HIV testing in the critical care setting: views of patients, family members and health providers from urban South Africa.

As antiretroviral treatment has led to decreased morbidity, HIV testing policy has increasingly shifted towards routine, provider-initiated approaches. Yet, few studies have examined the acceptability of provider-initiated HIV testing in the intensive, or critical care setting, where knowledge of HIV status is likely to impact on clinical management but explicit consent for testing is difficult to obtain. We conducted qualitative research in an urban hospital and clinic in Johannesburg. In-depth interviews were conducted among HIV testing clients (n = 20), recently discharged critical care patients (n = 13) and family members of critical care patients (n = 14). One focus group discussion was held with health care providers (n = 10). HIV testing in critical care was viewed as acceptable but challenging to implement. An overarching theme of ambivalence emerged from patients and families, who saw HIV testing as a pre-requisite to appropriate clinical care, but were concerned about the quality of its delivery. While providers were aware of the current "no testing without consent" policy, they expressed frustration in cases when testing was in the patient's best interest but consent could not be obtained. Furthermore, providers found it stressful to weigh up patient confidentiality against medical necessity when assessing patients' "best interests". Without specific guidelines, they often developed pragmatic, ad hoc ways to resolve dilemmas around testing in critical care. Our findings suggest that HIV testing guidelines specific to the critical care setting may help providers do their jobs more ethically and transparently. Provider-initiated approaches are likely to be acceptable to patients and may improve clinical outcomes, but training and support in policy implementation and ethical decision-making are essential.

"Mothers get really exhausted!" The lived experience of pregnancy in extreme heat: Qualitative findings from Kilifi, Kenya.

Heat exposure in pregnancy is associated with a range of adverse health and wellbeing outcomes, yet research on the lived experience of pregnancy in high temperatures is lacking. We conducted qualitative research in 2021 in two communities in rural Kilifi County, Kenya, a tropical savannah area currently experiencing severe drought. Pregnant and postpartum women, their male spouses and mothers-in-law, community health volunteers, and local health and environment stakeholders were interviewed or participated in focus group discussions. Pregnant women described symptoms that are classically regarded as heat exhaustion, including dizziness, fatigue, dehydration, insomnia, and irritability. They interpreted heat-related tachycardia as signalling hypertension and reported observing more miscarriages and preterm births in the heat. Pregnancy is conceptualised locally as a 'normal' state of being, and women continue to perform physically demanding household chores in the heat, even when pregnant. Women reported little support from family members to reduce their workload at this time, reflecting their relative lack of autonomy within the household, but also potentially the 'normalisation' of heat in these communities. Climate change risk reduction strategies for pregnant women in low-resource settings need to be cognisant of local household gender dynamics that constrain women's capacity to avoid heat exposures.

Predicting 5-fluorouracil toxicity in colorectal cancer patients from peripheral blood cell telomere length: a multivariate analysis.

BACKGROUND: Identifying various pretreatment factors that predict chemotherapy-induced toxicity in colorectal cancer (CRC) patients undergoing treatment for their disease is crucial to optimising patient care. METHODS: Seventy-three patients received adjuvant 5-fluorouracil (5FU)/leucovorin using either the Mayo Clinic (n=42) or a weekly schedule (n=31) and evaluated for clinical toxicity. Pretreatment blood analysis included measures of plasma uracil and dihydrouracil, peripheral blood mononuclear cell (PBMNC) telomere length (TL), standard biochemistry and cell differential analysis. On the first day of treatment 5FU-pharmacokinetic variables of area under the curve, half life and clearance were also measured. These variables together with age and gender were used in univariate and multivariate analysis as predictors of clinical toxicity. RESULTS: For the Mayo schedule the primary toxicities were neutropenia (69%), mucositis (58%) and leukopenia (46%), with 70% of patients presenting with haematological toxicity ≥grade 1 (neutropenia and/or leukopenia). Multivariate analysis showed that haematological toxicity was predicted by short TL, high platelet lymphocyte ratio (PLR) and low neutrophil count (R(2)=0.38, P<0.0006), whereas mucositis was predicted by age, TL and PLR (R(2)=0.34, P<0.001). For the weekly schedule diarrhoea predominated (16%), with female gender as the only predictive factor. Although measures of uracil metabolism correlated well with 5FU metabolism (r=0.45-0.49), they did not indicate abnormal pyrimidine metabolism in this cohort and not surprisingly failed to predict for 5FU toxicity. CONCLUSION: Short TL of PBMNC and an increased PLR were strong predictors of mucositis and haematological toxicity in CRC patients undergoing 5FU treatment in the adjuvant setting.

