescriptions dispensed in US retail pharmacies to assess trends in buprenorphine initiation and retention during 2016-2022. [ABSTRACT FROM AUTHOR]

This matched-cohort study uses data from the French National Health Insurance database to assess whether a 19.5-mg levonorgestrel intrauterine system, vs a 52-mg system, is associated with increased use of antidepressant, hypnotic, and anxiolytic medications. [ABSTRACT FROM AUTHOR]

Importance: Violence perpetration outcomes in individuals with schizophrenia spectrum disorders contribute to morbidity and mortality at a population level, disrupt care, and lead to stigma.Objective: To conduct a systematic review and meta-analysis of the risk of perpetrating interpersonal violence in individuals with schizophrenia spectrum disorders compared with general population control individuals.Data Sources: Multiple databases were searched for studies in any language from January 1970 to March 2021 using the terms violen* or homicid* and psychosis or psychoses or psychotic or schizophren* or schizoaffective or delusional and terms for mental disorders. Bibliographies of included articles were hand searched.Study Selection: The study included case-control and cohort studies that allowed risks of interpersonal violence perpetration and/or violent criminality in individuals with schizophrenia spectrum disorders to be compared with a general population group without these disorders.Data Extraction and Synthesis: The study followed the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines and the Meta-analyses of Observational Studies in Epidemiology (MOOSE) proposal. Two reviewers extracted data. Quality was assessed using the Newcastle-Ottawa Quality Assessment Scale. Data were pooled using a random-effects model.Main Outcomes and Measures: The main outcome was violence to others obtained either through official records, self-report and/or collateral-report, or medical file review and included any physical assault, robbery, sexual offenses, illegal threats or intimidation, and arson.Results: The meta-analysis included 24 studies of violence perpetration outcomes in 15 countries over 4 decades (N = 51 309 individuals with schizophrenia spectrum disorders; reported mean age of 21 to 54 years at follow-up; of those studies that reported outcomes separately by sex, there were 19 976 male individuals and 14 275 female individuals). There was an increase in risk of violence perpetration in men with schizophrenia and other psychoses (pooled odds ratio [OR], 4.5; 95% CI, 3.6-5.6) with substantial heterogeneity (I2 = 85%; 95% CI, 77-91). The risk was also elevated in women (pooled OR, 10.2; 95% CI, 7.1-14.6), with substantial heterogeneity (I2 = 66%; 95% CI, 31-83). Odds of perpetrating sexual offenses (OR, 5.1; 95% CI, 3.8-6.8) and homicide (OR, 17.7; 95% CI, 13.9-22.6) were also investigated. Three studies found increased relative risks of arson but data were not pooled for this analysis owing to heterogeneity of outcomes. Absolute risks of violence perpetration in register-based studies were less than 1 in 20 in women with schizophrenia spectrum disorders and less than 1 in 4 in men over a 35-year period.Conclusions and Relevance: This systematic review and meta-analysis found that the risk of perpetrating violent outcomes was increased in individuals with schizophrenia spectrum disorders compared with community control individuals, which has been confirmed in new population-based longitudinal studies and sibling comparison designs. [ABSTRACT FROM AUTHOR]

This study examines the association of sublingual buprenorphine/naloxone and dental adverse events using the IQVIA health claims database. [ABSTRACT FROM AUTHOR]

The article discusses that knowledge is power, scholarly journals as information gatekeepers play a potent role in promulgating it. Topics discussed include borne witness to deadly harms inflicted on communities of color, and these harms, journals continue disseminating content, including a recent JAMA podcast, that fails to recognize racism as a trans generational source of health inequity; and the existence of racism in health care is "not opinion or conjecture.

