Grey's Hospital

Summary The endothelial glycocalyx is an important part of the vascular barrier. The glycocalyx is intimately linked to the homoeostatic functions of the endothelium. Damage to the glycocalyx precedes vascular pathology. In the first part of this paper, we have reviewed the structure, physiology and pathology of the endothelial glycocalyx, based on a literature search of the past five years. In the second part, we have systematically reviewed interventions to protect or repair the glycocalyx. Glycocalyx damage can be caused by hypervolaemia and hyperglycaemia and can be prevented by maintaining a physiological concentration of plasma protein, particularly albumin. Other interventions have been investigated in animal models: these require clinical research before their introduction into medical practice.

OBJECTIVES: To further assess, in a phase 3 study, treatment with duloxetine for women with stress urinary incontinence (SUI) in other geographical regions, including Argentina, Australia, Brazil, Finland, Poland, South Africa and Spain, as previous trials in North America and Europe provided evidence for the safety and efficacy of duloxetine as a pharmacological treatment for SUI in women. PATIENTS AND METHODS: The study included 458 women aged 27-79 years enrolled in a double-blind, placebo-controlled trial. The patients with predominantly SUI were identified using a validated clinical algorithm. They were randomly assigned to receive placebo (231) or duloxetine 40 mg twice daily (227) for 12 weeks. The primary outcome variables included the incontinence episode frequency (IEF) and the Incontinence Quality of Life (I-QOL) questionnaire. Van Elteren's test was used to analyse the percentage changes in IEF where the stratification variable was weekly baseline IEF (IEF < 14 and > or = 14). Analysis of covariance was used to analyse I-QOL scores. RESULTS: The mean baseline IEF was 18.4/week; 55% of patients had a baseline IEF of > or = 14. There was a significantly greater median decrease in IEF with duloxetine with placebo (54% vs 40%, P = 0.05), with comparable significant improvements in quality of life (I-QOL score increases of 10.3 vs 6.4, P = 0.007). The improvements with duloxetine were associated with significantly greater increases in voiding intervals than with placebo (20.4 vs 8.5 min, P < 0.001). The placebo response was 10.7% and 12.5% higher than those reported in two European and North American phase 3 trials. This may have been related to more patients being naïve for incontinence management in the current trial. Discontinuation rates for adverse events were 1.7% for placebo and 17.2% for duloxetine (P < 0.001), with nausea being the most common reason for discontinuation (3.1%); it was the most common adverse event with duloxetine, but was mild or moderate in most (81%), did not worsen in any patient and resolved within 7 days in 60% and within 1 month in 86% of continuing patients; 88% of women who experienced nausea while taking duloxetine completed the trial. CONCLUSIONS: These results show improvements in incontinence and quality of life with duloxetine 40 mg twice daily for 12 weeks that are in keeping with those reported in two other recently completed phase 3 trials in Europe and North America.

The goal of this paper is to provide updated diagnostic criteria for the epilepsy syndromes that have a variable age of onset, based on expert consensus of the International League Against Epilepsy Nosology and Definitions Taskforce (2017-2021). We use language consistent with current accepted epilepsy and seizure classifications and incorporate knowledge from advances in genetics, electroencephalography, and imaging. Our aim in delineating the epilepsy syndromes that present at a variable age is to aid diagnosis and to guide investigations for etiology and treatments for these patients.

ispd guidelines

BackgroundIn South Africa, COVID-19 control measures to prevent SARS-CoV-2 spread were initiated on 16 March 2020. Such measures may also impact the spread of other pathogens, including influenza virus and respiratory syncytial virus (RSV) with implications for future annual epidemics and expectations for the subsequent northern hemisphere winter.MethodsWe assessed the detection of influenza and RSV through facility-based syndromic surveillance of adults and children with mild or severe respiratory illness in South Africa from January to October 2020, and compared this with surveillance data from 2013 to 2019.ResultsFacility-based surveillance revealed a decline in influenza virus detection during the regular season compared with previous years. This was observed throughout the implementation of COVID-19 control measures. RSV detection decreased soon after the most stringent COVID-19 control measures commenced; however, an increase in RSV detection was observed after the typical season, following the re-opening of schools and the easing of measures.ConclusionCOVID-19 non-pharmaceutical interventions led to reduced circulation of influenza and RSV in South Africa. This has limited the country's ability to provide influenza virus strains for the selection of the annual influenza vaccine. Delayed increases in RSV case numbers may reflect the easing of COVID-19 control measures. An increase in influenza virus detection was not observed, suggesting that the measures may have impacted the two pathogens differently. The impact that lowered and/or delayed influenza and RSV circulation in 2020 will have on the intensity and severity of subsequent annual epidemics is unknown and warrants close monitoring.