Association of thymidylate synthase enhancer region polymorphisms with thymidylate synthase activity in vivo.

Two known polymorphisms in the 5' enhancer region (ER) of the thymidylate synthase (TS) gene, a variable number of tandem repeats of a 28 bp sequence (2R/3R) and a further G>C single nucleotide substitution within the repeats, result in genotypes with 0-5 functional upstream stimulatory factor (USF) E-box consensus elements. However, the relationship between these polymorphisms, regulation of TS expression and patient response to fluoropyrimidine treatment has been inconsistent. In this study, seven possible TSER allele configurations showed similar patterns of luciferase gene expression regardless of cell type or USF-1 content, with no significant difference in promoter activity between the wild-type 2RGC and 3RGGC (1.40±0.37 vs 1.43±0.32, P=0.90), whereas the minor alleles, 2RCC and 3RGCC, were significantly reduced (0.84±0.17, P=0.01) and increased (3.19±0.72, P=0.001) respectively. Patient plasma levels of 2'-deoxyuridine, a surrogate marker of TS activity, were significantly different between genotypes (P<0.001) and inversely related to luciferase activity (P=0.02) but not to the absolute number of functional repeated elements (P=0.16), suggesting that the position, rather than the number of functional USF E-box repeats in the TSER, is responsible for determining gene expression in vitro and TS activity in vivo.

Prevalence and self-reported health consequences of vaginal practices in KwaZulu-Natal, South Africa: findings from a household survey.

OBJECTIVES: To investigate population-level prevalence of vaginal practices, their frequency and self-reported health consequences in KwaZulu-Natal, South Africa. METHODS: A household survey using multi-stage cluster sampling was conducted in 2007. Women aged 18-60 (n = 867) were interviewed on demographics, sexual behaviours and vaginal practices, focusing on intravaginal practices. Design-based analysis used multivariate logistic regression to identify factors associated with intravaginal or any practice. RESULTS: Most women currently perform vaginal practices (90.2%), with 34.8% reporting two and 16.3%≥3 practices. Internal cleansing, the commonest practice (63.3% of women), is undertaken frequently (61.6% cleansing twice daily; 20.0% using ≥2 products). Fewer report application (10.1%), insertion (11.6%) or ingestion (14.3%) practices. Hygiene is a common motivation, even for the 23.2% of women reporting intravaginal practices around the time of sex. Prevalence of any practice was lower among women with tertiary education than those without primary education (AOR = 0.26, 95% CI = 0.08-0.85), nearly twice as common in sexually active women (95% CI = 1.05-3.56) and increased as overall health status declined. Adjusted odds of intravaginal practices were 1.8-fold higher in women reporting unprotected sex (95% CI = 1.11-2.90). Few reported health problems with current practices (0.6%); though, 12.6% had ever-experienced adverse effects. CONCLUSIONS: Vaginal practices are common in KwaZulu-Natal. Although self-reported health problems with current practices are rare, high lifetime risk of adverse events and potential for asymptomatic but clinically important damage make continued research important.

Quality of counselling and support provided by the South African National AIDS Helpline: Content analysis of mystery client interviews.

BACKGROUND: Telephone helplines can facilitate referral, education and support for patients living with HIV or those concerned about the infection. The anonymity of helplines facilitates discussion of sensitive issues that are difficult to raise face to face. These services could support the expansion of HIV self-testing. However, maintaining quality and standardising messages in rapidly evolving fields such as HIV is challenging. OBJECTIVES: To evaluate the quality of the South African (SA) National AIDS Helpline. METHODS: Mystery clients posing as members of the public made 200 calls to the service in 2014. They presented several scenarios, including having received HIV-positive results from a doctor's secretary or through self-testing. Following the call, 'clients' completed a semistructured questionnaire on the information received and the caller-counsellor interaction. RESULTS: Calls were answered within a median of 5 seconds (interquartile range 2 - 14). Conversations took place in 8 of the 11 SA official languages, though mainly in English. Overall, 75% of callers felt that with the information they received they could locate a nearby clinic for further services. Counsellors expressed appropriate levels of concern about inadequate counselling that callers had received and confidentiality breaches in some scenarios. Eight counsellors incorrectly mentioned the need for a waiting period to confirm a positive result. Consistent with policy, almost all said that being foreign would not affect HIV treatment access. About 90% explained the need for CD4+ testing and antiretroviral therapy, but only 78% discussed HIV prevention. Counsellors were mostly empathetic (83%), though some adopted a neutral tone (10%) or were brusque (6%) or unhelpful (2%). CONCLUSIONS: Overall, helpline counsellors were proficient at providing information about local clinics, HIV testing and steps needed for initiating ART. Dissatisfaction with the caller-counsellor interactions, instances of incorrect information and the relatively low attention accorded to HIV prevention are worrying, however. Training for both refreshing and updating knowledge, and supervision and monitoring of calls, could target these areas.

