Development, implementation and evaluation of a seven-day clinical pharmacy service in a tertiary referral teaching hospital during surge-2 of the COVID-19 pandemic.

BACKGROUND: Seven-day clinical pharmacy services in the acute sector of the National Health Service are limited. There is a paucity of evidential patient benefit. This limits investment and infrastructure, despite United Kingdom wide calls. AIM: To optimise medicines seven-days a week during surge-2 of the COVID-19 pandemic through implementation of a seven-day clinical pharmacy service. This paper describes service development, evaluation and sustainability. SETTING: A tertiary-referral teaching hospital, London, United Kingdom. DEVELOPMENT: The seven-day clinical pharmacy service was developed to critical care, acute and general medical patients. Clinical leads developed the service specification and defined priorities, targeting complex patients and transfer of care. Contributing staff were briefed and training materials developed. IMPLEMENTATION: The service was implemented in January 2021 for 11 weeks. Multidisciplinary team communication brought challenges; strategies were employed to overcome these. EVALUATION: A prospective observational study was conducted in intervention wards over two weekends in February 2021. 1584 beds were occupied and 602 patients included. 346 interventions were reported and rated; 85.6% had high or moderate impact; 56.7% were time-critical. The proportion of medicines reconciliation within 24-h of admission was analysed across the hospital between November 2020 and May 2021. During implementation, patients admitted Friday-Sunday were more likely to receive medicines reconciliation within 24-h (RR 1.41 (95% CI 1.34-1.47), p < 0.001). Rostered services were delivered sustainably in terms of shift-fill rate and medicines reconciliation outcome. CONCLUSION: Seven-day clinical pharmacy services benefit patient outcome through early medicines reconciliation and intervention. Investment to permanently embed the service was sustained.

Acute kidney injury as a risk factor of hyperactive delirium: A case control study.

PURPOSE: Delirium and acute kidney injury (AKI) are common organ dysfunctions during critical illness. Both conditions are associated with serious short- and long-term complications. We investigated whether AKI is a risk factor for hyperactive delirium. METHODS: This was a single-centre case control study conducted in a 30 bedded mixed Intensive Care Unit in the UK. Hyperactive delirium cases were identified by antipsychotic initiation and confirmation of delirium diagnosis through validated chart review. Cases were compared with non-delirium controls matched by Acute Physiology and Chronic Health Evaluation II score and gender. AKI was defined by the KDIGO criteria. RESULTS: 142 cases and 142 matched controls were identified. AKI stage 3 was independently associated with hyperactive delirium [Odds ratio (OR) 5.40 (95% confidence interval (CI) 2.33-12.51]. Other independent risk factors were mechanical ventilation [OR 2.70 (95% CI 1.40-5.21)], alcohol use disorder [OR 5.80 (95% CI 1.90-17.72)], and dementia [OR 9.76 (95% CI 1.09-87.56)]. Hospital length of stay was significantly longer in delirium cases (29 versus 20 days; p = .004) but hospital mortality was not different. CONCLUSIONS: AKI stage 3 is independently associated with hyperactive delirium. Further research is required to explore the factors that contribute to this association.

Pharmacist's review and outcomes: Treatment-enhancing contributions tallied, evaluated, and documented (PROTECTED-UK).

PURPOSE: The purpose was to describe clinical pharmacist interventions across a range of critical care units (CCUs) throughout the United Kingdom, to identify CCU medication error rate and prescription optimization, and to identify the type and impact of each intervention in the prevention of harm and improvement of patient therapy. MATERIALS AND METHODS: A prospective observational study was undertaken in 21 UK CCUs from November 5 to 18, 2012. A data collection web portal was designed where the specialist critical care pharmacist reported all interventions at their site. Each intervention was classified as medication error, optimization, or consult. In addition, a clinical impact scale was used to code the interventions. Interventions were scored as low impact, moderate impact, high impact, and life saving. The final coding was moderated by blinded independent multidisciplinary trialists. RESULTS: A total of 20517 prescriptions were reviewed with 3294 interventions recorded during the weekdays. This resulted in an overall intervention rate of 16.1%: 6.8% were classified as medication errors, 8.3% optimizations, and 1.0% consults. The interventions were classified as low impact (34.0%), moderate impact (46.7%), and high impact (19.3%); and 1 case was life saving. Almost three quarters of interventions were to optimize the effectiveness of and improve safety of pharmacotherapy. CONCLUSIONS: This observational study demonstrated that both medication error resolution and pharmacist-led optimization rates were substantial. Almost 1 in 6 prescriptions required an intervention from the clinical pharmacist. The error rate was slightly lower than an earlier UK prescribing error study (EQUIP). Two thirds of the interventions were of moderate to high impact.

