Emerging research has provided support for the use of the Kessler Psychological Distress Scales in developing countries; however, this research has yet to be extended to southern Africa. This study sought to evaluate the performance of the Kessler scales in screening for depression and anxiety disorders in the South African population. The scales along with the Composite International Diagnostic Interview (CIDI) were included in the South African Stress and Health study, a nationally representative household survey. The K10/K6 demonstrated moderate discriminating ability in detecting depression and anxiety disorders in the general population; evidenced by area under the receiver operating curves of 0.73 and 0.72 respectively. However, both scales failed to meet our acceptability criteria of high sensitivity and high positive predictive value. Examinations of differences in responding by race/ethnicity revealed that the K10/K6 [Kessler Psychological Distress Scale 10-item (K10) and the abbreviated six-item (K6)] had significantly lower discriminating ability with respect to depression and anxiety disorders among the Black group (0.71) than among the combined minority race/ethnic groups of White, Colored, and Indian/Asian (0.78; p = 0.016). The difference in time period assessed on the K10/K6 (past 30 days) versus the CIDI (past 12 months) was a notable limitation of this study. Additional validation studies using clinician diagnostic instruments are recommended.
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: NCT02696824 https://clinicaltrials.gov/ct2/show/NCT02696824
Depression is prevalent among people living with HIV in South Africa and interferes with adherence to antiretroviral therapy. This study evaluated a nurse-delivered, cognitive behavioral therapy intervention for adherence and depression among antiretroviral therapy users with depression in South Africa (n = 14). Primary outcomes were depression, antiretroviral therapy adherence, feasibility, and acceptability. Findings support robust improvements in mood through a 3-month follow up. Antiretroviral therapy adherence was maintained during the intervention period. Participant retention supports acceptability; however, modest provider fidelity despite intensive supervision warrants additional attention to feasibility. Future effectiveness research is needed to evaluate this nurse-delivered cognitive behavioral therapy intervention for adherence and depression in this context.
SummaryClass lI genes of the human major histocompatibility complex (MHC) are highly polymorphic . Allelic variation of structural genes provides diversity in immune cell interactions, contributing to the formation of the T cell repertoire and to susceptibility to certain autoimmune diseases . We now report that allelic polymorphism also exists in the promoter and upstream regulatory regions (URR) ofhuman histocompatibility leukocyte antigen (HLA) class II genes. Nucleotide sequencing of these regulatory regions of seven alleles of the DQB locus reveals a number of allele-specific polymorphisms, some of which lie in functionally critical consensus regions thought to be highly conserved in class II promoters . These sequence differences also correspond to allelic differences in binding of nuclear proteins to the URR . Fragments of the URR of two DQB alleles were analyzed for binding to nuclear proteins extracted from human B lymphoblastoid cell lines (B-LCL) . Gel retardation assays showed substantially different banding patterns to the two promoters, including prominent variation in nuclear protein binding to the partially conserved X box regions and a novel upstream polymorphic sequence element . Comparison of these two polymorphic alleles in a transient expression system demonstrated a marked difference in their promoter strengths determined by relative abilities to initiate transcription of the chloramphenicol acetyltransferase reporter gene in human B-LCL . Shuttling of URR sequences between alleles showed that functional variation corresponded to both the X box and upstream sequence polymorphic sites . These findings identify an important source of MHC class II diversity, and suggest the possibility that such regulatory region polymorphisms may confer allelic differences in expression, inducibility, and/or tissue specificity of class II molecules .C lass II molecules of the MHC are cell surface heterodimers composed ofcx and 0 polypeptides. Structural variation among the MHC class II molecules is key to functional differences where, as part of the trimolecular complex with peptide and T cell receptor, the class II molecule participates in immune activation events which lead to histoincompatibility, immune recognition, and disease susceptibility (1-3). Variation among class II molecules is predominantly of two types, one of which is germline genetic polymorphism, with multiple alleles existing at various loci within the MHC gene complex (4) . This type ofpolymorphism leads to differential peptide recognition and binding by the class II molecules encoded by individual alleles (5, 6) . Another source of variation arises from the differential ability of certain u chains to pair with certain ,l3 chains to form combinatorial dimers on the cell surface (7, 8). We have examined a possible third type of polymorphism ; namely, transcriptional variation between different class II alleles .Regulated inducible and tissue-specific transcription of MHC class II genes is a complex system involving cis-acting sequence eleme...
