Treating depression and improving adherence in HIV care with task‐shared cognitive behavioural therapy in Khayelitsha,South Africa: a randomized controlled trial

IntroductionMajor depressive disorder, highly prevalent among people with HIV (PWH) globally, including South Africa, is associated with suboptimal adherence to antiretroviral therapy. Globally, there are insufficient numbers of mental health providers and tested depression treatments. This study''s aim was to test task‐shared cognitive‐behavioural therapy for adherence and depression (CBT‐AD) in HIV, delivered by clinic nurses in South Africa.MethodsThis was a two‐arm randomized controlled effectiveness trial (recruitment: 14 July 2016 to 4 June 2019, last follow 9 June 2020). One‐hundred‐sixty‐one participants with clinical depression and virally uncontrolled HIV were recruited from primary care clinics providing HIV care, in Khayelitsha, South Africa. Arm 1 was task‐shared, nurse‐delivered CBT‐AD; and arm 2 was enhanced treatment as usual (ETAU). Primary outcomes (baseline to 4 months) were blinded Hamilton Depression Rating Scale (HAM‐D) scores, and weekly adherence via real‐time monitoring (Wisepill). Secondary outcomes were adherence and depression over 4‐, 8‐ and 12‐month follow‐ups, proportion of participants with undetectable viremia and continuous CD4 cell counts at 12 months. Additional analyses involved viral load and CD4 over time.ResultsAt 4 months, the HAMD scores in the CBT‐AD condition improved by an estimated 4.88 points more (CI: –7.86, –1.87, p = 0.0016), and for weekly adherence, 1.61 percentage points more per week (CI: 0.64, 2.58, p = 0.001) than ETAU. Over follow‐ups, CBT‐AD had an estimated 5.63 lower HAMD scores (CI: –7.90, –3.36, p < 0.001) and 23.56 percentage points higher adherence (CI: 10.51, 34.21, p < 0.001) than ETAU. At 12 months, adjusted models indicated that the odds of having an undetectable viremia was 2.51 greater at 12 months (CI: 1.01, 6.66, p = 0.047), and 3.54 greater over all of the follow‐ups (aOR = 3.54, CI: 1.59, 20.50; p = 0.038) for those assigned CBT‐AD. CD4 was not significantly different between groups at 12 months or over time.ConclusionsTask‐shared, nurse‐delivered, CBT‐AD is effective in improving clinical depression, ART adherence and viral load for virally unsuppressed PWH. The strategy of reducing depression to allow patients with self‐care components of medical illness to benefit from adherence interventions is one to extend. Implementation science trials and analyses of cost‐effectiveness are needed to translate findings into clinical practice.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT02696824","term_id":"NCT02696824"}}NCT02696824 https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02696824","term_id":"NCT02696824"}}NCT02696824     

Health‐related quality of life of female sex workers living with HIV in South Africa: a cross‐sectional study

IntroductionHealth‐related quality of life (HRQoL) is an important HIV outcome beyond viral suppression. However, there are limited data characterizing HRQoL of key populations, including female sex workers (FSW) living with HIV.MethodsWe used baseline data (22 June 2018–23 March 2020) of FSW who were diagnosed with HIV and enrolled into a randomized trial in Durban, South Africa. HRQoL information was collected by a generic preference‐accompanied tool with five domains (EQ‐5D), and summarized into a single score (range 0–1), which represents health utility. We employed multivariable beta regression models to identify determinants of HRQoL and to estimate subgroup‐specific HRQoL score. Using external estimates of life expectancy and population size, we estimated the number of quality adjusted life years reduced among FSW living with HIV in South Africa associated with violence and drug use.ResultsOf 1,363 individuals (mean age: 32.4 years; mean HRQoL score: 0.857) in our analysis, 62.6% used drugs, 61.3% experienced physical or sexual violence and 64.6% self‐reported taking antiretroviral treatment (ART). The following were associated with a reduction in the average marginal HRQoL score: older age (per decade: 0.018 [95% confidence interval (CI): 0.008, 0.027]), drug use (0.022 [0.007, 0.036]), experience of violence (0.024 [0.010, 0.038]) and moderate (vs. no) level of internalized stigma (0.023 [0.004, 0.041]). Current ART use was associated with a 0.015‐point (–0.001, 0.031) increase in the HRQoL score. The estimated mean (95% CI) HRQoL scores ranged from 0.838 (0.816, 0.860) for FSW who used drugs, experienced violence and were not on ART; to 0.899 (0.883, 0.916) for FSW who did not use drugs nor experience violence and were on ART. Our results can be translated into a reduction in 37,184 and 39,722 quality adjusted life years related to drug use and experience of violence, respectively, in South Africa.ConclusionsThese results demonstrate the association of ART with higher HRQoL among FSW and the need to further address structural risks, including drug use, violence and stigma. Population‐specific estimates of HRQoL score can be further used to calculate quality‐adjusted life years in economic evaluations of individual and structural interventions addressing the needs of FSW living with HIV.Clinical Trial Registration{"type":"clinical-trial","attrs":{"text":"NCT03500172","term_id":"NCT03500172"}}NCT03500172 (April 17, 2018).     

