A collaborative and evolving response to the needs of frontline workers, patients and families during the COVID-19 pandemic at Tygerberg Hospital, Western Cape Province, South Africa.

The global devastation caused by the COVID-19 pandemic and its mental health impact is undeniable. The physical and psychological consequences are wide-ranging - affecting patients fighting the disease, frontline workers in the trenches with them, healthcare staff deployed in high-care settings, and families disconnected from their loved ones in their darkest hours. Within 6 weeks of the COVID-19 outbreak in South Africa, the Department of Psychiatry at Stellenbosch University established the TBH/SU COVID Resiliency Clinic to provide psychological support to frontline workers at Tygerberg Hospital. Identified barriers in healthcare workers accessing mental healthcare resulted in moving towards an on-site visibility to try to remove some of these barriers. This greater on-site presence enabled networking and building of relationships with frontline staff that over time highlighted other frontline needs, such as providing psychosocial and spiritual support to patients and their families. We share challenges, lessons learned and recommendations from two initiatives: the TBH/SU COVID-19 Resiliency Clinic, and an embedded COVID Care Team (CCT). We describe the establishment, roll-out and progress of the Clinic and the subsequent CCT.

Community engagement for paediatric MDR-TB clinical trials: principles to support ethical trial implementation.

The paediatric tuberculosis (TB) prevention and treatment landscape is moving into a new and exciting era, with knowledge from clinical trials offering real benefit to children. Community engagement is key to optimising the success of these trials. However, the clinical profile, epidemiology and social perceptions for paediatric multidrug-resistant TB (MDR-TB) complicate the operationalisation of this community engagement. We reflect on a diversity of recent experiences attempting to implement this type of research and the community engagement around it. We describe four recommendations and argue that these should guide the implementation of the community engagement agenda in the new landscape of paediatric MDR-TB clinical trials. Specifically, we argue for 1) dynamic, long-term continuity in community engagement platforms; 2) tiers of TB and research literacy; 3) multiple separate and joint platforms for holding 'stakes'; and 4) addressing the social/structural implications of family participation. We conclude that community-level stakeholders, such as health workers, parents and children, are willing to collaborate in paediatric MDR-TB clinical trials. Using these recommendations, there is considerable opportunity for effective community engagement in this new era of paediatric MDR-TB research.

Intimate partner violence in early adolescence:the role of gender; socioeconomic factors and the school

BACKGROUND:Intimate partner violence (IPV) among adolescents is common worldwide; but our understanding of perpetration; gender differences and the role of social-ecological factors remains limited.OBJECTIVES:To explore the prevalence of physical and sexual IPV perpetration and victimisation by gender; and associated risk and protective factors.METHODS:Young adolescents (N=2 839) from 41 randomly selected public high schools in the Western Cape region of South Africa (SA); participating in the PREPARE study; completed a self-administered questionnaire. RESULTS:The participants' mean age was 13.65 years (standard deviation 1.01); with 19.1% (541/2 839) reporting being victims/survivors of IPV and 13.0% (370/2 839) reporting perpetrating IPV. Girls were less likely to report being a victim/survivor of physical IPV (odds ratio (OR) 0.72; 95% confidence interval (CI) 0.57 - 0.92) and less likely to be a perpetrator of sexual IPV than boys (OR 0.33; 95% CI 0.21 - 0.52). Factors associated with perpetration of physical and sexual IPV were similar and included being a victim/survivor (physical IPV: OR 12.42; 95% CI 8.89 - 17.36; sexual IPV: OR 20.76; 95% CI 11.67 - 36.93); being older (physical IPV: OR 1.26; 95% CI 1.08 - 1.47; sexual IPV: OR 1.36; 95% CI 1.14 - 1.62 ); having lower scores on school connectedness (physical IPV: OR 0.59; 95% CI 0.46 - 0.75; sexual IPV: OR 0.56; 95% CI 0.42 - 0.76) and scoring lower on feelings of school safety (physical IPV: OR 0.66; 95% CI 0.57 - 0.77; sexual IPV: OR 0.50; 95% CI 0.40 - 0.62).CONCLUSIONS:Physical and sexual IPV was commonly reported among young adolescents in SA. Further qualitative exploration of the role of reciprocal violence by gender is needed; and the role of 'school climate'-related factors should be taken into account when developing preventive interventions

A randomized double blind, placebo controlled phase 2 trial of BIIL 284 BS (an LTB4 receptor antagonist) for the treatment of lung disease in children and adults with cystic fibrosis.

