Lymphocyte Subsets Show Different Response Patterns to In Vivo Bound Natalizumab—A Flow Cytometric Study on Patients with Multiple Sclerosis

Natalizumab is an effective monoclonal antibody therapy for the treatment of relapsing- remitting multiple sclerosis (RRMS) and interferes with immune cell migration into the central nervous system by blocking the α4 subunit of very-late activation antigen-4 (VLA-4). Although well tolerated and very effective, some patients still suffer from relapses in spite of natalizumab therapy or from unwanted side effects like progressive multifocal leukoencephalopathy (PML). In search of a routine-qualified biomarker on the effectiveness of natalizumab therapy we applied flow cytometry and analyzed natalizumab binding to α4 and α4 integrin surface levels on T-cells, B-cells, natural killer (NK) cells, and NKT cells from 26 RRMS patients under up to 72 weeks of therapy. Four-weekly infusions of natalizumab resulted in a significant and sustained increase of lymphocyte-bound natalizumab (p<0.001) which was paralleled by a significant decrease in detectability of the α4 integrin subunit on all lymphocyte subsets (p<0.001). We observed pronounced natalizumab accumulations on T and B cells at single measurements in all patients who reported clinical disease activity (n = 4). The natalizumab binding capacity of in vitro saturated lymphocytes collected during therapy was strongly diminished compared to treatment-naive cells indicating a therapy-induced reduction of α4. Summing up, this pilot study shows that flow cytometry is a useful method to monitor natalizumab binding to lymphocytes from RRMS patients under therapy. Investigating natalizumab binding provides an opportunity to evaluate the molecular level of effectiveness of natalizumab therapy in individual patients. In combination with natalizumab saturation experiments, it possibly even provides a means of studying the feasability of patient-tailored infusion intervals. A routine-qualified biomarker on the basis of individual natalizumab saturation on lymphocyte subsets might be an effective tool to improve treatment safety

How has the OSD affected our state hospitals?

The long-awaited occupation-specific dispensation (OSD) process for state-employed doctors has now been concluded. The final offer, signed and accepted in the bargaining chamber despite being rejected by 92% of doctors in a SAMA survey, has not received much attention or fanfare. At the conclusion of this process, which has been drawn out over several years, many points have emerged that are extremely worrying for the future of health care in this country

Risk factors for Coronavirus disease 2019 (Covid-19) death in a population cohort study from the Western Cape province, South Africa

Risk factors for coronavirus disease 2019 (COVID-19) death in sub-Saharan Africa and the effects of human immunodeficiency virus (HIV) and tuberculosis on COVID-19 outcomes are unknown. We conducted a population cohort study using linked data from adults attending public-sector health facilities in the Western Cape, South Africa. We used Cox proportional hazards models, adjusted for age, sex, location, and comorbidities, to examine the associations between HIV, tuberculosis, and COVID-19 death from 1 March to 9 June 2020 among (1) public-sector “active patients” (≥1 visit in the 3 years before March 2020); (2) laboratory-diagnosed COVID-19 cases; and (3) hospitalized COVID-19 cases. We calculated the standardized mortality ratio (SMR) for COVID-19, comparing adults living with and without HIV using modeled population estimates.Among 3 460 932 patients (16% living with HIV), 22 308 were diagnosed with COVID-19, of whom 625 died. COVID19 death was associated with male sex, increasing age, diabetes, hypertension, and chronic kidney disease. HIV was associated with COVID-19 mortality (adjusted hazard ratio [aHR], 2.14; 95% confidence interval [CI], 1.70–2.70), with similar risks across strata of viral loads and immunosuppression. Current and previous diagnoses of tuberculosis were associated with COVID-19 death (aHR, 2.70 [95% CI, 1.81–4.04] and 1.51 [95% CI, 1.18–1.93], respectively). The SMR for COVID-19 death associated with HIV was 2.39 (95% CI, 1.96–2.86); population attributable fraction 8.5% (95% CI, 6.1–11.1)

Evaluation of patient characteristics, management and outcomes for COVID-19 at district hospitals in the Western Cape, South Africa : descriptive observational study