Same‐day antiretroviral therapy initiation hub model at the Thai Red Cross Anonymous Clinic in Bangkok,Thailand: an observational cohort study

IntroductionWHO has recommended rapid antiretroviral therapy (ART) initiation, including same‐day ART (SDART). However, data on the feasibility in real‐world settings are limited. We implemented a cohort study at a stand‐alone HIV testing centre to examine its applicability and effectiveness.MethodsData were collected from the Thai Red Cross Anonymous Clinic in Bangkok, Thailand, between July 2017 and July 2018 from clients who were ART‐naïve and could return for follow‐up visits. Baseline laboratory tests and chest X‐ray were performed according to national guidelines, and clinical eligibility was determined based on physical examination and chest X‐ray findings. Primary outcomes were retention in care and viral load suppression at 3, 6 and 12 months.ResultsDuring the study period, 2427 people tested HIV positive. Of these, 2107 (2207/2427, 86.8%) met logistical criteria, and 1904 (1904/2427, 78.5%) agreed to SDART. One thousand seven hundred and twenty‐nine (1729/2427, 71.2%) were placed on ART, with 1257 received same‐day initiation and 1576 initiated ART within 7 days; 1198 clients were successfully referred to free, sustained ART sites. Retention among eligible clients who accepted SDART service at months 3, 6 and 12 was 79.8%, 75.2% and 75.3%, respectively.ConclusionsSame‐day ART initiation hub model at a stand‐alone HIV testing centre in an urban setting in Bangkok, Thailand, is highly feasible and has a potential for scaling up.Clinical Trial Number{"type":"clinical-trial","attrs":{"text":"NCT04032028","term_id":"NCT04032028"}}NCT04032028     

Histological analysis of fat grafting with platelet‐rich plasma for diabetic foot ulcers—A randomised controlled trial

Diabetic foot ulcers are often unresponsive to conventional therapy and are a leading cause of amputation. Animal studies have shown stem cells and growth factors can accelerate wound healing. Adipose‐derived stem cells are found in fat grafts and mixing them with platelet‐rich plasma (PRP) may improve graft survival. This study aimed to establish the histological changes when diabetic foot ulcers are treated with fat grafts and PRP. A three‐armed RCT was undertaken of 18 diabetic foot ulcer patients: fat grafting; fat grafting with PRP; and routine podiatry care. Biopsies were obtained at week 0, 1, and 4, and underwent quantitative histology/immunohistochemistry (H&E, CD31, and Ki67). Treatment with fat and PRP increased mean microvessel density at 1 week to 1645 (SD 96) microvessels/mm² (+32%‐45% to other arms, P = .035). PRP appeared to increase vascularity surrounding fat grafts, and histology suggested PRP may enhance fat graft survival. There was no clinical difference between arms. This study demonstrates PRP with fat grafts increased neovascularisation and graft survival in diabetic foot ulcers. The histology was not, however, correlated with wound healing time. Future studies should consider using apoptosis markers and fluorescent labelling to ascertain if enhanced fat graft survival is due to proliferation or reduced apoptosis. Trial registration {"type":"clinical-trial","attrs":{"text":"NCT03085550","term_id":"NCT03085550"}}NCT03085550.     

A qualitative exploration to understand barriers and facilitators to daily oral PrEP uptake and sustained adherence among HIV‐negative women planning for or with pregnancy in rural Southwestern Uganda

IntroductionAntiretroviral pre‐exposure prophylaxis (PrEP) may reduce periconception and pregnancy HIV incidence among women in settings, where gender power imbalances limit HIV testing, engagement in care and HIV viral suppression. We conducted qualitative interviews to understand factors influencing periconception and pregnancy PrEP uptake and use in a cohort of women (Trial registration: {"type":"clinical-trial","attrs":{"text":"NCT03832530","term_id":"NCT03832530"}}NCT03832530) offered safer conception counselling in rural Southwestern Uganda, where PrEP uptake was high.MethodsBetween March 2018 and January 2019, in‐depth interviews informed by conceptual frameworks for periconception risk reduction and PrEP adherence were conducted with 37 women including those with ≥80% and <80% adherence to PrEP doses measured by electronic pill cap, those who never initiated PrEP, and seven of their male partners. Content and dyadic analyses were conducted to identify emergent challenges and facilitators of PrEP use within individual and couple narratives.ResultsThe median age for women was 33 years (IQR 28, 35), 97% felt likely to acquire HIV and 89% initiated PrEP. Individual‐level barriers included unwillingness to take daily pills while healthy, side effects and alcohol use. Women overcame these barriers through personal desires to have control over their HIV serostatus, produce HIV‐negative children and prevent HIV transmission within partnerships. Couple‐level barriers included nondisclosure, mistrust and gender‐based violence; facilitators included shared goals and perceived HIV protection, which improved communication, sexual intimacy and emotional support within partnerships through a self‐controlled method. Community‐level barriers included multi‐level stigma related to HIV, ARVs/PrEP and serodifference; facilitators included active peer, family or healthcare provider support as women aspired to safely meet socio‐cultural expectations to conceive and preserve serodifferent relationships. Confidence in PrEP effectiveness was promoted by positive peer experiences with PrEP and ongoing HIV testing.ConclusionsMulti‐level forms of HIV‐, serodifference‐ and disclosure‐related stigma, side effects, pill burden, alcohol use, relationship dynamics, social, professional and partnership support towards adaptation and HIV risk reduction influence PrEP uptake and adherence among HIV‐negative women with plans for pregnancy in rural Southwestern Uganda. Confidence in PrEP, individually controlled HIV prevention and improved partnership communication and intimacy promoted PrEP adherence. Supporting individuals to overcome context‐specific barriers to PrEP use may be an important approach to improving uptake and prolonged use.     

