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PLoS Neglected Tropical Diseases Jun 2024Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans...
BACKGROUND
Salmonella enterica serotype Typhi (Salmonella Typhi) causes severe and occasionally life-threatening disease, transmitted through contaminated food and water. Humans are the only reservoir, inadequate water, sanitation, and hygiene infrastructure increases risk of typhoid. High-quality data to assess spatial and temporal relationships in disease dynamics are scarce.
METHODS
We analyzed data from a prospective cohort conducted in an urban slum area of Dhaka City, Bangladesh. Passive surveillance at study centers identified typhoid cases by microbiological culture. Each incident case (index case) was matched to two randomly selected index controls, and we measured typhoid incidence in the population residing in a geographically defined region surrounding each case and control. Spatial clustering was evaluated by comparing the typhoid incidence in residents of geometric rings of increasing radii surrounding the index cases and controls over 28 days. Temporal clustering was evaluated by separately measuring incidence in the first and second 14-day periods following selection. Incidence rate ratios (IRRs) were calculated using Poisson regression models.
RESULTS
We evaluated 141 typhoid index cases. The overall typhoid incidence was 0.44 per 100,000 person-days (PDs) (95% CI: 0.40, 0.49). In the 28 days following selection, the highest typhoid incidence (1.2 per 100,000 PDs [95% CI: 0.8, 1.6]) was in the innermost cluster surrounding index cases. The IRR in this innermost cluster was 4.9 (95% CI: 2.4, 10.3) relative to the innermost control clusters. Neither typhoid incidence rates nor relative IRR between index case and control populations showed substantive differences in the first and second 14-day periods after selection.
CONCLUSION
In the absence of routine immunization programs, geographic clustering of typhoid cases suggests a higher intensity of typhoid risk in the population immediately surrounding identified cases. Further studies are needed to understand spatial and temporal trends and to evaluate the effectiveness of targeted vaccination in disrupting typhoid transmission.
PubMed: 38913735
DOI: 10.1371/journal.pntd.0012273 -
PLoS Medicine Jun 2024Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting...
BACKGROUND
Broadly neutralizing antibodies (bnAbs) are a promising approach for HIV-1 prevention. In the Antibody Mediated Prevention (AMP) trials, a CD4-binding site targeting bnAb, VRC01, administered intravenously (IV), demonstrated 75% prevention efficacy against highly neutralization-sensitive viruses but was ineffective against less sensitive viruses. VRC07-523LS is a next-generation bnAb targeting the CD4-binding site and was engineered for increased neutralization breadth and half-life. We conducted a multicenter, randomized, partially blinded Phase I clinical trial to evaluate the safety and serum concentrations of VRC07-523LS, administered in multiple doses and routes to healthy adults without HIV.
METHODS AND FINDINGS
Participants were recruited between 2 February 2018 and 9 October 2018. A total of 124 participants were randomized to receive 5 VRC07-523LS administrations via IV (T1: 2.5 mg/kg, T2: 5 mg/kg, T3: 20 mg/kg), subcutaneous (SC) (T4: 2.5 mg/kg, T5: 5 mg/kg), or intramuscular (IM) (T6: 2.5 mg/kg or P6: placebo) routes at 4-month intervals. Participants and site staff were blinded to VRC07-523LS versus placebo for the IM group, while all other doses and routes were open-label. Safety data were collected for 144 weeks following the first administration. VRC07-523LS serum concentrations were measured by ELISA through Day 112 in all participants and by binding antibody multiplex assay (BAMA) thereafter in 60 participants (10 per treatment group) through Day 784. Compartmental population pharmacokinetic (PK) analyses were conducted to evaluate the VRC07-523LS serum PK. Neutralization activity was measured in a TZM-bl assay and antidrug antibodies (ADAs) were assayed using a tiered bridging assay testing strategy. Injections and infusions were well tolerated, with mild pain or tenderness reported commonly in the SC and IM groups, and mild to moderate erythema or induration reported commonly in the SC groups. Infusion reactions reported in 3 of 20 participants in the 20 mg/kg IV group. Peak geometric mean (GM) concentrations (95% confidence intervals [95% CIs]) following the first administration were 29.0 μg/mL (25.2, 