Importance: Substantial increases in both neonatal abstinence syndrome (NAS) and maternal opioid use disorder have been observed through 2014.Objective: To examine national and state variation in NAS and maternal opioid-related diagnoses (MOD) rates in 2017 and to describe national and state changes since 2010 in the US, which included expanded MOD codes (opioid use disorder plus long-term and unspecified use) implemented in International Classification of Disease, 10th Revision, Clinical Modification.Design, Setting, and Participants: Repeated cross-sectional analysis of the 2010 to 2017 Healthcare Cost and Utilization Project's National Inpatient Sample and State Inpatient Databases, an all-payer compendium of hospital discharge records from community nonrehabilitation hospitals in 47 states and the District of Columbia.Exposures: State and year.Main Outcomes and Measures: NAS rate per 1000 birth hospitalizations and MOD rate per 1000 delivery hospitalizations.Results: In 2017, there were 751 037 birth hospitalizations and 748 239 delivery hospitalizations in the national sample; 5375 newborns had NAS and 6065 women had MOD documented in the discharge record. Mean gestational age was 38.4 weeks and mean maternal age was 28.8 years. From 2010 to 2017, the estimated NAS rate significantly increased by 3.3 per 1000 birth hospitalizations (95% CI, 2.5-4.1), from 4.0 (95% CI, 3.3-4.7) to 7.3 (95% CI, 6.8-7.7). The estimated MOD rate significantly increased by 4.6 per 1000 delivery hospitalizations (95% CI, 3.9-5.4), from 3.5 (95% CI, 3.0-4.1) to 8.2 (95% CI, 7.7-8.7). Larger increases for MOD vs NAS rates occurred with new International Classification of Disease, 10th Revision, Clinical Modification codes in 2016. From a census of 47 state databases in 2017, NAS rates ranged from 1.3 per 1000 birth hospitalizations in Nebraska to 53.5 per 1000 birth hospitalizations in West Virginia, with Maine (31.4), Vermont (29.4), Delaware (24.2), and Kentucky (23.9) also exceeding 20 per 1000 birth hospitalizations, while MOD rates ranged from 1.7 per 1000 delivery hospitalizations in Nebraska to 47.3 per 1000 delivery hospitalizations in Vermont, with West Virginia (40.1), Maine (37.8), Delaware (24.3), and Kentucky (23.4) also exceeding 20 per 1000 delivery hospitalizations. From 2010 to 2017, NAS and MOD rates increased significantly for all states except Nebraska and Vermont, which only had MOD increases.Conclusions and Relevance: In the US from 2010 to 2017, estimated rates of NAS and MOD significantly increased nationally and for the majority of states, with notable state-level variation. [ABSTRACT FROM AUTHOR]

Importance: Current guidelines recommend ticagrelor as the preferred P2Y12 platelet inhibitor for patients with acute coronary syndrome (ACS), primarily based on a single large randomized clinical trial. The benefits and risks associated with ticagrelor vs clopidogrel in routine practice merits attention.Objective: To determine the association of ticagrelor vs clopidogrel with ischemic and hemorrhagic events in patients undergoing percutaneous coronary intervention (PCI) for ACS in clinical practice.Design, Setting, and Participants: A retrospective cohort study of patients with ACS who underwent PCI and received ticagrelor or clopidogrel was conducted using 2 United States electronic health record-based databases and 1 nationwide South Korean database from November 2011 to March 2019. Patients were matched using a large-scale propensity score algorithm, and the date of final follow-up was March 2019.Exposures: Ticagrelor vs clopidogrel.Main Outcomes and Measures: The primary end point was net adverse clinical events (NACE) at 12 months, composed of ischemic events (recurrent myocardial infarction, revascularization, or ischemic stroke) and hemorrhagic events (hemorrhagic stroke or gastrointestinal bleeding). Secondary outcomes included NACE or mortality, all-cause mortality, ischemic events, hemorrhagic events, individual components of the primary outcome, and dyspnea at 12 months. The database-level hazard ratios (HRs) were pooled to calculate summary HRs by random-effects meta-analysis.Results: After propensity score matching among 31 290 propensity-matched pairs (median age group, 60-64 years; 29.3% women), 95.5% of patients took aspirin together with ticagrelor or clopidogrel. The 1-year risk of NACE was not significantly different between ticagrelor and clopidogrel (15.1% [3484/23 116 person-years] vs 14.6% [3290/22 587 person-years]; summary HR, 1.05 [95% CI, 1.00-1.10]; P = .06). There was also no significant difference in the risk of all-cause mortality (2.0% for ticagrelor vs 2.1% for clopidogrel; summary HR, 0.97 [95% CI, 0.81-1.16]; P = .74) or ischemic events (13.5% for ticagrelor vs 13.4% for clopidogrel; summary HR, 1.03 [95% CI, 0.98-1.08]; P = .32). The risks of hemorrhagic events (2.1% for ticagrelor vs 1.6% for clopidogrel; summary HR, 1.35 [95% CI, 1.13-1.61]; P = .001) and dyspnea (27.3% for ticagrelor vs 22.6% for clopidogrel; summary HR, 1.21 [95% CI, 1.17-1.26]; P < .001) were significantly higher in the ticagrelor group.Conclusions and Relevance: Among patients with ACS who underwent PCI in routine clinical practice, ticagrelor, compared with clopidogrel, was not associated with significant difference in the risk of NACE at 12 months. Because the possibility of unmeasured confounders cannot be excluded, further research is needed to determine whether ticagrelor is more effective than clopidogrel in this setting. [ABSTRACT FROM AUTHOR]

This cross-sectional study compares health care spending among high-deductible health plan vs traditional plan enrollees with substance use and mental health disorders. [ABSTRACT FROM AUTHOR]

