Ivermectin exposures reported to the Poisons Information Helpline in South Africa during the COVID-19 pandemic.

BACKGROUND: Ivermectin is an antiparasitic drug that has shown in vitro activity against COVID­19. Clinical studies supporting ivermectin for COVID­19 prevention and treatment are conflicting, with important limitations. Public support for ivermectin is significant, with extensive off-label use despite the conflicting views on its efficacy. Ivermectin tablets and injectable formulations are not registered in South Africa for human use by the South African Health Products Regulatory Authority. The National Department of Health does not currently recommend the use of ivermectin for COVID­19. OBJECTIVES: To describe cases of ivermectin exposure reported to the Poisons Information Helpline of the Western Cape (PIHWC) before and after publication of the drug's in vitro activity against SARS-CoV-2. METHODS: In a retrospective review, ivermectin-related calls reported to the PIHWC from 1 June 2015 to 30 June 2020 (period 1) were compared with calls received from 1 July 2020 to 31 July 2021 (period 2), dichotomised according to the first publication indicating ivermectin activity against SARS-CoV-2. RESULTS: Seventy-one cases were screened, and 65 were included for analysis; 19 cases were reported during period 1 and 46 during period 2. During period 2, 25 ivermectin cases (54.3%) were related to COVID­19 use. Of these, 24 cases (52.2%) involved veterinary preparations, 3 (6.5%) human preparations and 19 (41.3%) unknown preparations. Fourteen cases (73.7%) during period 1 and 30 (65.2%) during period 2 were reported to be symptomatic. The most common organ systems involved were the central nervous (n=26 cases; 40.0%), gastrointestinal (n=18; 27.7%), ocular (n=9; 13.8%) and dermatological (n=5; 7.7%) systems. CONCLUSION: Ivermectin-related exposure calls increased during study period 2, probably as a result of ivermectin being used as preventive and definitive therapy for COVID­19 in the absence of robust evidence on efficacy, dosing recommendations or appropriate formulations.

Bleeding and thrombosis outcomes in hospitalised COVID-19 patients on low-molecular-weight heparin and antiplatelet therapy.

BACKGROUND: An increased incidence of thromboembolic events in hospitalised COVID­19 patients has been demonstrated despite the use of low-molecular-weight heparin (LMWH). Antiplatelet therapy prior to admission and early in the disease course has been hypothesised to be protective against thrombosis. OBJECTIVES: To describe the bleeding and thrombosis outcomes in hospitalised patients with confirmed COVID­19 receiving LMWH, with and without concomitant antiplatelet therapy. Secondary objectives were to explore predictors of bleeding and thrombosis outcomes, and dosing practices of antiplatelet therapy and LMWH. METHODS: We conducted a descriptive, cross-sectional study of bleeding and thrombosis outcomes at Tygerberg Academic Hospital, Cape Town, South Africa, during the first COVID­19 wave, in 808 hospitalised patients with confirmed COVID­19 receiving LMWH with and without concomitant antiplatelet therapy. Multivariate logistic regression analysis was performed if predictors were deemed statistically and clinically significant. RESULTS: Patients receiving both LMWH and antiplatelet therapy had similar bleeding outcomes compared with patients only receiving LMWH (odds ratio (OR) 1.5; 95% confidence interval (CI) 0.6 - 4.0). Patients receiving both LMWH and antiplatelet therapy had increased odds of developing thrombosis compared with patients only receiving LMWH (OR 4.8; 95% CI 2.1 - 10.7). CONCLUSION: The bleeding risk in COVID­19 patients receiving both LMWH and antiplatelet therapy was not significantly increased. A potentially higher risk of thrombosis in patients receiving LMWH and antiplatelet therapy was observed. However, this could reflect confounding by indication. Randomised studies are required to further evaluate the use of antiplatelet therapy to treat hospitalised patients with COVID­19.

Development of active tuberculosis in patients treated with biological disease-modifying antirheumatic drugs.