33.4), 58.5 μg/mL (49.4, 69.3), and 257.2 μg/mL (127.5, 518.9) in T1-T3 with IV dosing; 10.8 μg/mL (8.8, 13.3) and 22.8 μg/mL (20.1, 25.9) in T4-T5 with SC dosing; and 16.4 μg/mL (14.7, 18.2) in T6 with IM dosing. Trough GM (95% CIs) concentrations immediately prior to the second administration were 3.4 μg/mL (2.5, 4.6), 6.5 μg/mL (5.6, 7.5), and 27.2 μg/mL (23.9, 31.0) with IV dosing; 0.97 μg/mL (0.65, 1.4) and 3.1 μg/mL (2.2, 4.3) with SC dosing, and 2.6 μg/mL (2.05, 3.31) with IM dosing. Peak VRC07-523LS serum concentrations increased linearly with the administered dose. At a given dose, peak and trough concentrations, as well as serum neutralization titers, were highest in the IV groups, reflecting the lower bioavailability following SC and IM administration. A single participant was found to have low titer ADA at a lone time point. VRC07-523LS has an estimated mean half-life of 42 days across all doses and routes (95% CI: 40.5, 43.5), over twice as long as VRC01 (15 days).
CONCLUSIONS
VRC07-523LS was safe and well tolerated across a range of doses and routes and is a promising long-acting bnAb for inclusion in HIV-1 prevention regimens.
TRIAL REGISTRATION
ClinicalTrials.gov/ NCT03387150 (posted on 21 December 2017).
PubMed: 38913710
DOI: 10.1371/journal.pmed.1004329 -
PLoS Medicine Jun 2024Obesity and rapid weight gain are established risk factors for noncommunicable diseases and have emerged as independent risk factors for severe disease following...
BACKGROUND
Obesity and rapid weight gain are established risk factors for noncommunicable diseases and have emerged as independent risk factors for severe disease following Coronavirus Disease 2019 (COVID-19) infection. Restrictions imposed to reduce COVID-19 transmission resulted in profound societal changes that impacted many health behaviours, including physical activity and nutrition, associated with rate of weight gain. We investigated which clinical and sociodemographic characteristics were associated with rapid weight gain and the greatest acceleration in rate of weight gain during the pandemic among adults registered with an English National Health Service (NHS) general practitioner (GP) during the COVID-19 pandemic.
METHODS AND FINDINGS
With the approval of NHS England, we used the OpenSAFELY platform inside TPP to conduct an observational cohort study of routinely collected electronic healthcare records. We investigated changes in body mass index (BMI) values recorded in English primary care between March 2015 and March 2022. We extracted data on 17,742,365 adults aged 18 to 90 years old (50.1% female, 76.1% white British) registered with an English primary care practice. We estimated individual rates of weight gain before (δ-prepandemic) and during (δ-pandemic) the pandemic and identified individuals with rapid weight gain (>0.5 kg/m2/year) in each period. We also estimated the change in rate of weight gain between the prepandemic and pandemic period (δ-change = δ-pandemic-δ-prepandemic) and defined extreme accelerators as the 10% of individuals with the greatest increase in their rate of weight gain (δ-change ≥1.84 kg/m2/year) between these periods. We estimated associations with these outcomes using multivariable logistic regression adjusted for age, sex, index of multiple deprivation (IMD), and ethnicity. P-values were generated in regression models. The median BMI of our study population was 27.8 kg/m2, interquartile range (IQR) [24.3, 32.1] in 2019 (March 2019 to February 2020) and 28.0 kg/m2, IQR [24.4, 32.6] in 2021. Rapid pandemic weight gain was associated with sex, age, and IMD. Male sex (male versus female: adjusted odds ratio (aOR) 0.76, 95% confidence interval (95% CI) [0.76, 0.76], p < 0.001), older age (e.g., 50 to 59 years versus 18 to 29 years: aOR 0.60, 95% CI [0.60, 0.61], p < 0.001]); and living in less deprived areas (least-deprived-IMD-quintile versus most-deprived: aOR 0.77, 95% CI [0.77, 0.78] p < 0.001) reduced the odds of rapid weight gain. Compared to white British individuals, all other ethnicities had lower odds of rapid pandemic weight gain (e.g., Indian versus white British: aOR 0.69, 95% CI [0.68, 0.70], p < 0.001). Long-term conditions (LTCs) increased the odds, with mental health conditions having the greatest effect (e.g., depression (aOR 1.18, 95% CI [1.17, 1.18], p < 0.001)). Similar characteristics increased odds of extreme acceleration in the rate of weight gain between the prepandemic and pandemic periods. However, changes in healthcare activity during the pandemic may have introduced new bias to the data.
