Trend analysis of antibiotic resistance in KwaZulu-Natal : a retrospective study 2011- 2015.

Masters Degree. University of KwaZulu- Natal, Durban.Objective: Antimicrobial resistance is a global phenomenon which is limiting treatment options for common infections resulting in poor clinical outcomes, increased mortality and increased cost of healthcare. Antibiotic resistance trends in pathogen-drug combinations stipulated in the Global Antimicrobial Surveillance System (GLASS) of the World Health Organization were investigated for the period 2011-2015 in the province of KwaZulu Natal, South Africa. Methods: Antibiotic susceptibility data from blood, urine, faecal and urethral/cervical samples was retrospectively analyzed from six public hospitals. Pathogens included Escherichia coli, Streptococcus pneumoniae, Klebsiella pneumoniae, Salmonella spp., Acinetobacter baumannii, Staphylococcus aureus, Shigella spp. and N. gonorrhoea. Results were analyzed as MIC50, MIC90, percentage resistance, incidence of monitored infections in the population and proportion of nonsusceptible infections per pathogen. Results were also evaluated against South African treatment guidelines. Significant differences in resistance proportions by year were identified using the Pearson χ2 test. Comparison of MIC50 were analysed using the equality-of-medians test. Findings: Urine samples were most abundant (61.22%, n= 33 018) and E. coli (52%) was the most common pathogen. Most isolates were multi-drug resistant. Resistance to third and fourth generation cephalosporins and fluoroquinolones increased in K. pneumoniae, E. coli and Shigella spp. over the 5- year period. Notable changes in resistance were: K. pneumoniae from blood samples to carbapenems (1 – 26%, p50% for most pathogen-drug combinations. Conclusion: The results of this study show that antibiotic resistance in hospitals in KwaZulu-Natal generally increased from 2011 to 2015, although some pathogen-drug combinations showed a plateau or decline in resistance necessitating a review of the existing treatment guidelines. To our knowledge, this is the first South African report on ABR using GLASS metrics. There is a need for more extensive research in order to build an accurate, comparable picture of ABR in South Africa

The SCN8A encephalopathy mutation p.Ile1327Val displays elevated sensitivity to the anticonvulsant phenytoin

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/134291/1/epi13461_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/134291/2/epi13461.pd

Effect of a Lay Counselor Intervention on Prevention of Major Depression in Older Adults Living in Low- and Middle-Income Countries:A Randomized Clinical Trial

Importance: Preventing depression in older adults living in low- and middle-income countries is important because of the scarcity of treatment resources and the risk of disability, suicide, and dementia. Objective: To assess whether an intervention for depression prevention provided by lay counselors is effective in older adults from low- and middle-income countries. Design, Setting, and Participants: This parallel-group randomized clinical trial with masked outcome assessment was performed in 181 older adults (≥60 years) with subsyndromal depressive symptoms at rural and urban primary care clinics in Goa, India. The first participant entered the trial on March 31, 2015, and the last exited on June 2, 2017. Data analysis used the intention-to-treat approach. Interventions: Lay counselors provided problem-solving therapy, brief behavioral treatment for insomnia, education in self-care of common medical disorders such as diabetes, and assistance in accessing medical and social programs. Main Outcomes and Measures: The main outcome was incidence of major depressive episodes. The study also assessed symptom change during 12 months (12-item General Health Questionnaire [GHQ-12]; score range of 0 to 12, with higher scores indicating greater symptoms of depression and anxiety), functional status (World Health Organization Disability Assessment Schedule 2.0; score range of 12 to 60, with higher scores indicating greater disability), cognition (Hindi Mini-Mental State Examination; score range of 0 to 30, with higher scores indicating better cognitive functioning), blood pressure, and body mass index to provide further clinical context. Results: The study enrolled 181 participants (mean [SD] age, 69.6 [7.2] years; 114 [63.0%] female): 91 to the intervention arm (depression in later life [DIL] intervention) and 90 to care as usual (CAU). Incident episodes of major depression were lower in the DIL intervention than in the CAU group (4.40% vs 14.44%; log-rank P =.04; number needed to treat, 9.95; 95% CI, 5.12-182.43). The 12-month Kaplan-Meier estimates of percentage of depression-free participants were 95.1% (95% CI, 90.5%-99.9%) in the DIL group vs 87.4% (95% CI, 80.4%-95.1%) in the CAU group. The incidence of depressive symptoms (GHQ-12) was also less (12-month mean difference, -1.18; 95% CI, -2.03 to -0.31; group × time interaction P <.001). There were no changes in measures of disability or cognition. The DIL intervention was associated with a significantly greater lowering of systolic blood pressure (12-month mean difference, -6.98; 95% CI, -11.96 to -2.01; group × time interaction P <.001) and change in body mass index (12-month mean difference, 0.23; 95% CI, -0.97 to 1.43; P =.04). Conclusions and Relevance: The DIL intervention is effective for preventing episodes of major depression in older persons with subsyndromal symptoms. If replicated, the DIL intervention may be effective in older adults living in low- and middle-income countries

Antibiotic resistance trends of ESKAPE pathogens in Kwazulu-Natal, South Africa: A five-year retrospective analysis.

