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BACKGROUND: The mechanism for recording International Classification of Diseases (ICD) and diagnosis related groups (DRG) codes in a patients chart is through a certified medical coder who manually reviews the medical record at the completion of an admission. High-acuity ICD codes justify DRG modifiers, indicating the need for escalated hospital resources. In this manuscript, we demonstrate that value of rules-based computer algorithms that audit for omission of administrative codes and quantifying the downstream effects with regard to financial impacts and demographic findings did not indicate significant disparities. METHODS: All study data were acquired via the UCLA Department of Anesthesiology and Perioperative Medicines Perioperative Data Warehouse. The DataMart is a structured reporting schema that contains all the relevant clinical data entered into the EPIC (EPIC Systems, Verona, WI) electronic health record. Computer algorithms were created for eighteen disease states that met criteria for DRG modifiers. Each algorithm was run against all hospital admissions with completed billing from 2019. The algorithms scanned for the existence of disease, appropriate ICD coding, and DRG modifier appropriateness. Secondarily, the potential financial impact of ICD omissions was estimated by payor class and an analysis of ICD miscoding was done by ethnicity, sex, age, and financial class. RESULTS: Data from 34,104 hospital admissions were analyzed from January 1, 2019, to December 31, 2019. 11,520 (32.9%) hospital admissions were algorithm positive for a disease state with no corresponding ICD code. 1,990 (5.8%) admissions were potentially eligible for DRG modification/upgrade with an estimated lost revenue of $22,680,584.50. ICD code omission rates compared against reference groups (private payors, Caucasians, middle-aged patients) demonstrated significant p-values

BACKGROUND: Provisional Tic Disorder (PTD) is common in childhood. The received wisdom among clinicians is that PTD is short-lived and mild, with at most a few tics, and rarely includes complex tics, premonitory phenomena or comorbid illnesses. However, such conclusions come from clinical experience, with biased ascertainment and limited follow-up. METHODS: Prospective study of 89 children with tics starting 0-9 months ago (median 4 months), fewer than half from clinical sources. Follow-up at 12 (± 24, 36, 48) months after the first tic. RESULTS: At study entry, many children had ADHD (39), an anxiety disorder (27), OCD (9) or enuresis (17). All had at least two current tics, with a mean total since onset of 6.9 motor and 2.0 phonic tics. Forty-one had experienced a complex tic, and 69 could suppress some tics. Tics were clinically meaningful: 64 had tics severe enough for a clinical trial, and 76 families sought medical attention for the tics. At 12 months, 79 returned, and 78 still had tics. Of these, 29 manifested no tics during history and extended examination, but only via audio-visual monitoring when the child was seated alone. Only 12/70 now had plans to see a doctor for tics. Most who returned at 2-4 years still had tics known to the child and family, but medical impact was low. CONCLUSIONS: Our results do not contradict previous data, but overturn clinical lore. The data strongly argue against the longstanding but arbitrary tradition of separating tic disorders into recent-onset versus chronic.

BACKGROUND: Psychiatric disorders may be a risk factor for long COVID, broadly defined as COVID-19 conditions continuing three months post-acute infection. In US Veterans with high psychiatric burden, we examined associations between psychiatric disorders and clinical diagnosis of long COVID. METHODS: We conducted a retrospective cohort study using health records from VA patients with a positive SARS-CoV-2 test from February 2020 to February 2023. Generalized linear models estimated associations between any psychiatric disorder and likelihood of subsequent diagnosis with long COVID (i.e. two or more long COVID clinical codes). Models were adjusted for socio-demographic, medical, and behavioral factors. Secondary models examined individual psychiatric disorders and age-stratified associations. RESULTS: Among 660 217 VA patients with positive SARS-CoV-2 tests, 56.3% had at least one psychiatric disorder diagnosis and 1.4% were diagnosed with long COVID. Individuals with any psychiatric disorder had higher risk for long COVID diagnosis in models adjusted for socio-demographic factors, vaccination status, smoking, and medical comorbidities (relative risk, RR = 1.28, 95% CI 1.21-1.35), with the strongest associations in younger individuals. Considering specific disorders, depressive, anxiety, and stress-related disorders were associated with increased risk for long COVID diagnoses (RRs = 1.36-1.48), but associations were in the opposite direction for substance use and psychotic disorders (RRs = 0.78-0.88). CONCLUSIONS: Psychiatric disorder diagnoses were associated with increased long COVID diagnosis risk in VA patients, with the strongest associations observed in younger individuals. Improved surveillance, treatment, and prevention for COVID-19 and its long-term sequelae should be considered for individuals with psychiatric conditions.

BACKGROUND: The number of older adults entering opioid treatment programs (OTPs) to treat opioid use disorder (OUD) is increasing. However, the lived experiences of aging in OTPs have not been examined. OBJECTIVE: To explore the aging experience with OUD and barriers to medical care for older adults who receive care in OTPs. DESIGN: From November 2021 to July 2022, we conducted 1-to-1, semi-structured qualitative interviews in English and Spanish, audio-recorded, transcribed, systematically coded, and analyzed to identify key themes regarding the challenges of aging with OUD and managing chronic diseases. PARTICIPANTS: Thirty-six adults aged ≥ 55 enrolled in OTPs in San Diego, California. APPROACH: A descriptive qualitative approach was used. Major themes and subthemes were identified through thematic analysis until thematic saturation was reached. KEY RESULTS: All participants were on methadone and had a mean age of 63.4 (SD 5.1) years; 11 (30.6%) identified as female, 14 (39%) as Hispanic/Latino, and 11 (36%) as Black, with a mean duration of methadone treatment of 5.6 years. Chronic diseases were common, with 21 (58.3%) reporting hypertension, 9 (25%) reporting untreated hepatitis C, and 32 (88.9%) having ≥ 2 chronic diseases. Three major themes emerged: (1) avoidance of medical care due to multiple intersectional stigmas, including those related to drug use, substance use disorder (SUD) treatment, ageism, and housing insecurity; (2) increasing isolation with aging and loss of family and peer groups; (3) the urgent need for integrating medical and aging-focused care with OUD treatment in the setting of increasing health and functional challenges. CONCLUSIONS: Older adults with OUD reported increasing social isolation and declining health while experiencing multilevel stigma and discrimination. The US healthcare system must transform to deliver age-friendly care that integrates evidence-based geriatric models of care incorporated with substance use disorder treatment and addresses the intersectional stigma this population has experienced in healthcare settings.

Acute COVID-19 infection can be followed by diverse clinical manifestations referred to as Post Acute Sequelae of SARS-CoV2 Infection (PASC). Studies have shown an increased risk of being diagnosed with new-onset psychiatric disease following a diagnosis of acute COVID-19. However, it was unclear whether non-psychiatric PASC-associated manifestations (PASC-AMs) are associated with an increased risk of new-onset psychiatric disease following COVID-19. A retrospective electronic health record (EHR) cohort study of 2,391,006 individuals with acute COVID-19 was performed to evaluate whether non-psychiatric PASC-AMs are associated with new-onset psychiatric disease. Data were obtained from the National COVID Cohort Collaborative (N3C), which has EHR data from 76 clinical organizations. EHR codes were mapped to 151 non-psychiatric PASC-AMs recorded 28-120 days following SARS-CoV-2 diagnosis and before diagnosis of new-onset psychiatric disease. Association of newly diagnosed psychiatric disease with age, sex, race, pre-existing comorbidities, and PASC-AMs in seven categories was assessed by logistic regression. There were significant associations between a diagnosis of any psychiatric disease and five categories of PASC-AMs with odds ratios highest for neurological, cardiovascular, and constitutional PASC-AMs with odds ratios of 1.31, 1.29, and 1.23 respectively. Secondary analysis revealed that the proportions of 50 individual clinical features significantly differed between patients diagnosed with different psychiatric diseases. Our study provides evidence for association between non-psychiatric PASC-AMs and the incidence of newly diagnosed psychiatric disease. Significant associations were found for features related to multiple organ systems. This information could prove useful in understanding risk stratification for new-onset psychiatric disease following COVID-19. Prospective studies are needed to corroborate these findings.

BACKGROUND: Previous studies found that documentation of comorbidities differed when Veterans received care within versus outside Veterans Health Administration (VHA). Changes to medical center funding, increased attention to performance reporting, and expansion of Clinical Documentation Improvement programs, however, may have caused coding in VHA to change. METHODS: Using repeated cross-sectional data, we compared Elixhauser-van Walraven scores and Medicare Severity Diagnosis Related Group (DRG) severity levels for Veterans admissions across settings and payers over time, utilizing a linkage of VHA and all-payer discharge data for 2012-2017 in seven US states. To minimize selection bias, we analyzed records for Veterans admitted to both VHA and non-VHA hospitals in the same year. Using generalized linear models, we adjusted for patient and hospital characteristics. RESULTS: Following adjustment, VHA admissions consistently had the lowest predicted mean comorbidity scores (4.44 (95% CI 4.34-4.55)) and lowest probability of using the most severe DRG (22.1% (95% CI 21.4%-22.8%)). In contrast, Medicare-covered admissions had the highest predicted mean comorbidity score (5.71 (95% CI 5.56-5.85)) and highest probability of using the top DRG (35.3% (95% CI 34.2%-36.4%)). CONCLUSIONS: More effective strategies may be needed to improve VHA documentation, and current risk-adjusted comparisons should account for differences in coding intensity.

