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Understanding characteristics of patients with propensity scores in the tails of the propensity score (PS) distribution has relevance for inverse-probability-of-treatment-weighted and PS-based estimation in observational studies. Here we outline a method for identifying variables most responsible for extreme propensity scores. The approach is illustrated in 3 scenarios: 1) a plasmode simulation of adult patients in the National Ambulatory Medical Care Survey (2011-2015) and 2) timing of dexamethasone initiation and 3) timing of remdesivir initiation in patients hospitalized for coronavirus disease 2019 from February 2020 through January 2021. PS models were fitted using relevant baseline covariates, and tails of the PS distribution were defined using asymmetric first and 99th percentiles. After fitting of the PS model in each original data set, values of each key covariate were permuted and model-agnostic variable importance measures were examined. Visualization and variable importance techniques were helpful in identifying variables most responsible for extreme propensity scores and may help identify individual characteristics that might make patients inappropriate for inclusion in a study (e.g., off-label use). Subsetting or restricting the study sample based on variables identified using this approach may help investigators avoid the need for trimming or overlap weights in studies.
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Pontuação de Propensão , Humanos , Simulação por ComputadorRESUMO
Abuse-deterrent formulations of opioid analgesics (ADFs) were introduced to reduce opioid-related harms among pain patients, but post-marketing study results have been mixed. However, these studies may be subject to bias from selection criteria, comparator choice, and potential confounding by "indication," highlighting the need for thorough study design considerations. In a sample of privately insured patients prescribed ADF or non-ADF extended-release/long-acting (ER/LA) opioids in North Carolina, we implemented a version of the prevalent new-user design to evaluate the relationship between ADFs and opioid use disorder (OUD, n=235) and opioid overdose (n=18) through six months of follow-up using inverse probability-weighted cumulative incidence functions and Fine-Gray models. The weighted hazard [HRw] of opioid overdose among patients initiating ADFs was 0.87 (95% CI: 0.23, 3.24) times as high as among patients who initiated, restarted, or continued non-ADF ER/LA opioids. We observed a short-term benefit of ADFs for incident OUD (HRw=0.58; 95% CI: 0.35, 0.93) compared to non-ADF ER/LA opioids in the first six weeks of follow-up, but this benefit disappeared later in follow-up (HRw=1.30; 0.86, 1.95). In summary, our findings add to the expanding body of evidence that there is no clear long-term reduction in harm from ADF opioids among patients in outpatient use.
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PURPOSE: In drug studies, research designs requiring no prior exposure to certain drug classes may restrict important populations. Since abuse-deterrent formulations (ADF) of opioids are routinely prescribed after other opioids, choice of study design, identification of appropriate comparators, and addressing confounding by "indication" are important considerations in ADF post-marketing studies. METHODS: In a retrospective cohort study using claims data (2006-2018) from a North Carolina private insurer [NC claims] and Merative MarketScan [MarketScan], we identified patients (18-64 years old) initiating ADF or non-ADF extended-release/long-acting (ER/LA) opioids. We compared patient characteristics and described opioid treatment history between treatment groups, classifying patients as traditional (no opioid claims during prior six-month washout period) or prevalent new users. RESULTS: We identified 8415 (NC claims) and 147 978 (MarketScan) ADF, and 10 114 (NC claims) and 232 028 (MarketScan) non-ADF ER/LA opioid initiators. Most had prior opioid exposure (ranging 64%-74%), and key clinical differences included higher prevalence of recent acute or chronic pain and surgery among patients initiating ADFs compared to non-ADF ER/LA initiators. Concurrent immediate-release opioid prescriptions at initiation were more common in prevalent new users than traditional new users. CONCLUSIONS: Careful consideration of the study design, comparator choice, and confounding by "indication" is crucial when examining ADF opioid use-related outcomes.
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Formulações de Dissuasão de Abuso , Analgésicos Opioides , Transtornos Relacionados ao Uso de Opioides , Padrões de Prática Médica , Projetos de Pesquisa , Humanos , Analgésicos Opioides/administração & dosagem , Estudos Retrospectivos , Pessoa de Meia-Idade , Masculino , Feminino , Adulto , Transtornos Relacionados ao Uso de Opioides/prevenção & controle , Transtornos Relacionados ao Uso de Opioides/epidemiologia , Padrões de Prática Médica/estatística & dados numéricos , Padrões de Prática Médica/normas , Adulto Jovem , Adolescente , North Carolina/epidemiologia , Preparações de Ação Retardada , Estudos de Coortes , Prescrições de Medicamentos/estatística & dados numéricosRESUMO
OBJECTIVE: Rates of death due to homicide, suicide and overdose during pregnancy and the first year postpartum have increased substantially in the USA in recent years. The aims of this study were to use 2018-2019 data on deaths identified for review by the North Carolina Maternal Mortality Review Committee (NC-MMRC), data from the North Carolina Violent Death Reporting System (NC-VDRS) and data from the Statewide Unintentional Drug Overdose Reporting System (NC-SUDORS) to examine homicide, suicide and unintentional opioid-involved overdose deaths during pregnancy and the first year postpartum. METHODS: We linked data from the 2018-2019 NC-MMRC to suicide and homicide deaths among women ages 10-50 years from the 2018-2019 NC-VDRS and to unintentional opioid-involved overdose deaths among women ages 10-50 years from the 2018-2019 NC-SUDORS. We conducted descriptive analyses to examine the prevalence of demographic characteristics and the circumstances surrounding each cause of death. RESULTS: From 2018 to 2019 in North Carolina, there were 23 homicides, nine suicides and 36 unintentional opioid-involved overdose deaths (9.7, 3.8 and 15.1 per 100 000 live births, respectively) during pregnancy and the first year postpartum. Most homicide deaths (87.0%) were by firearm, and more than half (52.5%) were related to intimate partner violence. More than two-thirds of women who died by suicide had a current mental health problem (77.8%). Less than one-fourth (22.2%) of those who died by unintentional opioid-involved overdose had a known history of substance use disorder treatment. CONCLUSION: Our approach to quantifying and describing these causes of pregnancy-associated death can serve as a framework for other states to inform data-driven prevention.