Direct enzyme-substrate affinity determination by real-time hyperpolarized (13)C-MRS.

A specialized kinetic analysis of real-time hyperpolarized [1,1,2,2-D4, 1-(13)C]choline (13)C-magnetic resonance spectroscopy enabled the determination of initial rates of metabolic enzyme activity (choline oxidase), enzyme-substrate affinity (Km), and inhibition. In a clinical MRI scanner, metabolite levels lower than 16 µM were detected at a temporal resolution of 1 s.

Prevalence of overweight and obesity among children six to ten years of age in the north-east health region of Jamaica.

OBJECTIVE: To estimate the prevalence and correlates of overweight and obesity among children six to ten years old in the North-East Health Region (NEHR) ofJamaica. METHODS: Weights and heights were measured in a representative sample of 5710 children between the ages of six and ten years in 34 schools between October 2008 and March 2009. Overweight and obesity were defined as body mass index (BMI) Z-score > 1SD and >2SD, respectively based on the World Health Organization (WHO)-endorsed age and gender-specific growth standards for children. Point prevalence estimates of overweight and obesity were calculated. Odds ratios (OR) and 95% confidence intervals (CI) were used to estimate associations between overweight and obesity and age, gender and school location. RESULTS: Overweight and obesity prevalence among children six to ten years old in NEHR, Jamaica, was 10.6% and 7.1%, respectively. Overweight (OR = 1.11, 95% CI: 1.04, 1.18) and obesity (OR = 1.17, 95% CI: 1.08, 1.26) prevalence increased significantly with age. Overweight (OR = 1.51, 95% CI: 1.27, 1.80) and obesity (OR = 1.36, 95% CI: 1.11, 1.67) prevalence was significantly higher among girls than boys. Children attending rural-public schools had less risk of being overweight (OR = 0.57, 95% CI: 0.46, 0.70) and obese (OR = 0.35, 95% CI: 0.28, 0.44) when compared with urban-public schools and private schools. Both overweight (OR = 2.11, 95% CI: 1.60, 2.78) and obesity (OR = 1.68, 95% CI: 1.24, 2.28) were significantly more common among children attending private schools. After adjusting for age and gender the results still remained statistically significant. CONCLUSIONS: Overweight/obesity prevalence among children six to ten years old in NEHR of Jamaica is 17.7% with older children and girls having higher rates. Children attending urban-public and private schools have higher prevalence than those attending rural schools. Appropriately targeted interventions are needed to combat this problem.

Sex differences in quadriceps strength in OA.

The purposes of this study were to determine 1) whether sex differences in quadriceps torque and isotonic power persist when controlling for muscle volume (i. e., torque/muscle volume and power/muscle volume) in participants with knee osteoarthritis (OA) and 2) the factors responsible for potential sex differences. Isometric torque, isotonic power (the product of torque and velocity, measured at 10, 20, 30, 40 and 50% maximal voluntary contraction; MVC) and maximal unloaded velocity were assessed in men (n=16, mean age=62.1 ± 7.2) and women (n=17, mean age=60.4 ± 4.3) with knee OA. Torque and power were normalized to muscle volume. The interpolated twitch technique was used to measure voluntary activation (VA) and evoked twitch and torque-frequency characteristics were measured to obtain information about muscle fibre distribution. Torque and power at all loads were significantly lower in women (p<0.05). Sex differences in power were reduced by 50% when controlling for muscle volume but were still significant at 10-40% MVC (p<0.05). No differences in VA, torque-frequency properties or time-to-peak tension of the evoked twitch were observed (p>0.05). These results suggest that only minor sex differences in torque and power persist when controlling for muscle volume. As VA and contractile property differences were not observed, other factors seem to be responsible.

Quadriceps neuromuscular function and self-reported functional ability in knee osteoarthritis.