BACKGROUND AND HYPOTHESIS: Serious mental illness (SMI) may compromise diabetes self-management. This study assessed the association between SMI and glycemic control, and explored sociodemographic predictors and geographic clustering of this outcome among patients with and without SMI. STUDY DESIGN: We used electronic health record data for adult primary care patients with diabetes from 2 San Francisco health care delivery systems. The primary outcome was poor glycemic control (hemoglobin A1c >9.0%), which was modeled on SMI diagnosis status and sociodemographics. Geospatial analyses examined hotspots of poor glycemic control and neighborhood characteristics. STUDY RESULTS: The study included 11 694 participants with diabetes, 21% with comorbid SMI, of whom 22% had a schizophrenia spectrum or bipolar disorder. Median age was 62 years; 52% were female and 79% were Asian, Black, or Hispanic. In adjusted models, having schizophrenia spectrum disorder or bipolar disorder was associated with greater risk for poor glycemic control (vs participants without SMI, adjusted relative risk [aRR] = 1.24; 95% confidence interval, 1.02, 1.49), but having broadly defined SMI was not. People with and without SMI had similar sociodemographic correlates of poor glycemic control including younger versus older age, Hispanic versus non-Hispanic White race/ethnicity, and English versus Chinese language preference. Hotspots for poor glycemic control were found in neighborhoods with more lower-income, Hispanic, and Black residents. CONCLUSIONS: Poor diabetes control was significantly related to having a schizophrenia spectrum or bipolar disorder, and to sociodemographic factors and neighborhood. Community-based mental health clinics in hotspots could be targets for implementation of diabetes management services.

AIM: This paper describes the trajectory during 1 year of four patient-reported outcomes (PROs), namely, sleep, depressive symptoms, health-related quality of life (HrQoL), and well-being, in patients with heart failure (HF), their relationship and the patient characteristics associated with changes in these PROs. METHODS AND RESULTS: Data analyses of PROs from 603 patients (mean age 67 years; 29% female, 60% NYHA II) enrolled in the HF-Wii study. On short term, between baseline and 3 months, 16% of the patients experienced continuing poor sleep, 11% had sustained depressive symptoms, 13% had consistent poor HrQoL, and 13% consistent poor well-being. Across the entire 1-year period only 21% of the patients had good PRO scores at all timepoints (baseline, 3, 6, and 12 months). All others had at least one low score in any of the PROs at some timepoint during the study. Over the 12 months, 17% had consistently poor sleep, 17% had sustained symptoms of depression, 15% consistently rated a poor HrQoL, and 13% poor well-being. Different patient characteristics per PRO were associated with a poor outcomes across the 12 months. Age, education, New York Heart Association, and length of disease were related to two PRO domains and submaximal exercise capacity (6 min test), co-morbidity, and poor physical activity to one. CONCLUSION: In total, 79% of the patients with HF encountered problems related to sleep, depressive symptoms, HrQoL, and well-being at least once during a 1-year period. This underscores the need for continuous monitoring and follow-up of patients with HF and the need for dynamic adjustments in treatment and care regularly throughout the HF trajectory.

BackgroundWhile it is widely accepted that multiple sclerosis (MS) often causes cognitive dysfunction, it is thought that these cognitive symptoms rarely progress to dementia. However, this has not been thoroughly investigated. The objectives of this cohort study are to determine whether people with MS have an increased risk of dementia compared to the general population and to identify factors, such as geographic latitude, which may modify this association.MethodsWe studied data from a random sample of US veterans aged ≥ 55 years followed at Veterans Affairs Health Care Systems nationwide from 1999 to 2019. We identified all patients diagnosed with MS using ICD codes over a two-year baseline period. We then identified a comparison cohort of patients without MS matched 1:1 on sex, age, race, and first encounter date. We constructed Cox proportional hazards regression models to determine the association between MS and dementia while controlling for demographic factors and comorbidities, with additional models to examine subgroup effects. We used Fine-Gray subdistribution hazard models accounting for competing risk of death to evaluate the sensitivity of the findings.ResultsThe study included 4084 MS patients and a matched group of 4084 non-MS patients. Overall, patients had mean age 66, were 93.6% male, and 88.1% non-Hispanic White, with mean follow-up time 9.5 years (MS) and 10.8 years (non-MS). In unadjusted models, veterans with MS had greater risk of dementia compared to matched controls (cumulative incidence 16.7% vs 12.4%; Cox HR 1.58, 95% CI 1.41-1.78). The increased risk remained after adjustment for potential confounders (adjusted HR 1.56, 95% CI 1.39-1.76) and when considering death as a competing risk (Fine-Gray HR 1.36, 95% CI 1.21-1.53). The magnitude of the MS-dementia association increased with rising geographic latitude (North HR 1.86, 1.51-2.30; Central HR 1.61, 1.42-1.82; South HR 1.39, 1.18-1.64; interaction p = 0.04) and younger baseline age (interaction p

RationaleHIV and cardiometabolic disorders including hypertension and diabetes pose a serious double threat in Malawi. Supportive couple relationships may be an important resource for managing these conditions. According to the theory of communal coping, couples will more effectively manage illness if they view the illness as "our problem" (shared illness appraisal) and are united in shared behavioral efforts.MethodsThis study qualitatively investigated communal coping of 25 couples living with HIV and hypertension or diabetes in Zomba, Malawi. Partners were interviewed separately regarding relationship quality, shared illness appraisal, communal coping, and dyadic management of illness.ResultsMost participants (80%) were living with HIV, and more than half were also living with hypertension. Most participants expressed high levels of unity and the view that illness was "our problem." In some couples, partners expected but did not extend help and support and reported little collaboration. Communal coping and dyadic management were strongly gendered. Some women reported a one-sided support relationship in which they gave but did not receive support. Women were also more likely to initiate support interactions and offered more varied support than men. In couples with poor relationship quality and weak communal coping, dyadic management of illness was also weak. Partner support was particularly crucial for dietary changes, as women typically prepared meals for the entire family. Other lifestyle changes that could be supported or hindered by a partner included exercise, stress reduction, and medication adherence.ConclusionWe conclude that gendered power imbalances may influence the extent to which couple-level ideals translate into actual communal coping and health behaviors. Given that spouses and families of patients are also at risk due to shared environments, we call for a shift from an illness management paradigm to a paradigm of optimizing health for spouses and families regardless of diabetes or hypertension diagnosis.

BackgroundEstimating the medical complexity of people aging with HIV can inform clinical programs and policy to meet future healthcare needs. The objective of our study was to forecast the prevalence of comorbidities and multimorbidity among people with HIV (PWH) using antiretroviral therapy (ART) in the United States (US) through 2030.Methods and findingsUsing the PEARL model-an agent-based simulation of PWH who have initiated ART in the US-the prevalence of anxiety, depression, stage ≥3 chronic kidney disease (CKD), dyslipidemia, diabetes, hypertension, cancer, end-stage liver disease (ESLD), myocardial infarction (MI), and multimorbidity (≥2 mental or physical comorbidities, other than HIV) were forecasted through 2030. Simulations were informed by the US CDC HIV surveillance data of new HIV diagnosis and the longitudinal North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) data on risk of comorbidities from 2009 to 2017. The simulated population represented 15 subgroups of PWH including Hispanic, non-Hispanic White (White), and non-Hispanic Black/African American (Black/AA) men who have sex with men (MSM), men and women with history of injection drug use and heterosexual men and women. Simulations were replicated for 200 runs and forecasted outcomes are presented as median values (95% uncertainty ranges are presented in the Supporting information). In 2020, PEARL forecasted a median population of 670,000 individuals receiving ART in the US, of whom 9% men and 4% women with history of injection drug use, 60% MSM, 8% heterosexual men, and 19% heterosexual women. Additionally, 44% were Black/AA, 32% White, and 23% Hispanic. Along with a gradual rise in population size of PWH receiving ART-reaching 908,000 individuals by 2030-PEARL forecasted a surge in prevalence of most comorbidities to 2030. Depression and/or anxiety was high and increased from 60% in 2020 to 64% in 2030. Hypertension decreased while dyslipidemia, diabetes, CKD, and MI increased. There was little change in prevalence of cancer and ESLD. The forecasted multimorbidity among PWH receiving ART increased from 63% in 2020 to 70% in 2030. There was heterogeneity in trends across subgroups. Among Black women with history of injection drug use in 2030 (oldest demographic subgroup with median age of 66 year), dyslipidemia, CKD, hypertension, diabetes, anxiety, and depression were most prevalent, with 92% experiencing multimorbidity. Among Black MSM in 2030 (youngest demographic subgroup with median age of 42 year), depression and CKD were highly prevalent, with 57% experiencing multimorbidity. These results are limited by the assumption that trends in new HIV diagnoses, mortality, and comorbidity risk observed in 2009 to 2017 will persist through 2030; influences occurring outside this period are not accounted for in the forecasts.ConclusionsThe PEARL forecasts suggest a continued rise in comorbidity and multimorbidity prevalence to 2030, marked by heterogeneities across race/ethnicity, gender, and HIV acquisition risk subgroups. HIV clinicians must stay current on the ever-changing comorbidities-specific guidelines to provide guideline-recommended care. HIV clinical directors should ensure linkages to subspecialty care within the clinic or by referral. HIV policy decision-makers must allocate resources and support extended clinical capacity to meet the healthcare needs of people aging with HIV.