HIV disclosure and depressive symptoms among pregnant women living with HIV: a cross‐sectional study in the Democratic Republic of Congo

IntroductionDisclosure of one''s HIV status may decrease depression and improve the quality of life among people living with HIV. However, there is mixed evidence on the impact of disclosure to partners for pregnant women living with HIV (WLHIV) in areas of intersecting social concerns over disclosure and high prevalence of intimate partner violence (IPV). We assessed the association between HIV disclosure and depressive symptoms among pregnant WLHIV in the Democratic Republic of Congo (DRC) and examined whether the knowledge of partner''s status or recent IPV modified this association.MethodsWe utilized data from participants enrolled in a trial to evaluate the effect of continuous quality interventions on long‐term therapy outcomes among HIV‐positive pregnant and breastfeeding women in DRC ({"type":"clinical-trial","attrs":{"text":"NCT03048669","term_id":"NCT03048669"}}NCT03048669). Only pregnant women (n = 1392) were included in this cross‐sectional analysis. Between November 2016 and June 2019, enrolled participants completed a survey that included the Patient Health Questionnaire‐9 (PHQ‐9) to screen recent depressive symptoms, questions about disclosure, knowledge of partner''s status and IPV. We used linear models to calculate crude and adjusted mean differences (MDs) between disclosure and depressive symptoms. All analyses were stratified by timing of HIV diagnosis.ResultsDisclosure was higher among participants diagnosed prior to current pregnancy (41% to their partners and 24% to family, friends or others) relative to those diagnosed during current pregnancy (21% to partners and 12% to family). About one‐quarter of women reported any type of IPV in the past 12 months. Disclosure to a partner was associated with lower depressive symptoms among women diagnosed prior to current pregnancy (MD −0.55; 95% CI: −1.06, −0.04) but the opposite was observed among those diagnosed during current pregnancy (MD 0.5; 95% CI: −0.4, 1.4). Adjustment for IPV, knowledge of partner''s status, age, number of living children and primigravidae did not change MDs substantially.ConclusionsWomen in our sample mostly disclosed to partners despite high IPV burden. The observed association between disclosure to partners and lower depressive symptoms among women diagnosed prior to current pregnancy is consistent with cross‐national evidence. A prospective study among pregnant WLHIV is needed to examine longitudinal effects of HIV status disclosure.     

Safety and Efficacy of VP-102 (Cantharidin, 0.7% w/v) in Molluscum Contagiosum by Body Region: Post hoc Pooled Analyses from Two Phase III Randomized Trials

Trial Registration>ClinicalTrials.gov identifier nos. {"type":"clinical-trial","attrs":{"text":"NCT03377790","term_id":"NCT03377790"}}NCT03377790 (for CAMP-1) and {"type":"clinical-trial","attrs":{"text":"NCT03377803","term_id":"NCT03377803"}}NCT03377803 (for CAMP-2).BackgroundVP-102 is drug-device combination product containing cantharidin (0.7% w/v) and has undergone Phase III clinical trials for the treatment of molluscum contagiosum (molluscum). Efficacy and safety may differ by body region due to variable skin anatomy. ObjectiveWe investigated the pooled safety and efficacy of VP-102 by affected body region.MethodsIndividuals at least two years of age with molluscum were randomized to topical VP-102 or vehicle once every 21 days until clear (maximum of four applications). Participants were assigned to body region groups where lesions were present at baseline. Body region lesion counts were recorded at each visit. Efficacy was measured by the percentage of participants with complete clearance of lesions by region. Pre-specified adverse events (AEs) were analyzed for those treated in the region on that visit.ResultsParticipants had a mean of two regions affected at baseline. Complete clearance was significantly higher in the VP-102-treated group than with vehicle application in all regions at the last visit (P<0.01 for each region). The incidence of pre-specified AEs was consistent across regions. However, these analyses were post hoc, and individual lesions were not tracked for efficacy.Conclusion VP-102 treatment shows consistent safety and efficacy across molluscum body regions.     

Closing the gap: did delivery approaches complementary to home‐based testing reach men with HIV testing services during and after the HPTN 071 (PopART) trial in Zambia?

