Life Groenkloof Hospital

The Western Cape is South Africa's epicentre for tuberculosis (TB) and smoked drug use such as methamphetamine and methaqualone (Mandrax). Despite this, there are limited studies on people who smoke drugs (PWSD) with TB disease in South Africa, partly due to recruitment challenges. Respondent-driven sampling (RDS) is a network-based sampling method used to recruit such key populations. The aim of this qualitative study is to explore the appropriateness and feasibility of RDS as a method for recruiting PWSD for a planned study on TB transmission in this setting. We conducted ten focus group discussions (n = 84) with men and women from Worcester, a rural town in the Western Cape, who self-reported current methamphetamine and/or methaqualone use. Participants were recruited through an existing TB study or community-based outreach. Discussion topics included use of illicit drugs within social networks, feasibility of using RDS methods for recruiting PWSD, and logistical recommendations for the use of RDS and planned study participation. Data were analyzed using thematic analysis. Results indicate drug use by participants across large social networks which is favorable for RDS methods. The key themes were: 1) drug-use social network characteristics including demographic and geographic differences; 2) perspectives of PWSD on RDS methods; 3) potential challenges to proposed RDS recruitment and participation in a larger research study for PWSD, and 4) participant recommendations to enhance the uptake of RDS and study participation by PWSD. RDS seems to be a feasible method to recruit PWSD and improve the possibility of reaching a diverse sample of PWSD, with clear recommendations from participants regarding how to recruit participants for larger research studies. The current study indicates that conducting formative, qualitative research can assist researchers with RDS study design and planning for additional study activities. Trial Registration: ClinicalTrials.gov NCT041515602.

BackgroundElastic modulus is an important biomechanical component that indicates stiffness or elasticity of biological material. Recently the use of digital image correlation (DIC) in elastic modulus studies on fresh tissue has shown great accuracy in estimating elastic properties; thus, the aim of this study was to investigate the elasticity of capsular and tendinous layers of the rotator cuff complex employing this method.Materials and methodsThe supraspinatus, infraspinatus, and subscapularis from eight (n = 8) fresh/frozen tissue shoulders were reverse dissected from their origins. The muscles were separated from one another and dissected to produce 20 × 20 mm tendinous and capsular strips for each muscle. DIC was employed to measure the strain of the tendinous and capsular portions of each of the muscles during tensile testing, and tangent elastic modulus values were obtained.ResultsThe tendinous layers for supraspinatus, infraspinatus, and subscapularis yielded higher average tangent elastic moduli readings (62.1 MPa, 67.1 MPa, and 59.6 MPa, respectively) compared to their capsular counterparts (29.0 MPa, 32.5 MPa, and 41.5 MPa, respectively).ConclusionDifferent elastic moduli findings for the tendinous and capsular layers suggest these layers should be considered independently during surgical repair to avoid biomechanical imbalance which may result if these layers were to be repaired as one singular layer.

BackgroundThe COVID-19 pandemic negatively impacted tuberculosis (TB) treatment services, including directly observed therapy (DOT) programs used to promote medication adherence. We compared DOT adherence embedded in a research study before and after COVID-19 lockdowns in South Africa.MethodsWe analyzed data from 263 observational study participants undergoing drug susceptible (DS)-TB DOT between May 2017 to March 2022. Participants enrolled before October 2019 were considered ‘pre-COVID-19’ and those enrolled after September 2020 were considered ‘post-COVID-19 lockdown groups. Negative binomial regression models were used to compare DOT non-adherence rates between the two lockdown groups. We then conducted a sensitivity analysis which only included participants enrolled in the immediate period following the first COVID-19 lockdown.ResultsDOT non-adherence rate was higher in the post-COVID-19 lockdown group (aIRR = 1.42, 95% CI = 1.04–1.96; p = 0.028) compared to pre-COVID-19 lockdown period, adjusting for age, sex, employment status, household hunger, depression risk, and smoked substance use. DOT non-adherence was highest immediately following the initial lockdown (aIRR = 1.74, 95% CI = 1.17–2.67; p = 0.006).ConclusionThe COVID-19 lockdowns adversely effected adherence to TB DOT in the period after lockdowns were lifted. The change in DOT adherence persisted even after adjusting for socioeconomic and behavioral variables. We need a better understanding of what treatment adherence barriers were exacerbated by COVID-19 lockdowns to improve outcomes in post-pandemic times.Trial registrationClinicalTrials.gov Registration Number: NCT02840877. Registered on 19 July 2016.

There is a knowledge gap on the epidemiology of inflammatory bowel disease in Africa. To begin to address this issue, we formed a case reporting network of practitioners with an interest in inflammatory bowel disease across sub-Saharan Africa. Here, we report a series of 175 cases from 12 countries over 2 years.