BackgroundThere has been a longstanding effort to integrate behavioral health and HIV care for people with comorbid HIV and behavioral health needs, including those with severe mental illness (SMI). As this population frequents both behavioral health and HIV care settings, they were likely to experience new obstacles to the quality and availability of care during the COVID-19 pandemic. This study aims to describe how clinics for HIV services or behavioral healthcare-as well as co-located sites providing both-sought to rapidly shift protocols to maintain a standard of patient care for people with comorbid HIV and SMI while adapting to the unprecedented circumstances of the pandemic.MethodsWe interviewed HIV and behavioral healthcare providers, clinic leaders, and support service agencies that served clients impacted by both HIV and SMI. Seventeen key informants across three settings (HIV care settings, behavioral health care settings, and integrated or co-located care settings) were interviewed in 2022. Interviews focused on changes in clinical services, protocols, and care provision strategies during and at the onset of the COVID-19 pandemic. Interviews were transcribed and coded using thematic analysis.ResultsCommonly endorsed themes included both positive and negative changes in care and care provision during the pandemic. Negative impacts of the pandemic included the loss of physical space, exacerbated mental health needs and disengagement in HIV care, patient barriers to telehealth and the digital divide, and increased healthcare workforce burnout. Positive changes included improved healthcare delivery and care engagement through telehealth, new opportunities to provide a wide range of social services, paradoxical increases in engagement in HIV care for certain patients, and broad institution of workforce wellness practices.ConclusionsThough COVID-19 presented several complex barriers to care for providers serving patients with comorbid HIV and SMI, the increased flexibility afforded by telehealth and a greater focus on collaborative approaches to patient care may benefit this patient population in the future. Additionally, the focus on workforce wellness may serve to increase retention and avoid burnout among providers. The strategies and lessons learned through adapting to COVID-19 may be invaluable moving forward as healthcare systems respond to future pandemics.

BACKGROUND: The COVID-19 pandemic affected older adults worldwide. Sedentary older adults experienced more severe adverse health effects due to their shelter-in-place. Physical activity was strongly recommended during periods of social distancing. The present study evaluated the impact of a virtually supervised exercise program on the physical fitness and mental health of Mexican older adults during the pandemics lockdown. METHODS: Participants were 44 older adults who were assigned to one of four physical fitness groups: a healthy control group (Ctrl-H, n = 15), a comorbidity control group (Ctrl-COM, n = 9), an exercise group without comorbidities (Exe-H, n = 11), and an exercise group with comorbidities (Exe-COM, n = 9). The participants engaged in a 60-min, virtually-supervised concurrent exercise session three times/week for 12 weeks. Fitness was measured using the online Senior Fitness Tests and the 4-m Gait Speed Test. Mental health was evaluated through virtual interviews using the Hamilton Depression Rating Scale, the Geriatric Depression Scale, and the Connor-Davidson Resilience Scale. Within-subject pre vs. post-intervention comparisons tested for significant differences, between-groups and over time. RESULTS: Significant interactions were found in the scores of the Geriatric Depression Scale (p ≤ 0.0001; ηp2 = 0.35), the Hamilton Depression Scale (p ≤ 0.0001; ηp2 = 0.35), resilience scores (p ≤ 0.0001; ηp2 = 0.46), lower-body strength (p ≤ 0.0001; ηp2 = 0.32), timed up-and-go test (p = 0.018; ηp2 = 0.18), the 6MWT distance scores (p ≤ 0.0001; ηp2 = 0.39), and the 4-m gait speed test scores (p = 0.011; ηp2 = 0.20). CONCLUSION: A long-term virtually-supervised exercise program conducted during the COVID-19 lockdown period led to marked improvements in both the fitness and mental health of older Mexican adults. Comorbidities did not diminish these benefits. These findings provide empirical support for online exercise programs in the daily routines of older adults to make clinically meaningful improvements in both physical and mental well-being.

Background: Cardiovascular health and preventative strategies are influenced by the sex of the individuals. To forecast cardiac events or detect ischemic heart disease (IHD) early, machine-learning algorithms can analyze complex patient data patterns. Early detection allows for lifestyle changes, medication management, or invasive treatments to slow disease progression and improve outcomes. Aim: To compare and predict the differences in the primary sources of IHD burden between males and females in various age groups, geographical regions, death versus alive, and comorbidity levels. Methods: A predictive and retrospective design was implemented in this study. Electronic health records were extracted, which were equally distributed among males and females with IHD. The dataset consisted of patients who were admitted between 2015 and 2022. Two of the eight models generated by Modeler software were implemented in this study: the Bayesian network model, which achieved the highest area under curve score (0.600), and the Chi-squared automatic interaction detection (CHAID) model, which achieved the highest overall accuracy score (57.199%). Results: The study sample included 17,878 men and women, 58% of whom had no comorbidities and 1.7% who died. Age, the Charlson comorbidity index score, and geographical location all predicted IHD, but age was more influential. Bayesian network analysis showed that IHD odds were highest in males 40-59 and females 60-79, with the highest mortality risk in females 80-100. North and south Jordan had higher IHD rates and middle-aged males from north and middle governorates had higher IHD rates according to CHAID. Conclusion: By using artificial intelligence, clinicians can improve patient outcomes, treatment quality, and save lives in the fight against cardiovascular illnesses. To predict IHD early, machine-learning algorithms can analyze complex patient data patterns to improve outcomes. [ABSTRACT FROM AUTHOR]

Purpose: Epidemiological TB data indicate differences in infection prevalence, progression rates, and clinical disease incidence between sexes. In contrast, evidence on sex-specific differential (post) TB case fatality in Europe has not been synthesized systematically. Methods: We searched electronic databases and grey literature up to December 2020 for studies reporting sex-stratified TB death data for Europe. The JBI critical appraisal tools served for bias risk assessment and subgroup analyses for studying heterogeneity. Random-effects models meta-analyses enabled estimating pooled relative risks of sex-associated TB fatality. Considering associations of comorbidities and risk factors on fatality differences, we applied relative risk meta-regression. Results: Based on 17,400 records screened, 117 studies entered quantitative analyses. Seventy-five studies providing absolute participant data with moderate quality and limited sex stratification reported 33 to 235,000 TB cases and 7 to 27,108 deaths. The pooled male-to-female TB fatality risk ratio was 1.4 [1.3–1.5]. Heterogeneity was high between studies and subgroups. Study time, concurrent comorbidities (e.g., HIV, diabetes, cancers), and mean participant ages showed no effect modification. We identified higher male TB fatality in studies with higher homelessness (coefficient 3.18, 95% CI [-0.59 to 6.94], p-value 0.10) and lower migrants proportion (coefficient − 0.24, 95% CI [− 0.5 to 0.04], p-value 0.09). Conclusion: We found 30–50% higher TB case fatality for males in Europe. Except for homelessness, migration, and a trend for some comorbidities, assessing effect modification could not reduce our meta-analysis' high heterogeneity. Public health authorities should take heed of this higher risk of dying in male patients' treatment services. [ABSTRACT FROM AUTHOR]

BackgroundSystemic lupus erythematosus (SLE) patients are prone to frequent emergency department (ED) visits. This study explores the epidemiology and outcomes of ED visits by patients with SLE utilizing the Nationwide Emergency Department Sample (NEDS).MethodsUsing NEDS (2019), SLE ED visits identified using ICD-10 codes (M32. xx) were compared with non-SLE ED visits in terms of demographic and clinical features and primary diagnoses associated with the ED visits. Factors associated with inpatient admission were analyzed using logistic regression. Variations in ED visits by age and race were assessed.ResultsWe identified 414,139 (0.35%) ED visits for adults ≥ 18 years with SLE. ED visits with SLE comprised more women, Black patients, ages 31-50 years, Medicare as the primary payer, and had higher comorbidity burden. A greater proportion of Black and Hispanic SLE patients who visited the ED were in the youngest age category of 18-30 years (around 20%) compared to White patients (less than 10%). Non-White patients had higher Medicaid utilization (27%-32% vs 19% in White patients). Comorbidity patterns varied based on race, with more White patients having higher rates of hyperlipidemia and ischemic heart disease (IHD) and more Black patients having chronic kidney disease (CKD), hypertension, and heart failure. Categorizing by race, SLE/connective tissue disease (CTD) and infection were the most prevalent primary ED diagnosis in non-White and White patients, respectively. Age ≥ 65 years, male sex, and comorbidities were linked to a higher risk of admission. Black race (OR 0.86, p = .01) and lowest income quartile (OR 0.78, p = .003) had lower odds of inpatient admission.ConclusionInfection and SLE/CTD were among the top diagnoses associated with ED visits and inpatient admission. Despite comprising a significant proportion of SLE ED visits, Black patients had lower odds of admission. While the higher prevalence of older age groups, hyperlipidemia, and IHD among White patients may partly explain the disparate results, and further study is needed to understand the role of other factors including reliance on the ED for routine care compared among Black patients, differences in insurance coverage, and potential socioeconomic biases among healthcare providers.