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INTRODUCTION: Antiretroviral therapy (ART) is very effective in preventing vertical transmission of HIV but some women on ART experience different virologic, immunologic, and safety profiles. While most pregnant women are closely monitored for short-term effects of ART during pregnancy, few women receive similar attention beyond pregnancy. We aimed to assess retention in care and clinical and laboratory-confirmed outcomes over 3 years after starting ART under Malawi's Option B + program. METHODS: We conducted a prospective cohort study of pregnant women newly diagnosed with HIV who started tenofovir disoproxil fumarate/emtricitabine/efavirenz (TDF/3TC/EFV) for the first time at Bwaila Hospital in Lilongwe, Malawi between May 2015 and June 2016. Participants were followed for 3 years. We summarized demographic characteristics, pregnancy outcomes, and clinical and laboratory adverse events findings using proportions. Log-binomial regression models were used to estimate the overall risk ratios (RR) and the corresponding 95% confidence interval (CI) for the association between index pregnancy (i.e. index pregnancy vs. subsequent pregnancy) and preterm birth, and index pregnancy and low birthweight. RESULTS: Of the 299 pregnant women who were enrolled in the study, 255 (85.3%) were retained in care. There were 340 total pregnancies with known outcomes during the 36-month study period, 280 index pregnancies, and 60 subsequent pregnancies. The risks of delivering preterm (9.5% for index pregnancy and13.5% for subsequent pregnancy: RR = 0.70; 95% CI: 0.32-1.54), or low birth weight infant (9.8% for index pregnancy and 4.2% for subsequent pregnancy: RR = 2.36; 95% CI: 0.58-9.66) were similar between index and subsequent pregnancies. Perinatally acquired HIV was diagnosed in 6 (2.3%) infants from index pregnancies and none from subsequent pregnancies. A total of 50 (16.7%) women had at least one new clinical adverse event and 109 (36.5%) women had at least one incident abnormal laboratory finding. Twenty-two (7.3%) women switched to second line ART: of these 64.7% (8/17) had suppressed viral load and 54.9% (6/17) had undetectable viral load at 36 months. CONCLUSION: Most of the women who started TDF/3TC/EFV were retained in care and few infants were diagnosed with perinatally acquired HIV. Despite switching, women who switched to second line therapy continued to have higher viral loads suggesting that additional factors beyond TDF/3TC/EFV failure may have contributed to the switch. Ongoing support during the postpartum period is necessary to ensure retention in care and prevention of vertical transmission.
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Infecções por HIV , Nascimento Prematuro , Recém-Nascido , Gravidez , Lactente , Feminino , Humanos , Masculino , Malaui , Estudos Prospectivos , TenofovirRESUMO
OBJECTIVE: To examine the impact of three sequential statewide policy and legislative interventions on opioid prescribing practices among privately insured individuals in North Carolina. METHODS: An interrupted time series approach was used to examine level and trajectory changes of new and prevalent opioid prescription rates, days' supply, and daily morphine milligram equivalents before and after implementation of a 1) prescription drug monitoring program, 2) state medical board initiative, and 3) legislative action. Analyses were conducted using individual-level claims data from a large private health insurance provider serving North Carolina residents, ages 18-64 years, from January 2006 to August 2018. RESULTS: Rates of new and prevalent prescription opioid patients were relatively unaffected by the prescription monitoring program but sharply declined in the months immediately following both medical board (-3.7 new and -19.3 prevalent patients per 10,000 person months) and legislative (-14.1 new and -26.7 prevalent patients) actions. Among all opioid prescriptions, days' supply steadily increased on average over the study period but declined after legislative action (-1.5 days' supply per year). CONCLUSIONS: The voluntary prescription drug monitoring program launched in 2010 only marginally affected opioid prescribing patterns on its own, but its redeployment as an investigative and clinical tool in multifaceted public policy approaches by the state medical board and legislature later in the decade plausibly contributed to notable declines in prescription rates and days' supply. This study lends new emphasis to the importance of enforcement mechanisms for state and national policies seeking to reverse this critical public health crisis.