Importance: Understanding changes in the incidence rates and lethality of suicidal acts may explain increasing suicide rates.Objective: To examine trends in the incidence rates and lethality of suicidal acts from 2006 to 2015 among persons aged 10 to 74 years.Design, Setting, and Participants: This cross-sectional study was conducted from May 2, 2018, to January 30, 2019. Medically treated nonfatal suicide attempts were identified from the 2006 to 2015 Nationwide Inpatient Sample and Nationwide Emergency Department Sample databases. Suicides were identified from the 2006 to 2015 mortality files of the National Vital Statistics System.Main Outcomes and Measures: The incidence rate of suicidal acts was calculated by dividing the number of total suicidal acts by the US population. Lethality was measured through the case fatality rates (CFRs) of suicidal acts by dividing the number of suicides by the total number of suicidal acts.Results: A total of 1 222 419 (unweighted) suicidal acts, which included both suicides and nonfatal suicide attempts, were identified from 2006 to 2015. Overall, the incidence rates of total suicidal acts increased 10% from 2006 to 2015 (annual percentage change [APC], 0.8%; 95% CI, 0.3%-1.3%), and the CFRs of suicidal acts increased 13% during the 2006 to 2015 period (APC, 2.3%; 95% CI, 1.3%-3.3%). In subgroup analyses, incidence rates increased by 1.1% (95% CI, 0.6%-1.6%) per year for female individuals during the 2006 to 2015 period but remained stable for male individuals. The CFRs increased for both sexes (APC, 5.0% [95% CI, 3.1%-6.9%] since 2010 for female individuals; 1.6% [95% CI, 0.6%-2.5%] since 2009 for male individuals). Incidence rates increased among adolescents from 2011 to 2015 and among older adults aged 65 to 74 years throughout the 2006 to 2015 period. Conversely, the CFRs increased since 2009 among persons aged 20 to 44 years (APC, 3.7%; 95% CI, 2.5%-5.0%) and since 2012 for those aged 45 to 64 years (APC, 2.7%; 95% CI, 0.0%-5.4%). Persons aged 20 to 44 years and 45 to 64 years experienced increases in suicidal acts by more lethal means, whereas adolescents and older adults aged 65 to 74 years showed increased incidence by all means.Conclusions and Relevance: This study found increased suicidal acts among female persons, adolescents, and older adults aged 65 to 74 years, implying the need to address emerging or exacerbating suicide risk factors for these populations. The findings on the increased lethality particularly among persons aged 20 to 64 years highlighted the need to reduce access to materials that could be used as lethal means among persons at risk of suicide. These findings on population-level epidemiologic patterns can be used to guide the development of comprehensive suicide prevention strategies. [ABSTRACT FROM AUTHOR]

In the context of concerns about the appropriateness and costs to insurers and patients of laboratory testing, this study uses data from the IBM MarketScan Commercial Claims and Encounters Database to examine out-of-network laboratory test spending, utilization, and prices in the US in 2008-2016. [ABSTRACT FROM AUTHOR]

Importance: Evidence regarding associations of blood donor sex with mortality among red blood cell transfusion recipients is conflicting.Objective: To study associations of donor sex and prior pregnancy with mortality of transfusion recipients.Design, Setting, and Participants: Data from 3 retrospective cohorts of transfusion recipients (the Kaiser Permanente Northern California [KPNC] and Recipient Epidemiology and Donor Evaluation Study-III [REDS-III] databases of data from January 2013 to December 2016 and the Scandinavian Donations and Transfusions [SCANDAT] database with data from January 2003 to December 2012) were analyzed. Final dates of follow-up were December 31, 2016, for the KPNC and REDS-III cohorts and December 31, 2012, for the SCANDAT cohort. Stratified Cox regression models were used to estimate associations between donor exposure groups with risk of mortality, adjusting for the number of red blood cell unit transfusions.Exposures: The number of transfused red blood cell units from female donors, previously pregnant donors, and sex-discordant donors (male donor and female recipient or female donor and male recipient).Main Outcomes and Measures: In-hospital mortality.Results: The study population included 34 662 patients (mean age, 69 years; 18 652 [54%] women) from the KPNC cohort, 93 724 patients (mean age, 61 years; 48 348 [52%] women) from the REDS-III cohort, and 918 996 patients (mean age, 72 years; 522 239 [57%] women) from the SCANDAT cohort. The median number of red blood cell transfusions per patient was 3 in the KPNC cohort, 2 in the REDS-III cohort, and 3 in the SCANDAT cohort. The percentage of transfusions from previously pregnant or parous donors was 9% in the KPNC cohort, 18% in the REDS-III cohort, and 25% in the SCANDAT cohort. The percentage of transfusions in the 3 cohorts from female donors ranged from 39% to 43%, from previously pregnant or parous donors ranged from 9% to 25%, and from sex-discordant donors ranged from 44% to 50%. There were 3217 in-hospital deaths in the KPNC cohort, 8519 in the REDS-III cohort, and 198 537 in the SCANDAT cohort. There were no statistically significant associations between any of the 3 donor exposures and in-hospital mortality in the 3 cohorts. Hazard ratios for in-hospital mortality per transfused unit from female donors were 0.99 (95% CI, 0.96-1.03) for the KPNC cohort, 1.00 (95% CI, 0.99-1.01) for the REDS-III cohort, and 1.00 (95% CI, 0.99-1.00) for the SCANDAT cohort. For units from previously pregnant or parous female donors, hazard ratios were 1.00 (95% CI, 1.00-1.01) for the KPNC cohort, 1.01 (95% CI, 0.98-1.03) for the REDS-III cohort, and 1.00 (95% CI, 1.00-1.01) for the SCANDAT cohort. For units from sex-discordant transfusions, hazard ratios were 1.02 (95% CI, 0.99-1.05) for the KPNC cohort, 0.99 (95% CI, 0.98-1.00) for the REDS-III cohort, and 1.00 (95% CI, 0.99-1.00) for the SCANDAT cohort.Conclusions and Relevance: Among red blood cell transfusion recipients, transfusions from female, previously pregnant, or sex-discordant donors were not significantly associated with increased mortality. [ABSTRACT FROM AUTHOR]