BACKGROUND: To combat antimicrobial resistance, the World Health Organization developed a global priority pathogen list of antibiotic-resistant bacteria for prioritisation of research and development of new, effective antibiotics. OBJECTIVE: This study describes a five-year resistance trend analysis of the ESKAPE pathogens: Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp., from Kwazulu-Natal, South Africa. METHODS: This retrospective study used National Health Laboratory Services data on 64 502 ESKAPE organisms isolated between 2011 and 2015. Susceptibility trends were ascertained from minimum inhibitory concentrations and interpreted using Clinical and Laboratory Standards Institute guidelines. RESULTS: S. aureus was most frequently isolated (n = 24, 495, 38%), followed by K. pneumoniae (n = 14, 282, 22%). Decreasing rates of methicillin-resistant S. aureus (28% to 18%, p 70%). CONCLUSION: This study describes the magnitude of antimicrobial resistance in KwaZulu-Natal and provides a South African perspective on antimicrobial resistance in the global priority pathogen list, signalling the need for initiation or enhancement of antimicrobial stewardship and infection control measures locally

Combined exome and whole-genome sequencing identifies mutations in ARMC4 as a cause of primary ciliary dyskinesia with defects in the outer dynein arm

Primary ciliary dyskinesia (PCD) is a rare, genetically heterogeneous ciliopathy disorder affecting cilia and sperm motility. A range of ultrastructural defects of the axoneme underlie the disease, which is characterised by chronic respiratory symptoms and obstructive lung disease, infertility and body axis laterality defects. We applied a next-generation sequencing approach to identify the gene responsible for this phenotype in two consanguineous families

Changes in gene expression in space and time orchestrate environmentally mediated shaping of root architecture

Shaping of root architecture is a quintessential developmental response that involves the concerted action of many different cell types, is highly dynamic and underpins root plasticity. To determine to what extent the environmental regulation of lateral root development is a product of cell type preferential activities, we tracked transcriptomic responses to two different treatments that both change root development in Arabidopsis thaliana, at an unprecedented level of temporal detail. We found that individual transcripts are expressed with a very high degree of temporal and spatial specificity, yet biological processes are commonly regulated, in a mechanism we term response nonredundancy. Using causative gene network inference to compare the genes regulated in different cell types and during responses to nitrogen and a biotic interaction we found that common transcriptional modules often regulate the same gene families, but control different individual members of these families, specific to response and cell type. This reinforces that the activity of a gene cannot be defined simply as molecular function; rather, it is a consequence of spatial location, expression timing and environmental responsiveness

Complete Genome Sequence of a thermotolerant sporogenic lactic acid bacterium, Bacillus coagulans strain 36D1

Bacillus coagulans is a ubiquitous soil bacterium that grows at 50-55 °C and pH 5.0 and ferments various sugars that constitute plant biomass to L (+)-lactic acid. The ability of this sporogenic lactic acid bacterium to grow at 50-55 °C and pH 5.0 makes this organism an attractive microbial biocatalyst for production of optically pure lactic acid at industrial scale not only from glucose derived from cellulose but also from xylose, a major constituent of hemicellulose. This bacterium is also considered as a potential probiotic. Complete genome sequence of a representative strain, B. coagulans strain 36D1, is presented and discussed

Biallelic inherited SCN8A variants, a rare cause of SCN8A‐related developmental and epileptic encephalopathy