BACKGROUND: Biological disease-modifying antirheumatic drugs (bDMARDs) have been shown to be highly effective in the treatment of rheumatic conditions, but may increase the risk of infections. Development of tuberculosis (TB) while on bDMARD therapy is of particular concern in high TB burden settings such as Western Cape Province, South Africa. OBJECTIVES: To describe the diagnosis, management and outcome of patients who developed active TB while receiving a bDMARD. RESULTS: Ten patients who screened negative for TB prior to initiation of a bDMARD subsequently developed active TB. TB was diagnosed between 10 months and 9 years from bDMARD initiation, suggesting new infection, and included 6 cases of extrapulmonary TB. All patients required multiple tests to confirm the diagnosis of TB, and all were successfully treated. CONCLUSIONS: TB can occur in patients on bDMARD therapy despite initial screening, and may have unusual, extrapulmonary manifestations that pose a diagnostic challenge.

[Emergency management in the heart catheter laboratory : When intensive care physicians meet cardiologists]. / Notfallmanagement im Herzkatheterlabor : Wenn Intensivmediziner und Kardiologen zusammentreffen.

The establishment of primary percutaneous interventions for the treatment of myocardial infarction, increasingly complex coronary and noncoronary interventions in severely ill patients, and the increasing rise in the number of catheter examinations in elderly and morbid patients due to demographics frequently necessitates involvement of intensive care physicians for primary care of unstable patients and management of complications within the cath lab. In the context of complication and risk management, therefore, all cardiac catheter labs should develop a checklist in collaboration with the respective emergency/intensive care team. Team-oriented interdisciplinary management through standardization of emergency scenarios remains the key to success, despite all progress.

[Baroreceptor activation therapy for therapy-resistant hypertension: indications and patient selection : Recommendations of the BAT consensus group 2017]. / Barorezeptorakivierungstherapie bei therapierefraktärer Hypertonie: Indikation und Patientenselektion : Empfehlungen der BAT-Konsensusgruppe 2017.

Baroreceptor activation therapy (BAT) has been available for several years for treatment of therapy-refractory hypertension (trHTN). This procedure is currently being carried out in a limited number of centers in Germany, also with the aim of offering a high level of expertise through sufficient experience; however, a growing number of patients who are treated with BAT experience problems that treating physicians are confronted with in routine medical practice. In order to address these problems, a consensus conference was held with experts in the field of trHTN in November 2016, which summarizes the current evidence and experience as well as the problem areas in handling BAT patients.

[Mild therapeutic hypothermia in cardiogenic shock : Retrospective analysis of 80 patients with preclinical cardiac arrest due to cardiac causes]. / Milde therapeutische Hypothermie im kardiogenen Schock : Retrospektive Analyse von 80 Patienten mit präklinischem Herz-Kreislauf-Stillstand kardialer Ursache.

BACKGROUND: The mortality in patients with cardiogenic shock after out-of-hospital cardiac arrest (OHCA) remains high despite advances in resuscitation and early revascularization strategies. The use of mild therapeutic hypothermia (MTH) for improvement of survival and neurological outcome in patients with cardiogenic shock is currently subject to renewed discussion. OBJECTIVE: The aim of this study was the detection of risk factors for mortality and morbidity in patients under MTH in cardiogenic shock following preclinical resuscitation for OHCA. METHODS: A total of 80 consecutive patients in cardiogenic shock after successful resuscitation (mean age 60 ± 3.2 years) treated with MTH were retrospectively analyzed. Patients were cooled to 33 °C for 24 h using an endovascular cooling device. Neurological outcome was assessed after 2 months based on the Glasgow-Pittsburgh cerebral performance category (CPC) and correlated with various blood parameter values. RESULTS: After 2 months 31 patients (39 %) showed a good neurological recovery with CPC scores of 1-2, 20 patients (25 %) had a poor neurological outcome with CPC scores of 3-4 and 29 (36 %) patients enrolled in the trial died (CPC 5). Patients with a poor outcome showed significantly higher mean serum levels for lactate, creatinine and urea. In addition, these patients showed a continuous increase of serum neuron-specific enolase (NSE) values in contrast to patients with a good outcome (∆ NSE from admission to day 1, CPC 1 and 2: - 10.6 ± 3 µg/l and CPC 3-5: 33 ± 12 µg/l, p = 0.02). CONCLUSION: Changes in the course of serum creatinine, urea and NSE levels within the first 72 h after OHCA could provide valuable additional information for the early assessment of the neurological prognosis in patients treated with MTH.

