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The COVID-19 pandemic has been associated with increased opioid prescribing. It is not known if perceived COVID-19 related stress is associated with increased odds of long-term opioid use.To determine if greater COVID-19-related stress and worsening pain attributed to the pandemic was associated with LTOT over a 6-month observation period.Longitudinal cohort.Patients (n=477) from two midwestern health care systems, with any acute or chronic non-cancer pain, starting a new period of 30-90-day prescription opioid use, were invited to participate in the Prescription Opioids and Depression Pathways Cohort Study, a longitudinal survey study of pain, opioid use, and mental health outcomes.Baseline and 6-month follow-up assessments were used to measure the association between perceived COVID-19 stressors, the perception that pain was made worse by the pandemic and the odds of persistent opioid use, i.e., remaining a prescription opioid user at 6-month follow-up. Multivariate models controlled for demographics, opioid dose, and change in pain characteristics, mental health measures, and social support.Participants were, on average, 53.9 (±11.4) years of age, 67.1% White race, and 70.9% female. The most frequently endorsed COVID-19 stressor was "worry about health of self/others" (85.7% endorsed) and the least endorsed was "worsened pain due to pandemic" (26.2%). After adjusting for all covariates, "worsened pain due to pandemic" (OR=2.88; 95%CI: 1.33-6.22), change in pain interference (OR=1.20; 95%CI: 1.04-1.38), and change in vital exhaustion (OR=0.90; 95%CI: 0.82-0.99) remained significantly associated with persistent opioid use.Patients who attribute worsening pain to the COVID-19 pandemic are more likely to be persistent opioid users. Further research is warranted to identify mechanisms underlying this association. Clinicians may consider discussing pain in the context of the pandemic to identify patients at high risk for persistent opioid use.

Long-term opioid therapy (LTOT) is associated with increased risk for depression. It is not known if the frequency of opioid use during LTOT is associated with new onset depression. We used Optum's de-identified Integrated Claims-Clinical dataset (2010-2018) to create a cohort of 5,146 patients, 18 - 80 years of age with an encounter or claims in the year before new LTOT. New LTOT was defined by > 90 day opioid use after remaining 6-months opioid free. Opioid use frequency during the first 90 days of LTOT was categorized into occasional use (< 50% days covered), intermittent use (50% to < 80% days covered), frequent use (80% to < 90% days covered) and daily use (≥ 90% days covered). Propensity scores and inverse probability of exposure weighting controlled for confounding in models estimating risk for new onset depression. Patients were on average, 54.5 (SD±13.6) years of age, 55.7% were female, 72.5% were white and 9.5% were African-American. After controlling for confounding, daily users (HR=1.40; 95%CI:1.14-1.73) and frequent users (HR=1.34; 95%CI:1.05-1.71) were significantly more likely to develop new onset depression compared to occasional users. This association remained after accounting for the contribution of post-index pain diagnoses and opioid use disorder. In LTOT, risk for new depression episodes is up to 40% greater in near daily users compared to occasional users. Patients could reduce depression risk by avoiding opioid use on as many low pain days as possible. Repeated screening for depression during LTOT is warranted.

Background Two Taiwan based studies indicated influenza vaccinations are associated with lower risk for dementia in patient cohorts with chronic disease. We determined if such associations exist in a large, nationally distributed sample of U.S. patients not selected for chronic disease. Methods Data was obtained from Veterans Health Administration medical records (9/1/2009 – 8/31/19). Eligible patients were ≥65 years of age and free of dementia for two years prior to enrollment through the end of the first influenza season (9/1/2009 to 3/1/2012). Competing risk models estimated the risk of dementia in those with influenza vaccination (n = 66,822) compared to those without vaccination (n = 56,925). Propensity scores and inverse probability of treatment weighting controlled for confounding. Results On average, patients were 75.5 (±7.3) years of age, 3.8% were female and 91.6% were white race. After controlling for confounding, patients with influenza vaccination were significantly less likely to develop dementia compared to patients without vaccination (HR = 0.86; 95 %CI:0.83–0.88). Patients with 1, 2 or 3–5 vaccines vs. none had similar risks for dementia and patients with ≥ 6 influenza vaccines vs. none had a significant lower risk for dementia (HR = 0.88, 95 %CI: 0.83–0.94). Conclusions Repeated receipt of influenza vaccinations, compared to remaining unvaccinated, is associated with lower risk for dementia. This is consistent with the hypotheses that vaccinations may reduce risk of dementia by training the immune system and not by preventing specific infectious disease. If vaccines are identified as causative factors in reducing incident dementia, they offer an inexpensive, low-risk intervention with effects greater than any existing preventive measure.