Objective: Our study examined the impact of sex, ADHD subtype, and comorbid illnesses (depression/anxiety) on the timing of diagnosis and treatment for ADHD. Method: To analyze ADHD patients, four health databases were used to assess subtype, comorbid mood, and antidepressant or anxiolytic drug exposure. Analyses were stratified by sex and age. Standardized mean differences measured intergroup differences. Results: Females with ADHD were identified at older ages and had higher rates of depression and anxiety diagnoses and treatments before and after their initial ADHD diagnosis. Predominantly inattentive ADHD patients were diagnosed later and more likely to receive mood disorder diagnosis and treatment than hyperactive impulsive ADHD patients. Conclusions: Results suggest a more complex ADHD presentation in females, potentially causing late diagnosis and delayed treatment. [ABSTRACT FROM AUTHOR]

BACKGROUND: Traumatic brain injury (TBI) is associated with significant morbidity, but the association of TBI with long-term stroke risk in diverse populations remains less clear. Our objective was to examine the long-term associations of TBI with stroke and to investigate potential differences by age, sex, race and ethnicity, and time since TBI diagnosis. METHODS: Retrospective cohort study of US military veterans aged 18+ years receiving healthcare in the Veterans Health Administration system between October 1, 2002 and September 30, 2019. Veterans with TBI were matched 1:1 to veterans without TBI on age, sex, race and ethnicity, and index date, yielding 306 796 veterans with TBI and 306 796 veterans without TBI included in the study. In primary analyses, Fine-Gray proportional hazards models adjusted for sociodemographics and medical/psychiatric comorbidities were used to estimate the association between TBI and stroke risk, accounting for the competing risk of mortality. RESULTS: Participants were a mean age of 50 years, 9% were female, and 25% were of non-White race and ethnicity. Overall, 4.7% of veterans developed a stroke over a median follow-up of 5.2 years. Veterans with TBI had 1.69 times (95% CI, 1.64-1.73) increased risk of any stroke (ischemic or hemorrhagic) compared to veterans without TBI. This increased risk was highest in the first-year post-TBI diagnosis (hazard ratio [HR], 2.16 [95% CI, 2.03-2.29]) but remained elevated for 10+ years. Similar patterns were observed for secondary outcomes, with associations of TBI with hemorrhagic stroke (HR, 3.92 [95% CI, 3.59-4.29]) being stronger than with ischemic stroke (HR, 1.56 [95% CI, 1.52-1.61]). Veterans with both mild (HR, 1.47 [95% CI, 1.43-1.52]) and moderate/severe/penetrating injury (HR, 2.02 [95% CI, 1.96-2.09]) had increased risk of stroke compared to veterans without TBI. Associations of TBI with stroke were stronger among older compared to younger individuals (P interaction-by-age

BACKGROUND: The association of historical redlining policies, a marker of structural racism, with contemporary heart failure (HF) risk among White and Black individuals is not well established. METHODS: We aimed to evaluate the association of redlining with the risk of HF among White and Black Medicare beneficiaries. Zip code-level redlining was determined by the proportion of historically redlined areas using the Mapping Inequality Project within each zip code. The association between higher zip code redlining proportion (quartile 4 versus quartiles 1-3) and HF risk were assessed separately among White and Black Medicare beneficiaries using generalized linear mixed models adjusted for potential confounders, including measures of the zip code-level Social Deprivation Index. RESULTS: A total of 2 388 955 Medicare beneficiaries (Black n=801 452; White n=1 587 503; mean age, 71 years; men, 44.6%) were included. Among Black beneficiaries, living in zip codes with higher redlining proportion (quartile 4 versus quartiles 1-3) was associated with increased risk of HF after adjusting for age, sex, and comorbidities (risk ratio, 1.08 [95% CI, 1.04-1.12]; P

BACKGROUND: Little is known about specific obsessive-compulsive clinical features associated with lifetime history of suicide attempt in individuals with obsessive-compulsive disorder (OCD) and major depression. METHODS: The study sample included 515 adults with OCD and a history of major depression. In exploratory analyses, we compared the distributions of demographic characteristics and clinical features in those with and without a history of attempted suicide and used logistic regression to evaluate the association between specific obsessive-compulsive clinical features and lifetime suicide attempt. RESULTS: Sixty-four (12%) of the participants reported a lifetime history of suicide attempt. Those who had attempted suicide were more likely to report having experienced violent or horrific images (52% vs. 30%; p

BackgroundIn the City and County of San Francisco, frequent users of emergent and urgent services across different settings (i.e., medical, mental health (MH), substance use disorder (SUD) services) are referred to as high users of multiple systems (HUMS). While often grouped together, frequent users of the health care system are likely a heterogenous population composed of subgroups with differential management needs.ObjectiveTo identify subgroups within this HUMS population using a cluster analysis.DesignCross-sectional study of HUMS patients for the 2019-2020 fiscal year using the Coordinated Care Management System (CCMS), San Francisco Department of Public Health's integrated data system.ParticipantsWe calculated use scores based on nine types of urgent and emergent medical, MH, and SUD services and identified the top 5% of HUMS patients. Through k-medoids cluster analysis, we identified subgroups of HUMS patients.Main measuresSubgroup-specific demographic, comorbidity, and service use profiles.Key resultsThe top 5% of HUMS patients in the study period included 2657 individuals; 69.7% identified as men and 66.5% identified as non-White. We detected 5 subgroups: subgroup 1 (N = 298, 11.2%) who were relatively younger with prevalent MH and SUD comorbidities, and MH services use; subgroup 2 (N = 478, 18.0%), who were experiencing homelessness, with multiple comorbidities, and frequent use of medical services; subgroup 3 (N = 449, 16.9%), who disproportionately self-identified as Black, with prolonged homelessness, multiple comorbidities, and persistent HUMS status; subgroup 4 (N = 690, 26.0%), who were relatively older, disproportionately self-identified as Black, with prior homelessness, multiple comorbidities, and frequent use of medical services; and subgroup 5 (N=742, 27.9%), who disproportionately self-identified as Latinx, were housed, with medical comorbidities and frequent medical service use.ConclusionsOur study highlights the heterogeneity of HUMS patients. Interventions must be tailored to meet the needs of these diverse patient subgroups.

Translating our knowledge of the biological aging from animal models to humans may give rise to novel approaches of targeting multiple aging-related diseases simultaneously and increasing health span. Here, for the first time, we use transcriptomic signatures of monocytes to identify biological aging pathways underlying multiple aging-related diseases in humans. The ordinal logistic regression was used to cross-sectionally investigate transcriptomics of the comorbidity index in 1264 community-based Multi-Ethnic Study of Atherosclerosis (MESA) adults, 47% Caucasian, 32% Hispanic, 21% African American, and 51% female, aged 55-94 years. The comorbidity index was defined as the number of prevalent aging-related diseases including cardiovascular disease, type-2 diabetes, hypertension, cancer, dementia, chronic kidney disease, chronic obstructive pulmonary disease, and hip fracture. We identified 708 gene transcripts associated with the comorbidity index (FDR

BackgroundMajor depressive disorder (MDD) and chronic pain are highly comorbid, and pain symptoms are associated with a poorer response to antidepressant medication treatment. It is unclear whether comorbid pain also is associated with a poorer response to treatment with repetitive transcranial magnetic stimulation (rTMS).Methods162 MDD subjects received 30 sessions of 10 Hz rTMS treatment administered to the left dorsolateral prefrontal cortex (DLPFC) with depression and pain symptoms measured before and after treatment. For a subset of 96 patients, a resting-state electroencephalogram (EEG) was recorded at baseline. Clinical outcome was compared between subjects with and without comorbid pain, and the relationships among outcome, pain severity, individual peak alpha frequency (PAF), and PAF phase-coherence in the EEG were examined.Results64.8% of all subjects reported pain, and both depressive and pain symptoms were significantly reduced after rTMS treatment, irrespective of age or gender. Patients with severe pain were 27% less likely to respond to MDD treatment than pain-free individuals. PAF was positively associated with pain severity. PAF phase-coherence in the somatosensory and default mode networks was significantly lower for MDD subjects with pain who failed to respond to MDD treatment.ConclusionsPain symptoms improved after rTMS to left DLPFC in MDD irrespective of age or gender, although the presence of chronic pain symptoms reduced the likelihood of treatment response. Individual PAF and baseline phase-coherence in the sensorimotor and midline regions may represent predictors of rTMS treatment outcome in comorbid pain and MDD.

PurposeThe current study aimed to determine baseline clinical features among adults receiving varied levels of care for transdiagnostic eating disorders (N = 5206, 89.9% female, mean age 29 years old) that may be associated with increased care utilization.MethodsWe used negative binomial regression models to evaluate associations among eating disorder diagnoses, other psychiatric features (e.g., lifetime history of comorbid disorders), and the number of episodes of care for treatment of the eating disorder.ResultsHaving a diagnosis of binge eating disorder (p

BACKGROUND: The unified protocol (UP) is a promising transdisgnostic treatment for emotional disorders; limited data exists with trauma-exposed populations. This study compared effectiveness of the UP, presented centered therapy (PCT), and treatment as usual (TAU) in trauma-exposed veterans presenting to routine care. METHOD: Trauma-exposed veterans with one or more emotional disorder diagnoses participated in a pilot hybrid-1 effectiveness/preimplementation study. Thirty-seven male and female veterans were randomized to one of three conditions. RESULTS: Multilevel growth curve modeling demonstrated improvement over time across conditions with large effect sizes (range: -2.15 to -3.32), with the UP demonstrating the greatest change. The between group effect sizes for reductions in number of comorbid diagnoses were medium to small and statistically significant (TAU and UP, d = 0.49, p = .056; TAU and PCT d = 0.18, p = .166, UP and PCT d = 0.31, p = .229). Only the UP led to a decrease in the number of comorbid diagnoses (d = -0.71). Psychosocial functioning varied by group, with slight increases in impairment in PCT and TAU, and medium effect size reduction in the UP. Only the UP exhibited significant decreases in self-reported anxiety and depression. Between group differences for UP and PCT were medium to large and statistically significant for depression across two measures (d = -0.72 to d = -1.40). CONCLUSIONS: This represents the first trial examining effectiveness of the UP, PCT, and TAU in trauma-exposed veterans. Despite a small sample, large effect size differences demonstrated promising advantages for the UP. Trial Registration Number: NCT02944994.