CONCLUSIONS
We found female sex, younger age, deprivation, white British ethnicity, and mental health conditions were associated with rapid pandemic weight gain and extreme acceleration in rate of weight gain between the prepandemic and pandemic periods. Our findings highlight the need to incorporate sociodemographic, physical, and mental health characteristics when formulating research, policies, and interventions targeting BMI in the period of post pandemic service restoration and in future pandemic planning.
PubMed: 38913709
DOI: 10.1371/journal.pmed.1004398 -
PloS One 2024The well-established inverse relationship between socioeconomic status (SES) and risk of developing coronary heart disease (CHD) cannot be explained solely by...
BACKGROUND
The well-established inverse relationship between socioeconomic status (SES) and risk of developing coronary heart disease (CHD) cannot be explained solely by differences in traditional risk factors.
OBJECTIVE
To model the role SES plays in the burden of premature CHD in Argentina.
MATERIALS AND METHODS
We used the Cardiovascular Disease Policy Model-Argentina to project incident CHD events and mortality in low and high-SES Argentinean adults 35 to 64 years of age from 2015 to 2024. Using data from the 2018 National Risk Factor Survey, we defined low SES as not finishing high-school and/or reporting a household income in quintiles 1 or 2. We designed simulations to apportion CHD outcomes in low SES adults to: (1) differences in the prevalence of traditional risk factors between low and high SES adults; (2) nontraditional risk associated with low SES status; (3) preventable events if risk factors were improved to ideal levels; and (4) underlying age- and sex-based risk.
RESULTS
56% of Argentina´s 35- to 64-year-old population has low SES. Both high and low SES groups have poor control of traditional risk factors. Compared with high SES population, low SES population had nearly 2-fold higher rates of incident CHD and CHD deaths per 10 000 person-years (incident CHD: men 80.8 [95%CI 76.6-84.9] vs 42.9 [95%CI 37.4-48.1], women 39.0 [95%CI 36.-41.2] vs 18.6 [95%CI 16.3-20.9]; CHD deaths: men 10.0 [95%CI 9.5-10.5] vs 6.0 [95%CI 5.6-6.4], women 3.2 [95%CI 3.0-3.4] vs 1.8 [95%CI 1.7-1.9]). Nontraditional low SES risk accounts for 73.5% and 70.4% of the event rate gap between SES levels for incident CHD and CHD mortality rates, respectively.
DISCUSSION
CHD prevention policies in Argentina should address contextual aspects linked to SES, such as access to education or healthcare, and should also aim to implement known clinical strategies to achieve better control of CHD risk factors in all socioeconomic levels.
Topics: Humans; Argentina; Adult; Middle Aged; Male; Female; Coronary Disease; Social Class; Risk Factors; Prevalence; Low Socioeconomic Status
PubMed: 38913678
DOI: 10.1371/journal.pone.0305948 -
PloS One 2024Low-and-middle-income countries (LMICs) bear a disproportionate burden of communicable diseases. Social interaction data inform infectious disease models and disease...
BACKGROUND
Low-and-middle-income countries (LMICs) bear a disproportionate burden of communicable diseases. Social interaction data inform infectious disease models and disease prevention strategies. The variations in demographics and contact patterns across ages, cultures, and locations significantly impact infectious disease dynamics and pathogen transmission. LMICs lack sufficient social interaction data for infectious disease modeling.