Importance: Data sets linking comprehensive genomic profiling (CGP) to clinical outcomes may accelerate precision medicine.Objective: To assess whether a database that combines EHR-derived clinical data with CGP can identify and extend associations in non-small cell lung cancer (NSCLC).Design, Setting, and Participants: Clinical data from EHRs were linked with CGP results for 28 998 patients from 275 US oncology practices. Among 4064 patients with NSCLC, exploratory associations between tumor genomics and patient characteristics with clinical outcomes were conducted, with data obtained between January 1, 2011, and January 1, 2018.Exposures: Tumor CGP, including presence of a driver alteration (a pathogenic or likely pathogenic alteration in a gene shown to drive tumor growth); tumor mutation burden (TMB), defined as the number of mutations per megabase; and clinical characteristics gathered from EHRs.Main Outcomes and Measures: Overall survival (OS), time receiving therapy, maximal therapy response (as documented by the treating physician in the EHR), and clinical benefit rate (fraction of patients with stable disease, partial response, or complete response) to therapy.Results: Among 4064 patients with NSCLC (median age, 66.0 years; 51.9% female), 3183 (78.3%) had a history of smoking, 3153 (77.6%) had nonsquamous cancer, and 871 (21.4%) had an alteration in EGFR, ALK, or ROS1 (701 [17.2%] with EGFR, 128 [3.1%] with ALK, and 42 [1.0%] with ROS1 alterations). There were 1946 deaths in 7 years. For patients with a driver alteration, improved OS was observed among those treated with (n = 575) vs not treated with (n = 560) targeted therapies (median, 18.6 months [95% CI, 15.2-21.7] vs 11.4 months [95% CI, 9.7-12.5] from advanced diagnosis; P < .001). TMB (in mutations/Mb) was significantly higher among smokers vs nonsmokers (8.7 [IQR, 4.4-14.8] vs 2.6 [IQR, 1.7-5.2]; P < .001) and significantly lower among patients with vs without an alteration in EGFR (3.5 [IQR, 1.76-6.1] vs 7.8 [IQR, 3.5-13.9]; P < .001), ALK (2.1 [IQR, 0.9-4.0] vs 7.0 [IQR, 3.5-13.0]; P < .001), RET (4.6 [IQR, 1.7-8.7] vs 7.0 [IQR, 2.6-13.0]; P = .004), or ROS1 (4.0 [IQR, 1.2-9.6] vs 7.0 [IQR, 2.6-13.0]; P = .03). In patients treated with anti-PD-1/PD-L1 therapies (n = 1290, 31.7%), TMB of 20 or more was significantly associated with improved OS from therapy initiation (16.8 months [95% CI, 11.6-24.9] vs 8.5 months [95% CI, 7.6-9.7]; P < .001), longer time receiving therapy (7.8 months [95% CI, 5.5-11.1] vs 3.3 months [95% CI, 2.8-3.7]; P < .001), and increased clinical benefit rate (80.7% vs 56.7%; P < .001) vs TMB less than 20.Conclusions and Relevance: Among patients with NSCLC included in a longitudinal database of clinical data linked to CGP results from routine care, exploratory analyses replicated previously described associations between clinical and genomic characteristics, between driver mutations and response to targeted therapy, and between TMB and response to immunotherapy. These findings demonstrate the feasibility of creating a clinicogenomic database derived from routine clinical experience and provide support for further research and discovery evaluating this approach in oncology. [ABSTRACT FROM AUTHOR]

Two concerns about information from unethical experimentation are its legitimacy and trustworthiness. This article explores guidance about information use from the AMA Code of Medical Ethics. [ABSTRACT FROM AUTHOR]