ObjectiveMonoallelic de novo gain‐of‐function variants in the voltage‐gated sodium channel SCN8A are one of the recurrent causes of severe developmental and epileptic encephalopathy (DEE). In addition, a small number of de novo or inherited monoallelic loss‐of‐function variants have been found in patients with intellectual disability, autism spectrum disorder, or movement disorders. Inherited monoallelic variants causing either gain or loss‐of‐function are also associated with less severe conditions such as benign familial infantile seizures and isolated movement disorders. In all three categories, the affected individuals are heterozygous for a SCN8A variant in combination with a wild‐type allele. In the present study, we describe two unusual families with severely affected individuals who inherited biallelic variants of SCN8A.MethodsWe identified two families with biallelic SCN8A variants by diagnostic gene panel sequencing. Functional analysis of the variants was performed using voltage clamp recordings from transfected ND7/23 cells.ResultsWe identified three probands from two unrelated families with DEE due to biallelic SCN8A variants. Each parent of an affected individual carried a single heterozygous SCN8A variant and exhibited mild cognitive impairment without seizures. In both families, functional analysis demonstrated segregation of one allele with complete loss‐of‐function, and one allele with altered biophysical properties consistent with partial loss‐of‐function.SignificanceThese studies demonstrate that SCN8A DEE may, in rare cases, result from inheritance of two variants, both of which exhibit reduced channel activity. In these families, heterozygosity for the dominant variants results in less severe disease than biallelic inheritance of two variant alleles. The clinical consequences of variants with partial and complete loss of SCN8A function are variable and likely to be influenced by genetic background.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/153117/1/epi16371_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/153117/2/epi16371.pd

Global Prospective Safety Analysis of Rivaroxaban.

BACKGROUND: The efficacy of direct oral anticoagulants (DOACs) for stroke prevention in patients with atrial fibrillation (AF) has been established in clinical trials. However, well-conducted, prospective, real-world observational studies of the safety and effectiveness of DOACs are needed. OBJECTIVES: This study sought to assess the real-world safety profile of rivaroxaban through a pooled analysis of patients with AF enrolled in the XANTUS (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation) program worldwide. METHODS: A pre-planned pooled analysis of the XANTUS, XANAP (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation in Asia), and XANTUS-EL (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation in Latin America and EMEA Region) registries was performed. Patients with AF newly starting rivaroxaban for stroke prevention were followed for 1 year. Primary outcomes were treatment-emergent major bleeding, adverse events (AEs)/serious AEs, and all-cause death. Secondary outcomes included treatment-emergent thromboembolic events and nonmajor bleeding. Major outcomes were centrally adjudicated. RESULTS: Overall, 11,121 patients were included (mean age 70.5 ± 10.5 years; female 42.9%). Comorbidities included heart failure (21.2%), hypertension (76.2%), and diabetes (22.3%). Event rates were: events/100 patient-years: major bleeding 1.7 (95% confidence interval [CI]: 1.5 to 2.0; lowest: Latin America 0.7; highest: Western Europe, Canada, and Israel 2.3); all-cause death 1.9 (95% CI: 1.6 to 2.2; lowest: Eastern Europe 1.5; highest: Latin America, Middle East, and Africa 2.7); and stroke or systemic embolism 1.0 (95% CI: 0.8 to 1.2; lowest: Latin America 0; highest: East Asia 1.8). One-year treatment persistence was 77.4% (lowest: East Asia 66.4%; highest: Eastern Europe 84.4%). CONCLUSIONS: This large, prospective, real-world analysis in 11,121 patients from 47 countries showed low bleeding and stroke rates in rivaroxaban-treated patients with AF, with low treatment discontinuation in different regions of the world. Results were broadly consistent across regions. (Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation [XANTUS]; NCT01606995; Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation in Latin America and EMEA Region [XANTUS-EL]; NCT01800006; and Xarelto for Prevention of Stroke in Patients With Atrial Fibrillation in Asia [XANAP]; NCT01750788)

Intervention development for the indicated prevention of depression in later life: The “DIL” protocol in Goa, India

Because depression is a major source of the global burden of illness-related disability, developing effective strategies for reducing its incidence is an important public health priority, especially in low-income countries, where resources for treating depression are scarce. We describe in this report an intervention development project, funded by the US National Institute of Mental Health, to address “indicated” prevention of depression in older adults attending rural and urban primary care clinics in Goa, India. Specifically, participants in the “DIL” (“Depression in Later Life”) trial were older adults living with mild, subsyndromal symptoms of depression and anxiety and thus at substantial risk for transitioning to fully syndromal major depression and anxiety disorders. Building upon the MANAS treatment trial (“Promoting Mental Health”) led by Patel et al. in the same locale, we present here lessons learned in the development and implementation of a protocol utilizing lay health counsellors (LHCs) who deliver a multi-component depression prevention intervention organized conceptually around Problem Solving Therapy for Primary Care (PST), with additional components addressing brief behavioural treatment of sleep disturbances such as insomnia, meeting basic social casework needs, and education in self-management of prevalent comorbid chronic diseases, such as diabetes mellitus. To our knowledge, DIL is the first randomized clinical trial addressing the prevention of depressive disorders ever conducted in a low- or middle-income country