Severe disease presentation and poor outcomes among pediatric systemic lupus erythematosus patients in South Africa.

Background Systemic lupus erythematosus (SLE) is a life-threatening multisystem autoimmune disease that is more severe in patients of African ancestry and children, yet pediatric SLE on the African continent has been understudied. This study describes a cohort of pediatric SLE (PULSE) patients in South Africa. Methods Patients with a diagnosis of SLE (1997 American College of Rheumatology criteria) diagnosed prior to age 19 years in Cape Town, South Africa, were enrolled in this cross-sectional study from September 2013 to December 2014. Information on clinical and serological characteristics was extracted from medical records. Results were compared to a well-described North American pediatric SLE cohort. Results Seventy-two South African patients were enrolled in the study; mean age 11.5 years; 82% were girls. The racial distribution was 68% Coloured, 24% Black, 5% White and 3% Asian/Indian. Most patients presented with severe lupus nephritis documented by renal biopsy (61%). Of patients with lupus nephritis, 63% presented with International Society of Nephrology/Renal Pathology Society class III or IV. Patients in the PULSE cohort were more likely to be treated with cyclophosphamide, methotrexate and azathioprine. The PULSE cohort had high disease activity at diagnosis (mean Systemic Lupus Erythematosus Disease Activity Index-2K (SLEDAI-2K) 20.6). The SLEDAI-2K at enrolment in the PULSE cohort (5.0) did not differ from the North American pediatric SLE cohort (4.8). Sixty-three per cent of the PULSE cohort had end organ damage with Systemic Lupus International Collaborating Clinics Damage Index (SLICC-DI) score >0 (mean SLICC-DI 1.9), compared to 23% in a previously reported US cohort. Within the PULSE cohort, nine (13%) developed end-stage renal disease with six (8%) requiring transplant, strikingly higher than North American peers (transplant rate <1%). Conclusions The PULSE cohort had highly active multiorgan disease at diagnosis and significant disease damage at enrolment in the South African registry. South African patients have severe lupus nephritis and poor renal outcomes compared to North American peers. Our study revealed a severe disease phenotype in the PULSE cohort resulting in poor outcomes in this high-risk population.

Clinical features and outcome of lupus myocarditis in the Western Cape, South Africa.