CRISPR/Cas9 is a rapidly developing gene editing technology that will soon have many clinical applications. As with many other new technologies, somatic gene editing with CRISPR/Cas9 raises concerns about equitable access to therapies by historically disenfranchised racial and ethnic minorities. We describe justice concerns related to CRISPR/Cas9, including its potential impact on historically mistreated populations through underrepresentation of minorities in genomic databases and the potential for disparate access to somatic gene therapies when they become clinically available. We then describe ongoing work that aims to address these justice concerns. We conclude by highlighting important considerations to ensure equitable access to therapies going forward, including enhancing diversity in genomic sequencing efforts, improving education and transparency, and building partnerships with underserved and socially disenfranchised communities. [ABSTRACT FROM AUTHOR]

Importance: Individuals genetically predisposed to pancreatic cancer may benefit from early detection. Genes that predispose to pancreatic cancer and the risks of pancreatic cancer associated with mutations in these genes are not well defined.Objective: To determine whether inherited germline mutations in cancer predisposition genes are associated with increased risks of pancreatic cancer.Design, Setting, and Participants: Case-control analysis to identify pancreatic cancer predisposition genes; longitudinal analysis of patients with pancreatic cancer for prognosis. The study included 3030 adults diagnosed as having pancreatic cancer and enrolled in a Mayo Clinic registry between October 12, 2000, and March 31, 2016, with last follow-up on June 22, 2017. Reference controls were 123 136 individuals with exome sequence data in the public Genome Aggregation Database and 53 105 in the Exome Aggregation Consortium database.Exposures: Individuals were classified based on carrying a deleterious mutation in cancer predisposition genes and having a personal or family history of cancer.Main Outcomes and Measures: Germline mutations in coding regions of 21 cancer predisposition genes were identified by sequencing of products from a custom multiplex polymerase chain reaction-based panel; associations of genes with pancreatic cancer were assessed by comparing frequency of mutations in genes of pancreatic cancer patients with those of reference controls.Results: Comparing 3030 case patients with pancreatic cancer (43.2% female; 95.6% non-Hispanic white; mean age at diagnosis, 65.3 [SD, 10.7] years) with reference controls, significant associations were observed between pancreatic cancer and mutations in CDKN2A (0.3% of cases and 0.02% of controls; odds ratio [OR], 12.33; 95% CI, 5.43-25.61); TP53 (0.2% of cases and 0.02% of controls; OR, 6.70; 95% CI, 2.52-14.95); MLH1 (0.13% of cases and 0.02% of controls; OR, 6.66; 95% CI, 1.94-17.53); BRCA2 (1.9% of cases and 0.3% of controls; OR, 6.20; 95% CI, 4.62-8.17); ATM (2.3% of cases and 0.37% of controls; OR, 5.71; 95% CI, 4.38-7.33); and BRCA1 (0.6% of cases and 0.2% of controls; OR, 2.58; 95% CI, 1.54-4.05).Conclusions and Relevance: In this case-control study, mutations in 6 genes associated with pancreatic cancer were found in 5.5% of all pancreatic cancer patients, including 7.9% of patients with a family history of pancreatic cancer and 5.2% of patients without a family history of pancreatic cancer. Further research is needed for replication in other populations. [ABSTRACT FROM AUTHOR]

Importance: People who immigrate face unique health literacy, communication, and system navigation challenges, and they may have diverse preferences that influence end-of-life care.Objective: To examine end-of-life care provided to immigrants to Canada in the last 6 months of their life.Design, Setting, and Participants: This population-based cohort study (April 1, 2004, to March 31, 2015) included 967 013 decedents in Ontario, Canada, using validated linkages between health and immigration databases to identify immigrant (since 1985) and long-standing resident cohorts.Exposures: All decedents who immigrated to Canada between 1985 and 2015 were classified as recent immigrants, with subgroup analyses assessing the association of time since immigration, and region of birth, with end-of-life care.Main Outcomes and Measures: Location of death and intensity of care received in the last 6 months of life. Analysis included modified Poisson regression with generalized estimating equations, adjusting for age, sex, socioeconomic position, causes of death, urban and rural residence, and preexisting comorbidities.Results: Among 967 013 decedents of whom 47 514 (5%) immigrated since 1985, sex, socioeconomic status, urban (vs rural) residence, and causes of death were similar, while long-standing residents were older than immigrant decedents (median [interquartile range] age, 75 [58-84] vs 80 [68-87] years). Recent immigrant decedents were overall more likely to die in intensive care (15.6% vs 10.0%; difference, 5.6%; 95% CI, 5.2%-5.9%) after adjusting for differences in age, sex, income, geography, and cause of death (relative risk, 1.30; 95% CI, 1.27-1.32). In their last 6 months of life, recent immigrant decedents experienced more intensive care admissions (24.9% vs 19.2%; difference, 5.7%; 95% CI, 5.3%-6.1%), hospital admissions (72.1% vs 68.2%; difference, 3.9%; 95% CI, 3.5%-4.3%), mechanical ventilation (21.5% vs 13.6%; difference, 7.9%; 95% CI, 7.5%-8.3%), dialysis (5.5% vs 3.4%; difference, 2.1%; 95% CI, 1.9%-2.3%), percutaneous feeding tube placement (5.5% vs 3.0%; difference, 2.5%; 95% CI, 2.3%-2.8%), and tracheostomy (2.3% vs 1.1%; difference, 1.2%; 95% CI, 1.1%-1.4%). Relative risk of dying in intensive care for recent immigrants compared with long-standing residents varied according to recent immigrant region of birth from 0.84 (95% CI, 0.74-0.95) among those born in Northern and Western Europe to 1.96 (95% CI, 1.89-2.05) among those born in South Asia.Conclusions and Relevance: Among decedents in Ontario, Canada, recent immigrants were significantly more likely to receive aggressive care and to die in an intensive care unit compared with other residents. Further research is needed to understand the mechanisms behind this association. [ABSTRACT FROM AUTHOR]