BACKGROUND: Our objective was to estimate the effect of various childbirth care packages on neonatal mortality due to intrapartum-related events ("birth asphyxia") in term babies for use in the Lives Saved Tool (LiST). METHODS: We conducted a systematic literature review to identify studies or reviews of childbirth care packages as defined by United Nations norms (basic and comprehensive emergency obstetric care, skilled care at birth). We also reviewed Traditional Birth Attendant (TBA) training. Data were abstracted into standard tables and quality assessed by adapted GRADE criteria. For interventions with low quality evidence, but strong GRADE recommendation for implementation, an expert Delphi consensus process was conducted to estimate cause-specific mortality effects. RESULTS: We identified evidence for the effect on perinatal/neonatal mortality of emergency obstetric care packages: 9 studies (8 observational, 1 quasi-experimental), and for skilled childbirth care: 10 studies (8 observational, 2 quasi-experimental). Studies were of low quality, but the GRADE recommendation for implementation is strong. Our Delphi process included 21 experts representing all WHO regions and achieved consensus on the reduction of intrapartum-related neonatal deaths by comprehensive emergency obstetric care (85%), basic emergency obstetric care (40%), and skilled birth care (25%). For TBA training we identified 2 meta-analyses and 9 studies reporting mortality effects (3 cRCT, 1 quasi-experimental, 5 observational). There was substantial between-study heterogeneity and the overall quality of evidence was low. Because the GRADE recommendation for TBA training is conditional on the context and region, the effect was not estimated through a Delphi or included in the LiST tool. CONCLUSION: Evidence quality is rated low, partly because of challenges in undertaking RCTs for obstetric interventions, which are considered standard of care. Additional challenges for evidence interpretation include varying definitions of obstetric packages and inconsistent measurement of mortality outcomes. Thus, the LiST effect estimates for skilled birth and emergency obstetric care were based on expert opinion. Using LiST modelling, universal coverage of comprehensive obstetric care could avert 591,000 intrapartum-related neonatal deaths each year. Investment in childbirth care packages should be a priority and accompanied by implementation research and further evaluation of intervention impact and cost. FUNDING: This work was supported by the Bill and Melinda Gates Foundation through a grant to the US Fund for UNICEF, and to Saving Newborn Lives Save the Children, through Save the Children US.

BACKGROUND: In the latest (2011-2013) Saving Mothers report, the National Committee for Confidential Enquiries into Maternal Deaths in South Africa (SA) (NCCEMD) highlights the large number of maternal deaths associated with caesarean section (CS). The risk of a woman dying as a result of CS during the past triennium was almost three times that for vaginal delivery. Of all the mothers who died during or after a CS, 3.4% died during the procedure and 14.5% from haemorrhage afterwards. Including all cases of death from obstetric haemorrhage where a CS was done, there were 5.5 deaths from haemorrhage for every 10,000 CSs performed. OBJECTIVE: To scrutinise the contribution or effect of the surgical procedure on the ultimate cause of death by a cross-cutting analysis of the 2011-2013 national data. METHODS: Data from the 2011-2013 triennial review were entered into an Excel database and analysed on a national and provincial basis. RESULTS: There were 1,243 maternal deaths where a CS was the mode of delivery and 1 471 deaths after vaginal delivery. More mothers died as a result of CS in the provinces where there is a low overall CS rate. The following CS categories were identified as specific problems: bleeding during or after CS, pre-eclampsia and eclampsia, anaesthesia-related deaths, pregnancy-related sepsis and acute collapse and embolism. CONCLUSION: This is an area of concern, and a concentrated effort should be done to make CS in SA safer. Several recommendations are