Background Adult vaccinations may reduce risk for dementia. However, it has not been established whether tetanus, diphtheria, pertussis (Tdap) vaccination is associated with incident dementia. Methods Hypotheses were tested in a Veterans Health Affairs (VHA) cohort and replicated in a MarketScan medical claims cohort. Patients were at least 65 years of age and free of dementia for 2 years prior to index date. Patients either had or did not have a Tdap vaccination by the start of either of the 2 index periods (2011 or 2012). Follow-up continued through 2018. Controls had no Tdap vaccination for the duration of follow-up. Confounding was controlled using entropy balancing. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between Tdap vaccination and incident dementia in all patients and age subgroups (65–69, 70–74, and ≥75 years). Results VHA patients were, on average, 75.6 (SD ± 7.5) years of age, 4% female, and 91.2% were White. MarketScan patients were 69.8 (SD ± 5.6) years of age, on average and 65.4% were female. After controlling for confounding, patients with, compared to without, Tdap vaccination had a significantly lower risk for dementia in both cohorts (VHA: hazard ratio [HR] = 0.58; 95% confidence interval [CI]:0.54–0.63 and MarketScan: HR = 0.58; 95% CI:0.48–0.70). Conclusions Tdap vaccination was associated with a 42% lower dementia risk in 2 cohorts with different clinical and sociodemographic characteristics. Several vaccine types are linked to decreased dementia risk, suggesting that these associations are due to nonspecific effects on inflammation rather than vaccine-induced pathogen-specific protective effects.

Background: Patient beliefs about pain and opioids have been reported from qualitative data. To overcome limitations of unstructured assessments and small sample sizes, we determined if pain and pain medication beliefs varied by chronic pain status and opioid analgesic use (OAU) duration in primary care patients . Methods: Cross-sectional survey data obtained in 2017 and 2018 from 735 patients ≥ 18 years of age. The eight-item Barriers Questionnaire (BQ) measured beliefs about pain and pain medication. Patients reported OAU and use of other pain treatments. Multiple linear regression models estimated the association between never OAU, 1-90 day OAU and >90 day OAU and each BQ item . Results: Overall, respondents were 49.1 (±15.4) years old, 38.7 percent white, 28.4 percent African-American, 23.5 percent Hispanic, and 68.6 percent female. About one-third never used opioids, 41.8 percent had 1-90 day OAU, and 21.6 percent had > 90 day OAU. Multiple linear regression analyses showed that compared to never OAU, > 90 day OAU had lower average agreement that analgesics are addictive ( β = − 0.50; 95 percent CI: − 0.96, − 0.03), and 1-90 day OAU ( β = − 0.53; 95 percent CI: − 0.96, − 0.10) and > 90 OAU ( β = − 0.55; 95 percent CI: − 1.04, − 0.06) had lower average agreement that analgesics make people do or say embarrassing things . Conclusions: Patients with chronic OAU reported less concern about addiction and opioid-related behavior change. Never users were most likely to agree that opioids are addictive. There continues to be a need to educate patients about opioid risks. Assessing patients' beliefs may identify patients at risk for chronic OAU .

Background Lesbian, gay, bisexual, and questioning (LGBQ) adolescents are at increased risk of poor mental health due to minority stress, a chronic stress associated discrimination, social rejection, and victimization brought on by prejudicial attitudes towards LGBQ individuals. To improve understanding of the differential impact of various kinds of victimization on mental health outcomes for LGBQ adolescents, we analyzed data from the 2015 Youth Risk Behavior Survey (YRBS) for victimization and mental health symptom clusters and associations high school youth and compared by sexual orientation and gender. Methods Separate Latent Class Analysis (LCA) was conducted to identify profiles of both victimization and mental health symptoms for participants (N = 15,624). Subsequently, stratified weighted logistic regression models were used on an eligible analytic sample of 11,458 to assess differences in the association of victimization and mental health between LGBQ and heterosexual high school students. Results In each LCA, participants were assigned to one of 3 classes for victimization (minimal, 81.3%; bullying, 12.5%; or physical/sexual violence, 6.2%) and 1 of 2 classes for mental health symptoms (minimal, 81.2%; severe, 18.8%). LGBQ participants were overrepresented in physical/sexual violence and bullying victimization profiles. Both bullying and physical/sexual violence profiles were associated with almost 5 times the odds of endorsing severe mental health symptoms. Conclusions This study expands our understanding of the relationship between types and effect of peer victimization for LGBQ and heterosexual youth with implications for school health and prevention efforts through increased positive school climate for LGBQ students.