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Analgésicos Opioides , Programas de Monitoramento de Prescrição de Medicamentos , Adolescente , Adulto , Analgésicos Opioides/uso terapêutico , Prescrições de Medicamentos , Humanos , Pessoa de Meia-Idade , North Carolina/epidemiologia , Padrões de Prática Médica , Prescrições , Adulto JovemRESUMO
OBJECTIVES: Malawi's Option B+ universal antiretroviral therapy (ART) program for pregnant and breastfeeding women does not include routine laboratory monitoring. We report safety outcomes of pregnant women who initiated ART through Option B+. METHODS: We analysed 12-month data from an observational cohort study on Option B+ among women newly initiating tenofovir/lamivudine/efavirenz (TDF/3TC/EFV) at a government antenatal clinic in Lilongwe, Malawi. Proportions of women engaged in care, incidence of DAIDS grade ≥ 2 laboratory toxicity, grade ≥ 3 adverse events (AEs), viral suppression (<1000 copies/mL), birth outcomes and infant HIV infections are reported. RESULTS: At ART initiation, participants (n = 299) had a median age of 26 years (IQR 22-30), median CD4 count of 352 cells/µl (IQR 231-520) and 94% were in WHO Stage 1. We noted 76 incident DAIDS Grade ≥ 2 laboratory results among 58 women, most commonly elevated liver function tests (n = 30 events) and low haemoglobin (n = 27). No women had elevated creatinine. Clinical AEs (n = 45) were predominantly infectious diseases and Grade 3. Five participants (2%) discontinued TDF/3TC/EFV due to virologic failure (3) or toxicity (2). Twelve months after ART initiation, most women were engaged in care (89%) and had HIV RNA < 1000 copies/ml (90%). 8% of pregnancies resulted in preterm birth, 9% were low birthweight (<2500 g), and 2% resulted in infant HIV infection at 6 weeks post-delivery. CONCLUSION: Most women remained on ART and were virally suppressed 12 months after starting Option B+. Few infants contracted HIV perinatally. While some women experienced adverse laboratory events, clinical symptom monitoring is likely reasonable.
OBJECTIFS: Le programme de traitement antirétroviral (ART) universel Option B+ du Malawi pour les femmes enceintes et allaitantes n'inclut pas de suivi de routine en laboratoire. Nous rapportons les résultats en matière de sécurité des femmes enceintes qui ont commencé l'ART via l'Option B+. MÉTHODES: Nous avons analysé les données sur 12 mois d'une étude observationnelle de cohorte portant sur l'Option B+ chez des femmes initiant récemment le traitement par ténofovir/lamivudine/éfavirenz (TDF/3TC/EFV) dans une clinique prénatale du gouvernement à Lilongwe, au Malawi. Les proportions des femmes engagées dans les soins, l'incidence de DAIDS de stade ≥ 2 toxicités de laboratoire, de stade ≥ 3 événements indésirables (EI), la suppression virale (<1000 copies/mL), les résultats de naissance et l'infection infantile par le VIH sont rapportés. RÉSULTATS: A l'initiation de l'ART, les participantes (n = 299) avaient un âge médian de 26 ans (IQR 22-30), taux médian de CD4: 352 cellules/µL (IQR 231-520) et 94% étaient au stade 1 de l'OMS. Nous avons noté 76 incidents DAIDS de stade ≥ 2 résultats de laboratoire chez 58 femmes, le plus souvent, élévationdes tests de la fonction hépatique (n = 30 événements) et faible taux d'hémoglobine (n = 27). Aucune femme n'avait de créatinine élevée. Les EI cliniques (n = 45) étaient principalement des maladies infectieuses et le stade 3. Cinq participantes (2%) ont arrêté TDF/3TC/EFV en raison d'un échec virologique (n=3) ou d'une toxicité (n = 2). Douze mois après l'initiation de l'ART, la plupart des femmes suivaient des soins (89%) et avaient un ARN-VIH <1000 copies/ml (90%). 8% des grossesses ont abouti à une naissance prématurée, 9% avaient un faible poids à la naissance (<2500 g) et 2% ont résulté en une infection par le VIH chez le nourrisson à6 semaines après l'accouchement. CONCLUSION: La plupart des femmes sont restées sous ART et ont connu une suppression virale12 mois après le début de l'Option B+. Peu d'enfants ont contracté le VIH pendant la période périnatale. Bien que certaines femmes aient connu des effets adversesde laboratoire, la surveillance des symptômes cliniques est probablement raisonnable.