Medical News in Brief Letters reminding clinicians of a mandate to check a state prescription tracking database before prescribing opioids significantly increased clinician participation in the program. Each clinician was assigned to a control group that received no letter or to a group that received 1 of 3 letters: one focusing on a new state requirement to check the database before prescribing opioids; another with information about coprescribing opioids with other drugs; or a third combining the 2 messages. [Extracted from the article]

Importance: Trisomy 13 and 18 are genetic diagnoses with characteristic physical features, organ anomalies, and neurodevelopmental disability. Most children with these disorders die shortly after birth, although limited data suggest some children survive longer. Surgeries are controversial, and little evidence is available about outcomes.Objective: To describe survival and utilization of any type of surgery among children with trisomy 13 and 18 born over a 21-year period in Ontario, Canada.Design, Setting, and Participants: This retrospective cohort study used linked health administrative databases to identify children born in Ontario between April 1, 1991, and March 31, 2012, with a diagnosis code for trisomy 13 or 18 on a hospital record in the first year of life. Survival was calculated from birth and death dates; children living on March 31, 2013, were censored at their last clinical encounter.Exposures: All procedures classified as occurring in an operating room through March 31, 2013, were categorized as major, intermediate, or minor surgeries.Main Outcomes and Measures: Survival and surgical procedure utilization.Results: The cohorts included 174 children with trisomy 13 (mean [SD] birth weight, 2.5 [0.7] kg; 98 [56.3%] female); and 254 children with trisomy 18 (mean birth weight, 1.8 [0.7] kg; 157 [61.8%] female), with follow-up times of 0 to more than 7000 days. Median (interquartile range [IQR]) survival times were 12.5 (2-195) days for trisomy 13 and 9 (2-92) days for trisomy 18. Mean 1-year survival for trisomy 13 was 19.8% (95% CI, 14.2%-26.1%) and 12.6% (95% CI, 8.9%-17.1%) for trisomy 18. Ten-year survival for trisomy 13 was 12.9% (95% CI, 8.4%-18.5%) and 9.8% (95% CI, 6.4%-14.0%) for trisomy 18. Survival did not change over the study period. Forty-one children (23.6%) with trisomy 13 and 35 children (13.8%) with trisomy 18 underwent surgeries, ranging from myringotomy to complex cardiac repair. Median age at first surgery for trisomy 13 was 92 (IQR, 30.5-384.5) days and for trisomy 18, it was 205.5 (IQR, 20.0-518.0) days. Kaplan-Meier curves showed 1-year survival after first surgery of 70.7% (95% CI, 54.3%-82.2%; n = 23) for trisomy 13 and 68.6% (95% CI, 50.5%-81.2%; n = 29) for trisomy 18.Conclusions and Relevance: Among children born with trisomy 13 or 18 in Ontario, early mortality was the most common outcome, but 10% to 13% survived for 10 years. Among children who underwent surgical interventions, 1-year survival was high. [ABSTRACT FROM AUTHOR]

This pharmacoepidemiology study uses commercial claims database data to describe the rate of opioid overdose 1 to 3 months after surgical discharge by dose and procedure from 2004 to 2015. [ABSTRACT FROM AUTHOR]

This study uses commercial claims database data to characterize trends in testosterone prescribing in the United States from 2002 to 2016. [ABSTRACT FROM AUTHOR]

This study summarizes responses to trial registration fields on the ClinicalTrials.gov website asking users if they plan to share individual participant data and what information they would be willing to share. [ABSTRACT FROM AUTHOR]

This Viewpoint summarizes enrollment to date in the All of Us Research Program, a cohort study launched in 2018 designed to enroll ≥1 million participants, including those from historically underrepresented backgrounds, to diversify the human genome database and the infrastructure it is building to broadly share its data assets to improve and accelerate biomedical research. [ABSTRACT FROM AUTHOR]

The article focuses on a study related to the use of sublingual immunotherapy for the treatment of allergic rhinoconjunctivitis and asthma in the U.S. It informs that though sublingual immunotherapy is not approved by the U.S. Food and Drug Administration, yet some physicians use aqueous allergens for sublingual desensitization. Several databases and the Cochrane Central Register of Controlled Trials were searched. It also informs that overall evidence provides a moderate grade level of evidence to support the effectiveness of sublingual immunotherapy for the treatment of allergic rhinitis and asthma.