Transgender and nonbinary (TGNB) adults face significant barriers to healthcare, including healthcare denials, limited access to clinicians, and mistreatment by healthcare clinicians. While prior studies have explored the consequences of overt discrimination in healthcare, they often overlook the possible impacts of more subtle forms of discrimination.Is there a relationship between specific healthcare experiences, including both overt and subtle forms of discrimination, and mental health/substance use among TGNB adults?This study was a secondary analysis of the 2015 U.S. Transgender Survey (USTS), a cross-sectional survey conducted by the National Center for Transgender Equality (NCTE) that included 27,715 TGNB adults from across the US and several US territories. This study analyzed variables including healthcare experiences, mental health, and substance use outcomes.Doctors refusing to give non-TGNB-related care was associated with 71% increased odds of severe psychological distress and 95% increased odds of suicidal ideation. Further, having to teach doctors about TGNB care and doctors asking invasive questions were associated with all our studied negative mental health outcomes. Doctors asking invasive questions was additionally related to increased odds of heavy alcohol use, marijuana use, and illicit drug use.The results of this study indicate that negative health care experiences are significantly associated with mental health and substance use for TGNB adults. Specifically, these results emphasize the role of more subtle forms of discrimination, including a lack of clinician knowledge about the care of TGNB patients, asking invasive questions, and treating TGNB patients with respect.

Limited previous work has suggested that treatment of co-morbid patients with anti-depressant medication (ADM) is associated with improved glycemic control.To determine the association of ADM treatment on glycemic control at 3 time periods after diagnosis of diabetes.Retrospective cohort study.Propensity scores (PS) and inverse probability of treatment weighting (IPTW) controlled for confounding. Extended Cox models measured the association between adequate, inadequate vs. no treatment and glycemic control at 0 to 36 months, 36 to 72 months and ≥72 months.Optum®, a nationally distributed source dataset with a random sample of 5 million patients ≥18 years of age, from which we used de-identified data for 2011-2017.Eligible patients aged 18-64 had type 2 diabetes (T2DM) with poor glycemic control, and diagnosis of depression at least one year prior to diagnosis of T2DM. Exclusion criteria included steroid use, HIV, cancer, and inadequate data. 7,332 patients meeting inclusion criteria were identified.ADM treatment (identified by patient prescriptions within the EHR) was defined as adequately treated (≥12 weeks of antidepressants), inadequately treated (12 weeks) or untreated.Glycemic control was defined as A1c7.0%. Outcome was achievement of glycemic control at 0 to 36 months, 36 to 72 months and ≥72 months.After controlling for confounding, compared to no ADM treatment, adequate ADM treatment was significantly associated with achieving glycemic control within 36 months (HR 1.17, 95% CI 1.02-1.34). No association was observed beyond 36 months. There was no association between inadequate vs. no treatment and glycemic control.Receipt of adequate ADM therapy is associated with achieving glycemic control in the first 3 years after a T2DM diagnoses with uncontrolled A1c.

Existing studies designed to determine if depression treatment in patients with type 2 diabetes (T2D) is associated with improved glycemic control have produced inconsistent results. The present study investigated the link between acute phase antidepressant medication treatment and achievement of glycemic control in patients with T2D using nationally distributed electronic health record data.A retrospective cohort study (n = 7332) was conducted using nationally distributed Optum® de-identified electronic health record data from 2010 to 2018. Eligible patients were 18-64 years old and had T2D, depression, and poor glycemic control. Antidepressant medication treatment was categorized into acute phase treatment (≥12 weeks), less than acute phase (12 weeks) or no treatment. Glycemic control was defined as HbA1c 7.0 % (53 mmol/mol). Propensity scores (PS) and inverse probability of treatment weighting (IPTW) controlled for confounding. Extended Cox models measured the association between duration of antidepressant medication treatment and glycemic control at 0 to 36 months, 36 to 72 months and ≥72 months.After controlling for confounding, compared to no treatment, acute phase treatment was significantly associated with achieving glycemic control within 36 months (HR 1.17, 95 % CI 1.02-1.34). No association was observed beyond 36 months. There was no association between acute vs. less than acute phase treatment and glycemic control.We were unable to measure decreased depression severity which could contribute to glycemic control.For patients with T2D and hyperglycemia, acute phase antidepressant medication may enable glycemic control. Further research is needed to establish mechanisms for this association.

