Myofascial trigger point (MTrP) size and elasticity properties can be used to differentiate characteristics of MTrPs in lower back skeletal muscle.

Myofascial trigger points (MTrPs) are localized contraction knots that develop after muscle overuse or an acute trauma. Significant work has been done to understand, diagnose, and treat MTrPs in order to improve patients suffering from their effects. However, effective non-invasive diagnostic tools are still a missing gap in both understanding and treating MTrPs. Effective treatments for patients suffering from MTrP mediated pain require a means to measure MTrP properties quantitatively and diagnostically both prior to and during intervention. Further, quantitative measurements of MTrPs are often limited by the availability of equipment and training. Here we develop ultrasound (US) based diagnostic metrics that can be used to distinguish the biophysical properties of MTrPs, and show how those metrics can be used by clinicians during patient diagnosis and treatment. We highlight the advantages and limitations of previous US-based approaches that utilize elasticity theory. To overcome these previous limitations, we use a hierarchical approach to distinguish MTrP properties by patients' reported pain and clinician measured palpation. We show how US-based measurements can characterize MTrPs with this approach. We demonstrate that MTrPs tend to be smaller, stiffer, and deeper in the muscle tissue for patients with pain compared to patients without pain. We provide evidence that more than one MTrP within a single US-image field increases the stiffness of neighboring MTrPs. Finally, we highlight a combination of metrics (depth, thickness, and stiffness) that can be used by clinicians to evaluate individual MTrPs in combination with standard clinical assessments.

The state of kidney replacement therapy in Eastern Cape Province, South Africa: A call to action.

BACKGROUND: South Africa (SA) is one of the most financially unequal countries in the world. This situation is highlighted by disparate access to healthcare, particularly provision of kidney replacement therapy (KRT). Unlike the private sector, public sector access to KRT is highly rationed, and patient selection is based on suitability for transplantation and capacity. OBJECTIVES: To investigate the state of the KRT service in Eastern Cape Province, SA, by analysing access to and provision of KRT in the province for individuals with end-stage kidney disease, as well as disparities between the private and public healthcare systems. METHODS: This was a retrospective descriptive study to examine KRT provision and temporal trends in the Eastern Cape. Data were obtained from the South African Renal Registry and the National Transplant Waiting List. KRT provision was compared between the three main referral centres, in Gqeberha (formerly Port Elizabeth), East London and Mthatha, and between the private and public healthcare systems. RESULTS: There were 978 patients receiving KRT in the Eastern Cape, with an overall treatment rate of 146 per million population (pmp). The treatment rate for the private sector was 1 435 pmp, compared with 49 pmp in the public sector. Patients treated in the private sector were older at initiation of KRT (52 v. 34 years), and more likely to be male, to be HIV positive, and to receive haemodialysis as their KRT modality. Peritoneal dialysis was more commonly used in Gqeberha and East London as the first and subsequent KRT modality, compared with Mthatha. There were no patients from Mthatha on the transplant waiting list. There were no waitlisted HIV-positive patients in the public sector in East London, compared with 16% of the public sector patients in Gqeberha. The kidney transplant prevalence rate was 58 pmp in the private sector and 19 pmp in the public sector, with a combined prevalence of 22 pmp, constituting 14.9% of all patients on KRT. We estimated the shortfall of KRT provision in the public sector to be ~8 606 patients. CONCLUSION: Patients in the private sector were 29 times more likely to access KRT than their public sector counterparts, who were on average 18 years younger at initiation of KRT, probably reflecting selection bias in an overburdened public health system. Transplantation rates were low in both sectors, and lowest in Mthatha. A large public sector KRT provision gap exists in the Eastern Cape and needs to be addressed urgently.

Examining the barriers faced by female surgical trainees: a qualitative study.

INTRODUCTION: Today, women make up 56% of medical students, yet just 13% of surgical consultants - a number that has remained static since 2013. This qualitative study explored some of the barriers to female success in modern surgery. METHODS: Semistructured qualitative interviews were undertaken primarily with female surgical trainees to determine the barriers they face. Male trainees and training programme directors (TPDs) were also interviewed for triangulation. RESULTS: 20 interviews were performed (16 female trainees, 3 male trainees, and 1 TPD) between October 2019 and March 2020. Family pressures and becoming a mother were significant barriers for women training in surgery - a barrier that did not apply to male trainees who were fathers, often resulting in women choosing to train less than full time (LTFT). Unfortunately LTFT training presents further obstacles for female trainees. The set-up of the national training programme in surgery provides many non-gender-specific barriers, chiefly moving hospital every 6 months causing disrupted training and long commutes, disproportionately affecting females with child care responsibilities. Sexism and discrimination are still common, both from colleagues and patients. Many participants perceived inherent differences between genders in communication and methods for coping with stress. CONCLUSION: Greater gender equality in surgery may be achieved by changes in the structure and organisation of training to reduce the tension between the professional role and the predominantly female-led role of raising children. Better equality and diversity training and awareness at all levels in surgery may help to mitigate some of the conscious and unconscious bias that still exists.