A randomized controlled trial of fresh frozen plasma for coagulopathy in Russell's viper (Daboia russelii) envenoming.

Essentials Russell's viper envenoming is a major health issue in South Asia and causes coagulopathy. We studied the effect of fresh frozen plasma and two antivenom doses on correcting coagulopathy. Fresh frozen plasma did not hasten recovery of coagulopathy. Low-dose antivenom did not worsen coagulopathy. SUMMARY: Background Russell's viper (Daboia russelii) envenoming is a major health issue in South Asia and causes venom-induced consumption coagulopathy (VICC). Objectives To investigate the effects of fresh frozen plasma (FFP) and two antivenom doses in correcting VICC. Methods We undertook an open-label randomized controlled trial in patients with VICC at two Sri Lankan hospitals. Patients with suspected Russell's viper bites and coagulopathy were randomly allocated (1 : 1) to high-dose antivenom (20 vials) or low-dose antivenom (10 vials) plus 4 U of FFP. The primary outcome was the proportion of patients with an International Normalized Ratio (INR) of < 2 at 6 h after antivenom administration. Secondary outcomes included anaphylaxis, major hemorrhage, death, and clotting factor recovery. Results From 214 eligible patients, 141 were randomized: 71 to high-dose antivenom, and 70 to low-dose antivenom/FFP; five had no post-antivenom blood tests. The groups were similar except for a delay of 1 h in antivenom administration for FFP patients. Six hours after antivenom administration, 23 of 69 (33%) patients allocated to high-dose antivenom had an INR of < 2, as compared with 28 of 67 (42%) allocated to low-dose antivenom/FFP (absolute difference 8%; 95% confidence interval - 8% to 25%). Fifteen patients allocated to FFP did not receive it. Severe anaphylaxis occurred equally frequently in each group. One patient given FFP developed transfusion-related acute lung injury. Three deaths occurred in low-dose antivenom/FFP patients, including one intracranial hemorrhage. There was no difference in recovery rates of INR or fibrinogen, but there was more rapid initial recovery of factor V and FX in FFP patients. Conclusion FFP after antivenom administration in patients with Russell's viper bites did not hasten recovery of coagulopathy. Low-dose antivenom/FFP did not worsen VICC, suggesting that low-dose antivenom is sufficient.

Safeguarding maternal and child health in South Africa by starting the Child Support Grant before birth: Design lessons from pregnancy support programmes in 27 countries.

BACKGROUND: Deprivation during pregnancy and the neonatal period increases maternal morbidity, reduces birth weight and impairs child development, with lifelong consequences. Many poor countries provide grants to mitigate the impact of poverty during pregnancy. South Africa (SA) offers a post-delivery Child Support Grant (CSG), which could encompass support during pregnancy, informed by lessons learnt from similar grants. OBJECTIVES: To review design and operational features of pregnancy support programmes, highlighting features that promote their effectiveness and efficiency, and implications thereof for SA. METHODS: Systematic review of programmes providing cash or other support during pregnancy in low- and middle-income countries. RESULTS: Thirty-two programmes were identified, across 27 countries. Programmes aimed to influence health service utilisation, but also longer-term health and social outcomes. Half included conditionalities around service utilisation. Multifaceted support, such as cash and vouchers, necessitated complex parallel administrative procedures. Five included design features to diminish perverse incentives. These and other complex features were often abandoned over time. Operational barriers and administrative costs were lowest in programmes with simplified procedures and that were integrated within child support. CONCLUSIONS: Pregnancy support in SA would be feasible and effective if integrated within existing social support programmes and operationally simple. This requires uncomplicated enrolment procedures (e.g. an antenatal card), cash-only support, and few or no conditionalities. To overcome political barriers to implementation, the design might initially need to include features that discourage pregnancy incentives. Support could incentivise service utilisation, without difficult-to-measure conditionalities. Beginning the CSG in pregnancy would be operationally simple and could substantially transform maternal and child health.