BACKGROUND: Airway inflammation, mediated in part by LTB4, contributes to lung destruction in patients with cystic fibrosis (CF). LTB(4)-receptor inhibition may reduce airway inflammation. We report the results of a randomized, double-blind, placebo-controlled study of the efficacy and safety of the leukotriene B(4) (LTB(4))-receptor antagonist BIIL 284 BS in CF patients. METHODS: CF patients aged ≥6 years with mild to moderate lung disease were randomized to oral BIIL 284 BS or placebo once daily for 24 weeks. Co-primary endpoints were change in FEV(1) and incidence of pulmonary exacerbation. RESULTS: After 420 (155 children, 265 adults) of the planned 600 patients were randomized, the trial was terminated after a planned interim analysis revealed a significant increase in pulmonary related serious adverse events (SAEs) in adults receiving BIIL 284 BS. Final analysis revealed SAEs in 36.1% of adults receiving BIIL 284 BS vs. 21.2% receiving placebo (p = 0.007), and in 29.6% of children receiving BIIL 284 BS vs. 22.9% receiving placebo (p = 0.348). In adults, the incidence of protocol-defined pulmonary exacerbation was greater in those receiving BIIL 284 BS than in those receiving placebo (33.1% vs. 18.2% respectively; p = 0.005). In children, the incidence of protocol-defined pulmonary exacerbation was 19.8% in the BIIL 284 BS arm, and 25.7% in the placebo arm (p = 0.38). CONCLUSIONS: While the cause of increased SAEs and exacerbations due to BIIL 284 BS is unknown, the outcome of this trial provides a cautionary tale for the administration of potent anti-inflammatory compounds to individuals with chronic infections, as the potential to significantly suppress the inflammatory response may increase the risk of infection-related adverse events.

Herpes simplex virus type 2 infection as a biomarker for sexual debut among young people in sub-Saharan Africa: a literature review.

Biological markers are needed in order to provide objective measures to validate self-reported sexual behaviour and interpret prevention trial data. In this review, we evaluated herpes simplex type 2 virus (HSV-2), one of the most prevalent sexually transmitted infections in sub-Saharan Africa as a biological marker of sexual debut. Based on our findings, we do not recommend using HSV-2 as a biomarker for sexual debut due to its low transmission probabilities and the fact that HSV-2 prevalence is not 100% among potential sexual partners. We recommend that the validation of alternative biological measures should be prioritized, and included in future studies and trials of interventions to reduce sexual health risk.

Effect of ipratropium bromide treatment on oxygen saturation and sleep quality in COPD.

STUDY OBJECTIVES: Patients with COPD are at risk of experiencing a deterioration in arterial oxygen saturation (SaO2) during sleep, which is generally most pronounced during rapid eye movement (REM) sleep. Increased cholinergic tone has been suggested as a contributing factor to this decrease in SaO2. Therefore, we investigated whether 4-week treatment with ipratropium bromide inhalation solution 0.02% (qid) could improve sleep characteristics in COPD. DESIGN: Randomized, placebo-controlled, double-blind, two-arm parallel study of 4 weeks of treatment with ipratropium bromide solution or placebo. SETTING: Multicenter investigation. PATIENTS: Thirty-six patients with moderate-to-severe COPD (FEV1 < 65% of predicted). MEASUREMENTS AND RESULTS: Evaluation included polysomnographic, pulmonary function, and subjective quality of sleep (visual analog scale [VAS]) assessments. It was found that 4 week of treatment with ipratropium bromide solution in patients with COPD led to the following: (1) a significant (p = 0.05) improvement in mean nocturnal SaO2 with the more severe the nocturnal desaturation, the greater the improvement in SaO2; (2) significant (p = 0.03) improvement in perceived sleep quality (VAS: 5.5 +/- 0.5 after placebo; 7.2 +/- 0.5 after ipratropium); (3) a significant (p = 0.05) increase in REM sleep time (48.6 +/- 6.3 min after placebo; 66.5 +/- 6.4 min after ipratropium) with no effect on other sleep stages or total sleep time; and (4) a significant (p = 0.01) increase in pre-sleep FVC and flow rate at 50% of the vital capacity. CONCLUSIONS: These findings demonstrate that ipratropium bromide therapy can improve sleep SaO2 as well as sleep quality in patients with moderate-to-severe COPD.

A dose-response study of the efficacy and safety of ipratropium bromide nasal spray in the treatment of the common cold.