The purposes of this study were to determine 1) the relationships of self-reported function scores in patients with knee osteoarthritis (OA) to both maximal isometric torque and to isotonic power at a variety of loads, and 2) the degree to which muscle volume (MV) or voluntary activation (VA) are associated with torque and power measures in this population. Isometric maximal voluntary contraction (MVC) torque and isotonic power [performed at loads corresponding to 10, 20, 30, 40, and 50% MVC, and a minimal load ("Zero Load")] were measured in 40 participants with knee OA. Functional ability was measured with the Western Ontario and McMaster Osteoarthritis Index (WOMAC) function subscale. MV was determined with magnetic resonance imaging, and VA was measured with the interpolated twitch technique. In general, power measured at lower loads (Zero Load and 10-30% MVC, r(2) = 0.21-0.28, P < 0.05) predicted a greater proportion of the variance in function than MVC torque (r(2) = 0.18, P < 0.05), with power measured at Zero Load showing the strongest association (r(2) = 0. 28, P < 0.05). MV was the strongest predictor of MVC torque and power measures in multiple regression models (r(2) = 0.42-0.72). VA explained only 6% of the variance in MVC torque and was not significantly associated with power at any load (P > 0.05). Quadriceps MVC torque and power are associated with self-reported function in knee OA, but muscle power at lower loads is more predictive of function than MVC torque. The variance in MVC torque and power between participants is due predominantly to differences in MV and has little to do with deficits in VA.

Safety of nicotine replacement therapy in critically ill smokers: a retrospective cohort study.

PURPOSE: Nicotine replacement therapy (NRT) has been used to ameliorate nicotine withdrawal in the intensive care unit (ICU). Previous cohort studies have suggested an increased mortality with NRT use: methodological problems may call into question the validity of these findings. We undertook a retrospective cohort study to determine if NRT use was associated with adverse outcomes. METHODS: This retrospective cohort study was conducted in a 30-bed, university affiliated, teaching hospital ICU. RESULTS: We identified 423 smokers admitted over 2 years, of whom 73 received transdermal NRT. Cox proportional hazard regression models, with NRT modelled as a time-varying covariate, were used to test the hypothesis that NRT was associated with an altered ICU or hospital mortality. A second analysis utilized propensity scores. The unadjusted ICU and hospital mortalities were lower for the NRT group; although both differences were non-significant. The Cox models showed that, after adjustment for APACHE risk, age, sex and alcohol use, risk associated with NRT administration was not statistically different than non-administration for both ICU (hazard ratio 0.50, [95 % CI 0.20-1.24], p = 0.14) and hospital (hazard ratio 0.95, [95 % CI 0.52-1.75], p = 0.88) mortality. Similar findings occurred with the propensity matched analysis. CONCLUSION: We were unable to demonstrate any harm associated with NRT, with the ICU model actually trending towards benefit. We conclude that a randomised, blinded, placebo controlled trial is required to assess adequately the safety and efficacy of NRT as a treatment in critically ill smokers.

Patterns of sodium and potassium excretion and blood pressure in the African Diaspora.

Habitual levels of dietary sodium and potassium are correlated with age-related increases in blood pressure (BP) and likely have a role in this phenomenon. Although extensive published evidence exists from randomized trials, relatively few large-scale community surveys with multiple 24-h urine collections have been reported. We obtained three 24-h samples from 2704 individuals from Nigeria, Jamaica and the United States to evaluate patterns of intake and within-person relationships with BP. The average (±s.d.) age and weight of the participants across all the three sites were 39.9±8.6 years and 76.1±21.2 kg, respectively, and 55% of the total participants were females. Sodium excretion increased across the East-West gradient (for example, 123.9±54.6, 134.1±48.8, 176.6±71.0 (±s.d.) mmol, Nigeria, Jamaica and US, respectively), whereas potassium was essentially unchanged (for example, 46.3±22.9, 40.7±16.1, 44.7±16.4 (±s.d.) mmol, respectively). In multivariate analyses both sodium (positively) and potassium (negatively) were strongly correlated with BP (P<0.001); quantitatively the association was stronger, and more consistent in each site individually, for potassium. The within-population day-to-day variation was also greater for sodium than for potassium. Among each population group, a significant correlation was observed between sodium and urine volume, supporting the prior finding of sodium as a determinant of fluid intake in free-living individuals. These data confirm the consistency with the possible role of dietary electrolytes as hypertension risk factors, reinforcing the relevance of potassium in these populations.

The predictive value of urinary vanillylmandelic acid testing in the diagnosis of phaeochromocytoma at the University Hospital of the West Indies.