CITATION: Mash, R. J. et al. 2021. Evaluation of patient characteristics, management and outcomes for COVID-19 at district hospitals in the Western Cape, South Africa : descriptive observational study. BMJ Open, 11:e047016, doi:10.1136/bmjopen-2020-047016.The original publication is available at https://bmjopen.bmj.comENGLISH ABSTRACT: Objectives To describe the characteristics, clinical management and outcomes of patients with COVID-19 at district hospitals. Design A descriptive observational cross-sectional study. Setting District hospitals (4 in metro and 4 in rural health services) in the Western Cape, South Africa. District hospitals were small (<150 beds) and led by family physicians. Participants All patients who presented to the hospitals’ emergency centre and who tested positive for COVID-19 between March and June 2020. Primary and secondary outcome measures Source of referral, presenting symptoms, demographics, comorbidities, clinical assessment and management, laboratory turnaround time, clinical outcomes, factors related to mortality, length of stay and location. Results 1376 patients (73.9% metro, 26.1% rural). Mean age 46.3 years (SD 16.3), 58.5% females. The majority were self-referred (71%) and had comorbidities (67%): hypertension (41%), type 2 diabetes (25%), HIV (14%) and overweight/obesity (19%). Assessment of COVID-19 was mild (49%), moderate (18%) and severe (24%). Test turnaround time (median 3.0 days (IQR 2.0–5.0 days)) was longer than length of stay (median 2.0 day (IQR 2.0–3.0)). The most common treatment was oxygen (41%) and only 0.8% were intubated and ventilated. Overall mortality was 11%. Most were discharged home (60%) and only 9% transferred to higher levels of care. Increasing age (OR 1.06 (95% CI 1.04 to 1.07)), male (OR 2.02 (95% CI 1.37 to 2.98)), overweight/obesity (OR 1.58 (95% CI 1.02 to 2.46)), type 2 diabetes (OR 1.84 (95% CI 1.24 to 2.73)), HIV (OR 3.41 (95% CI 2.06 to 5.65)), chronic kidney disease (OR 5.16 (95% CI 2.82 to 9.43)) were significantly linked with mortality (p<0.05). Pulmonary diseases (tuberculosis (TB), asthma, chronic obstructive pulmonary disease, post-TB structural lung disease) were not associated with increased mortality. Conclusion District hospitals supported primary care and shielded tertiary hospitals. Patients had high levels of comorbidities and similar clinical pictures to that reported elsewhere. Most patients were treated as people under investigation. Mortality was comparable to similar settings and risk factors identified.https://bmjopen.bmj.com/content/bmjopen/11/1/e047016.full.pdfPublisher's versio

Collaborative International Research in Clinical and Longitudinal Experience Study in NMOSD

Objective To develop a resource of systematically collected, longitudinal clinical data and biospecimens for assisting in the investigation into neuromyelitis optica spectrum disorder (NMOSD) epidemiology, pathogenesis, and treatment. Methods To illustrate its research-enabling purpose, epidemiologic patterns and disease phenotypes were assessed among enrolled subjects, including age at disease onset, annualized relapse rate (ARR), and time between the first and second attacks. Results As of December 2017, the Collaborative International Research in Clinical and Longitudinal Experience Study (CIRCLES) had enrolled more than 1,000 participants, of whom 77.5% of the NMOSD cases and 71.7% of the controls continue in active follow-up. Consanguineous relatives of patients with NMOSD represented 43.6% of the control cohort. Of the 599 active cases with complete data, 84% were female, and 76% were anti-AQP4 seropositive. The majority were white/Caucasian (52.6%), whereas blacks/African Americans accounted for 23.5%, Hispanics/Latinos 12.4%, and Asians accounted for 9.0%. The median age at disease onset was 38.4 years, with a median ARR of 0.5. Seropositive cases were older at disease onset, more likely to be black/African American or Hispanic/Latino, and more likely to be female. Conclusions Collectively, the CIRCLES experience to date demonstrates this study to be a useful and readily accessible resource to facilitate accelerating solutions for patients with NMOSD

Siponimod versus placebo in secondary progressive multiple sclerosis (EXPAND): a double-blind, randomised, phase 3 study

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