Rhinorrhea is an annoying symptom of the common cold for which effective therapy is not currently available. Ipratropium bromide (IB) is an anticholinergic drug that has been shown to decrease glandular secretion when applied topically to the nasal mucosa. The purpose of this study was to compare the efficacy and safety of three doses of IB nasal spray versus either vehicle or no treatment in relieving rhinorrhea in patients with naturally acquired colds. Rhinorrhea severity was measured objectively by determining nasal discharge weights and subjectively by means of visual analog scale scores. Compared with either vehicle or no treatment, IB nasal spray produced a significant decrease in the severity of rhinorrhea. A dose of 84 micrograms (two sprays of a 0.06% solution in buffered saline solution) in each nostril was more efficacious than a 42 microgram per nostril dose and only marginally less efficacious than a 168 micrograms per nostril dose. The 84 micrograms per nostril dose also was associated with fewer adverse events than was the higher dose. None of the adverse events related to intranasal IB therapy was of a serious nature. The use of IB nasal spray appears to be a rational and safe approach to relieving rhinorrhea associated with the common cold.

Fungal-strain-dependent alterations in the time course and mortality of chronic murine pulmonary blastomycosis.

Intratracheal injection of 10(4) conidia of Blastomyces dermatitidis strain M1-A into mice was shown in previous work to induce chronic pulmonary and disseminated infection with histopathologic features of chronic human blastomycosis. Furthermore, 10-fold variations in inoculum density produced marked changes in mean survival times (MSTs), i.e., 32 days at 10(6), 36 days at 10(5), 97 days at 10(4), and 172 days at 10(3). A second strain (M1-B) failed to induce death in this model. To assess fungal-strain-dependent virulence, we extended these previous studies to 11 additional human isolates. Groups of male BALB/cByJ mice (6 to 8 weeks old) were injected intratracheally with 10(4) conidia from each of the 13 strains; the mice were weighed weekly and monitored for mortality, and their lungs were examined histopathologically. Infection rate and mortality were 100% in all groups except for the M1-B inoculated mice. For strains M1-B and M1-A, MST and mortality curves were not significantly different from those observed in our previously reported experiments. Four different survival patterns were noted in infected mice. The shortest MSTs were produced by strains M2-E, M2-B, M2-K, M2-H, and M2-A (24, 26, 26, 27, and 31 days, respectively), and the longest MST was seen in animal groups inoculated with strains M2-J and M2-G (130 and 134 days, respectively). Strains M2-I, M2-F, and M2-D produced intermediate MSTs of 65, 79, and 80 days, respectively. The 107-day MST induced by M1-A did not differ from strain M2-C-induced MST but differed significantly from the MST produced by the other strains. Pulmonary histopathology was similar in all animals dying with blastomycosis. The wide spectrum in survival times was not related to differences in clinical status of the patient from whom the isolate had been obtained, to fungal inoculum viability, or to individual mouse weight at inoculation. Strain-dependent virulence factors present in these fungal isolates alter the disease course in inbred mice in a fashion similar to that induced by 10-fold inoculum variation of strain M1-A conidia. These 13 isolates of B. dermatitidis, 1 avirulent and 12 with differing levels of virulence, provide tools for future studies into the nature of fungal virulence determinants in chronic blastomycosis.

Ocular tissues contain inhibitors of lymphocyte mitogenesis.

A fraction of bovine vitreous extract is a potent inhibitor of mitogen induced lymphocyte proliferation in vitro. Proliferation of lymphocytes induced in culture by lipopolysaccharide was more sensitive to inhibition by this fraction than were cultures of lymphocytes stimulated by Concanavalin A. We were unable to demonstrate such activity in similarly prepared fractions of cornea and lens.

Job stress and health in working women.

A questionnaire assessing subjective level of job stress and physical health over the past two years was completed by 173 women in university (non-faculty) positions. Health was divided into two categories: menstrual dysfunction and other non-menstrual symptoms. Two samples, matched for age, were selected: women in high-paying positions (N = 72) and women in low-paying positions (N = 101). Respondents also answered a Recent Life Changes Questionnaire (RLCQ) and an eight-item life satisfaction list. The hypothesis of a positive relationship between job stress and menstrual dysfunction was rejected. The predicted relationship held for non-menstrual symptoms. Subjective stress, RLCQ score, and life satisfaction accounted for 21% of the variance in non-menstrual symptoms. Thus, while both RLCQ and subjective job stress were related to symptom reports, their contributions were independent of one another. The female reproductive system does not seem particularly vulnerable to the levels of stress experienced in professional, managerial, and clerical occupations.