METHODS
To address this gap, we will collect qualitative and quantitative data from eight study sites (encompassing both rural and urban settings) across Guatemala, India, Pakistan, and Mozambique. We will conduct focus group discussions and cognitive interviews to assess the feasibility and acceptability of our data collection tools at each site. Thematic and rapid analyses will help to identify key themes and categories through coding, guiding the design of quantitative data collection tools (enrollment survey, contact diaries, exit survey, and wearable proximity sensors) and the implementation of study procedures. We will create three age-specific contact matrices (physical, nonphysical, and both) at each study site using data from standardized contact diaries to characterize the patterns of social mixing. Regression analysis will be conducted to identify key drivers of contacts. We will comprehensively profile the frequency, duration, and intensity of infants' interactions with household members using high resolution data from the proximity sensors and calculating infants' proximity score (fraction of time spent by each household member in proximity with the infant, over the total infant contact time) for each household member.
DISCUSSION
Our qualitative data yielded insights into the perceptions and acceptability of contact diaries and wearable proximity sensors for collecting social mixing data in LMICs. The quantitative data will allow a more accurate representation of human interactions that lead to the transmission of pathogens through close contact in LMICs. Our findings will provide more appropriate social mixing data for parameterizing mathematical models of LMIC populations. Our study tools could be adapted for other studies.
Topics: Humans; Mozambique; Developing Countries; Guatemala; Pakistan; India; Focus Groups; Female; Infant; Social Interaction; Male; Communicable Diseases; Rural Population; Research Design
PubMed: 38913670
DOI: 10.1371/journal.pone.0301638 -
PloS One 2024HIV, opioid use disorder (OUD), and mental health challenges share multiple syndemic risk factors. Each can be effectively treated with routine outpatient appointments,...
BACKGROUND
HIV, opioid use disorder (OUD), and mental health challenges share multiple syndemic risk factors. Each can be effectively treated with routine outpatient appointments, medication management, and psychosocial support, leading implementers to consider integrated screening and treatment for OUD and mental health in HIV care. Provider perspectives are crucial to understanding barriers and strategies for treatment integration.
METHODS
We conducted in-depth qualitative interviews with 21 HIV treatment providers and social services providers (12 individual interviews and 1 group interview with 9 participants) to understand the current landscape, goals, and priorities for integrated OUD, mental health, and HIV care. Providers were purposively recruited from known clinics in Mecklenburg County, North Carolina, U.S.A. Data were analyzed using applied thematic analysis in the NVivo 12 software program and evaluated for inter-coder agreement.
RESULTS
Participants viewed substance use and mental health challenges as prominent barriers to engagement in HIV care. However, few organizations have integrated structured screening for substance use and mental health into their standard of care. Even fewer screen for opioid use. Although medication assisted treatment (MAT) is effective for mitigating OUD, providers struggle to connect patients with MAT due to limited referral options, social barriers such as housing and food insecurity, overburdened staff, stigma, and lack of provider training. Providers believed there would be clear benefit to integrating OUD and mental health treatment in HIV care but lacked resources for implementation.
CONCLUSIONS
Integration of screening and treatment for substance use and mental health in HIV care could mitigate many current barriers to treatment for all three conditions. Efforts are needed to train HIV providers to provide MAT, expand resources, and implement best practices.
Topics: Humans; HIV Infections; Opioid-Related Disorders; Male; Female; Qualitative Research; Mass Screening; Adult; Mental Health; Middle Aged; Health Personnel; North Carolina
PubMed: 38913659
DOI: 10.1371/journal.pone.0305174 -
PloS One 2024With a globally aging population, there is a need to better understand how brain structure relates to function in healthy older and younger adults. (Comparative Study)
Comparative Study
OBJECTIVE
With a globally aging population, there is a need to better understand how brain structure relates to function in healthy older and younger adults.
METHODS
34 healthy participants divided into older (17; Mean = 70.9, SD = 5.4) and younger adults (17; Mean = 28.1, SD = 2.8) underwent diffusion-weighted imaging and neuropsychological assessment, including the California Verbal Learning Test 2nd Edition and the Trail Making Test (TMT-A and TMT-B). Differences in white matter microstructure for older and younger adults and the association between DTI metrics (fractional anisotropy, FA; mean diffusivity, MD) and cognitive performance were analyzed using tract-based spatial statistics (p < 0.05, corrected).