PurposeGiven data suggesting common co-occurrence and worse outcomes for individuals with eating disorders (EDs) and post-traumatic stress disorder (PTSD), it is critical to identify integrated treatment approaches for this group of patients. Past work has explored the feasibility and initial efficacy of intervention approaches that draw on evidence-based treatments for both EDs and PTSD; however, this work remains limited in scope. In the current study, we explored the feasibility and naturalistic outcomes of PTSD treatment delivered within the context of intensive ED treatment.MethodParticipants were 57 adult men and women with DSM-5 EDs and comorbid PTSD who completed a course of either Prolonged Exposure (PE; n = 22) or Cognitive Processing Therapy (CPT; n = 35) (Msessions = 10.40; SD = 5.13) and weekly validated measurements of clinical symptoms while enrolled in ED programming.ResultsMulti-level models for PTSD symptoms indicated a significant linear effect of time, such that participants demonstrated significant decreases over time in PTSD symptoms, regardless of treatment modality.ConclusionOur preliminary investigation provides support for the feasibility and efficacy of an integrated approach to treating EDs and PTSD. It is critical for future work to undertake randomized tests of this integrated approach using large, heterogeneous samples.Level of evidenceLevel IV, multiple time series with intervention.

Objective: To describe the clinical characteristics of male adolescents and young adults hospitalized for medical complications of atypical anorexia nervosa (atypical AN) and to compare their clinical characteristics with females with atypical AN and males with anorexia nervosa (AN). Method: A retrospective review of electronic medical records for patients with atypical AN and AN aged 9–25 admitted to the UCSF Eating Disorders Program from May 2012 to August 2020 was conducted. Results: Among 21 males with atypical AN (mean age 15.1 ± 2.7, mean %mBMI 102.0 ± 11.8), medical complications evidenced by admission laboratory values included anemia (52.9%), vitamin D insufficiency/deficiency (52.6%), and zinc deficiency (31.6%). Compared with females with atypical AN (n = 69), males with atypical AN had longer length of stay (11.4 vs 8.4 days, p =.004), higher prescribed kcal at discharge (4114 vs 3045 kcal, p <.001), lower heart rate nadir (40.0 vs 45.8, p =.038), higher aspartate transaminase (AST, 37.9 vs 26.2 U/L, p =.032), higher alanine transaminase (ALT, 30.6 vs 18.3 U/L, p =.005), and higher rates of anemia (52.9% vs 19.4%, p =.005), with no differences in vitamin D, zinc, and vital signs. Compared with males with AN (n = 40), males with atypical AN had no significant differences in vital signs or laboratory assessments during the hospitalization. Discussion: Atypical AN in males leads to significant medical comorbidity, and males with atypical AN require longer hospital stays compared to females with atypical AN. Rates of abnormal vital signs and abnormal serum laboratory values during hospital admissions do not differ in males with atypical AN compared to AN. Public Significance: Adolescent and young adult males with atypical anorexia nervosa experience significant medical complications. Males with atypical anorexia nervosa had longer hospitalizations and higher prescribed nutrition at discharge than females. Medical complications of atypical anorexia nervosa in male adolescents and young adults were generally equal to those of male adolescents and young adults with anorexia nervosa. Clinicians should be aware of unique medical complications of males with atypical anorexia nervosa. [ABSTRACT FROM AUTHOR]

ObjectivePatient presentations to the emergency department (ED) for alcohol-involved injury represent a growing public health burden, but their characteristics and sequelae remain understudied. This study examined mortality rates among ED patients presenting with alcohol-involved injuries and assessed how mortality varied by injury intent and other characteristics.MethodThis retrospective cohort study used statewide, longitudinally linked ED patient record and mortality data from California. Participants comprised all residents presenting to a licensed ED in 2009-2012 with a nonfatal injury that involved comorbid diagnosis of alcohol use disorder (AUD; n = 261,222; 59.3% male). Injury intent was defined using International Classification of Diseases, 9th Revision, Clinical Modification external cause-of-injury codes. Cox regression was used to investigate factors associated with 12-month all-cause mortality rates. Age-, sex-, and race/ethnicity-adjusted standardized mortality ratios (SMRs) were calculated using statewide mortality data.ResultsMost ED injury visits involving an AUD diagnosis were coded as unintentional (75.9%). Following the index ED visit, all-cause mortality among AUD-involved injury patients was 5,205 per 100,000 person-years, five times higher than the demographically matched population (SMR = 5.3; 95% confidence interval [5.2, 5.4]). Adjusted Cox regression models indicated that patients whose index injury was unintentional, and whose AUD was for acute intoxication, had significantly higher mortality. Most deaths among unintentionally injured patients were from natural causes, whereas external-cause deaths were relatively more common in the other patient groups.ConclusionsAUD-involved injury presentations to the ED in California are common and associated with high patient mortality burden, which varies by injury intent. Interventions are needed to reduce excess mortality in these patients.

BackgroundAccumulating evidence indicates that behaviors in Alzheimer's disease and related dementias could result in incarceration. Yet, the proportion of persons diagnosed with dementia and mild cognitive impairment (MCI) before they were incarcerated is largely unknown. By leveraging a national sample of mid- to late-life adults who were incarcerated, we determined the prevalence of dementia and MCI before their incarceration.MethodsIn this current study, participants were Medicare-eligible U.S. veterans who transitioned from incarceration to the community in mid- to late-life from October 1, 2012, to September 30, 2018, after having been incarcerated for ≤10 consecutive years (N = 17,962). Medical claims data were used to determine clinical diagnoses of dementia and MCI up to three years before incarceration. Demographics, comorbidities, and duration of incarceration among those with dementia and MCI were compared to those with neither diagnosis.ResultsParticipants were >97% male, 65% non-Hispanic white, 30% non-Hispanic black, and 3.3% had a diagnosis of either dementia (2.5%) or MCI (0.8%) before their most recent incarceration. Individuals with MCI or dementia diagnoses were older, were more likely to be non-Hispanic white, had more medical and psychiatric comorbidities, and experienced homelessness and traumatic brain injury at higher rates than those with neither diagnosis. Average duration of incarceration was significantly shorter among those with MCI (201.8 [±248.0] days) or dementia (312.8 [±548.3] days), as compared to those with neither diagnosis (497.0 [±692.7] days) (p

BackgroundThe risks associated with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its associated illness, coronavirus disease 2019 (COVID-19), among patients with a cancer diagnosis have not been fully characterized. This study leverages data from a multi-institutional cohort study, the University of California Cancer COVID Consortium, to evaluate outcomes associated with SARS-CoV-2 infection among patients with cancer.MethodsClinical data were collected from March to November 2020 and included patient demographics, cancer history and treatment, SARS-CoV-2 exposure and testing, and COVID-19 clinical management and outcomes. Multivariate ordinal logistic regression permitting unequal slopes was used to evaluate the impact of demographic, disease, and treatment factors on SARS-CoV-2 related hospitalization, intensive care unit (ICU) admission, and mortality.FindingsAmong all evaluated patients (n = 303), 147 (48%) were male, 118 (29%) were older adults (≥65 years old), and 104 (34%) were non-Hispanic white. A subset (n = 63, 21%) had hematologic malignancies and the remaining had solid tumors. Patients were hospitalized for acute care (n = 79, 26%), ICU-level care (n = 28, 9%), or died (n = 21, 7%) due to COVID-19. Patients with ≥2 comorbidities were more likely to require acute care (odds ratio [OR] 2.09 [95% confidence interval (CI), 1.23-3.55]). Cough was identified as a significant predictor of ICU hospitalization (OR 2.16 [95% CI, 1.03-4.57]). Importantly, mortality was associated with an active cancer diagnosis (OR 3.64 [95% CI, 1.40-9.5]) or advanced age (OR 3.86 [95% CI, 1.2-12.44]).InterpretationThis study observed that patients with active cancer or advanced age are at an increased risk of death from COVID-19. These study observations can inform risk counseling related to COVID-19 for patients with a cancer diagnosis.