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Fármacos Anti-HIV/uso terapêutico , Antirretrovirais/uso terapêutico , Benzoxazinas/uso terapêutico , Infecções por HIV/tratamento farmacológico , Lamivudina/uso terapêutico , Complicações Infecciosas na Gravidez/tratamento farmacológico , Tenofovir/uso terapêutico , Adulto , Alcinos , Estudos de Coortes , Ciclopropanos , Quimioterapia Combinada , Feminino , Humanos , Lactente , Recém-Nascido , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Malaui , Gravidez , Adulto JovemRESUMO
Depression is a known risk factor for antiretroviral therapy (ART) non-adherence, but little is known about the mechanisms explaining this relationship. Identifying these mechanisms among people living with HIV (PLHIV) after release from prison is particularly important, as individuals during this critical period are at high risk for both depression and poor ART adherence. 347 PLHIV recently released from prison in North Carolina and Texas were included in analyses to assess mediation of the relationship between depressive symptoms at 2 weeks post-release and ART adherence (assessed by unannounced telephone pill counts) at weeks 9-21 post-release by the hypothesized explanatory mechanisms of alcohol use, drug use, adherence self-efficacy, and adherence motivation (measured at weeks 6 and 14 post-release). Indirect effects were estimated using structural equation models with maximum likelihood estimation and bootstrapped confidence intervals. On average, participants achieved 79% ART adherence. The indirect effect of depression on adherence through drug use was statistically significant; greater symptoms of depression were associated with greater drug use, which was in turn associated with lower adherence. Lower adherence self-efficacy was associated with depressive symptoms, but not with adherence. Depression screening and targeted mental health and substance use services for depressed individuals at risk of substance use constitute important steps to promote adherence to ART after prison release.
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Fármacos Anti-HIV/uso terapêutico , Terapia Antirretroviral de Alta Atividade/métodos , Depressão/psicologia , Infecções por HIV/tratamento farmacológico , Adesão à Medicação/psicologia , Prisioneiros/psicologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Adulto , Depressão/complicações , Feminino , Infecções por HIV/psicologia , Humanos , Masculino , Adesão à Medicação/estatística & dados numéricos , Saúde Mental , Pessoa de Meia-Idade , Motivação , North Carolina , Fatores de Risco , Autoeficácia , Transtornos Relacionados ao Uso de Substâncias/complicações , Telefone , TexasRESUMO
Little is known about disparities in depression prevalence, treatment, and remission by psychiatric comorbidities and substance use among persons living with HIV (PLWH). We conducted a cross-sectional analysis in a large cohort of PLWH in routine care and analyzed conditional probabilities of having an indication for depression treatment, receiving treatment, receiving indicated treatment adjustments, and achieving remission, stratified by alcohol use, illicit drug use, and panic symptoms. Overall, 34.7% (95% CI 33.9-35.5%) of participants had an indication for depression treatment and of these, 55.3% (53.8-56.8%) were receiving antidepressants. Among patients receiving antidepressants, 33.0% (31.1-34.9%) had evidence of remitted depression. In a subsample of sites with antidepressant dosage data, only 8.8% (6.7-11.5%) of patients received an indicated treatment adjustment. Current drug users (45.8%, 95% CI 43.6-48.1%) and patients reporting full symptoms of panic disorder (75.0%, 95% CI 72.9-77.1%) were most likely to have an indication for antidepressant treatment, least likely to receive treatment given an indication (current drug use: 47.6%, 95% CI 44.3-51.0%; full panic symptoms: 50.8%, 95% CI 48.0-53.6%), or have evidence of remitted depression when treated (22.3%, 95% CI 18.5-26.6%; and 7.3%, 95% CI 5.5-9.6%, respectively). In a multivariable model, drug use and panic symptoms were independently associated with poorer outcomes along the depression treatment cascade. Few differences were evident by alcohol use. Current drug users were most likely to have an indication for depression treatment, but were least likely to be receiving treatment or to have remitted depression. These same disparities were even more starkly evident among patients with co-occurring symptoms of panic disorder compared to those without. Achieving improvements in the depression treatment cascade will likely require attention to substance use and psychiatric comorbidities.
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Antidepressivos/uso terapêutico , Depressão/tratamento farmacológico , Usuários de Drogas/estatística & dados numéricos , Infecções por HIV/psicologia , Disparidades em Assistência à Saúde , Pânico , Transtornos Relacionados ao Uso de Substâncias/complicações , Adulto , Consumo de Bebidas Alcoólicas/epidemiologia , Consumo de Bebidas Alcoólicas/psicologia , Comorbidade , Estudos Transversais , Depressão/epidemiologia , Depressão/psicologia , Usuários de Drogas/psicologia , Feminino , Infecções por HIV/epidemiologia , Humanos , Masculino , Prevalência , Transtornos Relacionados ao Uso de Substâncias/epidemiologia , Transtornos Relacionados ao Uso de Substâncias/psicologia , Estados UnidosRESUMO
Many people living with HIV (PLWH) pass through correctional facilities each year, a large proportion of whom do not maintain viral suppression following release. We examined the effects of imPACT, an intervention designed to promote post-release viral suppression, on antiretroviral therapy (ART) adherence. PLWH awaiting release from prisons in two southern states were randomized to imPACT (consisting of motivational interviewing, care linkage coordination, and text message medication reminders) versus standard care (SC). ART adherence, measured by unannounced monthly telephone pill counts, was compared between study arms over 6 months post-release. Of 381 participants eligible for post-release follow-up, 302 (79%) completed ≥ 1 of 6 possible pill counts (median: 4; IQR 1-6). Average adherence over follow-up was 80.3% (95% CI 77.5, 83.1) and 81.0% (78.3, 83.6) of expected doses taken in the imPACT and SC arms, respectively. There was no difference between arms when accounting for missing data using multiple imputation (mean difference = - 0.2 percentage points [- 3.7, 3.3]), controlling for study site and week of follow-up. Of the 936 (40.9%) pill counts that were missed, 212 (22.7%) were due to re-incarceration. Those who missed pill counts for any reason were more likely to be unsuppressed, suggesting that they had lower adherence. However, missingness was balanced between arms. Among PLWH released from prison, ART adherence averaged > 80% in both study arms over 6 months-a level higher than seen with most other chronic diseases. However, missing data may have led to an overestimate of adherence. Factors independent of the intervention influence ART adherence in this population and should be identified to inform future targeted interventions.