RESULTS
Older adults had significantly lower FA and higher MD than younger adults in widespread brain regions. There was a significant negative correlation between executive function (TMT-B) and MD for older adults in the right superior/anterior corona radiata and the corpus callosum. No significant relationship was detected between DTI metrics and executive function in younger adults or with memory performance in either group.
CONCLUSIONS
The findings underscore the need to examine brain-behaviour relationships as a function of age. Future studies should include comprehensive assessments in larger lifespan samples to better understand the aging brain.
Topics: Humans; White Matter; Aged; Male; Female; Adult; Neuropsychological Tests; Diffusion Tensor Imaging; Aging; Middle Aged; Executive Function; Cognition; Young Adult; Diffusion Magnetic Resonance Imaging; Brain; Aged, 80 and over; Anisotropy
PubMed: 38913655
DOI: 10.1371/journal.pone.0305818 -
JAMA Network Open Jun 2024Racial and ethnic disparities exist in anticoagulation therapy for atrial fibrillation (AF). Whether medical center racial and ethnic composition is associated with...
IMPORTANCE
Racial and ethnic disparities exist in anticoagulation therapy for atrial fibrillation (AF). Whether medical center racial and ethnic composition is associated with these disparities is unclear.
OBJECTIVE
To determine whether medical center racial and ethnic composition is associated with overall anticoagulation and disparities in anticoagulation for AF.
DESIGN, SETTING, AND PARTICIPANTS
Retrospective cohort study of Black, White, and Hispanic patients with incident AF from 2018 to 2021 at 140 Veterans Health Administration medical centers (VAMCs). Data were analyzed from March to November 2023.
EXPOSURE
VAMC racial and ethnic composition, defined as the proportion of patients from minoritized racial and ethnic groups treated at a VAMC, categorized into quartiles. VAMCs in quartile 1 (Q1) had the lowest percentage of patients from minoritized groups (ie, the reference group).
MAIN OUTCOMES AND MEASURES
The odds of initiating any anticoagulant, direct-acting oral anticoagulant (DOAC), or warfarin therapy within 90 days of an index AF diagnosis, adjusting for sociodemographics, medical comorbidities, and facility factors.
RESULTS
The cohort comprised 89 791 patients with a mean (SD) age of 73.0 (10.1) years; 87 647 (97.6%) were male, 9063 (10.1%) were Black, 3355 (3.7%) were Hispanic, and 77 373 (86.2%) were White. Overall, 64 770 individuals (72.1%) initiated any anticoagulant, 60 362 (67.2%) initiated DOAC therapy, and 4408 (4.9%) initiated warfarin. Compared with White patients, Black and Hispanic patients had lower rates of any anticoagulant and DOAC therapy initiation but higher rates of warfarin initiation across all quartiles of VAMC racial and ethnic composition. Any anticoagulant therapy initiation was lower in Q4 than Q1 (69.8% vs 74.9%; adjusted odds ratio [aOR], 0.80; 95% CI, 0.69-0.92; P < .001). DOAC and warfarin initiation were also lower in Q4 than in Q1 (DOAC, 69.4% vs 65.3%; aOR, 0.85; 95% CI, 0.74-0.97; P < .001; warfarin, 5.4% vs 4.5%; aOR, 0.82; 95% CI, 0.67-1.00; P < .001). In adjusted models, patients in Q4 were significantly less likely to initiate any anticoagulant therapy than those in Q1 (aOR, 0.88; 95% CI, 0.78-0.99). Patients in Q3 (aOR, 0.75; 95% CI, 0.60-0.93) and Q4 (aOR, 0.69; 95% CI, 0.55-0.87) were significantly less likely to initiate warfarin therapy than those in Q1. There was no significant difference in the adjusted odds of initiating DOAC therapy across racial and ethnic composition quartiles. Although significant Black-White and Hispanic-White differences in initiation of any anticoagulant, DOAC, and warfarin therapy were observed, interactions between patient race and ethnicity and VAMC racial composition were not significant.