Introduction Improvement in posttraumatic stress disorder (PTSD) is associated with better health behavior such as better medication adherence and greater use of nutrition and weight loss programs. However, it is not known if reducing PTSD severity is associated with smoking cessation, a poor health behavior common in patients with PTSD. Aims and Methods Veterans Health Affairs (VHA) medical record data (2008–2015) were used to identify patients with PTSD diagnosed in specialty care. Clinically meaningful PTSD improvement was defined as ≥20 point PTSD Checklist (PCL) decrease from the first PCL ≥50 and the last available PCL within 12 months and at least 8 weeks later. The association between clinically meaningful PTSD improvement and smoking cessation within 2 years after baseline among 449 smokers was estimated in Cox proportional hazard models. Entropy balancing controlled for confounding. Results On average, patients were 39.4 (SD = 12.9) years of age, 86.6% were male and 71.5% were white. We observed clinically meaningful PTSD improvement in 19.8% of participants. Overall, 19.4% quit smoking in year 1 and 16.6% in year 2. More patients with versus without clinically meaningful PTSD improvement stopped smoking (n = 36, cumulative incidence = 40.5% vs. 111, cumulative incidence = 30.8%, respectively). After controlling for confounding, patients with versus without clinically meaningful PTSD improvement were more likely to stop smoking within 2 years (hazard ratio = 1.57; 95% confidence interval: 1.04–2.36). Conclusions Patients with clinically meaningful PTSD improvement were significantly more likely to stop smoking. Further research should determine if targeted interventions are needed or whether improvement in PTSD symptoms is sufficient to enable smoking cessation. Implications Patients with PTSD are more likely to develop chronic health conditions such as heart disease and diabetes. Poor health behaviors, including smoking, partly explain the risk for chronic disease in this patient population. Our results demonstrate that clinically meaningful PTSD improvement is followed by greater likelihood of smoking cessation. Thus, PTSD treatment may enable healthier behaviors and reduce risk for smoking-related disease.

Multiple types of vaccinations are associated with lower risk for dementia, but it is not known if receiving more than one vaccination type is associated with a greater decrease in incident dementia as compared with receiving only one type. We determined if dementia risk is lowest in patients who receive both herpes zoster (HZ) and tetanus, diphtheria, pertussis (Tdap) vaccinations as compared with receipt of only one or the other type of vaccination.Primary analysis in a Veterans Health Administration (VA) cohort was replicated in private sector medical claims data. Eligible patients were ≥65 years of age and free of dementia for 2 years prior to baseline (VHA n = 80,070; MarketScan n = 129,200). At index, patients either had both HZ and Tdap, only HZ, only Tdap, or neither vaccination. Confounding was controlled with generalized boosted propensity scores and inverse probability of treatment weighting. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between vaccination status and incident dementia.VHA patients' mean age was 76.8 ± 7.6 years, 4.4% were female and 90.9% were White, and MarketScan patients' mean age was 70.5 ± 5.9 and 65.4% were female. In both cohorts, having both HZ and Tdap vaccinations compared with no vaccination was significantly associated with lower dementia risk (VHA HR = 0.50; 95% CI: 0.43-0.59; MarketScan HR = 0.58; 95% CI: 0.38-0.89). In both cohorts, compared with neither vaccination, patients with only one or the other vaccination types had a significantly lower risk for dementia. Incident dementia was lower in patients with both vaccinations versus only one vaccination type.Receiving two types of vaccinations versus one type was associated with lower dementia risk. Vaccinations may have non-specific associations with incident dementia. Low cost and accessible, common adult vaccinations may be an overlooked intervention for reducing dementia risk.

Suicide rates among Hispanics in the United States are much lower than rates among Whites. The reasons for this difference are uncertain, therefore we compared patient characteristics between Hispanic and White patients with a suicide attempt.Patients with a suicide attempt (n = 8641) between 2012 and 2018 were identified by ICD-9 and ICD-10 codes in a nationally distributed electronic health record data base. Patient demographics, geographic region, health services use, depression treatment, psychiatric and physical comorbidities were measured in the 2 years prior to a suicide attempt.Most patients with a suicide attempt were White (78.6%) and 6.2% were Hispanic, a majority were 36-64 years of age and 57.3% were female. Younger age and lack of health insurance were significantly (p .0001) more common among Hispanic compared to White patients with a suicide attempt. Depression treatment was significantly (p .0001) less common among Hispanic vs. White patients. Sleep disorder and all psychiatric and substance use disorders, except for drug use disorder, were significantly (p-value range: 0.026-0.0001) more prevalent in the two years before suicide attempt in White patients.Diagnosed psychopathology is more common among White vs. Hispanic patients who attempt suicide. Lack of insurance and low depression treatment rates may be associated with suicide attempt among Hispanics. Additional research is needed to determine the mix of factors that predict suicide attempt among Whites, Hispanics, and other minorities.