Introduction South Africa (SA) has the highest number of people living with HIV (PLWH) globally, and a significant burden of alcohol and other drug use (AOD). Although integrating AOD treatment into HIV care may improve antiretroviral therapy (ART) adherence, this is not typically routine practice in SA or other low‐resource settings. Identifying interventions that are feasible and acceptable for implementation is critical to improve HIV and AOD outcomes. Methods A pilot randomized hybrid type 1 effectiveness‐implementation trial (N = 61) was conducted to evaluate the feasibility and acceptability of Khanya, a task‐shared, peer‐delivered behavioral intervention to improve ART adherence and reduce AOD in HIV care in SA. Khanya was compared to enhanced treatment as usual (ETAU), a facilitated referral to on‐site AOD treatment. Implementation outcomes, defined by Proctor’s model, included feasibility, acceptability, appropriateness and fidelity. Primary pilot effectiveness outcomes were ART adherence at post‐treatment (three months) measured via real‐time electronic adherence monitoring, and AOD measured using biomarker and self‐report assessments over six months. Data collection was conducted from August 2018 to April 2020. Results and discussion Ninety‐one percent of participants (n = 56) were retained at six months. The intervention was highly feasible, acceptable, appropriate and delivered with fidelity (>90% of components delivered as intended by the peer). There was a significant treatment‐by‐time interaction for ART adherence (estimate = −0.287 [95% CI = −0.507, −0.066]), revealing a 6.4 percentage point increase in ART adherence in Khanya, and a 22.3 percentage point decline in ETAU. Both groups evidenced significant reductions in alcohol use measured using phosphatidylethanol (PEth) (F(2,101) = 4.16, p = 0.01), significantly decreased likelihood of self‐reported moderate or severe AOD (F(2,104) = 7.02, p = 0.001), and significant declines in alcohol use quantity on the timeline follow‐back (F(2,102) = 21.53, p < 0.001). Among individuals using drugs and alcohol, there was a greater reduction in alcohol use quantity in Khanya compared to ETAU over six months (F(2,31) = 3.28, p = 0.05). Conclusions Results of this pilot trial provide initial evidence of the feasibility and acceptability of the Khanya intervention for improving adherence in an underserved group at high risk for ongoing ART non‐adherence and HIV transmission. Implementation results suggest that peers may be a potential strategy to extend task‐sharing models for behavioral health in resource‐limited, global settings.
The pluripotent rat islet tumor cell line MSL-G2 expresses primarily glucagon or cholecystokinin and not insulin in vitro but changes phenotype completely after prolonged in vivo cultivation to yield small-sized hypoglycemic tumors composed almost entirely of insulin-producing beta cells. When a genomic DNA fragment containing the coding and upstream regulatory regions of the human insulin gene was stably transfected into MSL-G2 cells no measurable amounts of insulin or insulin mRNA were detected in vitro. However, successive transplantation of two transfected clones resulted in hypoglycemic tumors that efficiently coexpressed human and rat insulin as determined by human C-peptide-specific immunoreagents. These results demonstrate that cis-acting tissuespecific insulin gene enhancer elements are conserved between rat and human insulin genes. We propose that the in vivo differentiation of MSL-G2 cells and transfected subclones into insulin-producing cells reflects processes of natural beta-cell ontogeny leading to insulin gene expression.Each of the four distinctive cell types that occurs in the pancreatic islets is highly differentiated and produces its distinctive hormonal product(s) (1) arising in each case from a single precursor molecule-i.e., for beta cells, preproinsulin (2-4); for alpha cells, preproglucagon (5); for delta cells, preprosomatostatin (6); and for PP cells, prepropancreatic polypeptide (7).The developmental derivation of the islet cells from the embryonic ductal epithelium (8) presupposes the existence of a pluripotent islet progenitor or stem cell to give rise to the four known mature islet cell types. We have established (9) a series of transformed islet cell lines (MSL cells) derived from a liver metastasis of an x-ray-induced islet cell tumor (10). All MSL clones tested so far remain heterogeneous and secrete multiple hormones [i.e., insulin, glucagon, somatostatin, and cholecystokinin (CCK)], even upon repeated cellular cloning (9). Immunocytochemical analysis indicates that the proportion of cells expressing a particular hormone in any given clone is fairly stable over time. In contrast, however, the hormone profile (i.e., the proportion of cells producing insulin, glucagon, somatostatin, and CCK) varies widely among the various clones (9). These results strongly suggest that the MSL cells represent transformed pluripotent islet stem cells with differing, but related, differentiation potentials. Further support for this hypothesis is the independent isolation of two RINm clones (11) and one RINr clone (12) producing insulin, somatostatin, and glucagon, respectively, from the original x-ray-induced tumor.This study used clone MSL-G2, in which glucagon and CCK are produced at high levels in vitro but insulin is secreted at a virtually undetectable level (9). We present data showing that cells from this clone gradually shift toward the expression of the beta-cell phenotype when successively transplanted in vivo, resulting in insulin-producing tumors that cause severe hypoglycemia....
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