One-year mortality after hospital admission as an indicator of palliative care need: A retrospective cohort study.

BACKGROUND: Globally there is increasing awareness of the need for end-of-life care and palliative care in hospitalised patients who are in their final year of life. Limited data are available on palliative care requirements in low- and middle-income countries, hindering the design and implementation of effective policies and health services for these patients. OBJECTIVES: To determine the proportion of patients who die within 1 year of their date of admission to public hospitals in South Africa (SA), as a proxy for palliative care need in SA. METHODS: This was a retrospective cohort study using record linkage of admission and mortality data. The setting was 46 acute-care public hospitals in Western Cape Province, SA. RESULTS: Of 10 761 patients (median (interquartile range (IQR)) age 44 (31 - 60) years) admitted to the 46 hospitals over a 2-week period in March 2012, 1 570 (14.6%) died within 1 year, the majority within the first 3 months. Mortality rose steeply with age. The median (IQR) age of death was 57.5 (45 - 70) years. A greater proportion of patients admitted to medical beds died within 1 year (21.3%) compared with those admitted to surgical beds (7.7%). CONCLUSIONS: Despite a median age <60 years at admission, a substantial percentage of patients admitted to public sector hospitals in SA are in the final year of their lives. This finding should be seen in the context of SA's high communicable and non-communicable disease burden and resource-limited public health system, and highlights the need for policy development, planning and implementation of end-of-life and palliative care strategies for hospitals and patients.

Low mortality of people living with diabetes mellitus diagnosed with COVID-19 and managed at a field hospital in Western Cape Province, South Africa.

BACKGROUND: The novel coronavirus disease 2019 (COVID-19) was declared an international pandemic by the World Health Organization in March 2020. Throughout the pandemic, the association between diabetes mellitus (DM) and more severe COVID-19 has been well described internationally, with limited data, however, on South Africa (SA). The role of field hospitals in the management of patients with COVID-19 in SA has not yet been described. OBJECTIVES: To describe the mortality and morbidity of people living with DM (PLWD) and comorbid COVID-19, as well as to shed light on the role of intermediate facilities in managing DM and COVID-19 during the pandemic. METHODS: This is a single-centre cross-sectional descriptive study that included all patients with confirmed COVID-19 and pre-existing or newly diagnosed DM (of any type) admitted to the Cape Town International Convention Centre (CTICC) Intermediate Care Bed Facility from June 2020 to August 2020. This study presents the profile of patients admitted to the CTICC, and reports on the clinical outcome of PLWD diagnosed with COVID-19, and additionally determines some associations between risk factors and death or escalation of care in this setting. RESULTS: There were 1 447 admissions at the CTICC, with a total of 674 (46.6%) patients who had confirmed DM, of whom 125 (19%) were newly diagnosed diabetics and 550 (81%) had pre-existing DM. Included in this group were 57 referrals from the telemedicine platform - a platform that identified high-risk diabetic patients with COVID-19 in the community, and linked them directly to hospital inpatient care. Of the 674 PLWD admitted, 593 were discharged alive, 45 were escalated to tertiary hospital requiring advanced care and 36 died. PLWD who died were older, had more comorbidities (specifically chronic obstructive pulmonary disease, congestive cardiac failure and chronic kidney disease) and were more likely to be on insulin. CONCLUSIONS: In a resource-limited environment, interdisciplinary and interfacility collaboration ensured that complicated patients with DM and COVID-19 were successfully managed in a field hospital setting. Telemedicine offered a unique opportunity to identify high-risk patients in the community and link them to in-hospital monitoring and care. Future studies should explore ways to optimise this collaboration, as well as to explore possibilities for early identification and management of high-risk patients.

Delirium in HIV-infected patients admitted to acute medical wards post universal access to antiretrovirals in South Africa.