Gender identity change efforts (GICE) and sexual orientation change efforts (SOCE) continue to be practiced by mental health professionals and religious organizations. It is frequently sought out by families who are rejecting loved ones with marginalized sexual orientations and gender identities. This study explored the impact of religious and nonreligious GICE on the mental health of transgender and nonbinary adults through a secondary data analysis of the U.S. Transgender Survey. Results found that both nonreligious and religious GICE were associated with increased odds of suicidal ideation and attempts. Only nonreligious GICE was associated with severe psychological distress. Black individuals showed increased odds of binge alcohol consumption when exposed to nonreligious change efforts, while White individuals showed decreased odds with both nonreligious and religious GICE. This study supports ethical and legal bans on GICE.

Having a mental health diagnosis is associated with contraceptive non-adherence and user-related contraceptive failures of short-acting methods. There is a lack of research on the relationship between mental health diagnoses and early discontinuation of highly effective long-acting reversible (LARC) methods such as the intrauterine device (IUD) and subdermal implant (SDI).Using a Primary Care and Obstetrics and Gynecology Patient Data Registry, we conducted a cross-sectional analysis of the relationship between any mental health diagnosis (any anxiety disorder or depression) and early LARC removal (1 year post-insertion) among 385 reproductive-aged (14-50 years) women in 2008-16. Adjusted logistic regression was used to calculate odds ratios and 95% confidence intervals.Almost 10% (n = 37) of the sample had an early LARC removal, of which 62.2% were hormonal IUD and 37.8% were SDI. Women with a mental health diagnosis had a higher prevalence of early LARC removal (13.6% vs. 8.0%, p = =.090). Although non-significant, there was a trend in adjusted analyses indicating twice the odds of early removal for women with a mental health diagnosis versus no diagnosis (OR = =2.04, 95% CI = =0.97-4.27).This study is limited by a small sample size and availability of variables from a reportable medical record database. Pregnancy intentions and side effects of method use could not be accounted for which may have impacted timing of removal.Understanding why women choose early LARC removal can inform counseling to help women make informed choices about their contraceptive method that meets their reproductive needs.

Refugees are an often understudied population and vulnerable to poor health outcomes. No large-scale analyses have evaluated the prevalence of overweight and obesity in US-bound refugees. Using data obtained from the Centers for Disease Control (CDC) Electronic Disease Notification system, we quantified the prevalence of overweight and obesity in adult US-bound refugees by nationality from 2009 through 2017. This repeated cross-sectional analysis used CDC data to quantify and examine body mass index (BMI) trends in US-bound adult refugees during 2009-2017. Utilizing data from an overseas medical exam required for all US-bound refugees, we determined BMI for 334,746 refugees ≥ 18 years old who arrived in the United States during January 1, 2009-December 31, 2017. We calculated and compared the prevalence of overweight and obesity as well as changes in demographic characteristics (age, sex, and nationality) by year. Adjusted prevalence and prevalence ratios (APR) for yearly trends were assessed using a modified Poisson regression model with robust error variances. After adjusting for age, sex, and nationality, we observed a significant linear trend in the prevalence of overweight/obesity with an average annual relative percent increase of 3% for refugees entering the United States from 2009 through 2017 (APR = 1.031; 95% CI 1.029-1.033). The adjusted prevalence of overweight/obesity increased from 35.7% in 2009 to 44.7% in 2017. The prevalence of overweight and obesity in US-bound refugees increased steadily over the analysis period. Investigation into pre-migration and post-resettlement interventions is warranted.

Background: The literature on results from primary care–based opioid-prescribing protocols is small and results have been mixed. To advance this field, we evaluated whether opioid prescribing changed after a comprehensive protocol was implemented and whether change was associated with the number and type of risk reduction tools adopted. Methods: Electronic medical record data were obtained for 2607 patients. Demographics, Patient Health Questionnaire–9 scores, body mass index, and utilization levels of protocol elements were measured for 24 months prior and 18 months post implementation of an opioid-prescribing protocol within a federally qualified health center. χ2 and t-tests were computed to estimate change in opioid prescribing, morphine-equivalent dose, comedication prescribing, and number and type of protocol elements utilized. Results: The opioid protocol was associated with an increase in urine drug screens from 18.3% to 26.8% from pre to postimplementation (P Conclusions: Implementing a multi-faceted opioid-prescribing protocol was not associated with change in number or dose of opioid prescriptions but was associated with greater use of urine drug screens, and risk reduction tools were used more often in high-risk patients. Implementation research is needed to identify barriers to maximizing adherence to opioid protocols.