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Antirretrovirais/uso terapêutico , Terapia Antirretroviral de Alta Atividade , Infecções por HIV/tratamento farmacológico , Infecções por HIV/psicologia , Adesão à Medicação/estatística & dados numéricos , Prisioneiros/psicologia , Carga Viral/efeitos dos fármacos , Adulto , Continuidade da Assistência ao Paciente , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Motivação , Entrevista Motivacional , Prisões , RNA Viral/sangue , Sistemas de Alerta , Telefone , Envio de Mensagens de Texto , Resultado do Tratamento , Viremia/tratamento farmacológicoRESUMO
Tracking the emergence and spread of pathogen variants is an important component of monitoring infectious disease outbreaks. To that end, accurately estimating the number and prevalence of pathogen variants in a population requires carefully designed surveillance programs. However, current approaches to calculating the number of pathogen samples needed for effective surveillance often do not account for the various processes that can bias which infections are detected and which samples are ultimately characterized as a specific variant. In this article, we introduce a framework that accounts for the logistical and epidemiological processes that may bias variant characterization, and we demonstrate how to use this framework (implemented in a publicly available tool) to calculate the number of sequences needed for surveillance. Our framework is designed to be easy to use while also flexible enough to be adapted to various pathogens and surveillance scenarios.
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Surtos de Doenças , Tamanho da Amostra , ViésRESUMO
BACKGROUND: The potential misapplication of current opioid prescribing policies remains understudied and may have substantial adverse implications for patient safety. METHODS: We used autoregressive integrated moving average models to assess level and trend changes in monthly 1) prescribing rates, 2) days' supply, and 3) daily morphine milligram equivalents (MME) of incident opioid prescriptions relative to 1) a state medical board initiative to reduce high-dose and -volume opioid prescribing and 2) legislation to limit initial opioid prescriptions for acute and postsurgical pain. We examined outcomes by pain indication overall and by cancer history, using prescribing patterns for benzodiazepines to control for temporal trends. We used large private health insurance claims data to include North Carolina residents, aged 18-64, insured at any point between January 2012 and August 2018. RESULTS: After the medical board initiative, prescribing patterns for chronic pain patients did not change; conversely, acute and postsurgical pain patients experienced immediate declines in daily MME. Post-legislation prescription rates did not decline for those with acute, postsurgical, and non-cancer pain, but instead declined among cancer patients with chronic pain. Chronic pain patients experienced the largest days' supply declines post-legislation, instead of acute and postsurgical pain patients. CONCLUSIONS: We found mixed evidence on the potential impact of two opioid prescribing policies, with some observed declines in a group not intended to be impacted by the policy. This study provides evidence of the need for clearer opioid prescribing policies to ensure impacts on intended populations and avoid unintended consequences.
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Analgésicos Opioides , Dor Crônica , Humanos , Analgésicos Opioides/uso terapêutico , Dor Crônica/tratamento farmacológico , North Carolina , Análise de Séries Temporais Interrompida , Padrões de Prática Médica , Dor Pós-Operatória/induzido quimicamente , Dor Pós-Operatória/tratamento farmacológico , Políticas , Prescrições de MedicamentosRESUMO
Importance: Rapid reduction or discontinuation of long-term opioid therapy may increase risk of opioid overdose or opioid use disorder (OUD). Current guidelines for chronic pain management caution against rapid dose reduction but are based on limited evidence. Objective: To characterize the association between rapid reduction or abrupt discontinuation of opioid therapy (vs maintained or gradual reduction) and incidence of opioid overdose and OUD among patients prescribed high-dose, long-term opioid therapy (HDLTOT). Design, Setting, and Participants: This retrospective cohort study was conducted among patients aged 18 to 64 years who were prescribed HDLTOT (≥90 daily morphine milligram equivalents for ≥90% of 90 days) from January 2006 to September 2018, with follow-up up to 4 years after cohort entry. Claims data were drawn from a large private health insurer in North Carolina and analyzed from March 1, 2006, to September 30, 2018. Exposures: Time-varying exposure of rapid dose reduction or discontinuation (>10% dose reduction/week) vs maintenance, increase, or gradual reduction or discontinuation. Main Outcomes and Measures: The main outcome was incident opioid overdose (fatal or nonfatal) or diagnosed OUD. Inverse probability-weighted cumulative incidence of outcomes were estimated using the cumulative incidence function and hazard ratios (HRs) using marginal structural Fine-Gray models as a function of rapid dose tapering or discontinuation (vs gradual reduction or discontinuation or maintained or increased), accounting for competing risks. Results: A total of 19â¯443 patients (median [IQR] age, 49 [41-55] years; 10â¯073 [51.8%] men) who received HDLTOT were identified. Rapid reduction or discontinuation was associated with higher risk of fatal and nonfatal overdoses compared with gradual reduction after the first year (year 1: HR, 1.43; 95% CI, 0.94-2.18; years 2-4: HR, 1.95; 95% CI, 1.31-2.90). There was no association between rapid reduction or discontinuation and diagnosed OUD through 2 years of follow-up; however, the hazard of incident OUD among patients exposed to rapid tapering or discontinuation was greater 25 to 48 months after the start of follow-up (HR, 1.28; 95% CI, 1.01-1.63). Conclusions and Relevance: In this cohort study, rapid dose reduction or discontinuation was associated with increased risk of opioid overdose and OUD during long-term follow-up. These findings reinforce prior concerns about safety of rapid dose reductions for patients receiving HDLTOT and highlight the need for caution when reducing opioid doses.