IntroductionThe HPTN 071 (PopART) trial demonstrated that universal HIV testing‐and‐treatment reduced community‐level HIV incidence. Door‐to‐door delivery of HIV testing services (HTS) was one of the main components of the intervention. From an early stage, men were less likely to know their HIV status than women, primarily because they were not home during service delivery. To reach more men, different strategies were implemented during the trial. We present the relative contribution of these strategies to coverage of HTS and the impact of community hubs implemented after completion of the trial among men.MethodsBetween 2013 and 2017, three intervention rounds (IRs) of door‐to‐door HTS delivery were conducted in eight PopART communities in Zambia. Additional strategies implemented in parallel, included: community‐wide “Man‐up” campaigns (IR1), smaller HTS campaigns at work/social places (IR2) and revisits to households with the option of HIV self‐testing (HIVST) (IR3). In 2018, community “hubs” offering HTS were implemented for 7 months in all eight communities. Population enumeration data for each round of HTS provided the denominator, allowing for calculation of the proportion of men tested as a result of each strategy during different time periods.ResultsBy the end of the three IRs, 65–75% of men were reached with HTS, primarily through door‐to‐door service delivery. In IR1 and IR2, “Man‐up” and work/social place campaigns accounted for ∼1 percentage point each and in IR3, revisits with the option of self‐testing for ∼15 percentage points of this total coverage per IR. The yield of newly diagnosed HIV‐positive men ranged from 2.2% for HIVST revisits to 9.9% in work/social places. At community hubs, the majority of visitors accepting services were men (62.8%). In total, we estimated that ∼36% (2.2% tested HIV positive) of men resident but not found at their household during IR3 of PopART accessed HTS provided at the hubs after trial completion.ConclusionsAchieving high coverage of HTS among men requires universal, home‐based service delivery combined with an option of HIVST and delivery of HTS through community‐based hubs. When men are reached, they are willing to test for HIV. Reaching men thus requires implementers to adapt their HTS delivery strategies to meet men''s needs.Clinical Trial Number{"type":"clinical-trial","attrs":{"text":"NCT01900977","term_id":"NCT01900977"}}NCT01900977     

Effects of a Knowledge-Translation Intervention on Early Dialysis Initiation: A Cluster Randomized Trial

BackgroundThe Initiating Dialysis Early and Late (IDEAL) trial, published in 2009, found no clinically measurable benefit with respect to risk of mortality or early complications with early dialysis initiation versus deferred dialysis start. After these findings, guidelines recommended an intent-to-defer approach to dialysis initiation, with the goal of deferring it until clinical symptoms arise.MethodsTo evaluate a four-component knowledge translation intervention aimed at promoting an intent-to-defer strategy for dialysis initiation, we conducted a cluster randomized trial in Canada between October 2014 and November 2015. We randomized 55 clinics, 27 to the intervention group and 28 to the control group. The educational intervention, using knowledge-translation tools, included telephone surveys from a knowledge-translation broker, a 1-year center-specific audit with feedback, delivery of a guidelines package, and an academic detailing visit. Participants included adults who had at least 3 months of predialysis care and who started dialysis in the first year after the intervention. The primary efficacy outcome was the proportion of patients who initiated dialysis early (at eGFR >10.5 ml/min per 1.73 m²). The secondary outcome was the proportion of patients who initiated in the acute inpatient setting.ResultsThe analysis included 3424 patients initiating dialysis in the 1-year follow-up period. Of these, 509 of 1592 (32.0%) in the intervention arm and 605 of 1832 (33.0%) in the control arm started dialysis early. There was no difference in the proportion of individuals initiating dialysis early or in the proportion of individuals initiating dialysis as an acute inpatient.ConclusionsA multifaceted knowledge translation intervention failed to reduce the proportion of early dialysis starts in patients with CKD followed in multidisciplinary clinics.Clinical Trial registry name and registration number:ClinicalTrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT02183987","term_id":"NCT02183987"}}NCT02183987. Available at: https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT02183987","term_id":"NCT02183987"}}NCT02183987     

Comparison between pulsed irrigation enhanced evacuation and polyethylene glycol-electrolyte lavage solution for bowel preparation prior to elective colonoscopy in veterans with spinal cord injury

BackgroundPoor preparation for elective colonoscopy is common in persons with spinal cord injury (SCI). This unsatisfactory outcome is likely due to long-standing difficulty with evacuation and decreased colonic motility. Our objective was to determine the most effective preparation for elective colonoscopy applying a novel and traditional approach to bowel cleansing.MethodsTwenty-four subjects with SCI were consented and scheduled to receive one of the two possible arms: pulsed irrigation enhanced evacuation (PIEE) or polyethylene glycol-electrolyte lavage solution (PEG; CoLyte^®). The quality of the preparation was scored during the colonoscopy by applying the Ottawa scoring system.ResultsPatients with SCI who received PIEE tended to have lower Ottawa scores and a higher percentage of acceptable preparations than did those who received PEG; however, the results were not statistically different.ConclusionIn this preliminary study in subjects with SCI, neither PIEE nor PEG produced acceptable bowel preparation for elective colonoscopy. Future studies should confirm our findings and consider studying alternative, more efficacious approaches to bowel cleansing prior to colonoscopic procedures in patients with SCI, which should provide better outcomes.Registration number for clinicaltrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT00745095","term_id":"NCT00745095"}}NCT00745095.     