Background Depression is associated with receipt of opioids in non-cancer pain. Objectives To determine whether the receipt of opioid therapy modifies the relationship of depression and use of multiple non-opioid pain treatments. Methods Patients (n = 320) with chronic low back pain (CLBP) were recruited from family medicine clinics and completed questionnaires that measured use of home remedies, physical treatments requiring a provider and non-opioid medication treatments. A binary variable defined use (yes/no) of all three non-opioid treatment categories. Depression (yes/no) was measured with the PHQ-2. The use of opioids (yes/no) was determined by medical record abstraction. Unadjusted and adjusted logistic regression models, stratified on opioid use, estimated the association between depression and use of all three non-opioid treatments. Results Participants were mostly female (71.3%), non-white (57.5%) and 69.4% were aged 18 to 59 years. In adjusted analyses stratified by opioid use, depression was not significantly associated with using three non-opioid treatments (OR = 2.20; 95% CI = 0.80–6.07) among non-opioid users; but among opioid users, depression was significantly associated with using three non-opioid treatments (OR = 3.21; 95% CI: 1.14–8.99). These odds ratios were not significantly different between opioid users and non-users (P = 0.609). Conclusion There is modest evidence to conclude that patients with CLBP and comorbid depression, compared with those without depression, were more likely to try both opioid and non-opioid pain treatments. Non-response to other pain treatments may partly explain why depression is associated with greater prescription opioid use.

Understanding trends in substance use by gender among jail-based treatment program participants can inform policies and programs tailored to this population. Preprogram assessment data from 3509 individuals entering a jail-based substance use disorder treatment program in Missouri between 1998 and 2016 were analyzed. Primary outcome was program participants' strongly preferred substances. Demographic covariates and drug preferences were compared between males and females. Average yearly trends in preferred substances were calculated. While 25.8% of the sample preferred heroin, it was more strongly preferred by women (36.4%) than men (22.0%, p < 0.0001). Alcohol and marijuana were preferred more by males. Overall, preferences for heroin and methamphetamine increased over time while alcohol, marijuana, and other stimulants decreased. Women being more likely to prefer heroin and the increasing preference for heroin over time are consistent with national trends. Offering evidence-based treatment like pharmacotherapy and gender-sensitive approaches can help address the needs of this vulnerable population.

Objective To compare incident dementia risk among patients who initiated treatment with metformin or sulfonylurea in Veterans Health Affairs (VHA) patients with replication in Kaiser Permanente Washington (KPW) patients to determine whether first-choice antidiabetic medications are associated with reduced risk of dementia. Patients and Methods Cohorts contained 75,187 VHA patients and 10,866 KPW patients, 50 years and older, who initiated monotherapy with metformin or sulfonylurea. Patients were free of dementia diagnoses and any diabetes treatment for 2 years before cohort entry. Variables were extracted from electronic health data from VHA (1999-2015) and KPW (1996-2015), which included diagnosis codes, pharmacy data, laboratory values, and demographic characteristics. Propensity scores and inverse probability of treatment weighting controlled for confounding. Results Veterans Health Affairs patients were 60.8±6.8 years of age on average, and KPW patients were 63.1±9.5 years of age. In the VHA sample, 72,769 (96.8%) were male; and in the KPW sample, 5480 (50.4%). After adjusting for confounding, metformin initiation was associated with a significantly (P=.02) lower risk of dementia in VHA (hazard ratio, 0.9; 95% CI, 0.9-1.0), with a similar point estimate in KPW (hazard ratio, 0.9; 95% CI, 0.7-1.1). Metformin was not associated with dementia risk in patients 75 years and older. Conclusion Existing epidemiological studies of metformin and incident dementia have been inconsistent. Using a similar study design in 2 patient populations that differed in clinical and demographic characteristics, our results provide robust evidence that metformin use is associated with a modestly lower risk of incident dementia.

Objective Comorbid psychiatric and pain-related conditions are common in patients with fibromyalgia. Most studies in this area have used data from patients in specialty care and may not represent the characteristics of fibromyalgia in primary care patients. We sought to fill gaps in the literature by determining if the association between psychiatric diagnoses, conditions associated with chronic pain, and fibromyalgia differed by gender in a primary care patient population. Design Retrospective cohort. Setting and Subjects Medical record data obtained from 38,976 patients, ≥18 years of age with a primary care encounter between July 1, 2008, to June 30, 2016. Methods International Classification of Diseases–9 codes were used to define fibromyalgia, psychiatric diagnoses, and conditions associated with chronic pain. Unadjusted associations between patient demographics, comorbid conditions, and fibromyalgia were computed using binary logistic regression for the entire cohort and separately by gender. Results Overall, 4.6% of the sample had a fibromyalgia diagnosis, of whom 76.1% were women. Comorbid conditions were more prevalent among patients with vs without fibromyalgia. Depression and arthritis were more strongly related to fibromyalgia among women (odds ratio [OR] = 2.80, 95% confidence interval [CI] = 2.50–3.13; and OR = 5.19, 95% CI = 4.62–5.84) compared with men (OR = 2.16, 95% CI = 1.71–2.71; and (OR = 3.91, 95% CI = 3.22–4.75). The relationship of fibromyalgia and other diagnoses did not significantly differ by gender. Conclusions Except for depression and arthritis, the burden of comorbid conditions in patients with fibromyalgia is similar in women and men treated in primary care. Fibromyalgia comorbidities in primary care are similar to those found in specialty care.