BACKGROUND: Delirium is associated with increased mortality and length of hospital stay. Limited data are available from HIV-infected acute hospital admissions in developing countries. We conducted a prospective study of delirium among acute medical admissions in South Africa (SA), a developing country with universal antiretroviral therapy (ART) access and high burdens of tuberculosis (TB) and non-communicable disease. OBJECTIVES: To identify the prevalence of, risk factors for and outcomes of delirium in HIV-infected individuals in acute general medical admissions. METHODS: Three cohorts of adult acute medical admissions to Groote Schuur and Victoria Wynberg hospitals, Cape Town, SA, were evaluated for prevalent delirium within 24 hours of admission. Reference delirium testing was performed by either consultant physicians or neuropsychologists, using the Confusion Assessment Method. RESULTS: The study included 1 182 acute medical admissions, with 318 (26.9%) HIV-infected. The median (interquartile range) age and CD4 count were 35 (30 - 43) years and 132 (61 - 256) cells/µL, respectively, with 140/318 (44.0%) using ART on admission. The prevalence of delirium was 17.6% (95% confidence interval (CI) 13.7 - 22.1) among HIV-infected patients, and delirium was associated with increased inpatient mortality. In multivariable logistic regression analysis, factors associated with delirium were age ≥55 years (adjusted odds ratio (aOR) 6.95 (95% CI 2.03 - 23.67); p=0.002), and urea ≥15 mmol/L (aOR 4.83 (95% CI 1.7 - 13.44); p=0.003), while ART use reduced risk (p=0.014). A low CD4 count, an unsuppressed viral load and active TB were not predictors of delirium; nor were other previously reported risk factors such as non-opportunistic acute infections or polypharmacy. CONCLUSIONS: Delirium is common and is associated with increased mortality in HIV-infected acute medical admissions in endemic settings, despite increased ART use. Older HIV-infected patients with renal dysfunction are at increased risk for inpatient delirium, while those using ART on admission have a reduced risk.

In Vitro Clot Trapping Efficiency of the FDA Generic Inferior Vena Cava Filter in an Anatomical Model: An Experimental Fluid-Structure Interaction Benchmark.

PURPOSE: Robust experimental data for performing validation of fluid-structure interaction (FSI) simulations of the transport of deformable solid bodies in internal flow are currently lacking. This in vitro experimental study characterizes the clot trapping efficiency of a new generic conical-type inferior vena cava (IVC) filter in a rigid anatomical model of the IVC with carefully characterized test conditions, fluid rheological properties, and clot mechanical properties. METHODS: Various sizes of spherical and cylindrical clots made of synthetic materials (nylon and polyacrylamide gel) and bovine blood are serially injected into the anatomical IVC model under worst-case exercise flow conditions. Clot trapping efficiencies and their uncertainties are then quantified for each combination of clot shape, size, and material. RESULTS: Experiments reveal the clot trapping efficiency increases with increasing clot diameter and length, with trapping efficiencies ranging from as low as approximately 42% for small 3.2 mm diameter spherical clots up to 100% for larger clot sizes. Because of the asymmetry of the anatomical IVC model, the data also reveal the iliac vein of clot origin influences the clot trapping efficiency, with the trapping efficiency for clots injected into the left iliac vein up to a factor of 7.5 times greater than that for clots injected into the right iliac (trapping efficiencies of approximately 10% versus 75%, respectively). CONCLUSION: Overall, this data set provides a benchmark for validating simulations predicting IVC filter clot trapping efficiency and, more generally, low-Reynolds number FSI modeling.

Prevalence and outcome of delirium among acute general medical inpatients in Cape Town, South Africa.