Comparison of disc and wire electrodes to restore cough via lower thoracic spinal cord stimulation

ObjectiveTo compare the safety and effectiveness of wire (WE) vs. disc (DE) electrodes to restore cough in subjects with spinal cord injury (SCI).DesignClinical trials assessing the effectiveness and clinical outcomes associated with two electrode systems to activate the expiratory muscles.SettingInpatient hospital setting for DE or WE electrode insertion; outpatient evaluation of cough efficacy and instructions for home use.ParticipantsTwenty-nine subjects with SCI; 17 participants with DE and 12 with WE implants.InterventionSurgical implantation of WE or DE to restore cough. Daily application of spinal cord stimulation (SCS) at home.Main outcome measure(s)Airway pressure (P) and peak airflow (F) generation achieved with SCS; clinical parameters including ease in raising secretions, incidence of acute respiratory tract infections (RTI) and side effects.ResultsP and F achieved with DE and WE were not significantly different. For example, at total lung capacity (TLC) with participant effort, P was 128 ± 12 cmH₂O and 118 ± 14 cmH₂O, with DE and WE, respectively. The degree of difficulty in raising secretions improved markedly in both groups. The incidence of RTI per year fell from 1.3 ± 0.3 and 1.3 ± 0.5–0.3 ± 0.1 and 0.1 ± 0.1 for DE and WE groups, respectively (P < 0.01 for both when compared to pre-implant values and NS between DE and WE groups). The only significant side effect i.e. short-term autonomic dysreflexia was also similar between groups.ConclusionsThe results of this investigation indicate that both DE and WE result in comparable degrees of expiratory muscle activation, clinical benefits and side effects. Importantly, SCS to restore cough can be achieved with use of WE which can be placed using minimally invasive techniques and associated reduction in cost, surgical time and overall risk.Trial registration: ClinicalTrials.gov identifier: {"type":"clinical-trial","attrs":{"text":"NCT00116337","term_id":"NCT00116337"}}NCT00116337., {"type":"clinical-trial","attrs":{"text":"NCT01659541","term_id":"NCT01659541"}}NCT01659541, FDA IDE: G980267     

Ten‐year attrition and antiretroviral therapy response among HIV‐positive adults: a sex‐based cohort analysis from eight West African countries

IntroductionSex differences have already been reported in sub‐Saharan Africa for attrition and immunological response after antiretroviral therapy (ART) initiation, but follow‐up was usually limited to the first two to three years after ART initiation. We evaluated sex differences on the same outcomes in the 10 years following ART initiation in West African adults.MethodsWe used cohort data of patients included in the IeDEA West Africa collaboration, who initiated ART between 2002 and 2014. We modelled no‐follow‐up and 10‐year attrition risks, and immunological response by sex using logistic regression analysis, survival analysis with random effect and linear mixed models respectively.ResultsA total of 71,283 patients (65.8% women) contributed to 310,007 person‐years of follow‐up in 16 clinics in eight West African countries. The cumulative attrition incidence at 10‐year after ART initiation reached 75% and 68% for men and women respectively. Being male was associated with an increased risk of no follow‐up after starting ART (5.1% vs. 4.0%, adjusted Odds Ratio: 1.25 [95% CI: 1.15 to 1.35]) and of 10‐year attrition throughout the 10‐year period following ART initiation: adjusted Hazard Ratios were 1.22 [95% CI: 1.17 to 1.27], 1.08 [95% CI: 1.04 to 1.12] and 1.04 [95% CI: 1.01 to 1.08] during year 1, years 2 to 4 and 5 to 10 respectively. A better immunological response was achieved by women than men: monthly CD4 gain was 30.2 and 28.3 cells/mL in the first four months and 2.6 and 1.9 cells/μL thereafter. Ultimately, women reached the average threshold of 500 CD4 cells/μL in their sixth year of follow‐up, whereas men failed to reach it even at the end of the 10‐year follow‐up period. The proportion of patients reaching the threshold was much higher in women than in men after 10 years since ART initiation (65% vs. 44%).ConclusionsIn West Africa, attrition is unacceptably high in both sexes. Men are more vulnerable than women on both attrition and immunological response to ART in the 10 years following ART initiation. Innovative tracing strategies that are sex‐adapted are needed for patients in care to monitor attrition, detect early high‐risk groups so that they can stay in care with a durably controlled infection.     

Uptake and outcomes of a novel community‐based HIV post‐exposure prophylaxis (PEP) programme in rural Kenya and Uganda