Gut dysbiosis, defined as pathogenic alterations in the distribution and abundance of different microbial species, is associated with neuropathic pain in a variety of clinical conditions, but this has not been explored in the context of neuropathy in people with HIV (PWH). We assessed gut microbial diversity and dysbiosis in PWH and people without HIV (PWoH), some of whom reported distal neuropathic pain (DNP). DNP was graded on a standardized, validated severity scale. The gut microbiome was characterized using 16S rRNA sequencing and diversity was assessed using phylogenetic tree construction. Songbird analysis (https://github.com/mortonjt/songbird) was used to produce a multinomial regression model predicting counts of specific microbial taxa through metadata covariate columns. Participants were 226 PWH and 101 PWoH, mean (SD) age 52.0 (13.5), 21.1% female, 54.7% men who have sex with men, 44.7% non-white. Among PWH, median (interquartile range, IQR) nadir and current CD4 were 174 (21, 302) and 618 (448, 822), respectively; 90% were virally suppressed on antiretroviral therapy. PWH and PWoH did not differ with respect to microbiome diversity as indexed by Faith's phylogenetic diversity (PD). More severe DNP was associated with lower alpha diversity as indexed by Faith's phylogenetic diversity in PWH (Spearman's ρ = .224, P = 0.0007), but not in PWoH (Spearman's ρ = .032, P = .748). These relationships were not confounded by demographics or disease factors. In addition, the log-ratio of features identified at the genus level as Blautia to Lachnospira was statistically significantly higher in PWH with DNP than in PWH without DNP (t-test, P = 1.01e-3). Furthermore, the log-ratio of Clostridium features to Lachnospira features also was higher in PWH with DNP than in those without (t-test, P = 6.24e-5). Our results, in combination with previous findings in other neuropathic pain conditions, suggest that gut dysbiosis, particularly reductions in diversity and relative increases in the ratios of Blautia and Clostridium to Lachnospira, may contribute to prevalent DNP in PWH. Two candidate pathways for these associations, involving microbial pro-inflammatory components and microbially-produced anti-inflammatory short chain fatty acids, are discussed. Future studies might test interventions to re-establish a healthy gut microbiota and determine if this prevents or improves DNP. PERSPECTIVE: The association of neuropathic pain in people with HIV with reduced gut microbial diversity and dysbiosis raises the possibility that re-establishing a healthy gut microbiota might ameliorate neuropathic pain in HIV by reducing proinflammatory and increasing anti-inflammatory microbial products.

We report severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine effectiveness against infection (VE-I) and death (VE-D) by vaccine type in 780,225 veterans in the Veterans Health Administration, covering 2.7% of the US population. From February to October 2021, VE-I declined for all vaccine types, and the decline was greatest for the Janssen vaccine, resulting in a VE-I of 13.1%. Although breakthrough infection increased risk of death, vaccination remained protective against death in persons who became infected during the Delta variant surge. From July to October 2021, VE-D for age

Little is known about the associations between pain, stress, and co-occurring symptoms in oncology patients. Purpose was to identify subgroups of patients with distinct worst pain profiles and evaluate for differences among the subgroups in demographic and clinical characteristics, as well as stress and symptom scores. Oncology outpatients (n = 1305) completed questionnaires prior to their second or third chemotherapy cycle. Worst pain intensity was assessed 6 times over 2 chemotherapy cycles using a 0 to 10 numeric rating scale. The 371 patients (28.4%) who had ≤1 occurrence of pain over the 6 assessments were classified as the None class. For the remaining 934 patients whose data were entered into the latent profile analysis, 3 distinct worst pain profiles were identified (ie Mild [12.5%], Moderate [28.6%], Severe [30.5%]). Compared to None class, Severe class had fewer years of education and a lower annual income; were less likely to be employed and married; less likely to exercise on a regular basis, had a higher comorbidity burden, and a worse functional status. Compared to None class, Severe class reported higher levels of general, disease-specific, and cumulative life stress and lower levels of resilience, as well as higher levels of depressive symptoms, anxiety, fatigue, sleep disturbance, and cognitive dysfunction. This study is the first to identify distinct worst pain profiles in a large sample of oncology patients receiving chemotherapy and associated risk factors. PERSPECTIVE: Unrelieved pain remains a significant problem for oncology patients receiving chemotherapy. High levels of stress and co-occurring symptoms contribute to a more severe pain profile in these patients.

Extending from the triple wave epidemic of opioid-related overdose deaths, a fourth wave of high mortality involving methamphetamine and cocaine use has been gathering force. This article provides a review of the published literature on stimulants including epidemiology, pharmacology, neurobiology, medical and psychiatric consequences, withdrawal management, and medical and behavioral treatments.

Background and aimsObesity has been reported to be one of the most frequent comorbidities in COVID-19 patients and associated with higher rates of in-hospital mortality compared to non-obese patients. Acute kidney injury (AKI) is also known to be a complication associated with obesity in critically-ill COVID-19 patients. We aimed to investigate whether obesity was associated with increased risk of in-hospital mortality and AKI among patients with COVID-19 treated with corticosteroids.MethodsWe utilized 9965 hospitalized COVID-19 patient data and divided patients who were treated with corticosteroids into 6 groups by body mass index (BMI) (less than 18.5, 18.5-25, 25-30, 30-35, 35-40, 40 kg/m2 or greater). The association between BMI and in-hospital mortality and between BMI and incidence rate of AKI during admission among COVID-19 patients receiving corticosteroids were retrospectively investigated.ResultsThere were 4587 study participants receiving corticosteroids (mean age 66.5 ± 15.5 years, men 56.6%, mean BMI 29.0 ± 7.2 kg/m2). The smooth spline curve suggested a J-shape association between BMI and in-hospital mortality. Patients with BMI above 40 kg/m2 exhibited a higher in-hospital mortality and higher incidence rate of AKI during admission compared to patients with BMI between 25 and 30 kg/m2. The differences in in-hospital mortality and the rate of AKI were larger among patients with severe COVID-19.ConclusionsClass III obesity was associated with high in-hospital mortality and AKI in patients with COVID-19 treated by corticosteroids. Clinicians must stay vigilant on the impact of class III obesity and development of AKI to disease trajectory of COVID-19 patients.

A descriptive analysis of COVID-19 infection in patients with multiple sclerosis (MS) receiving fingolimod or siponimod. We reviewed the cases of COVID-19 from postmarketing or ongoing clinical trials reported to Novartis through December 27, 2020. As of December 27, 2020, 283 cases had been reported in fingolimod-treated patients. The mean age was 44 years (from n = 224; range 11-69 years), and 190 were women. Of 161 cases with available information, 138 were asymptomatic (6), mild (100), or moderate (32); 50 cases required hospitalization. At the last follow-up, 140 patients were reported as recovered/recovering, condition was unchanged in 22, and deteriorated in 3 patients; 4 patients had a fatal outcome. Information was not available for 114 patients. Of the 54 cases of COVID-19 reported in siponimod-treated patients, 45 were from the postmarketing setting and 9 from an ongoing open-label clinical trial. The mean age was 54 years (from n = 45; range 31-70), and 30 were women. Of 28 cases with available information, 24 were asymptomatic (2), mild (17), or moderate (5); 9 cases required hospitalization. At the last follow-up, 27 patients were reported as recovered/recovering, condition remained unchanged for 1, and 3 patients had a fatal outcome. Information was not available for 23 patients. Based on a review of available information, the risk of more severe COVID-19 in patients receiving fingolimod or siponimod seems to be similar to that reported in the general population and the MS population with COVID-19. However, limitations of spontaneous reporting, especially missing data, should be considered in the interpretation of these observations.

Alzheimer's Disease (AD) is a neurodegenerative disorder that is still not fully understood. Sex modifies AD vulnerability, but the reasons for this are largely unknown. We utilize two independent electronic medical record (EMR) systems across 44,288 patients to perform deep clinical phenotyping and network analysis to gain insight into clinical characteristics and sex-specific clinical associations in AD. Embeddings and network representation of patient diagnoses demonstrate greater comorbidity interactions in AD in comparison to matched controls. Enrichment analysis identifies multiple known and new diagnostic, medication, and lab result associations across the whole cohort and in a sex-stratified analysis. With this data-driven method of phenotyping, we can represent AD complexity and generate hypotheses of clinical factors that can be followed-up for further diagnostic and predictive analyses, mechanistic understanding, or drug repurposing and therapeutic approaches.

BackgroundPeople with HIV (PWH) have increased frailty risk at younger ages compared with the general population. Multimorbidity is associated with frailty, yet effects of specific comorbidities on transition to frailty in PWH are unknown.SettingProspective study of 219 PWH age 45 years or older in the National NeuroAIDS Tissue Consortium.MethodsFrailty status was categorized using Fried frailty phenotype criteria. Comorbidities [bone disease, cardiovascular disease, cerebrovascular disease, liver disease, renal disease, diabetes, chronic obstructive pulmonary disease (COPD), hypertension, obesity, cancers, neuropsychiatric conditions] were assessed from longitudinal data. Associations between baseline comorbidities and transition to frailty within 30 months were analyzed using Kaplan-Meier and Cox regression models. Grip strength was assessed using mixed-effects models.ResultsAt baseline, the median age was 61 years, 73% were male 98% were on antiretroviral therapy, 29% had ≥3 comorbidities, 27% were robust, and 73% were pre-frail. Cerebrovascular disease, diabetes, and COPD were independent predictors of transition to frailty within 30 months in models adjusted for age, sex, and multimorbidity (≥3 additional comorbidities) [hazard ratios (95% confidence intervals) 2.52 (1.29 to 4.93), 2.31 (1.12 to 4.76), and 1.82 (0.95 to 3.48), respectively]. Furthermore, cerebrovascular disease, diabetes, COPD, or liver disease co-occurring with multimorbidity was associated with substantially increased frailty hazards compared with multimorbidity alone (hazard ratios 4.75-7.46). Cerebrovascular disease was associated with decreased baseline grip strength (P = 0.0001), whereas multimorbidity, diabetes, and COPD were associated with declining grip strength (P < 0.10).ConclusionsIn older PWH, cerebrovascular disease, diabetes, COPD, or liver disease co-occurring with multimorbidity is associated with substantially increased risk of becoming frail within 30 months. Interventions targeting these comorbidities may ameliorate frailty and age-related functional decline in PWH.