BACKGROUND: Delirium is a common, serious, underdiagnosed condition in medical and surgical inpatients with acute conditions. It is associated with increased risk of mortality and morbidity. Data of geriatric cohorts are largely limited to developed countries. OBJECTIVES: To describe prevalence, risk factors and outcomes of delirium among general medical patients admitted to two hospitals in Cape Town, South Africa. METHODS: This was a prospective cohort study of patients with acute conditions admitted to a general medical inpatient service in secondary- and tertiary-level public hospitals in the Metro West area of Cape Town. Patients ≥18 years of age were recruited daily from all acute medical admissions. Patients were excluded if they were aphasic or their Glasgow coma scale was <8/15. Delirium was diagnosed using the validated confusion assessment method (CAM) tool and performed by trained neuropsychologists. Demographic data were collected by a clinical team and short- and long-term mortality data were obtained using linkage analysis of hospitalised patients and routinely collected provincial death certification records. RESULTS: The median age of inpatients was 51 (interquartile range 36 - 65) years, 29% were HIV-infected and the overall prevalence of delirium was 12.3%. Multivariate predictors of delirium included the presence of an indwelling urinary catheter (odds ratio (OR) 4.47; confidence interval (CI) 2.43 - 8.23), admission with a central nervous system disease (OR 4.34; CI 2.79 - 7.90), pre-existing cognitive impairment (OR 3.02; CI 1.22 - 7.43) and immobility (OR 1.88; CI 1.01 - 3.51). HIV infection was not associated with increased risk of delirium. Delirium was associated with an increased risk of inhospital (delirium v. no delirium: 29% v. 12%; p<0.01) and 12-month (30% v. 20%; p<0.01) mortality, as well as increased length of hospital stay (7 days v. 5 days; p<0.01). CONCLUSIONS: In this cohort of medical inpatients (relatively young and with a high HIV prevalence) 1 of 8 (12.3%) patients was delirious. Delirium was associated with adverse outcomes. Delirium risk factors in this young cohort were similar to those in geriatric cohorts in developed countries, and neither HIV nor opportunistic infections increased risk.

A 10-year analysis of organ donor referrals to a South African tertiary public sector hospital.

BACKGROUND: South Africa (SA) has one of the lowest deceased organ donor rates in the world (1.4 donors per million population), with thousands of patients awaiting solid-organ transplantation. In order to improve access to transplantation we have to clearly define the reasons for the low deceased donation rate, specific to the population we serve. OBJECTIVES: Review of actual donor statistics highlights our successes, yet is not able to contextualise the factors responsible for the unsuccessful conversion of referred organ donors to actual organ donors. In an attempt to identify key factors preventing referred donors from becoming actual donors, we analysed the donor referral patterns at our institution over a 10-year period. METHODS: This was a retrospective descriptive study of consecutive deceased donor referrals at Groote Schuur Hospital, Cape Town, SA (from January 2007 to December 2016), utilising a regional donor referral registry. Qualitative and quantitative data were collected and presented as descriptive statistics and temporal trends. RESULTS: Over the 10-year study period, 861 possible organ donors were referred, with a steady increase in the number of referrals over time. Of the referrals, 514 (59.7%) were eligible for donation of at least one solid organ. Of the 508 families that were approached for consent to donation, 342 declined consent for a variety of reasons, resulting in a consent rate of 32.7%. Ultimately, at least one solid organ was obtained from 159 of the 166 consented donors. Despite the increasing number of possible and eligible donors, a statistically significant decline in consent rate was observed over time (ptrend=0.023). Furthermore, increasing trends in medical (as opposed to trauma) (ptrend<0.001) and extended criteria (as opposed to standard criteria) donor referrals (ptrend<0.001) were observed over the 10-year study period. CONCLUSIONS: Donor referral patterns have changed over time, with a notable increase in medical and extended criteria donors. Despite the increase in possible and eligible donors, the consent rate has declined. Further qualitative and quantitative research studies are required to understand and address this trend.

CYP3A5 polymorphisms and their effects on tacrolimus exposure in an ethnically diverse South African renal transplant population.