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Overdose de Drogas , Overdose de Opiáceos , Transtornos Relacionados ao Uso de Opioides , Analgésicos Opioides/uso terapêutico , Estudos de Coortes , Overdose de Drogas/etiologia , Redução da Medicação , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , North Carolina/epidemiologia , Transtornos Relacionados ao Uso de Opioides/tratamento farmacológico , Estudos RetrospectivosRESUMO
INTRODUCTION: Long-term care engagement of women on antiretroviral therapy (ART) is essential to effective HIV public health measures. We sought to explore factors associated with a history of HIV treatment interruption among pregnant women living with HIV presenting to an antenatal clinic in Lilongwe, Malawi. METHODS: We performed a cross-sectional study of pregnant women living with HIV who had a history of ART interruption presenting for antenatal care. Women were categorized as either retained in HIV treatment or reinitiating care after loss-to-follow up (LTFU). To understand factors associated with treatment interruption, we surveyed socio-demographic and partner relationship characteristics. Crude and adjusted prevalence ratios (aPR) for factors associated with ART interruption were estimated using modified Poisson regression with robust variance. We additionally present patients' reasons for ART interruption. RESULTS: We enrolled 541 pregnant women living with HIV (391 retained and 150 reinitiating). The median age was 30 years (interquartile range (IQR): 25-34). Factors associated with a history of LTFU were age <30 years (aPR 1.46; 95% CI: 1.33-1.63), less than a primary school education (aPR 1.25; CI: 1.08-1.46), initiation of ART during pregnancy or breastfeeding (aPR 1.49, CI: 1.37-1.65), nondisclosure of HIV serostatus to their partner (aPR 1.39, CI: 1.24-1.58), lack of awareness of partner's HIV status (aPR 1.41, CI: 1.27-1.60), and no contraception use at conception (aPR 1.60, CI 1.40-1.98). Access to care challenges were the most common reasons reported by women for treatment interruption (e.g., relocation, transport costs, or misplacing health documentation). CONCLUSIONS: Interventions that simplify the ART clinic transfer process, facilitate partner disclosure, and provide counseling about the importance of lifelong ART beyond pregnancy and breastfeeding should be further evaluated for improving retention in ART treatment of women living with HIV in Malawi.
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Infecções por HIV/tratamento farmacológico , Complicações Infecciosas na Gravidez , Gestantes/psicologia , Adulto , Estudos Transversais , Feminino , Infecções por HIV/epidemiologia , Infecções por HIV/psicologia , Humanos , Malaui/epidemiologia , Gravidez , Complicações Infecciosas na Gravidez/tratamento farmacológico , Complicações Infecciosas na Gravidez/epidemiologiaRESUMO
BACKGROUND: Malawi's PMTCT Option B+ program has expanded the reach of ART services among pregnant and breastfeeding women, but retention in lifelong HIV care remains challenging. Given that depression can undermine retention, it is important to understand how depression changes over the perinatal period, varies across treatment and retention groups, and could be buffered by social support. METHODS: Data are from an observational study conducted among women enrolled in Malawi's PMTCT Option B+ program. We used multilevel generalized linear models to estimate the odds of probable depression by time, treatment and retention group, and social support. Probable depression was assessed with the Edinburgh Postnatal Depression Scale and Patient Health Questionnaire-9. RESULTS: Of 468 women, 15% reported probable depression at antenatal enrollment and prevalence differed across newly diagnosed individuals, second line therapy users, and previous defaulters (18%, 21%, 5%, pâ¯=â¯0.001). Odds of probable perinatal depression decreased over time (OR per month: 0.87, 95% CI: 0.82-0.92) but were higher among those newly diagnosed (OR: 3.25, 95% CI: 1.59-6.65) and on second line therapy (OR: 3.39, 95% CI: 1.44-7.99) as compared to previous defaulters. Odds of probable postpartum depression were lower for participants with high social support (OR: 0.19, 95% CI: 0.09-0.39). LIMITATIONS: Lack of diagnostic psychiatric evaluation precludes actual diagnosis of depression. CONCLUSIONS: Probable depression varied across the perinatal period and across treatment and retention groups. Social support was protective for postpartum depression among all participants. Depression screening and provision of social support should be considered in PMTCT programs.