IntroductionAntiretroviral‐based HIV prevention, including pre‐exposure prophylaxis (PrEP), is expanding in generalized epidemic settings, but additional prevention options are needed for individuals with periodic, high‐risk sexual exposures. Non‐occupational post‐exposure prophylaxis (PEP) is recommended in global guidelines. However, in Africa, awareness of and access to PEP for sexual exposures are limited. We assessed feasibility, acceptability, uptake and adherence in a pilot study of a patient‐centred PEP programme with options for facility‐ or community‐based service delivery.MethodsAfter population‐level HIV testing with universal access to PrEP for persons at elevated HIV risk (SEARCH Trial:{"type":"clinical-trial","attrs":{"text":"NCT01864603","term_id":"NCT01864603"}}NCT01864603), we conducted a pilot PEP study in five rural communities in Kenya and Uganda between December 2018 and May 2019. We assessed barriers to PEP in the population and implemented an intervention to address these barriers, building on existing in‐country PEP protocols. We used community leaders for sensitization. Test kits and medications were acquired through the Ministry of Health supply chain and healthcare providers based at the Ministry of Health clinics were trained on PEP delivery. Additional intervention components were (a)PEP availability seven days/week, (b)PEP hotline staffed by providers and (c)option for out‐of‐facility medication delivery. We assessed implementation using the Proctor framework and measured seroconversions via repeat HIV testing. Successful “PEP completion” was defined as self‐reported adherence over four weeks of therapy with post‐PEP HIV testing.ResultsCommunity leaders were able to sensitize and mobilize for PEP. The Ministry of Health supplied test kits and PEP medications; after training, healthcare providers delivered the 28‐day regimen with high completion rates. Among 124 persons who sought PEP, 66% were female, 24% were ≤25 years and 42% were fisherfolk. Of these, 20% reported exposure with a serodifferent partner, 72% with a new or existing relationship and 7% from transactional sex. 12% of all visits were conducted at out‐of‐facility community‐based sites; 35% of participants had ≥1 out‐of‐facility visit. No serious adverse events were reported. Overall, 85% met the definition of PEP completion. There were no HIV seroconversions.ConclusionsAmong individuals with elevated‐risk exposures in rural East African communities, patient‐centred PEP was feasible, acceptable and provides a promising addition to the current prevention toolkit.     

Early postoperative pain after subxiphoid uniportal thoracoscopic major lung resection: a prospective,single- blinded,randomized controlled trial

Open in a separate window OBJECTIVESPreoperative selection bias led to the inability to generalize the proposed benefit of subxiphoid uniportal video-assisted thoracoscopic surgery (SVATS) as having less postoperative pain than uniportal intercostal VATS. So, we conducted this prospective, single-blinded, randomized controlled trial to investigate the hypothesis that SVATS may have less early postoperative pain than UVATS in patients who undergo major lung resection for early-stage lung cancer.METHODSA total of262 patients were randomly allocated between 2 groups (each with 131 patients), the first being the UVATS group and the second being the SVATS group. The values indicated on the numerical rating scale (NRS) of pain were collected at 24 h and 48 h during rest and during coughing. In addition, different perioperative variables were analysed and compared between the 2 groups.RESULTSMultiple linear regression analysis showed that the type of surgical approach was a significant predictor of the postoperative NRS values. The postoperative NRS pain values were significantly lower in the SVATS group after 24 h during rest and coughing and after 48 h during coughing. Postoperatively, patients in the SVATS group got out of bed significantly earlier [16.37 (2.54) vs 18.05 (3.29) h, p < 0.001]. The SVATS group showed a significantly higher rate of intraoperative arrhythmia [20 (15.3%) vs 3 (2.3%) patients, p = 0.03].CONCLUSIONSSVATS major pulmonary resection in early-stage lung cancer is associated with less early postoperative pain than the UVATS approach. Operating on patients with cardiac problems using the SVATS approach is still a limiting factor for randomization due to the potential compression on the heart with resulting arrhythmia.Clinical trial registrationThe trial was registered under clinical trials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT03331588","term_id":"NCT03331588"}}NCT03331588. https://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT03331588","term_id":"NCT03331588"}}NCT03331588.     

Patient-reported Outcomes in Chinese Subjects Treated with OnabotulinumtoxinA for Crow’s Feet Lines

BackgroundCrow’s feet lines (CFLs) can impact the emotional state, self-perception, and consciousness regarding appearance of patients.ObjectiveThis study sought to assess patient-reported outcomes after onabotulinumtoxinA treatment for CFLs among Chinese subjects.MethodsA five-month, double-blind, randomized, parallel-group, placebo-controlled Phase III clinical study was conducted including Chinese adults with moderate-to-severe CFLs at maximum smile. Subjects were randomized 3:1 to 24 U of onabotulinumtoxinA or placebo and completed the 11-item Facial Line Outcomes (FLO-11) questionnaire and Facial Line Satisfaction Questionnaire (FLSQ) at baseline; on Days 8, 15, and 30; and monthly thereafter until Day 150. Item-level and/or domain analyses for the FLO-11 and FLSQ were conducted.ResultsOf 417 treated subjects, 316 received onabotulinumtoxinA and 101 received placebo. For all 10 validated stand-alone FLO-11 items, there was a significantly greater proportion of responders in the onabotulinumtoxinA group versus placebo (P<0.001) at Day 30 that was maintained through Day 150. Significant improvements at Day 30 were reported for all FLSQ items and the FLSQ Follow-up Impact Domain (P≤0.01).ConclusionFLO-11 and FLSQ data indicated high satisfaction and significant improvements in appearance-related and emotional impacts through Day 150 in patients treated with onabotulinumtoxinA for moderate-to-severe CFLs in Chinese subjects.Trial RegistrationClinicalTrials.gov identifier no. {"type":"clinical-trial","attrs":{"text":"NCT02195687","term_id":"NCT02195687"}}NCT02195687     

Impact of early quantitative morbidity on 1-year outcomes in coronary artery bypass graft surgery