BACKGROUND: Tacrolimus forms the cornerstone for immunosuppression in solid-organ transplantation. It has a narrow therapeutic window with wide inter- and intra-patient variability (IPV). Cytochrome P-450 3A5 (CYP3A5) is the main enzyme involved in tacrolimus metabolism, and rs776746A>G is the most frequently studied polymorphism in the CYP3A5 gene. The rs776746A>G (i.e. CYP3A5*3) single-nucleotide polymorphism in CYP3A5 alters tacrolimus predose trough concentration (C0) and may also affect IPV, which may lead to immune- and/or drug-mediated allograft injury. CYP3A5*3 may result in absent (*3/*3), partial (*1/*3) or normal (*1/*1) CYP3A5 expression. The effect of CYP3A5*3 on tacrolimus exposure and variability has not been examined in South African (SA) transplant recipients. OBJECTIVES: To determine the frequencies and effect of CYP3A5 and adenosine triphosphate-binding cassette subfamily B member 1 (ABCB1) polymorphisms on tacrolimus C0/dose ratios in different ethnic groups attending a tertiary renal transplant clinic in SA, and other factors that may explain inter- and IPV in tacrolimus C0. METHODS: All consenting stable renal transplant recipients on tacrolimus at the Livingstone Hospital Renal Unit in Port Elizabeth, SA, were included. Tacrolimus concentrations were obtained using a microparticle enzyme immunoassay method (ARCHITECT analyser, Abbott Laboratories). Polymerase chain reaction/restriction fragment length polymorphism was used to genotype for CYP3A5*3 and *6 allelic variants. RESULTS: There were 43 participants (35% black African, 44% mixed ancestry and 21% white), with a mean age of 44.5 years, median duration post-transplant of 47 months and median (interquartile range) creatinine and estimated glomerular filtration rate levels of 118 (92 - 140) µmol/L and 62 (49 - 76) mL/min at study inclusion. The mean tacrolimus C0 in the study was 6.7 ng/mL, with no difference across the different ethnic groups. However, the mean total daily dose of tacrolimus required was 9.1 mg (0.12 mg/kg), 7.2 mg (0.09 mg/kg) and 4.3 mg (0.06 mg/kg) in black, mixed-ancestry and white patients, respectively (p=0.017). The frequencies for CYP3A5 expressors (i.e. CYP3A5*1/*1 + CYP3A5*1/*3 genotypes) were 72%, 100%, 76% and 12% for all patients combined and black, mixed-ancestry and white patients, respectively. The frequencies for CYP3A5 non-expressors (i.e. CYP3A5*3/*3 genotypes) were 0%, 24% and 88% among the black, mixed-ancestry and white patients, respectively. None of the patients carried the CYP3A5*6 allele. CYP3A5*1/*1 and CYP3A5*1/*3 genotype carriers required a two-fold increase in dose compared with the non-expressor genotype carriers, CYP3A5*3/*3 (p<0.05). CYP3A5*3/*3 carriers also demonstrated higher IPV than CYP3A5*1/*1 and *1/*3 carriers (18.1% v. 14.2%; p=0.125). CONCLUSIONS: Compared with global transplant populations, SA renal transplant recipients demonstrated a very high rate of CYP3A5 expression, with a significant impact on tacrolimus pharmacokinetics. Genetic variation in CYP3A5 expression affects tacrolimus dosing requirements, and knowing the CYP3A5 genotype of transplant patients may allow better dose prediction compared with current standard dosing recommendations in a multi-ethnic population. Overall, black African patients required higher doses of tacrolimus than their white counterparts. While further prospective studies are needed to better evaluate dosing algorithms, it would appear that the starting dose of tacrolimus should be higher in black and mixed-race patients.

The changing landscape of infective endocarditis in South Africa.

BACKGROUND: Little is known about the current clinical profile and outcomes of patients with infective endocarditis (IE) in South Africa (SA). OBJECTIVES: To provide a contemporary and descriptive overview of IE in a representative SA tertiary centre. METHODS: We conducted a retrospective review of the records of patients admitted to Groote Schuur Hospital, Cape Town, between 2009 and 2016 fulfilling universal criteria for definite or possible IE, in search of demographic, clinical, microbiological, echocardiographic, treatment and outcome information. RESULTS: A total of 105 patients fulfilled the modified Duke criteria for IE. The median age of the cohort was 39 years (interquartile range (IQR) 29 - 51), with a male preponderance (61.9%). The majority of the patients (72.4%) had left-sided native valve endocarditis, 14.3% had right-sided disease, and 13.3% had prosthetic valve endocarditis. A third of the cohort had rheumatic heart disease. Although 41.1% of patients with left-sided disease had negative blood cultures, the three most common organisms cultured in this subgroup were Staphylococcus aureus (18.9%), Streptococcus spp. (16.7%) and Enterococcus spp. (6.7%). Participants with right-sided endocarditis were younger (29 years, IQR 27 - 37) and were mainly intravenous drug users (73.3%), and the majority cultured positive for S. aureus (73.3%) with frequent septic pulmonary complications (40.0%). The overall in-hospital mortality was 16.2%, with no deaths in the group with right-sided endocarditis. Predictors of death in our patients were heart failure (odds ratio (OR) 8.16, 95% confidence interval (CI) 1.77 - 37.70; p=0.007) and age >45 years (OR 4.73, 95% CI 1.11 - 20.14; p=0.036). Valve surgery was associated with a reduction in mortality (OR 0.09, 95% CI 0.02 - 0.43; p=0.001). CONCLUSIONS: IE remains an important clinical problem in a typical teaching tertiary care centre in SA. In this setting, it continues to affect mainly young people with post-inflammatory valve disease and congenital heart disease. The in-hospital mortality associated with IE remains high. Intravenous drug-associated endocarditis caused by S. aureus is an important IE subset, comprising ~10% of all cases, which was not reported 15 years ago, and culture-negative endocarditis remains highly prevalent. Heart failure in IE carries a significant risk of death and needs a more intensive level of care in hospital. Finally, cardiac surgery was associated with reduced mortality, with the largest impact in patients with heart failure.