BACKGROUND: Fluid therapy is one of the most ubiquitous medical therapeutic interventions. There is a debate over whether colloids or crystalloids are better for fluid resuscitation. Recent large trials and meta-analyses suggest no mortality benefit and possible harm with hydroxyethyl starch (HES) use. However, these trials were conducted in critically ill and septic patients and their applicability to perioperative patients has been challenged. OBJECTIVE: We aimed to evaluate the impact of HES use in scheduled and elective surgical patients. DESIGN: Systematic review and meta-analysis of randomised controlled trials (RCTs). ELIGIBILITY CRITERIA: Only RCTs comparing the use of the synthetic colloid HES with any crystalloid in adults undergoing noncardiac surgery (up to 24 h postop) were considered eligible. For each eligible trial, we extracted the outcomes of all-cause mortality within 90 days, length of hospital stay, major infectious complications, acute kidney injury (AKI) and renal replacement therapy (RRT). RESULTS: We identified 1555 citations, selected 90 for full-text evaluation, and identified 13 eligible RCTs. Trials were small (n = 20 to 202) with low event rates. There was a trend to increased mortality with HES within 90 days [13/373 vs. 3/368; risk ratio 2.97; 95% confidence interval (95% CI) 0.96 to 9.19; I = 0%], no difference in AKI and RRT (risk ratio 1.11; 95% CI 0.26 to 4.69; I = 34%), and no difference in major infectious complications (risk ratio 1.19; 95% CI 0.59 to 2.39; I = 0%). Patients resuscitated with HES had a shorter length of hospital stay (mean difference -1.52 days; 95% CI -2.87 to -0.18), although heterogeneity was high (I = 90%). CONCLUSION: This meta-analysis, based on small studies with low event rates, suggests that there are currently insufficient data to identify a difference in outcomes associated with crystalloids and HES in scheduled or elective noncardiac surgery.

Pin track-associated complications are almost universal findings with the use of external fixation. These complications are catastrophic if it leads to the failure of the bone-pin interface and could lead to pin loosening, fracture non-union and chronic osteomyelitis. Strategies proposed for the prevention and management of pin track complications are diverse and constantly changing. Prevention of external fixation pin track infection is a complex and ongoing task that requires attention to detail, meticulous surgical technique and constant vigilance.

Werner syndrome (WS) is a rare autosomal recessive disorder characterized by a constellation of adult onset phenotypes consistent with an acceleration of intrinsic biological aging. It is caused by pathogenic variants in the WRN gene, which encodes a multifunctional nuclear protein with exonuclease and helicase activities. WRN protein is thought to be involved in optimization of various aspects of DNA metabolism, including DNA repair, recombination, replication, and transcription. In this update, we summarize a total of 83 different WRN mutations, including eight previously unpublished mutations identified by the International Registry of Werner Syndrome (Seattle, WA) and the Japanese Werner Consortium (Chiba, Japan), as well as 75 mutations already reported in the literature. The Seattle International Registry recruits patients from all over the world to investigate genetic causes of a wide variety of progeroid syndromes in order to contribute to the knowledge of basic mechanisms of human aging. Given the unusually high prevalence of WS patients and heterozygous carriers in Japan, the major goal of the Japanese Consortium is to develop effective therapies and to establish management guidelines for WS patients in Japan and elsewhere. This review will also discuss potential translational approaches to this disorder, including those currently under investigation.

BACKGROUND: Printed educational materials (PEMs) are commonly used simple interventions that can be used alone or with other interventions to disseminate clinical evidence. They have been shown to have a small effect on health professional behaviour. However, we do not know whether they are effective in primary care. We investigated whether PEMs improve primary care physician (PCP) knowledge, behaviour, and patient outcomes. METHODS: We conducted a systematic review of PEMs developed for PCPs. Electronic databases were searched for randomized controlled trials, quasi randomized controlled trials, controlled before and after studies, and interrupted time series. We combined studies using meta-analyses when possible. Statistical heterogeneity was examined, and meta-analysis was performed using a random effects model when significant statistical heterogeneity was present and a fixed effects model otherwise. The template for intervention description and replication (TIDieR) checklist was used to assess the quality of intervention description. RESULTS: Our search identified 12,439 studies and 40 studies met our inclusion criteria. We combined outcomes from 26 studies in eight meta-analyses. No significant effect was found on clinically important patient outcomes, physician behaviour, or physician cognition when PEMs were compared to usual care. In the 14 studies that could not be included in the meta-analyses, 14 of 71 outcomes were significantly improved following receipt of PEMs compared to usual care. Most studies lacked details needed to replicate the intervention. CONCLUSIONS: PEMs were not effective at improving patient outcomes, knowledge, or behaviour of PCPs. Further trials should explore ways to optimize the intervention and provide detailed information on the design of the materials. PROTOCOL REGISTRATION: PROSPERO, CRD42013004356.