The article presents information on the effect of gender difference in physicians' payments and the arguments which mentions the cause of difference as due to the effect of work hours, specialization and productivity. A study conducted in 1853 recipients in using the Computer Retrieval of Information on Scientific Projects (CRISP) in the U.S. based on linear regression model of current annual salary showed that gender difference existed in mid-career academic physicians. The efforts for mitigating the gender differences are discussed.

The article presents an introduction to a report within the issue by R. M. Califf and colleagues concerning clinical studies registered in the ClinicalTrials.gov database of the U.S.

The article examines the basic characteristics of interventional clinical trials in cardiovascular, mental health and oncology therapeutic areas contained in the ClinicalTrials.gov database of the U.S. The discrepancies between guidelines-based treatment recommendations and evidence from clinical trials that reinforce those recommendations are addressed. A data set of 96,346 clinical studies from the registry was downloaded and entered into a relational database to examine aggregate data. The results showed an increase in the number of registered interventional clinical trials and a general decline in the number of missing data elements.

The article discusses a study of the accuracy of historical characteristics, symptoms, bedside maneuvers and basic laboratory test results that distinguish upper gastrointestinal bleeding (GIB) from lower GIB. The researchers searched the Medical Literature Analysis and Retrieval System medical information database and identified 2628 citations, of which eight were kept that tested methods of identifying an upper GIB and 18 that characterized ways of understanding the severity of upper GIB. They found that a range of factors increase the possibility that a patient has an upper GIB which include a history of melena and a serum urea nitrogen.

The article discusses a study which investigated the differences on the impact of cardiac resynchronization therapy (CRT) in patients with moderately or severely prolonged QRS duration. Databases used for the randomized CRT trials were MEDLINE, SCOPUS and Cochrane. Findings showed a reduction in composite clinical trials with CRT in patients with prolonged QRS.

The article describes a meta-analysis of prospective cohort studies to investigate whether television (TV) viewing is associated with risk of type 2 diabetes, cadiovascular disease, and all-cause mortality. The meta-analysis examined studies published in MEDLINE and EMBASE databases. Prolonged TV viewing is considered to be the most common and pervasive sedentary behavior among people in industrialized countries. The meta-analysis concluded that prolonged TV viewing is linked to risk for cardiovascular disease, type 2 diabetes and all-cause mortality.

The article discusses a study on the association of cannabis use and other psychoactive substances with an earlier onset of psychotic illness. It aims to establish the extent to which the use of cannabis, alcohol and other psychoactive substances affect the age at onset of psychosis by meta-analysis. Systematic searches of multiple databases were used while the effect size for age was calculated using a random-effects meta-analysis. The results indicated strong evidence that reducing cannabis use can delay or prevent some cases of psychotic illness.

The article discusses a study on variations in hospital costs and hospital mortality rates of patients with sepsis in the U.S. The study involved 309 hospitals in the Perspective database of Premier Healthcare Informatics in North Carolina from June 1, 2004 to June 30, 2006. Results showed minimal correlation between overall levels of spending and hospital survival. Also noted is the small percentage of patients discharged to hospice.

The article presents a study on the effect of ß-blockers on chronic obstructive pulmonary disease (COPD) patients. Researchers conducted an observational cohort study using data from the Utrecht General Practitioners Network database in Utrecht, Netherlands. The study found that ß-blockers might reduce the risk of exacerbations and mortality of COPD patients.

The article discusses a study which reviewed a literature on the prevalence, diagnosis, management and prevention of food allergies. One of the electronic databases search for this study is the Cochrane Database of Systematic Reviews. Database searches have been restricted to English-language articles from January 1988 to September 2009. Also, the review is restricted to studies that covered food allergies to cow's milk, hen's egg, peanut, tree nut, fish and shellfish. Results of the study showed that 56 reviews of food allergy cited the involvement of immunoglobulin E-mediated reactions. The study also found that there are various diagnostic approaches including self-report or skin prick testing. Also included is information on management strategies for food allergy.

The article details a study which compared the treatment effects of stopping randomized controlled trials (RCT) early. The study utilized data from MEDLINE, EMBASE, Current Contents and full-text journal content databases to search for truncated RCT until January 2007. RCTs that were selected for this study were those that were stopped early for benefit and matching nontruncated RCT from systemic reviews. Study researchers concluded that truncated RCTs were associated with greater effect sizes compared to RCTs that were not stopped early.