Quality of life after total laryngectomy: evaluating the effect of socioeconomic status.

OBJECTIVE: Total laryngectomy is considered the primary treatment modality for advanced laryngeal carcinoma. This study assessed the quality of life in patients after total laryngectomy, and ascertained whether quality of life is affected by socioeconomic status. METHOD: Forty-seven patients (20 state- and 27 private-sector) who underwent total laryngectomy between 1998 and 2014 responded to the University of Washington Quality of Life Questionnaire, the Voice-Related Quality of Life Questionnaire and the Brief Illness Perception Questionnaire. RESULTS: Significant differences were found in socioeconomic status between state- and private-sector patients (p < 0.001). There was no significant difference in overall quality of life between groups (p = 0.210). State-sector patients scored significantly higher Voice-Related Quality of Life Questionnaire scores (p = 0.043). Perception of illness did not differ significantly between groups. CONCLUSION: Overall quality of life after total laryngectomy appears to be similar in patients from different socioeconomic backgrounds. However, patients from lower socioeconomic circumstances have better voice-related quality of life. The results illustrate the importance of including socioeconomic status when reporting voice outcomes in total laryngectomy patients.

The prognostic significance of the 12-lead ECG in peripartum cardiomyopathy.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is an important cause of pregnancy-associated heart failure, which appears in previously healthy women towards the end of pregnancy or within five months following delivery. Although the ECG is widely used in clinical practice, its prognostic value has not been established in PPCM. METHODS: We analysed 12-lead ECGs of patients with PPCM, taken at index presentation and follow-up visits at 6 and 12 months. Poor outcome was determined by the composite endpoint of death, readmission, NYHA functional class III/IV or left ventricular ejection fraction (LVEF) of ≤35% at follow-up. RESULTS: This cohort of 66 patients had a median age of 28.59 (IQR 25.43-32.19). The median LVEF at presentation (33%, IQR 25-40) improved significantly at follow-up (LVEF 49%, IQR 38-55, P < 0.001 at 6 months; 52% IQR 38-57, P = 0.001 at 12 months). Poor outcome occurred in 27.91% at 6 months and 41.18% at 1 year. Whereas sinus tachycardia at baseline was an independent predictor of poor outcome at 12 months (OR 6.56, 95% CI 1.17-20.41, P = 0.030), sinus arrhythmia was associated with event free survival (log rank P = 0.013). T wave inversion was associated with an LVEF ≤35% at presentation (P = 0.038), but did not predict poor outcome. A prolonged QTc interval at presentation (found in almost half of the cohort) was an independent predictor of poor outcome at 6 months (OR 6.34, 95% CI 1.06-37.80, P = 0.043). CONCLUSION(S): A prolonged QTc and sinus tachycardia at baseline were independent predictors of poor outcome in PPCM at 6 months and 1 year respectively.

The changing landscape of infective endocarditis in South Africa

Background. Little is known about the current clinical profile and outcomes of patients with infective endocarditis (IE) in South Africa (SA). Objectives. To provide a contemporary and descriptive overview of IE in a representative SA tertiary centre. Methods. We conducted a retrospective review of the records of patients admitted to Groote Schuur Hospital, Cape Town, between 2009 and 2016 fulfilling universal criteria for definite or possible IE, in search of demographic, clinical, microbiological, echocardiographic, treatment and outcome information. Results. A total of 105 patients fulfilled the modified Duke criteria for IE. The median age of the cohort was 39 years (interquartile range (IQR) 29 - 51), with a male preponderance (61.9%). The majority of the patients (72.4%) had left-sided native valve endocarditis, 14.3% had right-sided disease, and 13.3% had prosthetic valve endocarditis. A third of the cohort had rheumatic heart disease. Although 41.1% of patients with left-sided disease had negative blood cultures, the three most common organisms cultured in this subgroup were Staphylococcus aureus (18.9%), Streptococcus spp. (16.7%) and Enterococcus spp. (6.7%). Participants with right-sided endocarditis were younger (29 years, IQR 27 - 37) and were mainly intravenous drug users (73.3%), and the majority cultured positive for S. aureus (73.3%) with frequent septic pulmonary complications (40.0%). The overall in-hospital mortality was 16.2%, with no deaths in the group with right-sided endocarditis. Predictors of death in our patients were heart failure (odds ratio (OR) 8.16, 95% confidence interval (CI) 1.77 - 37.70; p=0.007) and age >45 years (OR 4.73, 95% CI 1.11 - 20.14; p=0.036). Valve surgery was associated with a reduction in mortality (OR 0.09, 95% CI 0.02 - 0.43; p=0.001). Conclusions. IE remains an important clinical problem in a typical teaching tertiary care centre in SA. In this setting, it continues to affect mainly young people with post-inflammatory valve disease and congenital heart disease. The in-hospital mortality associated with IE remains high. Intravenous drug-associated endocarditis caused by S. aureus is an important IE subset, comprising ~10% of all cases, which was not reported 15 years ago, and culture-negative endocarditis remains highly prevalent. Heart failure in IE carries a significant risk of death and needs a more intensive level of care in hospital. Finally, cardiac surgery was associated with reduced mortality, with the largest impact in patients with heart failure