CONCLUSIONS AND RELEVANCE
In a national cohort of VA patients with AF, initiation of any anticoagulant and warfarin, but not DOAC therapy, was lower in VAMCs serving more minoritized patients.
Topics: Humans; Atrial Fibrillation; Male; Female; Aged; Anticoagulants; Retrospective Studies; United States; Healthcare Disparities; United States Department of Veterans Affairs; Middle Aged; Warfarin; Hispanic or Latino; Aged, 80 and over; Ethnicity; White People
PubMed: 38913375
DOI: 10.1001/jamanetworkopen.2024.18114 -
JAMA Network Open Jun 2024Major concerns regarding individuals who adhere to a vegan diet are whether they meet protein and essential amino acid recommendations and how reliant they are on...
IMPORTANCE
Major concerns regarding individuals who adhere to a vegan diet are whether they meet protein and essential amino acid recommendations and how reliant they are on ultraprocessed foods.
OBJECTIVES
To investigate whether individuals who adhere to a vegan diet meet protein and essential amino acid recommendations and, as secondary objectives, to determine ultraprocessed food intake and potential factors associated with inadequate protein intake in this population.
DESIGN, SETTING, AND PARTICIPANTS
This cross-sectional survey study was conducted between September 2021 and January 2023 in Brazil among male and female adults (aged 18 years or older) who adhered to a vegan diet recruited from social media platforms.
EXPOSURE
Adherence to a vegan diet and unprocessed and minimally processed foods and ultraprocessed food consumption.
MAIN OUTCOMES AND MEASURES
Protein and essential amino acid intake and food consumption by processing level were assessed using a 1-day food diary. Nutrient adequacy ratios were calculated by dividing nutrient intake by its recommendation (using scores truncated at 1) for each participant and then finding the mean across participants for each nutrient. The mean adequacy ratio was the mean of all nutrient adequacy ratios.
RESULTS
Of 1014 participants who completed the survey, 774 individuals (median [IQR] age, 29 [24-35] years; 637 female [82.3%]) were confirmed as adhering to a vegan diet and provided adequate food recalls, among whom 558 individuals reported body weight and so had relative protein and amino acid intake values available. The median (IQR) body mass index (calculated as weight in kilograms divided by height in meters squared) of participants was 22.6 (20.3-24.8). The nutrient adequacy ratio of protein was 0.93 (95% CI, 0.91-0.94); for essential amino acids, ratios ranged from 0.90 (95% CI, 0.89-0.92) for lysine to 0.98 (95% CI, 0.97-0.99) for phenylalanine and tyrosine. The mean adequacy ratio for protein and all amino acids was 0.95 (95% CI, 0.94-0.96). The median intake level was 66.5% (95% CI, 65.0%-67.9%) of total energy intake for unprocessed and minimally processed food and 13.2% (95% CI, 12.4%-14.4%) of total energy intake for ultraprocessed food. Adjusted logistic regression models showed that consuming protein supplements (odds ratio [OR], 0.06 [95% CI 0.02-0.14]; P < .001) or textured soy protein (OR, 0.32 [95% CI, 0.17-0.59]; P < .001) was associated with decreased odds of inadequate protein intake. Higher ultraprocessed food intake levels were also associated with decreased odds of inadequate protein intake (eg, fourth vs first quartile of intake: OR, 0.16 [95% CI, 0.07-0.33]; P < .001), and higher unprocessed and minimally processed protein intake levels were associated with increased odds of inadequate protein intake (eg, fourth vs first quartile of intake: OR, 12.42 [95% CI, 5.56-29.51]; P < .001).
CONCLUSIONS AND RELEVANCE
In this study, most individuals who adhered to a vegan diet attained protein and essential amino acid intake recommendations, largely based their diet of unprocessed and minimally processed food, and had a significantly lower proportion of ultraprocessed food intake compared with previous reports. Participants consuming less ultraprocessed food were more likely to have inadequate protein intake, suggesting a significant reliance on ultraprocessed proteins for this population.