4518 Background: ctDNA is emerging as a potential biomarker of disease in early-stage bladder cancer but is less understood in advanced UC. We present a retrospective analysis of pre-treatment and on-treatment ctDNA data by clinical outcomes with pembro monotherapy versus chemo in pts with advanced UC from the phase 3 KEYNOTE-361 trial (NCT02853305). Methods: Pts with previously untreated advanced UC were randomly assigned 1:1:1 to pembro + chemo, pembro alone, or chemo alone. Tumor tissue mutations were evaluated with whole exome sequencing of tumor and matched normal DNA. Plasma ctDNA was evaluated using the Guardant Health (GH) Guardant 360 LDT assay. ctDNA changes from pre-treatment cycle 1(C1) to on-treatment cycle 2 (C2) were quantified by maximum variant allele frequency (maxVAF) of tumor tissue–specific mutations (tumor-informed [TI] approach) or GH molecular response (MR) score. Association between C2/C1 ratios or baseline TI maxVAF and clinical outcomes (ORR, PFS, and OS) were evaluated. Nominal statistical significance of maxVAF was prespecified at 0.05 (hypothesis, negative). Results: ctDNA samples from 263 pts (n = 131, chemo; n = 132, pembro) were analyzed. Clinical characteristics and baseline ctDNA levels within arms were similar. Lower C1 maxVAF was associated with improved ORR, PFS, and OS in the pembro arm ( P < 0.01) and was robust to adjustment for TMB and PD-L1, but not in the chemo arm ( P > 0.05). Larger C2 reductions in ctDNA levels were observed in the chemo vs pembro arm (median ratio of C2/C1 TI maxVAF, 0.03 vs 0.71, respectively); similar observations were made for MR score. ctDNA reductions were associated with improved ORR, PFS ( P < 0.001), and OS ( P < 0.01) for TI maxVAF in the chemo arm; MR score was significantly associated with ORR and PFS ( P < 0.01). Associations were stronger in the pembro arm ( P < 0.001) and were robust to adjustment for TMB and PD-L1. ctDNA changes from C1 to C2 did not show independent explanatory value for OS when RECIST v1.1 response status was added as a variable. Conclusions: ctDNA levels at baseline appear prognostic for pembro. Reductions in ctDNA during the first treatment cycle were associated with outcome. Distinct patterns of ctDNA response were observed with the different treatments, and stronger associations with long-term clinical outcome were observed with pembro. Association of OS for both pembro and chemo was not retained when adjusting for tumor response. Early ctDNA dynamics did not offer additional benefit in predicting outcome beyond radiographic assessment of tumor size change. Clinical trial information: NCT02853305 .

Primary malignant bone tumours are a scarce entity with limited population-based data from developing countries. The aim of the study is to investigate the frequency and anatomical distribution of primary malignant bone tumours in a local South African population.This will be an epidemiological retrospective study. Data will be used of patients that were diagnosed with primary malignant bone tumours over a period of nine years spanning from 1 January 2014 to 31 December 2022. This data will be received from private and government laboratories. Data to be considered are type of primary malignant bone tumours diagnosed, incidence of primary malignant bone tumours over a period of nine years and the most common anatomical sites of primary malignant bone tumours. The rationale behind our study is to assess the frequency of different primary malignant bone tumours in another geographic area of South Africa and to compare these findings to local and international literature. With a projected increase in diagnosis of primary malignant bone tumours in developing countries it is important to have more available data about primary malignant bone tumours from these areas to have a better understanding of these conditions and to understand the impact of the burden they impose on healthcare systems so that management of these conditions can also be improved. Preliminary results show that 23.83% of primary malignant bone tumours occurred in the age group 0–24 years of age, 49.22% in the 25–59 age group and 26.95% in the 60+ age group. The most common tumour that occurred was chondrosarcoma (49.21%) followed by osteosarcoma (41.80%) then Ewing's sarcoma (4,69%) and lastly chordoma (4.30%). From the 256 samples that met the inclusion criteria the five most common anatomical sites were distal femur (63), proximal tibia (41), proximal humerus (38), pelvis (34) and proximal femur (20).

J.L.S. reports having received speaker honoraria from Eli Lilly, Insulet, Medtronic, and Zealand and serves on advisory boards of Bigfoot Biomedical, Cecelia Health, Insulet Corporation, Medtronic Diabetes, JDRF T1D Fund, and Vertex. She has been a consultant for Insulet and Medtronic. J.L.S.'s institution received research grant support from JDRF, Medtronic, Insulet, and NIDDK. M.S. reports research grant support, paid to her institution, from Tandem Diabetes Care, Insulet, Medtronic, JDRF, and NIDDK. T.S. has no conflict to disclose. L.R. reports speaker fees from Sanofi, Pfizer, NovoNordisk. T.B. reports speaker fees, consulting honoraria or research support from AstraZeneca, Ascensia, DexCom, Medtronic, NovoNordisk, Roche, Sanofi, and Ypsomed. Since 2021, he is member of the Expert group for medical devices of the European Medicines Agency. A.G. received speaker honoraria from Ypsomed. A.G.'s institution received research support from the European Commission (H2020 program). J.V. has no conflict to disclose. M.E.H. receives research grant support from NIDDK, JDRF, and The Leona M. and Harry B. Helmsley Charitable Trust. C.B. has been a consultant for Insulet. L.A.D. reports that in the last 3 years she has consulted for Vertex and served on a Mannkind, Merck, and Abata adivosry board. She has also recieved research support to her instiution from Caladrius, Lilly, Mannkind, Medtronic, Provention, and Zealand. The peer review history for this article is available at https://publons.com/publon/10.1111/pedi.13421. JLS reviewed the literature, drafted sections of the guidelines, oversaw completion of the first draft of the guidelines, and edited the manuscript. MS, TD, LR, TB, AG, JV, MEH and CB reviewed the literature, provided drafts of sections and edited the manuscript. LAD outlined the guidelines, reviewed the literature, edited the manuscript, and served as the senior author. The authors gratefully acknowledge the editorial assistance of Dr. Leena Priyambada. Data sharing not applicable to this article as no datasets were generated or analysed during the current study.