Altered stimulus representation in rat auditory cortex is not causal for loss of consciousness under general anaesthesia.

BACKGROUND: Current concepts suggest that impaired representation of information in cortical networks contributes to loss of consciousness under anaesthesia. We tested this idea in rat auditory cortex using information theory analysis of multiunit responses recorded under three anaesthetic agents with different molecular targets: isoflurane, propofol, and dexmedetomidine. We reasoned that if changes in the representation of sensory stimuli are causal for loss of consciousness, they should occur regardless of the specific anaesthetic agent. METHODS: Spiking responses were recorded with chronically implanted microwire arrays in response to acoustic stimuli incorporating varied temporal and spectral dynamics. Experiments consisted of four drug conditions: awake (pre-drug), sedation (i.e. intact righting reflex), loss of consciousness (a dose just sufficient to cause loss of righting reflex), and recovery. Measures of firing rate, spike timing, and mutual information were analysed as a function of drug condition. RESULTS: All three drugs decreased spontaneous and evoked spiking activity and modulated spike timing. However, changes in mutual information were inconsistent with altered stimulus representation being causal for loss of consciousness. First, direction of change in mutual information was agent-specific, increasing under dexmedetomidine and decreasing under isoflurane and propofol. Second, mutual information did not decrease at the transition between sedation and LOC for any agent. Changes in mutual information under anaesthesia correlated strongly with changes in precision and reliability of spike timing, consistent with the importance of temporal stimulus features in driving auditory cortical activity. CONCLUSIONS: The primary sensory cortex is not the locus for changes in representation of information causal for loss of consciousness under anaesthesia.

Radiological differences between HIV-positive and HIV-negative children with cholesteatoma.

INTRODUCTION: HIV-positive children are possibly more prone to developing cholesteatoma. Chronic inflammation of the middle ear cleft may be more common in patients with HIV and this may predispose HIV-positive children to developing cholesteatoma. There are no studies that describe the radiological morphology of the middle ear cleft in HIV-positive compared to HIV-negative children with cholesteatoma. OBJECTIVES: Compare the radiological differences of the middle ear cleft in HIV-positive and HIV-negative children with cholesteatoma. METHODS: A retrospective, cross-sectional, observational analytical review of patients with cholesteatoma at our institute over a 6 year period. RESULTS: Forty patients were included in the study, 11 of whom had bilateral cholesteatoma and therefore 51 ears were eligible for our evaluation. HIV-positive patients had smaller (p=0.02) mastoid air cell systems (MACS). Forty percent of HIV-positive patients had sclerotic mastoids, whereas the rate was 3% in HIV-negative ears (p<0.02). Eighty-two percent of the HIV-positive patients had bilateral cholesteatoma compared to 7% of the control group (p<0.02). There was no difference between the 2 groups with regards to opacification of the middle ear cleft, bony erosion of middle ear structures, Eustachian tube obstruction or soft tissue occlusion of the post-nasal space. CONCLUSION: HIV-positive paediatric patients with cholesteatoma are more likely to have smaller, sclerotic mastoids compared to HIV-negative patients. They are significantly more likely to have bilateral cholesteatoma. This may have implications in terms of surveillance of HIV-positive children, as well as, an approach to management, recurrence and follow-up. HIV infection should be flagged as a risk factor for developing cholesteatoma.

The aetiology, clinical presentation and treatment of patients with pulmonary hypertension in Cape Town: A preliminary report from the Groote Schuur Hospital Pulmonary Hypertension Registry.