BACKGROUND: African American ethnicity is independently associated with lupus myocarditis compared with other ethnic groups. In the mixed racial population of the Western Cape, South Africa, no data exists on the clinical features/outcome of lupus myocarditis. OBJECTIVES: The objective of this study was to give a comprehensive description of the clinical features and outcome of acute lupus myocarditis in a mixed racial population. METHODS: Clinical records (between 2008 and 2014) of adult systemic lupus erythematosus (SLE) patients at a tertiary referral centre were retrospectively screened for a clinical and echocardiographic diagnosis of lupus myocarditis. Clinical features, laboratory results, management and outcome were described. Echocardiographic images stored in a digital archive were reanalysed including global and regional left ventricular function. A poor outcome was defined as lupus myocarditis related mortality or final left ventricular ejection fraction (LVEF) <40%. RESULTS: Twenty-eight of 457 lupus patients (6.1%) met inclusion criteria: 92.9% were female and 89.3% were of mixed racial origin. Fifty-three per cent of patients presented within three months after being diagnosed with SLE. Seventy-five per cent had severely active disease (SLE disease activity index ≥ 12) and 67.9% of patients had concomitant lupus nephritis. Laboratory results included: lymphopenia (69%) and an increased aRNP (61.5%). Treatment included corticosteroids (96%) and cyclophosphamide (75%); 14% of patients required additional immunosuppression including rituximab. Diastolic dysfunction and regional wall motion abnormalities occurred in > 90% of patients. LVEF improved from 35% to 47% (p = 0.023) and wall motion score from 1.88 to 1.5 (p = 0.017) following treatment. Overall mortality was high (12/28): five patients (17.9%) died due to lupus myocarditis (bimodal pattern). Patients who died of lupus myocarditis had a longer duration of SLE (p = 0.045) and a lower absolute lymphocyte count (p = 0.041) at diagnosis. LVEF at diagnosis was lower in patients who died of lupus myocarditis (p = 0.099) and in those with a persistent LVEF < 40% (n = 5; p = 0.046). CONCLUSIONS: This is the largest reported series on lupus myocarditis. The mixed racial population had a similar prevalence, but higher mortality compared with other ethnic groups (internationally published literature). Patients typically presented with high SLE disease activity and the majority had concomitant lupus nephritis. Lymphopenia and low LVEF at presentation were of prognostic significance, associated with lupus myocarditis related mortality or a persistent LVEF < 40%.

[Baroreflex activation therapy. A novel interventional approach to treat heart failure with reduced ejection fraction]. / Baroreflexaktivierungstherapie. Ein neuer interventioneller Ansatz zur Behandlung der systolischen Herzinsuffizienz.

Sympathovagal imbalance plays an important role in the progression of heart failure with reduced ejection fraction. Baroreflex activation therapy (BAT), i. e. electrical stimulation of baroreceptors located at the carotid sinus, can reduce sympathetic and enhance parasympathetic tone. Large animal studies on BAT demonstrated improvements in cardiac function, arrhythmogenic risk and a survival benefit compared to untreated controls. The recently published Neo Randomized Heart Failure Study, the first multicenter, randomized and controlled trial of optimal medical and device therapy alone or plus BAT in patients with a left ventricular ejection fraction ≤ 35 %, demonstrated a reasonable safety profile of BAT in this severely ill patient population and no relevant interactions with other devices. The study found significant improvements in the New York Heart Association (NYHA) class of heart failure, quality of life as well as 6 min walking distance and data pointed to a reduction in hospitalization rates. Moreover, N-terminal pro-brain natriuretic peptide (NT-proBNP) levels were significantly reduced. This review gives an overview on BAT for the treatment of heart failure with reduced ejection fraction, from the rationale and animal experiments to the most recent clinical data and future perspectives.

Src kinase function controls progenitor cell pools during regeneration and tumor onset in the Drosophila intestine.

Src non-receptor kinases have been implicated in events late in tumor progression. Here, we study the role of Src kinases in the Drosophila intestinal stem cell (ISC) lineage, during tissue homeostasis and tumor onset. The adult Drosophila intestine contains only two progenitor cell types, division-capable ISCs and their daughters, postmitotic enteroblasts (EBs). We found that Drosophila Src42a and Src64b were required for optimal regenerative ISC division. Conversely, activation of Src42a, Src64b or another non-receptor kinase, Ack, promoted division of quiescent ISCs by coordinately stimulating G1/S and G2/M cell cycle phase progression. Prolonged Src kinase activation caused tissue overgrowth owing to cytokine receptor-independent Stat92E activation. This was not due to increased symmetric division of ISCs, but involved accumulation of weakly specified Notch(+) but division-capable EB-like cells. Src activation triggered expression of a mitogenic module consisting of String/Cdc25 and Cyclin E that was sufficient to elicit division not only of ISCs but also of EBs. A small pool of similarly division-capable transit-amplifying Notch(+) EBs was also identified in the wild type. Expansion of intermediate cell types that do not robustly manifest their transit-amplifying potential in the wild type may also contribute to regenerative growth and tumor development in other tissues in other organisms.