Open in a separate window OBJECTIVESWe applied the Clavien-Dindo Complications Classification (CDCC) and the Comprehensive Complication Index (CCI) to the CORONARY trial to assess whether quantitative early morbidity affects outcomes at 1 year.METHODSAll postoperative hospitalization and 30-day follow-up complications were assigned a CDCC grade. CCI were calculated for all patients (n = 4752). Kaplan–Meier analysis examined 1-year mortality and 1-year co-primary outcome (i.e. death, non-fatal stroke, non-fatal myocardial infarction, new-onset renal failure requiring dialysis or repeat coronary revascularization) by CDCC grade. Multivariable logistic regression evaluated the predictive value of CCI for both outcomes.RESULTSFor off-pump and on-pump coronary artery bypass graft surgery, median CDCC were 1 [interquartile range: 0, 2] and 2 [1, 2] (P < 0.001), while median CCI were 8.7 [0, 22.6] and 20.9 [8.7, 29.6], respectively (P < 0.001). In on-pump, there were more grade I and grade II complications, particularly grade I and II transfusions (P < 0.001) and grade I acute kidney injury (P = 0.039), and more grade IVa respiratory failures (P = 0.047). Patients with ≥IIIa complications had greater cumulative 1-year mortality (P < 0.001). The median CCI was 8.7 [0, 22.6] in patients who survived and 22.6 [8.7, 44.3] in patients who died at 1 year (P < 0.001). The CCI remained an independent risk factor for 1-year mortality and 1-year co-primary outcome after multivariable adjustment (P < 0.001).CONCLUSIONSOn-pump coronary artery bypass graft surgery had a greater number of complications in the early postoperative period, likely driven by transfusions, respiratory outcomes and acute kidney injury. This affects 1-year outcomes. Similar analyses have not yet been used to compare both techniques and could prove useful to quantify procedural morbidity.Clinical trial registration https://www.clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00463294","term_id":"NCT00463294"}}NCT00463294; Unique Identifier: {"type":"clinical-trial","attrs":{"text":"NCT00463294","term_id":"NCT00463294"}}NCT00463294.     

Mental health and initiation of antiretroviral treatment at enrolment into HIV care in Cameroon under a national “treat all” policy: a cross‐sectional analysis

IntroductionRapid antiretroviral treatment (ART) initiation reduces time from HIV infection to viral suppression, decreasing HIV transmission risk. Mental health symptoms may influence timing of ART initiation. This study estimated the prevalence of ART initiation at enrolment into HIV care and the relationship between mental health and ART initiation at enrolment into HIV care.MethodsWe conducted interviews with 426 individuals initiating HIV care in Cameroon between June 2019 and March 2020 to estimate the association between mental health and timing of ART initiation. Depression (Patient Health Questionnaire‐9; cut‐point 10), anxiety (Generalized Anxiety Disorder‐7; cut‐point 10), post‐traumatic stress disorder (PTSD) (PTSD Checklist for DSM‐5; cut‐point 31) and harmful alcohol use (Alcohol Use Disorders Identification Test; cut‐point 16) were dichotomized to represent those with and without each exposure at first HIV care appointment. Date of ART initiation (date ART prescribed) was ascertained from medical records. Separate multivariable log‐binomial regression models were used to estimate the association between mental health exposures and ART initiation at enrolment into care.Results and discussionOverall, 87% initiated ART at enrolment into HIV care. Approximately 20% reported depressive symptoms, 15% reported PTSD symptoms, 12% reported anxiety symptoms and 13% reported harmful alcohol use. In multivariable analyses, individuals with moderate to severe depressive symptoms had 1.7 (95% confidence interval [CI] 1.1, 2.7) times the prevalence of not initiating ART at enrolment into HIV care compared to those with no or mild depressive symptoms. Those with symptoms of PTSD, compared to those without, had 1.9 (95% CI 1.2, 2.9) times the prevalence of not initiating ART at enrolment into HIV care. Symptoms of anxiety or harmful drinking were not associated with ART initiation at enrolment into HIV care in multivariable models.ConclusionsSymptoms of depression and PTSD were associated with lower prevalence of ART initiation at enrolment into HIV care among this sample of individuals initiating HIV care in Cameroon under a “treat all” policy. Research should examine barriers to timely ART initiation, whether incorporating mental health services into HIV care improves timely ART initiation, and whether untreated symptoms of depression and PTSD drive suboptimal HIV care outcomes.     

Clinical Efficacy of Intra‐Articular Injection with P‐PRP Versus that of L‐PRP in Treating Knee Cartilage Lesion: A Randomized Controlled Trial