BackgroundAlcohol use disorders (AUD) can lead to poor health outcomes. Little is known about AUD treatment among persons with HIV (PWH). In an integrated health system in Northern California, 2014-2017, we compared AUD treatment rates between PWH with AUD and persons without HIV (PWoH) with AUD.MethodsUsing Poisson regression with GEE, we estimated prevalence ratios (PRs) comparing the annual probability of receiving AUD treatment (behavioral intervention or dispensed medication), adjusted for sociodemographics, psychiatric comorbidities, insurance type, and calendar year. Among PWH, we examined independent AUD treatment predictors using PRs adjusted for calendar year only.ResultsPWH with AUD (N = 633; 93% men, median age 49) were likelier than PWoH with AUD (N = 7006; 95% men, median age 52) to have depression (38% vs. 21%) and a non-alcohol substance use disorder (SUD, 48% vs. 25%) (both P

BackgroundThe novel coronavirus pandemic has had a differential impact on communities of color across the US. The University of California hospital system serves a large population of people who are often underrepresented elsewhere. Data from hospital stays can provide much-needed localized information on risk factors for severe cases and/or death.MethodsPatient-level retrospective case series of laboratory-confirmed COVID-19 hospital admissions at five UC hospitals (N = 4730). Odds ratios of ICU admission, death, and a composite of both outcomes were calculated with univariate and multivariate logistic regression based on patient characteristics, including sex, race/ethnicity, and select comorbidities. Associations between comorbidities were quantified and visualized with a correlation network.ResultsOverall mortality rate was 7.0% (329/4,730). ICU mortality rate was 18.8% (225/1,194). The rate of the composite outcome (ICU admission and/or death) was 27.4% (1298/4730). Comorbidity-controlled odds of a composite outcome were increased for age 75-84 (OR 1.47, 95% CI 1.11-1.93) and 85-59 (OR 1.39, 95% CI 1.04-1.87) compared to 18-34 year-olds, males (OR 1.39, 95% CI 1.21-1.59) vs. females, and patients identifying as Hispanic/Latino (OR 1.35, 95% CI 1.14-1.61) or Asian (OR 1.43, 95% CI 1.23-1.82) compared to White. Patients with 5 or more comorbidities were exceedingly likely to experience a composite outcome (OR 2.74, 95% CI 2.32-3.25).ConclusionsMales, older patients, those with multiple pre-existing comorbidities, and those identifying as Hispanic/Latino or Asian experienced an increased risk of ICU admission and/or death. These results are consistent with reported risks among the Hispanic/Latino population elsewhere in the United States, and confirm multiple concerns about heightened risk among the Asian population in California.

BackgroundLefamulin, a first-in-class pleuromutilin antibiotic approved for intravenous and oral use in adults with community-acquired bacterial pneumonia (CABP), was noninferior to moxifloxacin in the Lefamulin Evaluation Against Pneumonia (LEAP) 1 intravenous-to-oral switch study and the LEAP 2 oral-only study. Using pooled LEAP 1/2 data, we examined lefamulin efficacy/safety overall and within subgroups of patients presenting with comorbidities typical in CABP management.MethodsIn LEAP 1, adults with CABP were randomized to receive intravenous lefamulin (150 mg every 12 h) for 5‒7 days or moxifloxacin (400 mg every 24 h) for 7 days, with optional intravenous-to-oral switch if predefined improvement criteria were met. In LEAP 2, adults with CABP were randomized to receive oral lefamulin (600 mg every 12 h) for 5 days or moxifloxacin (400 mg every 24 h) for 7 days. Both studies assessed early clinical response (ECR) at 96 ± 24 h after first study drug dose and investigator assessment of clinical response (IACR) at test-of-cure (5‒10 days after last dose). Pooled analyses of the overall population used a 10% noninferiority margin.ResultsLefamulin (n = 646) was noninferior to moxifloxacin (n = 643) for ECR (89.3% vs 90.5%, respectively; difference  - 1.1%; 95% CI  - 4.4 to 2.2); IACR success rates at test-of-cure were similarly high (≥ 85.0%). High efficacy with both lefamulin and moxifloxacin was also demonstrated across all well-represented patient subgroups, including those with advanced age, diabetes mellitus, a history of cardiovascular diseases (e.g., hypertension, congestive heart failure, or arrhythmia) or chronic lung diseases (e.g., asthma or chronic obstructive pulmonary disease), elevated liver enzymes, or mild-to-moderate renal dysfunction. No new safety signals were identified.ConclusionsLefamulin may provide a valuable intravenous/oral monotherapy alternative to fluoroquinolones or macrolides for empiric treatment of patients with CABP, including cases of patients at risk for poor outcomes due to age or various comorbidities.Trial registrationClinicalTrials.gov LEAP 1 (NCT02559310; Registration Date: 24/09/2015) and LEAP 2 (NCT02813694; Registration Date: 27/06/2016).

BackgroundLeft ventricular free wall rupture (LVFWR) is a rare complication after myocardial infarction and usually occurs 1 to 4 days after the infarct. Over the past decade, the overall incidence of LVFWR has decreased given the advancements in reperfusion therapies. However, during the COVID-19 pandemic, there has been a significant delay in hospital presentation of patients suffering myocardial infarctions, leading to a higher incidence of mechanical complications from myocardial infarctions such as LVFWR.Case presentationWe present a case in which a patient suffered a LVFWR as a mechanical complication from myocardial infarction due to delay in seeking care over fear of contracting COVID-19 from the medical setting. The patient had been having chest pain for a few days but refused to seek medical care due to fear of contracting COVID-19 from within the medical setting. He eventually suffered a cardiac arrest at home from a massive inferior myocardial infarction and found to be in cardiac tamponade from a left ventricular perforation. He was emergently taken to the operating room to attempt to repair the rupture but he ultimately expired on the operating table.ConclusionsThe occurrence of LVFWR has been on a more significant rise over the course of the COVID-19 pandemic as patients delay seeking care over fear of contracting COVID-19 from within the medical setting. Clinicians should consider mechanical complications of MI when patients present as an out-of-hospital cardiac arrest, particularly during the COVID-19 pandemic, as delay in seeking care is often the exacerbating factor.

ObjectiveTo investigate the relationship between hypotension and neurologic outcome in adults with return of spontaneous circulation after out-of-hospital cardiac arrest.MethodsBlood pressure and medication data were extracted from adult patients who had ROSC after OHCA in Alameda County and matched with neurologic outcome using the CARES database from January 1, 2018 through July 1, 2019. We used univariate logistic regression with p ≤ 0.2 followed by multivariate logistic regression and reported an odds ratio with 95% confidence intervals.ResultsAmong the 781 adult patients who had ROSC after OHCA, 107 (13.7%) were noted to be hypotensive and 61 (57% of the hypotensive group) received vasopressors. Patients with a final prehospital blood pressure recording of

Chronic pain and post-traumatic stress disorder (PTSD) frequently co-occur, and research suggests that these 2 conditions exacerbate one another producing greater impact on normal functioning in combination than separately. The influence of traumatic experiences on both pain and PTSD has been shown, but the nature of this interplay remains unclear. Although Criterion A trauma is required for the diagnosis of PTSD, whether the association between PTSD and chronic pain is dependent on Criterion A is underexplored. In this observational cohort study, we examined the association between pain and PTSD-like symptoms in the context of Criterion A trauma in 5,791 men from the Vietnam Era Twin Registry. Correlations and mixed-effects regression models were used to evaluate the relationship between PTSD Checklist-Civilian Version symptoms and multiple indicators of pain from the Short Form McGill Pain Questionnaire across trauma history and chronic pain conditions. 53.21% of the participants experienced trauma consistent with DSM-IV Criterion A for PTSD. The associations between pain indicators and PTSD-like symptoms was stronger for individuals with a history of trauma but remained robust for individuals without trauma history. Small but significant interactions between past trauma and pain indicators and PTSD-like symptoms were observed. Findings were similar in a subsample of participants with history of chronic pain conditions. The relationship between PTSD-like symptoms and indicators of pain were largely independent of trauma consistent with Criterion A, highlighting the need to better understand and address stressful life events in chronic pain patients and pain concerns in individuals reporting trauma. PERSPECTIVE: This article demonstrates that the relationship between PTSD-like symptoms and indicators of pain is largely independent of trauma consistent with Criterion A. This finding highlights the need to better understand and address stressful life events in chronic pain patients and pain concerns in individuals reporting trauma.