The Southern African Journal of HIV Medicine is focused on HIV/AIDS treatment, prevention and related topics relevant to clinical and public health practice. The purpose of the journal is to disseminate original research results and support high-level learning related to HIV Medicine. It publishes original research articles, editorials, case reports/case series, reviews of state-of-the-art clinical practice and correspondence.

OBJECTIVE: We compared the epidemiology of laboratory-confirmed paediatric cryptococcal disease with adult-onset disease in the South African population. METHODS: The study was an active, prospective, population-based, laboratory-based surveillance in South Africa. We compared cases of paediatric cryptococcosis (<15 years) with cases of adult-onset cryptococcosis that were reported to the surveillance programme between 1 January 2005 and 31 December 2007. The case definition was based on a positive India ink test, cryptococcal antigen test or cryptococcal culture. Clinical case data were obtained at enhanced surveillance sites. RESULTS: Of 16,192 incident episodes of cryptococcosis in South Africa, 361 (2%) episodes occurred among children. In 2007, incidence was one and 19 cases per 100,000 persons in the general paediatric and adult populations and was 47 and 120 cases per 100,000 persons for HIV-infected children and adults, respectively. Among children, a bimodal peak in incidence was evident in the less than 1-year age group and in the 5 age group. Most children (64%) and adults (63%) were severely immunocompromised (CD4 T-lymphocyte cell count < 50 cells/μl) at the time of diagnosis. On multivariable analysis, children were significantly more likely than adults to be male, diagnosed on blood culture, infected with Cryptococcus gattii, treated with amphotericin B and admitted for a longer stay in hospital. CONCLUSION: This series of 361 cases of paediatric cryptococcosis is by far the largest described to date. The diagnosis of cryptococcosis should be considered in the paediatric HIV-infected population, especially among those who are severely immunocompromised.

BACKGROUND: Aseptic stem loosening following reverse shoulder arthroplasty (RSA) is an uncommon complication. The timing and the factors contributing to aseptic stem loosening remain poorly understood. METHODS: We performed a systematic review that identified 75 articles; 65 of the included articles were case series (Level-IV evidence), 8 were cohort studies (7 Level III, 1 Level II), and 2 were prospective randomized controlled trials (Level I). A meta-analysis of 1,660 cemented and 805 uncemented RSA stems was performed. We compared the rates of aseptic stem loosening, humeral radiolucent lines, and revision for stem loosening (1) between cemented and uncemented stems in cohorts with short and long mean follow-up periods (<5 and ≥5 years) as well as in all cohorts combined, and (2) among different etiological subgroups. RESULTS: Aseptic stem loosening occurred more commonly in the cohort with long compared with short follow-up time (2% versus 0.8%, p = 0.01). When comparing cemented with uncemented stems, there was no significant difference in the rates of aseptic stem loosening or revision for stem loosening in either the short or long-term follow-up groups. Humeral radiolucent lines were more common with cemented compared with uncemented stems (15.9% versus 9.5%, p = 0.002). Analyzed by etiology, the highest rate of aseptic stem loosening occurred in the tumor subgroup (10.8%), followed by RSA as a revision procedure after a failed arthroplasty (3.7%). No stems in the acute fracture or fracture sequelae subgroups developed aseptic stem loosening. CONCLUSIONS: Aseptic stem loosening occurred more commonly in cohorts with longer follow-up. There were no differences in the rates of aseptic stem loosening or revision for stem loosening between cemented and uncemented stems. Patients treated with RSA following excision of proximal humeral tumors and RSA as a revision procedure after a failed arthroplasty were at greater risk of aseptic stem loosening. LEVEL OF EVIDENCE: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence.