Topics: Humans; Female; Male; Adult; Brazil; Cross-Sectional Studies; Dietary Proteins; Vegans; Young Adult; Diet, Vegan; Food Handling; Middle Aged; Eating; Amino Acids; Amino Acids, Essential
PubMed: 38913373
DOI: 10.1001/jamanetworkopen.2024.18226 -
JAMA Network Open Jun 2024There is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration. (Randomized Controlled Trial)
Randomized Controlled Trial
IMPORTANCE
There is significant concern regarding increasing long-term antidepressant treatment for depression beyond an evidence-based duration.
OBJECTIVE
To determine whether adding internet and telephone support to a family practitioner review to consider discontinuing long-term antidepressant treatment is safe and more effective than a practitioner review alone.
DESIGN, SETTING, AND PARTICIPANTS
In this cluster randomized clinical trial, 131 UK family practices were randomized between December 1, 2018, and March 31, 2022, with remote computerized allocation and 12 months of follow-up. Participants and researchers were aware of allocation, but analysis was blind. Participants were adults who were receiving antidepressants for more than 1 year for a first episode of depression or more than 2 years for recurrent depression who were currently well enough to consider discontinuation and wished to do so and who were at low risk of relapse. Of 6725 patients mailed invitations, 330 (4.9%) were eligible and consented.
INTERVENTIONS
Internet and telephone self-management support, codesigned and coproduced with patients and practitioners.
MAIN OUTCOMES AND MEASURES
The primary (safety) outcome was depression at 6 months (prespecified complete-case analysis), testing for noninferiority of the intervention to under 2 points on the 9-item Patient Health Questionnaire (PHQ-9). Secondary outcomes (testing for superiority) were antidepressant discontinuation, anxiety, quality of life, antidepressant withdrawal symptoms, mental well-being, enablement, satisfaction, use of health care services, and adverse events. Analyses for the main outcomes were performed on a complete-case basis, and multiple imputation sensitivity analysis was performed on an intention-to-treat basis.
RESULTS
Of 330 participants recruited (325 eligible for inclusion; 178 in intervention practices and 147 in control practices; mean [SD] age at baseline, 54.0 [14.9] years; 223 women [68.6%]), 276 (83.6%) were followed up at 6 months, and 240 (72.7%) at 12 months. The intervention proved noninferior; mean (SD) PHQ-9 scores at 6 months were slightly lower in the intervention arm than in the control arm in the complete-case analysis (4.0 [4.3] vs 5.0 [4.7]; adjusted difference, -1.1; 95% CI, -2.1 to -0.1; P = .03) but not significantly different in an intention-to-treat multiple imputation sensitivity analysis (adjusted difference, -0.9 (95% CI, -1.9 to 0.1; P = .08). By 6 months, antidepressants had been discontinued by 66 of 145 intervention arm participants (45.5%) who provided discontinuation data and 54 of 129 control arm participants (41.9%) (adjusted odds ratio, 1.02; 95% CI, 0.52-1.99; P = .96). In the intervention arm, antidepressant withdrawal symptoms were less severe, and mental well-being was better compared with the control arm; differences were small but significant. There were no significant differences in the other outcomes; 28 of 179 intervention arm participants (15.6%) and 22 of 151 control arm participants (14.6%) experienced adverse events.
CONCLUSIONS AND RELEVANCE
In this cluster randomized clinical trial of adding internet and telephone support to a practitioner review for possible antidepressant discontinuation, depression was slightly better with support, but the rate of discontinuation of antidepressants did not significantly increase. Improvements in antidepressant withdrawal symptoms and mental well-being were also small. There were no significant harms. Family practitioner review for possible discontinuation of antidepressants appeared safe and effective for more than 40% of patients willing and well enough to discontinue.
TRIAL REGISTRATION
ISRCTN registry Identifiers: ISRCTN15036829 (internal pilot trial) and ISRCTN12417565 (main trial).
Topics: Humans; Female; Male; Antidepressive Agents; Middle Aged; Telephone; Adult; Internet; Depression; United Kingdom
PubMed: 38913372
DOI: 10.1001/jamanetworkopen.2024.18383