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Depressão Pós-Parto , Infecções por HIV , Complicações Infecciosas na Gravidez , Depressão/epidemiologia , Depressão Pós-Parto/diagnóstico , Depressão Pós-Parto/epidemiologia , Depressão Pós-Parto/psicologia , Feminino , Infecções por HIV/epidemiologia , Humanos , Transmissão Vertical de Doenças Infecciosas/prevenção & controle , Malaui/epidemiologia , Gravidez , Apoio SocialRESUMO
BACKGROUND: Early in the pandemic, transmission risk from asymptomatic infection was unclear, making it imperative to monitor infection in workplace settings. Further, data on SARS-CoV-2 seroprevalence within university populations has been limited. METHODS: We performed a longitudinal study of University research employees on campus July-December 2020. We conducted questionnaires on COVID-19 risk factors, RT-PCR testing, and SARS-CoV-2 serology using an in-house spike RBD assay, laboratory-based Spike NTD assay, and standard nucleocapsid platform assay. We estimated prevalence and cumulative incidence of seroconversion with 95% confidence intervals using the inverse of the Kaplan-Meier estimator. RESULTS: 910 individuals were included in this analysis. At baseline, 6.2% (95% CI 4.29-8.19) were seropositive using the spike RBD assay; four (0.4%) were seropositive using the nucleocapsid assay, and 44 (4.8%) using the Spike NTD assay. Cumulative incidence was 3.61% (95% CI: 2.04-5.16). Six asymptomatic individuals had positive RT-PCR results. CONCLUSIONS: Prevalence and incidence of SARS-CoV-2 infections were low; however, differences in target antigens of serological tests provided different estimates. Future research on appropriate methods of serological testing in unvaccinated and vaccinated populations is needed. Frequent RT-PCR testing of asymptomatic individuals is required to detect acute infections, and repeated serosurveys are beneficial for monitoring subclinical infection.
Assuntos
COVID-19 , COVID-19/diagnóstico , COVID-19/epidemiologia , Humanos , Estudos Longitudinais , Pandemias , Estudos Prospectivos , SARS-CoV-2/genética , Estudos SoroepidemiológicosRESUMO
INTRODUCTION: In March 2016, the Centers for Disease Control and Prevention issued opioid prescribing guidelines for chronic noncancer pain. In response, in April 2016, the North Carolina Medical Board launched the Safe Opioid Prescribing Initiative, an investigative program intended to limit the overprescribing of opioids. This study focuses on the association of the Safe Opioid Prescribing Initiative with immediate and sustained changes in opioid prescribing among all patients who received opioid and opioid discontinuation and tapering among patients who received high-dose (>90 milligrams of morphine equivalents), long-term (>90 days) opioid therapy. METHODS: Controlled and single interrupted time series analysis of opioid prescribing outcomes before and after the implementation of Safe Opioid Prescribing Initiative was conducted using deidentified data from the North Carolina Controlled Substances Reporting System from January 2010 through March 2017. Analysis was conducted in 2019-2020. RESULTS: In an average study month, 513,717 patients, including patients who received 47,842 high-dose, long-term opioid therapy, received 660,912 opioid prescriptions at 1.3 prescriptions per patient. There was a 0.52% absolute decline (95% CI= -0.87, -0.19) in patients receiving opioid prescriptions in the month after Safe Opioid Prescribing Initiative implementation. Abrupt discontinuation, rapid tapering, and gradual tapering of opioids among patients who received high-dose, long-term opioid therapy increased by 1% (95% CI= -0.22, 2.23), 2.2% (95% CI=0.91, 3.47), and 1.3% (95% CI=0.96, 1.57), respectively, in the month after Safe Opioid Prescribing Initiative implementation. CONCLUSIONS: Although Safe Opioid Prescribing Initiative implementation was associated with an immediate decline in overall opioid prescribing, it was also associated with an unintended immediate increase in discontinuations and rapid tapering among patients who received high-dose, long-term opioid therapy. Better policy communication and prescriber education regarding opioid tapering best practices may help mitigate unintended consequences of statewide policies.