ObjectivePlatelet‐rich plasma（PRP), with different concentration of leukocytes, may lead to varying effects in the treatment of cartilage lesions. So far, current research has not shown enough evidence on this. To evaluate the clinical efficacy and safety of intra‐articular injection with pure platelet‐rich plasma (P‐PRP) versus those of leukocyte platelet‐rich plasma (L‐PRP) in treating knee cartilage lesions, we conducted a double‐blind, randomized controlled clinical trial with a larger sample and longer follow‐up period.MethodsFrom October 2019 to October 2020, 95 patients were invited to participate in our study, and 60 (63.2%) were randomized to P‐PRP (n = 30) or L‐PRP (n = 30) groups. Patients from the two groups were treated with knee intra‐articular injections of P‐PRP or L‐PRP. Visual analog scale (VAS) and Western Ontario and McMaster Universities Arthritis Index (WOMAC) scores were assessed using an unpaired t‐test for independent samples preoperatively and at 6 weeks, 12 weeks, 6 months, and 12 months after intervention.ResultsWe followed up 27 cases in the P‐PRP group and 26 cases in the L‐PRP group. No significant differences in VAS and WOMAC scores were found between the two groups before the intervention (p > 0.05). The WOMAC Pain and VAS‐Motions scores of the P‐PRP group were significantly lower than those of the L‐PRP group at 6 weeks after the intervention (p < 0.05). While the long‐term clinical efficacy of both injections was similar and weakened after 12 months, more adverse events were found in the L‐PRP group.ConclusionsThe short‐term results demonstrate a positive effect in reducing pain and improving function in patients with knee cartilage lesions in the two groups. While the P‐PRP injection showed better clinical efficacy in the early phase of postoperative rehabilitation and resulted in fewer adverse events, long‐term follow‐up showed similar and weakened efficacy after 12 months.Trial RegistrationChiCTR1900026365. Registered on October 3, 2019, http://www.chictr.org.cn/showproj.aspx?proj=43911.     

Evaluation of the Skin Sensitization,Photoirritation, and Photoallergic Potential of Ingenol Mebutate Gel in Healthy Volunteers

Objectives: Phase 1 studies were conducted to determine the sensitization (PEP005-005; {"type":"clinical-trial","attrs":{"text":"NCT00357916","term_id":"NCT00357916"}}NCT00357916; http://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00357916","term_id":"NCT00357916"}}NCT00357916), photoirritation (PEP005-023; {"type":"clinical-trial","attrs":{"text":"NCT00850811","term_id":"NCT00850811"}}NCT00850811; http://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00850811","term_id":"NCT00850811"}}NCT00850811?term=PEP005-023&rank=1), and photoallergic (photosensitizing) potential (PEP005-024; {"type":"clinical-trial","attrs":{"text":"NCT00850681","term_id":"NCT00850681"}}NCT00850681; http://clinicaltrials.gov/ct2/show/{"type":"clinical-trial","attrs":{"text":"NCT00850681","term_id":"NCT00850681"}}NCT00850681?term=PEP005-024&rank=1) of ingenol mebutate gel 0.01% versus vehicle on normal skin. Design, setting, participants, and measurements: Healthy volunteers were enrolled in single-center, randomized, controlled, within-subject comparison trials. PEP005-005 was designed as a repeat-insult patch test study. In PEP005-023, treatment areas were examined after irradiation for photoirritation potential; dermal reactions were evaluated. In PEP005-024, irradiation was performed to determine the photoallergic (photosensitizing) potential of the medication. All treatment areas were graded immediately prior to irradiation and 24, 48, and 72 hours following irradiation. In all studies, local tolerability was assessed visually using an ordinal scoring system at set intervals before and after medication application/irradiation. Results: In PEP005-005 (n=238), a significant difference (p<0.001) was seen between ingenol mebutate and vehicle for mean and total cumulative irritation scores. In PEP005-023 (n=34), mild erythema in all irradiated treatment areas was as expected for the ultraviolet dose. There was no clinically significant irritation in response to ingenol mebutate or vehicle, irrespective of irradiation. In PEP005-024 (n=60), there was no significant irritation in response to either ingenol mebutate or vehicle at their irradiated treatment areas. Conclusion: Results from three pharmacology studies in healthy volunteers indicate a favorable topical safety profile for ingenol mebutate gel, with no evidence seen of skin sensitization, photoirritation, or photoallergic potential.Actinic keratosis (AK) is a field disease that manifests as multiple clinical and subclinical dysplastic skin lesions. It is common in fair-skinned people with a history of long-term ultraviolet (UV) radiation exposure.1-4 Coupled with its rising incidence and subsequent risk factors, the burden of AK is substantial as AK lesions have the potential to progress and transform into invasive squamous cell carcinoma.5 Effective field therapy is therefore important.6-8Ingenol mebutate gel is a novel field therapy indicated for the topical treatment of adults with AK; specific dosing regimens have been developed for treating AK lesions on the face and scalp and on the trunk and extremities.9 Ingenol mebutate has been extensively refined from the sap of the plant Euphorbia peplus to create an active pharmaceutical ingredient, which is an AK lesion-directed cell death inducer and immune response modifier.10-14For lesions on the face and scalp, ingenol mebutate 0.015% is self-applied once daily for three consecutive days; for lesions on the trunk and extremities, ingenol mebutate 0.05% is self-applied once daily for two consecutive days. Treatment with ingenol mebutate has a short local skin response duration and was effective and well tolerated in Phase 2 and 3 clinical studies.15,16Ingenol mebutate does not absorb light in the UV range. During the clinical development program, the potential of ingenol mebutate to induce skin sensitization, photoirritation, and photoallergy was investigated in three early Phase 1 clinical studies. In this paper, the authors present for the first time in full, the collective results from these three randomized controlled studies with 0.01% ingenol mebutate gel in healthy volunteers.