The article focuses on a study which estimated the relative benefit of medication versus placebo across a wide range of initial symptom severity in patients diagnosed with depression using information from several databases, which include the Cochrane Library database. The study observed that as a function of baseline severity, medication and placebo differences varied substantially. It concluded that the magnitude benefit of antidepressant medication compared with placebo increases with severity of depression symptoms, but it can also be minimal or nonexistent, on average, in patients with mild or moderate symptoms.

A letter to the editor is presented on a case of subsequent maltreatment in children with disabilities after an unsubstantiated report for neglect.

The article offers information on a study which calculated the proportion of the U.S. population living within one and two hours by rotary air transport or ground transport of a burn care facility. Data analyzed by the researchers for the cross-sectional study were taken from the Atlas and Database of Air Medical Services database and the 2008 American Burn Association Directory. Research findings revealed a discrepancy in regional variation in access to a verified burn center by both ground and rotary air transport.

The article presents a study that examines the use of statins in the prevention and treatment of infections. Methods of the study include finding electronic databases since inception through December 2007 for randomized trials and cohort analysis and the extraction of data characteristics, statin measurement, results and quality assessment. Meta-analysis results suggest that the use of statin may be linked with beneficial effect in the treatment and prevention of infection.

The article presents a systematic review and meta-analysis which compared the long-term mortality in cancer patients with and without preexisting diabetes. The MEDLINE and EMBASE databases were searched for English-language, original investigations in humans with at least three months of follow-up. The search included articles through May 15, 2008. 48 articles met the criteria. A meta-analysis included studies reporting Cox proportional hazard ratios (HR) and Poisson relative risks. Diabetes was found to be associated with an increased mortality HR according to a random-effects model meta-analysis of 23 articles. Researchers concluded that cancer patients with preexisting diabetes have an increased risk for long-term, all-cause mortality compared with those without diabetes.

The article provides information on a study on the comparative effectiveness of various β-blockers. It cites the statistics of chronic heart failure victims in the U.S. which affect more than 5 million Americans. The researchers compared mortality linked with different β-blockers after being hospitalized due to heart failure between 2001 and 2003. The patient characteristics were identified via administrative, state mortality, and Social Security Administration databases. Results showed that about 7976 out of 11,326 adults surviving a hospitalization for heart failure received β-blockers. It suggests that randomized trials within real-world settings be conducted to reassure the clinical effectiveness of β-blockers for heart failure.

The article focuses on the study regarding the effectiveness of Get With The Guidelines-Coronary Artery Disease (GWTG-CAD) program of the American Heart Association (AHA). It aims to evaluate whether participation in the GWTG increases the adherence to the guidelines for CAD. The study was conducted among participating hospitals in the GWTG-CAD program on January 1, 2004. Information on the other databases used is presented. The hospital-based, opportunity-based and specificity analysis are also taken into account.

This article presents a case study regarding the effect of electronic alerts on isolation precautions for patients with multidrug-resistant bacteria. In a 750-bed, acute care university hospital with a patient information system covering the entire hospital, a database that included all patients with multidrug-resistant bacteria was developed and was merged daily with the admission-discharge-transfer application. Findings shows that a computer alert system can lead to a lasting and effective improvement in the implementation of isolation precautions for patients with multidrug-resistant bacteria in health care institutions.

The article reports on a study which evaluated serious adverse drug reaction (ADR) descriptions in the U.S. Food and Drug Administration (FDA) and Research on Adverse Drug events And Reports (RADAR) databases. The comprehensiveness of notifications sent out by drug manufacturers and the RADAR researchers was also studied. Results indicated that the proactive safety activities of the RADAR researchers are more comprehensive than those performed by drug companies and the FDA.

This cohort study uses data from state health care databases to determine the incidence and timing of infectious complications following cochlear implant surgery among patients in 5 US states between 2006 and 2016. [ABSTRACT FROM AUTHOR]

B In Reply b We would like to thank Pennap and colleagues for their thoughtful letter. To emphasize this point, we cite a recent study of postpartum women that demonstrated that detection of suicidal behavior through natural language processing of clinical notes resulted in an 11-fold greater estimate of suicide attempts than in those based solely on diagnostic data.[2] However, as Pennap and colleagues note in their Letter, while this underestimate most assuredly affects an estimate of the risk difference, it may not affect the relative risk of suicide attempts. Therefore, we believe that it is safe to conclude that while the diagnostic data reported in our study[1] most likely underestimate the true prevalence of suicide attempts and the risk difference, it is probably a reasonable estimate of the relative risk of suicide attempts in the children of parents who use opioids on a regular basis. [Extracted from the article]

The article discusses a study that used data from the Surveillance, Epidemiology, and End Results-Medical database to describe the time delays in the initial diagnosis and treatment of primary breast carcinoma in women across diverse ethnic/social groups. There was a diagnostic delay of two months in African American women versus white women. There was a month delay in treatment for African American women versus white women.