Telomere length predicts neutrophil recovery in the absence of G-CSF after autologous peripheral blood stem cell transplantation.

SUMMARY: Haemopoietic regeneration after autologous peripheral blood progenitor cell (PBPC) transplantation can be delayed in some patients despite adequate infusion of CD34(+) cells. This suggests variability in the proliferation potential of the implanted cells, a capacity that may be predicted by their telomere length. To test this theory, telomere length was measured on stored apheresis samples from 36 patients aged 46.6+/-11.1 years, who had undergone successful autologous PBPC transplantation with a median of 5.6 x 10(6)/kg (1.3 x 10(6)-36.1 x 10(6)/kg) CD34(+) cells. The mean PBPC telomere length for the cohort was 9.4+/-2.3 kbp. For patients who did not receive G-CSF post transplantation (n=7), days to absolute neutrophil recovery (ANC), >/=0.1, 0.5 and 1.0 x 10(9) cells/l, were significantly inversely correlated with telomere length of the infused PBPC (r=-0.88, -0.81, -0.77, respectively; P<0.05,). However, no correlation was found for patients who received G-CSF from day 1 post transplantation (n=20). These data suggest that for transplantation with sufficient CD34(+) cells, neutrophil recovery is less efficient in patients receiving infusions of cells with short telomeres, but this deficiency can be corrected with adequate post transplantation administration of G-CSF. Bone Marrow Transplantation (2004) 34, 439-445. doi:10.1038/sj.bmt.1704607 Published online 19 July 2004

A randomized controlled trial of fresh frozen plasma for treating venom-induced consumption coagulopathy in cases of Australian snakebite (ASP-18).

BACKGROUND: Venom-induced consumption coagulopathy (VICC) is a major effect of snake envenoming. OBJECTIVES: To investigate whether fresh frozen plasma (FFP) given after antivenom resulted in more rapid correction of coagulation. PATIENTS/METHODS: This was a multicenter open-label randomized controlled trial in patients with VICC of FFP vs. no FFP within 4 h of antivenom administration. Patients (> 2 years) recruited to the Australian snakebite project with VICC (International Normalized Ratio [INR] > 3) were eligible. Patients were randomized 2 : 1 to receive FFP or no FFP. The primary outcome was the proportion with an INR of < 2 at 6 h after antivenom administration. Secondary outcomes included time from antivenom administration to discharge, adverse effects, major hemorrhage, and death. RESULTS: Of 70 eligible patients, 65 consented to be randomized: 41 to FFP, and 24 to no FFP. Six hours after antivenom administration, more patients randomized to FFP had an INR of < 2 (30/41 [73%] vs. 6/24 [25%]; absolute difference, 48%; 95% confidence interval 23-73%; P = 0.0002). The median time from antivenom administration to discharge was similar (34 h, range 14-230 h vs. 39 h, range 14-321 h; P = 0.44). Seven patients developed systemic hypersensitivity reactions after antivenom administration - two mild and one severe (FFP arm), and three mild and one severe (no FFP). One serious adverse event (intracranial hemorrhage and death) occurred in an FFP patient with pre-existing hypertension, who was hypertensive on admission, and developed a headache 6 h after FFP administration. Post hoc analysis showed that the median time from bite to FFP administration was significantly shorter for non-responders to FFP than for responders (4.7 h, interquartile range [IQR] 4.2-6.7 h vs. 7.3 h, IQR 6.1-8 h; P = 0.002). CONCLUSIONS: FFP administration after antivenom administration results in more rapid restoration of clotting function in most patients, but no decrease in discharge time. Early FFP administration (< 6-8 h) post-bite is less likely to be effective.

Hump-nosed pit viper (Hypnale hypnale) envenoming causes mild coagulopathy with incomplete clotting factor consumption.