Candidemia in the intensive care unit: analysis of direct treatment costs and clinical outcome in patients treated with echinocandins or fluconazole.

Direct treatment costs caused by candidemia in German intensive care unit (ICU) patients are currently unknown. We analyzed treatment costs and the impact of antifungal drug choice. Comprehensive data of patients who had at least one episode of candidemia while staying in the ICU between 01/2005 and 12/2010 were documented in a database using the technology of the Cologne Cohort of Neutropenic Patients (CoCoNut). A detailed analysis of all disease-associated treatment costs was performed. Patients treated with echinocandins (i.e., anidulafungin, caspofungin, micafungin) or fluconazole were analyzed separately and compared. Forty-one and 64 patients received echinocandins and fluconazole, respectively. The mean Acute Physiology and Chronic Health Evaluation (APACHE) IV score was 114 (95 % confidence interval [CI]: 106-122) vs. 95 (95 % CI: 90-101, p = <0.001). Twenty-three (56 %) and 33 (52 %, p = 0.448) patients survived hospitalization, while 17 (41 %) and 22 (34 %, p = 0.574) survived one year after diagnosis. In the echinocandin and fluconazole groups, the mean costs per patient of ICU treatment were 20,338 (95 % CI: 12,893-27,883) vs. 11,932 (95 % CI: 8,016-15,849, p = 0.110), and the total direct treatment costs per patient were 37,995 (95 % CI: 26,614-49,376) vs. 22,305 (95 % CI: 16,817-27,793, p = 0.012), resulting in daily costs per patient of 1,158 (95 % CI: 1,036-1,280) vs. 927 (95 % CI: 828-1,026, p = 0.001). Our health economic analysis shows the high treatment costs of patients with candidemia in the ICU. Sicker patients had a prolonged hospitalization and were more likely to receive echinocandins, leading to higher treatment costs. Outcomes were comparable to those achieved in less sick patients with fluconazole.

[Public access defibrillation: successful cardiopulmonary resuscitation due to automatic external defibrillator at traffic accident]. / Public-Access-Defibrillation: erfolgreiche Reanimation durch Einsatz eines automatischen externen Defibrillators nach Verkehrsunfall.

HISTORY: A 65-year-old man collapsed after he stepped out of his car after a traffic accident. TREATMENT: Fortunately, two police officers on a routine patrol in the area were quickly on the scene and started cardiopulmonary resuscitation. A passerby noticed that the patient was in distress and that an automatic defibrillator was nearby. He attached the electrodes of the defibrillator to the chest of the patient in accordance with instructions on the defibrillator and terminated the ventricular fibrillation (200 joule, biphasic). COURSE: Emergency cardiac catheterization revealed a subtotal stenosis proximally in the right coronary artery, which was successfully treated with a stent. Based on the ideal basic life support, the immediate care by emergency mobile system and coronary angioplasty with successful revascularisation the patient could be released without any neurological deficit. CONCLUSION: This case illustrates that laypersons can use automatic external defibrillator in case of cardiac resuscitation sufficiently and quickly.

Superheroes in autoimmune warfare: biologic therapies in current South African practice.

Biologic drugs targeting immune cells or cytokines underlying systemic inflammation have dramatically improved outcomes in patients with rheumatological and autoimmune diseases. Nine biologic drugs are currently available in South Africa (SA)--all showing good efficacy and safety profiles. Their high cost and potential adverse events preclude them from being used as first-line agents. They are therefore indicated for severe disease refractory to standard therapies, and their use must be initiated by a specialist. The most important adverse effect of this class of drugs is infection and, in SA, tuberculosis is of particular concern. As new targets in the immune system are identified, new biologics will be developed. The current challenges are to optimise standard care for all patients with autoimmune diseases, and to offer the appropriate biologic to patients with refractory disease.