BACKGROUND: Economic burden estimates are essential to guide policy-making for influenza vaccination, especially in resource-limited settings. METHODS: We estimated the cost, absenteeism, and years of life lost (YLL) of medically and non-medically attended influenza-associated mild and severe respiratory, circulatory and non-respiratory/non-circulatory illness in South Africa during 2013-2015 using a modified version of the World Health Organization (WHO) worksheet based tool for estimating the economic burden of seasonal influenza. Additionally, we restricted the analysis to influenza-associated severe acute respiratory illness (SARI) and influenza-like illness (ILI; subsets of all-respiratory illnesses) as suggested in the WHO manual. RESULTS: The estimated mean annual cost of influenza-associated illness was $270.5 million, of which $111.3 million (41%) were government-incurred costs, 40.7 million (15%) were out-of-pocket expenses, and $118.4 million (44%) were indirect costs. The cost of influenza-associated medically attended mild illness ($107.9 million) was 2.3 times higher than that of severe illness ($47.1 million). Influenza-associated respiratory illness costs ($251.4 million) accounted for 93% of the total cost. Estimated absenteeism and YLL were 13.2 million days and 304 867 years, respectively. Among patients with influenza-associated WHO-defined ILI or SARI, the costs ($95.3 million), absenteeism (4.5 million days), and YLL (65 697) were 35%, 34%, and 21% of the total economic and health burden of influenza. CONCLUSION: The economic burden of influenza-associated illness was substantial from both a government and a societal perspective. Models that limit estimates to those obtained from patients with WHO-defined ILI or SARI substantially underestimated the total economic and health burden of influenza-associated illness.

INTRODUCTION: We aimed to obtain an in-depth understanding on recent antimicrobial resistance trends and molecular epidemiology trends of S. aureus bacteraemia (SAB). METHODS: Thirteen academic centres in South Africa were included from June 2010 until July 2012. S. aureus susceptibility testing was performed on the MicroScan Walkaway. Real-time PCR using the LightCycler 480 II was done for mecA and nuc. SCCmec and spa-typing were finalized with conventional PCR. We selected one isolate per common spa type per province for multilocus sequence typing (MLST). RESULTS: S. aureus from 2709 patients were included, and 1231 (46%) were resistant to methicillin, with a significant decline over the three-year period (p-value = 0.003). Geographical distribution of MRSA was significantly higher in Gauteng compared to the other provinces (P<0.001). Children <5 years were significantly associated with MRSA with higher rates compared to all other age groups (P = 0.01). The most prevalent SCCmec type was SCCmec type III (531 [41%]) followed by type IV (402 [31%]). Spa-typing discovered 47 different spa-types. The five (87%) most common spa-types were t037, t1257, t045, t064 and t012. Based on MLST, the commonest was ST612 clonal complex (CC8) (n = 7) followed by ST5 (CC5) (n = 4), ST36 (CC30) (n = 4) and ST239 (CC8) (n = 3). CONCLUSIONS: MRSA rate is high in South Africa. Majority of the isolates were classified as SCCmec type III (41%) and type IV (31%), which are typically associated with hospital and community- acquired infections, respectively. Overall, this study reveals the presence of a variety of hospital-acquired MRSA clones in South Africa dominance of few clones, spa 037 and 1257. Monitoring trends in resistance and molecular typing is recommended to detect changing epidemiological trends in AMR patterns of SAB.

INTRODUCTION: Pain in paediatric inpatients is common, underrecognised, and undertreated in resource-rich countries. Little is known about the status of paediatric pain prevention and treatment in low- and middle-income countries. OBJECTIVES: This audit aimed to describe the prevalence and severity of pain in paediatric patients at a tertiary hospital in South Africa. METHOD: A single-day prospective observational cross-sectional survey and medical chart review of paediatric inpatients at Grey's Hospital, Pietermaritzburg, South Africa. RESULTS: Sixty-three children were included, and mean patient age was 9.7 years (SD 6.17). Most patients (87%) had pain during admission, with 29% reporting preexisting (possibly chronic) pain. At the time of the study, 25% had pain (median pain score 6/10). The worst pain reported was from needle procedures, including blood draws, injections, and venous cannulation (34%), followed by surgery (22%), acute illness/infection (18%), and other procedures (14%). Pharmacological treatments included WHO step 1 (paracetamol and ibuprofen) and step 2 (tramadol, tilidine, and morphine) analgesics. The most effective integrative interventions were distraction, swaddling, and caregiver participation. Although a pain narrative was present in the majority of charts, only 16% had documented pain intensity scores. CONCLUSION: The prevalence of pain in hospitalised children in a large South African Hospital was high and pain assessment inadequately documented. There is an urgent need for pain education and development of guidelines and protocols, to achieve better pain outcomes for children. This audit will be repeated as part of a quality-improvement initiative.