Background & aimsIn patients with chronic liver disease (CLD) with or without cirrhosis, existing studies on the outcomes with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection have limited generalizability. We used the National COVID Cohort Collaborative (N3C), a harmonized electronic health record dataset of 6.4 million, to describe SARS-CoV-2 outcomes in patients with CLD and cirrhosis.MethodsWe identified all patients with CLD with or without cirrhosis who had SARS-CoV-2 testing in the N3C Data Enclave as of July 1, 2021. We used survival analyses to associate SARS-CoV-2 infection, presence of cirrhosis, and clinical factors with the primary outcome of 30-day mortality.ResultsWe isolated 220,727 patients with CLD and SARS-CoV-2 test status: 128,864 (58%) were noncirrhosis/negative, 29,446 (13%) were noncirrhosis/positive, 53,476 (24%) were cirrhosis/negative, and 8941 (4%) were cirrhosis/positive patients. Thirty-day all-cause mortality rates were 3.9% in cirrhosis/negative and 8.9% in cirrhosis/positive patients. Compared to cirrhosis/negative patients, cirrhosis/positive patients had 2.38 times adjusted hazard of death at 30 days. Compared to noncirrhosis/positive patients, cirrhosis/positive patients had 3.31 times adjusted hazard of death at 30 days. In stratified analyses among patients with cirrhosis with increased age, obesity, and comorbid conditions (ie, diabetes, heart failure, and pulmonary disease), SARS-CoV-2 infection was associated with increased adjusted hazard of death.ConclusionsIn this study of approximately 221,000 nationally representative, diverse, and sex-balanced patients with CLD; we found SARS-CoV-2 infection in patients with cirrhosis was associated with 2.38 times mortality hazard, and the presence of cirrhosis among patients with CLD infected with SARS-CoV-2 was associated with 3.31 times mortality hazard. These results provide an additional impetus for increasing vaccination uptake and further research regarding immune responses to vaccines in patients with severe liver disease.

BackgroundWe described the demographics, cancer subtypes, comorbidities, and outcomes of patients with a history of cancer and coronavirus disease 2019 (COVID-19). Second, we compared patients hospitalized with COVID-19 to patients diagnosed with COVID-19 and patients hospitalized with influenza.MethodsWe conducted a cohort study using eight routinely collected health care databases from Spain and the United States, standardized to the Observational Medical Outcome Partnership common data model. Three cohorts of patients with a history of cancer were included: (i) diagnosed with COVID-19, (ii) hospitalized with COVID-19, and (iii) hospitalized with influenza in 2017 to 2018. Patients were followed from index date to 30 days or death. We reported demographics, cancer subtypes, comorbidities, and 30-day outcomes.ResultsWe included 366,050 and 119,597 patients diagnosed and hospitalized with COVID-19, respectively. Prostate and breast cancers were the most frequent cancers (range: 5%-18% and 1%-14% in the diagnosed cohort, respectively). Hematologic malignancies were also frequent, with non-Hodgkin's lymphoma being among the five most common cancer subtypes in the diagnosed cohort. Overall, patients were aged above 65 years and had multiple comorbidities. Occurrence of death ranged from 2% to 14% and from 6% to 26% in the diagnosed and hospitalized COVID-19 cohorts, respectively. Patients hospitalized with influenza (n = 67,743) had a similar distribution of cancer subtypes, sex, age, and comorbidities but lower occurrence of adverse events.ConclusionsPatients with a history of cancer and COVID-19 had multiple comorbidities and a high occurrence of COVID-19-related events. Hematologic malignancies were frequent.ImpactThis study provides epidemiologic characteristics that can inform clinical care and etiologic studies.

BackgroundMalaria causes significant mortality and morbidity in sub-Saharan Africa, especially among children under five years of age and places a huge economic burden on individuals and health systems. While this burden has been assessed previously, few studies have explored how malaria comorbidities affect inpatient costs. This study in a malaria endemic area in Western Kenya, assessed the total treatment costs per malaria episode including comorbidities in children and adults.MethodsTotal economic costs of malaria hospitalizations were calculated from a health system and societal perspective. Patient-level data were collected from patients admitted with a malaria diagnosis to a county-level hospital between June 2016 and May 2017. All treatment documented in medical records were included as health system costs. Patient and household costs included direct medical and non-medical expenses, and indirect costs due to productivity losses.ResultsOf the 746 patients admitted with a malaria diagnosis, 64% were female and 36% were male. The mean age was 14 years (median 7 years). The mean length of stay was three days. The mean health system cost per patient was Kenyan Shilling (KSh) 4288 (USD 42.0) (95% confidence interval (CI) 95% CI KSh 4046-4531). The total household cost per patient was KSh 1676 (USD 16.4) (95% CI KSh 1488-1864) and consisted of: KSh 161 (USD1.6) medical costs; KSh 728 (USD 7.1) non-medical costs; and KSh 787 (USD 7.7) indirect costs. The total societal cost (health system and household costs) per patient was KSh 5964 (USD 58.4) (95% CI KSh 5534-6394). Almost a quarter of patients (24%) had a reported comorbidity. The most common malaria comorbidities were chest infections, diarrhoea, and anaemia. The inclusion of comorbidities compared to patients with-out comorbidities led to a 46% increase in societal costs (health system costs increased by 43% and patient and household costs increased by 54%).ConclusionsThe economic burden of malaria is increased by comorbidities which are associated with longer hospital stays and higher medical costs to patients and the health system. Understanding the full economic burden of malaria is critical if future malaria control interventions are to protect access to care, especially by the poor.

BackgroundPreoperative SARS-CoV-2 vaccination could support safer elective surgery. Vaccine numbers are limited so this study aimed to inform their prioritization by modelling.MethodsThe primary outcome was the number needed to vaccinate (NNV) to prevent one COVID-19-related death in 1 year. NNVs were based on postoperative SARS-CoV-2 rates and mortality in an international cohort study (surgical patients), and community SARS-CoV-2 incidence and case fatality data (general population). NNV estimates were stratified by age (18-49, 50-69, 70 or more years) and type of surgery. Best- and worst-case scenarios were used to describe uncertainty.ResultsNNVs were more favourable in surgical patients than the general population. The most favourable NNVs were in patients aged 70 years or more needing cancer surgery (351; best case 196, worst case 816) or non-cancer surgery (733; best case 407, worst case 1664). Both exceeded the NNV in the general population (1840; best case 1196, worst case 3066). NNVs for surgical patients remained favourable at a range of SARS-CoV-2 incidence rates in sensitivity analysis modelling. Globally, prioritizing preoperative vaccination of patients needing elective surgery ahead of the general population could prevent an additional 58 687 (best case 115 007, worst case 20 177) COVID-19-related deaths in 1 year.ConclusionAs global roll out of SARS-CoV-2 vaccination proceeds, patients needing elective surgery should be prioritized ahead of the general population.

BackgroundSubphenotypes have been identified in patients with sepsis and ARDS and are associated with different outcomes and responses to therapies.Research questionCan unique subphenotypes be identified among critically ill patients with COVID-19?Study design and methodsUsing data from a multicenter cohort study that enrolled critically ill patients with COVID-19 from 67 hospitals across the United States, we randomly divided centers into discovery and replication cohorts. We used latent class analysis independently in each cohort to identify subphenotypes based on clinical and laboratory variables. We then analyzed the associations of subphenotypes with 28-day mortality.ResultsLatent class analysis identified four subphenotypes (SP) with consistent characteristics across the discovery (45 centers; n = 2,188) and replication (22 centers; n = 1,112) cohorts. SP1 was characterized by shock, acidemia, and multiorgan dysfunction, including acute kidney injury treated with renal replacement therapy. SP2 was characterized by high C-reactive protein, early need for mechanical ventilation, and the highest rate of ARDS. SP3 showed the highest burden of chronic diseases, whereas SP4 demonstrated limited chronic disease burden and mild physiologic abnormalities. Twenty-eight-day mortality in the discovery cohort ranged from 20.6% (SP4) to 52.9% (SP1). Mortality across subphenotypes remained different after adjustment for demographics, comorbidities, organ dysfunction and illness severity, regional and hospital factors. Compared with SP4, the relative risks were as follows: SP1, 1.67 (95% CI, 1.36-2.03); SP2, 1.39 (95% CI, 1.17-1.65); and SP3, 1.39 (95% CI, 1.15-1.67). Findings were similar in the replication cohort.InterpretationWe identified four subphenotypes of COVID-19 critical illness with distinct patterns of clinical and laboratory characteristics, comorbidity burden, and mortality.

Many US states published crisis standards of care (CSC) guidelines for allocating scarce critical care resources during the COVID-19 pandemic. However, the performance of these guidelines in maximizing their population benefit has not been well tested. In 2,272 adults with COVID-19 requiring mechanical ventilation drawn from the Study of the Treatment and Outcomes in Critically Ill Patients with COVID-19 (STOP-COVID) multicenter cohort, we test the following three approaches to CSC algorithms: Sequential Organ Failure Assessment (SOFA) scores grouped into ranges, SOFA score ranges plus comorbidities, and a hypothetical approach using raw SOFA scores not grouped into ranges. We find that area under receiver operating characteristic (AUROC) curves for all three algorithms demonstrate only modest discrimination for 28-day mortality. Adding comorbidity scoring modestly improves algorithm performance over SOFA scores alone. The algorithm incorporating comorbidities has modestly worse predictive performance for Black compared to white patients. CSC algorithms should be empirically examined to refine approaches to the allocation of scarce resources during pandemics and to avoid potential exacerbation of racial inequities.