Adult vaccinations may reduce risk for dementia. We determined whether tetanus, diphtheria, pertussis (Tdap) vaccination is associated with lower risk for dementia. Analysis conducted with Veterans Health Affairs (VHA) administrative medical record data and replicated in private sector medical claims data. Patients were ≥65 years of age and free of dementia for 2 years prior to index date. Tdap vaccination in 2011 or 2012. Follow-up through 2018. Controls had no Tdap vaccination for the duration of follow-up. After controlling for confounding, patients with, compared to without Tdap vaccination, had a significantly lower risk for dementia in both cohorts (VHA: HR=0.58; 95%CI:0.54 - 0.63 and MarketScan: HR=0.58; 95%CI:0.48 - 0.70). Results were replicated in two cohorts with different clinical and sociodemographic characteristics. Several vaccine types are linked to decreased dementia risk, suggesting that these associations are due to nonspecific effects on inflammation rather than vaccine-induced pathogen-specific protective effects.

Due to a large number of small studies and limited control for confounding, existing evidence regarding patient characteristics associated with PrEP initiation is inconsistent. We used a large electronic health record cohort to determine which demographic, physical morbidity and psychiatric conditions are associated with PrEP initiation. Eligible adult (≥18 years) patients were selected from the Optum® de-identified Electronic Health Record dataset (2010-2018). Non-HIV sexually transmitted diseases and high risk sexual behavior was used to identify patients eligible for PrEP. A fully adjusted Poisson regression model estimated the association between age, gender, race, insurance status, comorbidity index, depression, anxiety, dysthymia, severe mental illness, substance use disorder and nicotine dependence/smoking and rate of PrEP initiation. The cohort (n = 30,909) was mostly under 40 years of age (64.3%), 67.6% were female and 58.2% were White. The cumulative incidence of PrEP initiation was 1.3% (n = 408). Patients ≥60 years of age, compared to 18-29 year olds and Black compared to White patients had significantly lower rates of PrEP initiation. Anxiety disorder was significantly associated with higher rate of PrEP initiation (RR = 1.67; 95%CI:1.20-2.33) and nicotine dependence/smoking with a lower rate (RR = 0.73; 95%CI:0.54-0.97). PrEP is underutilized, and a race disparity exists in PrEP initiation. In the context of existing research, nicotine dependence/smoking is the patient characteristic most consistently associated lower rates of starting PrEP. Given the high prevalence of smoking in PrEP eligible patients, physicians may want to integrate discussions of smoking cessation in patient-provider decisions to start PrEP.

Long-term opioid therapy (LTOT) is associated with increased risk for depression. It is not known if the frequency of opioid use during LTOT is associated with new-onset depression. We used Optum's de-identified Integrated Claims-Clinical dataset (2010-2018) to create a cohort of 5146 patients, 18 to 80 years of age, with an encounter or claims in the year before new LTOT. New LTOT was defined by90-day opioid use after remaining opioid free for 6 months. Opioid use frequency during the first 90 days of LTOT was categorized into occasional use (50% days covered), intermittent use (50% to80% days covered), frequent use (80% to90% days covered), and daily use (≥90% days covered). Propensity scores and inverse probability of exposure weighting controlled for confounding in models estimating risk for new-onset depression. Patients were on average 54.5 (SD ± 13.6) years of age, 55.7% were female, 72.5% were White, and 9.5% were African American. After controlling for confounding, daily users (hazard ratio = 1.40; 95% confidence interval: 1.14-1.73) and frequent users (hazard ratio = 1.34; 95% confidence interval: 1.05-1.71) were significantly more likely to develop new-onset depression compared with occasional users. This association remained after accounting for the contribution of post-index pain diagnoses and opioid use disorder. In LTOT, risk for new depression episodes is up to 40% greater in near-daily users compared with occasional users. Patients could reduce depression risk by avoiding opioid use on as many low pain days as possible. Repeated screening for depression during LTOT is warranted.