Wide resection of infected bone improves the odds of achieving remission of infection in patients with chronic osteomyelitis. Aggressive debridement is followed by the creation of large bone defects. The use of antibiotic-impregnated PMMA spacers, as a customized dead space management tool, has grown in popularity. In addition to certain biological advantages, the spacer offers a therapeutic benefit by serving as a vehicle for delivery of local adjuvant antibiotics. In this study, we investigate the efficacy of physician-directed antibiotic-impregnated PMMA spacers in achieving remission of chronic tibial osteomyelitis. This retrospective case series involves eight patients with chronic osteomyelitis of the tibial diaphysis managed with bone transport through an induced membrane using circular external fixation. All patients were treated according to a standardized treatment protocol. A review of the anatomical nature of the disease, the physiological status of the host and the outcome of treatment in terms of remission of infection, time to union and the complications that occurred was carried out. Seven patients, with a mean bone defect of 7 cm (range 5-8 cm), were included in the study. At a mean follow-up of 28 months (range 18-45 months), clinical eradication of osteomyelitis was achieved in all patients without the need for further reoperation. The mean total external fixation time was 77 weeks (range 52-104 weeks), which equated to a mean external fixation index of 81 days/cm (range 45-107). Failure of the skeletal reconstruction occurred in one patient who was not prepared to continue with further reconstructive surgery and requested amputation. Four major and four minor complications occurred. The temporary insertion of antibiotic-impregnated PMMA appears to be a useful dead space management technique in the treatment of post-infective tibial bone defects. Although the technique does not appear to offer an advantage in terms of the external fixation index, it may serve as a useful adjunct in order to achieve resolution of infection.

This collective review of relevant research literature was to better understand the influence of cultural experience upon chronic pain perception. Using a structured review guideline, literature search was guided by a search strategy, quality grading of studies, data extraction and thematic, tabulated analysis of data. Themes were identified in three levels (1) patient, (2) the patient-provider interaction and (3) healthcare system. Clinical practice implications of the study included improving clinician cultural awareness, improving clinician cultural competency, culturally relevant pain measures and developing culturally-equitable systems of care. Research implications were the need for appropriate research based in a research agenda that brings the learnings of existing research to bear upon local contexts to enhance patient care.

BACKGROUND: Tuberculosis (TB) is the most common opportunistic infection in HIV-infected adults in developing countries. Isoniazid (INH) is recommended for treatment of latent TB infection, however non-adherence is common. The purpose of this study was to apply in-house prepared isoniazid (INH) urine test strips in a clinical setting, and identify predictors of positive test results in an adherence questionnaire in HIV-infected adults taking INH for prevention of TB. METHODS: Cross-sectional study of adherence using a questionnaire and urine test strips for detection of INH metabolites at two hospitals in Pietermaritzburg, South Africa. Participants were aged at least 18 years, HIV positive, and receiving INH for prevention of tuberculosis disease. Univariate and multivariate analyses are used to identify factors relevant to adherence. RESULTS: 301 consecutive patients were recruited. 28% of participants had negative urine tests. 32 (37.2%, 95% CI25.4, 45.0) of the 86 patients who received INH from peripheral pharmacies said the pharmacy had run out of INH at some time, compared with central hospital pharmacies (p = 0.0001). In univariate analysis, a negative test was associated with self-reported missed INH doses (p = 0.043). Each 12-hour increment since last reported dose increased the likelihood of a negative test by 34% (p = 0.0007). Belief in INH safety was associated with a positive test (p = 0.021). In multivariate analysis, patients who believed INH is important for prevention of TB disease were more likely to be negative (p = 0.0086). CONCLUSION: Adequate drug availability at peripheral pharmacies remains an important intervention for TB prevention. Key questions may identify potentially non-adherent patients. In-house prepared urine tests strips are an effective and cheap method of objectively assessing INH adherence, and could be used an important tool in TB control programs.