CONTEXT: Limited information exists on the coagulopathy caused by hump-nosed pit viper (Hypnale hypnale) envenoming. OBJECTIVES: This study aimed to characterise the coagulopathy in hump-nosed pit viper bites by measuring laboratory clotting times and factor studies. MATERIALS AND METHODS: Cases of hump-nosed pit viper envenoming were included from a prospective cohort study of Sri Lankan snake-bite patients. Patient age, sex, snake identification, time of bite and clinical effects were recorded. Patients did not receive anti-venom because no specific anti-venom to hump-nosed vipers exists. All patients received supportive care and serial 20-min whole blood clotting tests (WBCT20). The prothrombin time (PT), international normalised ratio (INR), activated partial thromboplastin time (aPTT), coagulation factors I, II, V, VII, VIII, IX and X, von Willebrand factor (vWF) antigen and D-Dimer concentrations were measured. The median of highest or lowest test result for each patient was reported with interquartile range (IQR). Results. There were 80 hump-nosed pit viper bites, median age was 37 years (IQR: 26-51 years) and 48 were male. The WBCT20 was positive in one patient. The median highest INR was 1.9 (1.5-2.2; Range: 1.3 to > 12) and median highest aPTT was 54 s (46-72 s; Range: 35-170 s). There was low fibrinogen [median: 1.3 g/L;1, -1.8 g/L; Range: < 0.2-2.9], low factor VIII levels [median: 23%; 16-37%] and low factor V levels [median: 43%; 23-74%]. D-Dimer concentrations [median: 3.4 mg/L; 2-7.4 mg/L] were slightly elevated. Factors II, VII and X and vWF antigen concentrations were normal. DISCUSSION AND CONCLUSIONS: Hump-nosed pit viper bites result in a mild coagulopathy which is usually not detected by a WBCT20. It is characterised by mild elevation of INR, low fibrinogen and Factors V and VIII which may be consistent with the venom containing a thrombin-like enzyme.

Factor deficiencies in venom-induced consumption coagulopathy resulting from Australian elapid envenomation: Australian Snakebite Project (ASP-10).

BACKGROUND: Limited information exists on the dynamics of hemostasis in patients with venom-induced consumption coagulopathy (VICC) from snake envenomation. OBJECTIVE: The aim of the present study was to investigate specific factor deficiencies and their time course in Australasian elapid envenomation. METHODS: We measured coagulation parameters and factor concentrations in patients recruited to the Australian Snakebite Project, an observational cohort study. There were 112 patients with complete VICC, defined as an international normalized ratio (INR) > 3, and 18 with partial VICC. Serial citrated plasma samples were collected from 0.5 to 60 h post-bite. INR, activated partial thromboplastin time (aPTT), coagulation factors (F)I, II, V, VII, VIII, IX, X, von Willebrand factor antigen (VWF:Ag) and D-dimer concentrations were measured. RESULTS: Complete VICC was characterized by near/total depletion of fibrinogen, FV and FVIII, with an INR and aPTT that exceeded the upper limits of detection, within 2 h of snakebite. Prothrombin levels never fell below 60% of normal, suggesting that the toxins were rapidly eliminated or inactivated and re-synthesis of clotting factors occurred irrespective of antivenom. Partial VICC caused limited depletion of fibrinogen and FV, and almost complete consumption of FVIII. Onset of VICC was more rapid with brown snake (Pseudonaja spp.) venom, which contains a group C prothrombin activator toxin, compared with the tiger snake group, which contains a group D prothrombin activator toxin and requires human FVa formation. Resolution of VICC occurred within 24-36 h irrespective of snake type. CONCLUSIONS: These results suggest that Australasian elapid prothrombin activators have a potent but short duration of action. Antivenom is unlikely to be administered in time to prevent VICC.

Use of modern and traditional products to self-treat symptoms of sexually transmitted infections in South African women.

The objective of the study is to investigate products used by women self-treating symptoms of reproductive tract infections (RTIs), including sexually transmitted infections (STIs), and their methods of administration. A household survey using a multi-stage cluster sample design was undertaken in KwaZulu-Natal, South Africa. Women aged 18-60 years were interviewed (n = 867) and information was collected on demographics, reproductive health and sexual behaviours. A fifth of women reported having RTI/STI symptoms (20.5%), of whom 41.9% were treating these symptoms (mostly discharge [79.1%], ulcers [6.8%] and itching [7.7%]). Only three women were using medication prescribed by a health provider, while the remainder were self-treating using traditional medicines and modern products, including antiseptics, soaps, petroleum jelly, menthol creams and alum. Products were administered in various ways. Although RTI/STI treatment is widely available and free in public health facilities, many women are still self-treating. Potential harm of products for self-treatment requires further investigation and efforts should be made to improve STI service uptake.