BACKGROUND: There is a paucity of knowledge about pulmonary hypertension (PH) in sub-Saharan Africa and an urgent need for its investigation in this context. The impact of HIV infection in PH is also unknown. OBJECTIVES: To determine the aetiology, clinical presentation, severity and current management of PH at a tertiary-level hospital in Cape Town, South Africa (SA). METHODS: Demographic and clinical data, including from special investigations, were captured retrospectively for all patients referred to the Groote Schuur Hospital Pulmonary Hypertension Clinic between October 2015 and November 2017 (n=58) and entered into an online registry. Descriptive statistics were used to present the baseline data at enrolment. RESULTS: Patients were mainly young and female and almost half (48.3%) had severe symptoms according to World Health Organization classification. The main aetiologies were pulmonary arterial hypertension (PAH) and chronic thromboembolic PH. More than a fifth of the patients were HIV-positive, with nine patients presenting with HIV-associated PAH. The median time from initial presentation to referral to a specialist centre was 227 days (interquartile range: 72 - 625 days). Only a small number of patients were on PH-specific treatment at enrolment and a notable number never underwent right-heart catheterisation. CONCLUSION: PH diagnosis is often delayed and even at a tertiary institution with a dedicated clinic and access to special investigations, PH is suboptimally investigated and managed. Expansion of this registry to better understand the phenotype of this disease in SA can improve outcomes for these patients through awareness, early identification and effective management.

Climate induced human demographic and cultural change in northern Europe during the mid-Holocene.

The transition from hunter-gatherer-fisher groups to agrarian societies is arguably the most significant change in human prehistory. In the European plain there is evidence for fully developed agrarian societies by 7,500 cal. yr BP, yet a well-established agrarian society does not appear in the north until 6,000 cal. yr BP for unknown reasons. Here we show a sudden increase in summer temperature at 6,000 cal. yr BP in northern Europe using a well-dated, high resolution record of sea surface temperature (SST) from the Baltic Sea. This temperature rise resulted in hypoxic conditions across the entire Baltic sea as revealed by multiple sedimentary records and supported by marine ecosystem modeling. Comparison with summed probability distributions of radiocarbon dates from archaeological sites indicate that this temperature rise coincided with both the introduction of farming, and a dramatic population increase. The evidence supports the hypothesis that the boundary of farming rapidly extended north at 6,000 cal. yr BP because terrestrial conditions in a previously marginal region improved.

High prevalence of "non-dipping" blood pressure and vascular stiffness in HIV-infected South Africans on antiretrovirals.

BACKGROUND: HIV-infected individuals are at increased risk of tissue inflammation and accelerated vascular aging ('inflamm-aging'). Abnormal diurnal blood pressure (BP) rhythms such as non-dipping may contribute to an increased risk of cardiovascular and cerebrovascular events in HIV infected individuals. However, little data exists on ambulatory blood pressure (ABP) and measures of vascular stiffness in the black African HIV infected population. METHODS: This is a cross-sectional analysis of otherwise well, HIV infected outpatients on ART for >5 years. Study assessments included: 24hr ABP monitoring, pulse wave velocity (PWV) and central aortic systolic pressure (CASP) using a AtCor Medical Sphygmocor device, fasting lipogram, oral glucose tolerance test, high-sensitivity C-reactive protein (hsCRP) and anthropometric data. Patients completed a questionnaire of autonomic symptoms. CD4+ counts and viral loads were obtained from the National Laboratory results system. RESULTS: Sixty seven black participants were included in the analysis of whom 91% (n = 61) were female with a mean age of 42.2 ± 8.6 years. The median duration on ART was 7.5 years (IQR = 6-10), 84% were virally supressed and the median CD4 count was 529.5cells/mm3 (IQR = 372.0-686.5). The majority (67%) were classified as overweight and 76% had an increased waist circumference, yet only 88% of participants were normotensive. A hsCRP level in the high cardiovascular risk category was found in 68% of participants. The prevalence of non-dipping BP was 65%. Interestingly, there was no association on multivariable analysis between dipping status and traditional risk factors for non-dipping BP, such as: obesity, autonomic dysfunction and older age. CONCLUSION: This relatively young cross-sectional sample of predominantly normotensive, but overweight black women on effective ART >5 years showed: a high prevalence of non-dipping BP, inflammation and vascular stiffness. Causality cannot be inferred but cardiovascular risk reduction should be emphasized in these patients.