Background Herpes zoster (HZ) infection increases dementia risk, but it is not known if herpes zoster vaccination is associated with lower risk for dementia. We determined if HZ vaccination, compared to no HZ vaccination, is associated with lower risk for incident dementia. Methods and findings Data was obtained from Veterans Health Affairs (VHA) medical records (10/1/2008–9/30/2019) with replication in MarketScan® commercial and Medicare claims (1/1/2009-12/31/2018). Eligible patients were ≥65 years of age and free of dementia for two years prior to baseline (VHA n = 136,016; MarketScan n = 172,790). Two index periods (either start of 2011 or 2012) were defined, where patients either had or did not have a HZ vaccination. Confounding was controlled with propensity scores and inverse probability of treatment weighting. Competing risk (VHA) and Cox proportional hazard (MarketScan) models estimated the association between HZ vaccination and incident dementia in all patients and in age (65–69, 70–74, ≥75) and race (White, Black, Other) sub-groups. Sensitivity analysis measured the association between HZ vaccination and incident Alzheimer’s dementia (AD). HZ vaccination at index versus no HZ vaccination throughout follow-up. VHA patients mean age was 75.7 (SD±7.4) years, 4.0% were female, 91.2% white and 20.2% had HZ vaccination. MarketScan patients mean age was 69.9 (SD±5.7) years, 65.0% were female and 14.2% had HZ vaccination. In both cohorts, HZ vaccination compared with no vaccination, was significantly associated with lower dementia risk (VHA HR = 0.69; 95%CI: 0.67–0.72; MarketScan HR = 0.65; 95%CI:0.57–0.74). HZ vaccination was not related to dementia risk in MarketScan patients aged 65–69 years. No difference in HZ vaccination to dementia effects were found by race. HZ vaccination was associated with lower risk for AD. Conclusions HZ vaccination is associated with reduced risk of dementia. Vaccination may provide nonspecific neuroprotection by training the immune system to limit damaging inflammation, or specific neuroprotection that prevents viral cytopathic effects.

Opioid doses declined after the Centers for Disease Control (CDC) opioid prescribing guideline was published. However, it is unknown if dose declines occurred in patients with ≥ 3 years of continuous opioid use.Optum® de-identified integrated Electronic Health Record and claims data were used to create an adult sample (n = 400) with continuous opioid use for 18 months before and after the guideline publication. Based on the morphine milligram equivalent (MME) distribution at Month 1, patients were categorized into 1-50, 51-100, 101-200, and200 mg baseline MME. Interrupted time series analysis using segmented mixed linear regression models stratified on baseline MME estimated average monthly changes in MME in the 18-months pre- and post-guideline, before and after adjusting for time-varying pain conditions, psychiatric disorders and benzodiazepine prescription.Patients were 59.6 (SD±11.8) years of age, 55.8% female and 84.0% white race. For 1-50 MME, monthly dose slope was significantly (p0.0001) flatter post-guideline (pre b = 0.34 MME/month vs. post b = 0.12 MME/month). For 51-100 MME, the pre- and post-guideline dose slopes did not significantly differ (pre b = 0.60 MME/month vs. post b = 0.27 MME/month). For 101-200 MME, post-guideline dose slope was significantly (p0.0001) steeper and decreasing post-guideline (pre b = 0.11 MME/month vs. post b= -1.33 MME/month). Among200 MME, dose decreased in the pre- and post-guideline periods, and post-guideline decline was significantly (p0.0001) steeper (b= -1. 86 MME/month vs. b= -4.13 MME/month).Among patients on multiyear opioid therapy, the CDC guideline was associated with a modest change in dosing, except for patients on very high doses. The guideline was not associated with decreasing MME among lower-dose, long-term users.

Background Surgical strategies are being adapted to face the COVID‐19 pandemic. Recommendations on the management of acute appendicitis have been based on expert opinion, but very little evidence is available. This study addressed that dearth with a snapshot of worldwide approaches to appendicitis. Methods The Association of Italian Surgeons in Europe designed an online survey to assess the current attitude of surgeons globally regarding the management of patients with acute appendicitis during the pandemic. Questions were divided into baseline information, hospital organization and screening, personal protective equipment, management and surgical approach, and patient presentation before versus during the pandemic. Results Of 744 answers, 709 (from 66 countries) were complete and were included in the analysis. Most hospitals were treating both patients with and those without COVID. There was variation in screening indications and modality used, with chest X‐ray plus molecular testing (PCR) being the commonest (19·8 per cent). Conservative management of complicated and uncomplicated appendicitis was used by 6·6 and 2·4 per cent respectively before, but 23·7 and 5·3 per cent, during the pandemic (both P, The COVID‐19 pandemic required reorganization of surgical services, affecting patients with common surgical diseases including acute appendicitis. No evidence is available on the topic. This study found global variation in screening policies, use of personal protective equipment and intraoperative directives. There has been increased adoption of non‐operative management and open appendicectomy. Hands off