Assuntos
Analgésicos Opioides , Dor Crônica , Analgésicos Opioides/efeitos adversos , Dor Crônica/tratamento farmacológico , Prescrições de Medicamentos , Humanos , Análise de Séries Temporais Interrompida , North Carolina , Políticas , Padrões de Prática MédicaRESUMO
Importance: Brief disruptions in insurance coverage among eligible participants are associated with poorer health outcomes for children. Objective: To describe factors associated with coverage disruptions among children enrolled in North Carolina Medicaid from 2016 to 2018 and estimate the outcome of preventing such disruptions on medical expenditures. Design Setting and Participants: This was a retrospective cohort study using North Carolina Medicaid claims data. All enrolled individuals were aged 1 to 20 years on January 1, 2016, and with 30 days of prior continuous enrollment. Children were observed from January 1, 2016, until December 31, 2018. Analyses were conducted from June 2020 through December 2020. Main Outcomes and Measures: Risk of Medicaid coverage disruptions of 1 to less than 12 months was assessed. Among children who disenrolled from Medicaid for 30 or more days, the risk of reenrollment within 1 to 6 months and 7 to 11 months was assessed. An inverse probability of censoring weights method was then used to estimate the outcome of an intervention to reduce coverage disruptions through preventing disenrollment on per member per month (PMPM) cost. Results: The study population included 831 173 Medicaid beneficiaries aged 1 to 5 years (23%), 6 to 17 years (68%), and 18 to 20 years (9%); 35% were Black, 44% were White, and 14% were Hispanic/Latinx. Among those with a first disenrollment (n = 214 401, 26%), the risk of reenrollment within 6 months and 7 to 11 months was 19% and 7%, respectively. Risk of coverage disruption was higher for Black children (hazard ratio [HR], 1.21; 95% CI, 1.18-1.24), children of other races (Asian, American Indian, Hawaiian or Pacific Islander, multiple races, or unreported; HR, 1.37; 95% CI, 1.33-1.40), and Latinx children (HR, 1.65; 95% CI, 1.60-1.70) compared with White children. Risk of coverage disruption was also higher for children with higher medical complexity (HR, 1.15; 95% CI, 1.12-1.19). The risk of coverage disruption was lower for children living in counties with the highest unemployment rates (HR, 0.89; 95% CI, 0.85-0.94), and comparisons between county-level measures of child poverty and graduation rates showed little or no difference. The estimated PMPM cost for the full population under a scenario in which all medical costs were included was $125.73. Estimated PMPM cost for the full cohort in a counterfactual scenario in which disenrollment was prevented was slightly lower ($122.14). Across all subgroups, estimated PMPM costs were modestly lower ($2-$8) in the scenario in which disenrollment was prevented. Conclusions and Relevance: In this cohort study, the risk of Medicaid coverage disruption was high, with many eligible children in historically marginalized communities continuing to experience unstable enrollment. In addition to improving health outcomes, preventing coverage gaps through policies that decrease disenrollment may also reduce Medicaid costs.
Assuntos
Cobertura do Seguro , Medicaid , Criança , Estudos de Coortes , Humanos , North Carolina/epidemiologia , Estudos Retrospectivos , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Prescription records, manual chart review, and patient self-report are each imperfect measures of depression treatment in HIV-infected adults. METHODS: We compared antidepressant prescription records in an electronic data warehouse with antidepressant treatment and psychotherapy identified via manual chart review and self-report for patients at 6 academic HIV treatment centers. We examined concordance among these three sources, and used latent class analysis (LCA) to estimate sensitivity and specificity of each measure. RESULTS: In our charts sample (n = 586), 59% had chart indication of "any depression treatment" and 46% had a warehouse prescription record. Antidepressant use was concordant between charts and data warehouse for 77% of the sample. In our self-report sample (n = 677), 52% reported any depression treatment and 43% had a warehouse prescription record. Self-report of antidepressant treatment was consistent with prescription records for 71% of the sample. LCA estimates of sensitivity and specificity for "any depression treatment" were 67% and 90% (warehouse), 87% and 75% (self-report), and 96% and 77% (chart). LIMITATIONS: There is no gold standard to measure depression treatment. Antidepressants may be prescribed to patients for conditions other than depression. The results may not be generalizable to patient populations in non-academic HIV clinics. Regarding LCA, dependence of errors may have led to overestimation of sensitivity and specificity. CONCLUSIONS: Prescription records were largely concordant with self-report and chart review, but there were discrepancies. Studies of depression in HIV-infected patients would benefit from using multiple measures of depression treatment or correcting for exposure misclassification.
Assuntos
Antidepressivos/uso terapêutico , Depressão/terapia , Infecções por HIV/psicologia , Atenção Primária à Saúde/estatística & dados numéricos , Psicoterapia/estatística & dados numéricos , Adulto , Depressão/virologia , Prescrições de Medicamentos/estatística & dados numéricos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: In Malawi's PMTCT Option B+ program, HIV-infected pregnant women who are already receiving ART are continued on their current therapy regimen without testing for treatment failure at the first antenatal care (ANC) visit. HIV RNA screening at ANC may identify women with treatment failure and ensure that viral suppression is maintained throughout the pregnancy. METHODS: We conducted a cross-sectional study of HIV-infected pregnant women who had been receiving ART for at least 6 months at the first ANC visit under the PMTCT Option B+ program at Bwaila Hospital in Lilongwe, Malawi from June 2015 to December 2017. Poisson regression models with robust variance were used to investigate the predictors of ART treatment failure defined as viral load ≥1000 copies/ml. RESULTS: The median age of 864 women tested for ART failure was 31.1 years (interquartile range: 26.9-34.5). The prevalence of treatment failure was 7.6% (95% confidence interval (CI): 6.0-9.6). CD4 cell count (adjusted prevalence ratio (aPR) = 0.57; 95% CI: 0.50-0.65) was strongly associated with treatment failure. CONCLUSION: The low prevalence of treatment failure among women presenting for their first ANC in urban Malawi demonstrates success of Option B+ in maintaining viral suppression and suggests progress towards the last 90% of the UNAIDS 90-90-90 targets. Women failing on ART should be identified early for adherence counseling and may require switching to an alternative ART regimen.