OBJECTIVE: To investigate the positive predictive value (PPV) of urinary vanillylmandelic acid (VMA) testing in the diagnosis of phaeochromocytoma and to describe the features associated with phaeochromocytoma at the University Hospital of the West Indies (UHWI). SUBJECTS AND METHODS: There were 551 VMA tests performed from January 2003 to June 2009 and 122 tests in 85 patients were elevated (ie > or = 35 micromol/24 hr). The study patients were categorized as: (i) 'surgical' (5 patients who underwent surgery) or (ii) 'non-surgical' (remaining 80 patients). Forty medical charts (out of 85) were reviewed using a standardized data extraction form. RESULTS: The median age for patients in the non-surgical group (with charts reviewed, n = 35) was 36 years (range 9-70) and the median VMA was 43 micromol/24 hr (IQR 38-51). Of these patients, 83% had one or no symptom typical of phaeochromocytoma. In the surgical group the median VMA was 58 micromol/24 hr (IQR 44-101); phaeochromocytoma was confirmed histologically in 3 patients, all of whom had several symptoms typical of catecholamine excess. VMA testing had a PPV of 8%, specificity of 79% and sensitivity of 100%. CONCLUSIONS: VMA testing at UHWI has poor specificity and high sensitivity. These results contrast with international data showing that VMA testing is poorly sensitive but highly specific. The use of assays with higher specificity (eg plasma or urinary metanephrines) may represent a more cost-effective approach to biochemical screening at UHWI.

A preliminary examination of the effects of genetic variants of redox enzymes on susceptibility to oedematous malnutrition and on percentage cytotoxicity in response to oxidative stress in vitro.

BACKGROUND: The causes of oedematous vs non-oedematous childhood malnutrition (OM vs NOM) remain elusive. It is possible that inherited differences in handling oxidant stressors are a contributing factor. AIMS: To test for associations between polymorphisms in five genes and (i) risk of OM, a case-control study, and (ii) percentage cytotoxicity in peripheral blood mononuclear cells (PBMCs) exposed to hydrogen peroxide (H(2)O(2)), an in vitro cell challenge study. METHODS: Participants had been admitted previously for treatment of OM (cases, n = 74) or NOM (controls, n = 50), or were an independent set of healthy pregnant women (n = 47) who donated peripheral blood mononuclear cells. We tested for associations between genetic variation and outcome using single markers or a bivariate score constructed by counting numbers of deleterious alleles for each of 15 possible pairs of markers. RESULTS: In the case-control study there were no significant single-marker associations with OM. We did find that higher bivariate scores were associated with OM for the pair of NAD(P)H:quinone oxidoreductase 1 and catalase (odds ratio 2·00, 95% CI 1·05-3·82). In the cell challenge experiments, there were no significant associations with percentage cytotoxicity. CONCLUSIONS: Variation in this small set of genes seems unlikely to have a large impact on either risk of OM or cytotoxicity after H(2)O(2) exposure. The use of larger sample sizes to test the effects of a much larger set of genetic variants will be required in order to determine whether genetic variation contributes to the risk of OM. Such studies have potential for improving our understanding of causal pathways in OM.

Association of common DNA sequence variants at 33 genetic loci with blood lipids in individuals of African ancestry from Jamaica.

The relevance of loci associated with blood lipids recently identified in European populations in individuals of African ancestry is unknown. We tested association between lipid traits and 36 previously described single-nucleotide polymorphisms (SNPs) in 1,466 individuals of African ancestry from Spanish Town, Jamaica. For the same allele and effect direction as observed in individuals of European ancestry, SNPs at three loci (1p13, 2p21, and 19p13) showed statistically significant association (p < 0.05) with LDL, two loci (11q12 and 20q13) showed association with HDL cholesterol, and two loci (11q12 and 2p24) showed association with triglycerides. The most significant association was between a SNP at 1p13 and LDL cholesterol (p = 4.6 × 10(-8)). This SNP is in a linkage disequilibrium region containing four genes (CELSR2, PSRC1, MYBPHL, and SORT1) and was recently shown to relate to risk for myocardial infarction. Overall, the results of this study suggest that much of the genetic variation which influences blood lipids is shared across ethnic groups.

Prospective evaluation and characteristics of patients with suspected primary hyperaldosteronism.

Primary hyperaldosteronism (PH), resulting in hypokalaemic hypertension, may be due to an aldosterone-producing adenoma (APA) or bilateral zona glomerulosa hyperplasia. Six patients with suspected PH were identified at the University Hospital of the West Indies and standardized screening was carried out. Plasma renin activity (PRA) and serum aldosterone concentrations (SAC) were measured, followed by confirmatory intravenous saline suppression test. The patients were all women, of median age 48 years (interquartile range, IQR: 41-51.7 years). They tended to be overweight with suboptimal blood pressure control. Median serum potassium was 3.1 mmol/L (IQR 2.7 - 3.3 mmol/l) and kaliuresis was elevated or inappropriately normal. All individuals had suppressed PRA (< 0.6 ng/ml/hr) and elevated SAC (> 30 ng/dl), with SAC/PRA ratios > 50. Five patients had confirmed PH (ie post-saline SAC > 10 ng/dl); PH could not be definitely excluded in the sixth patient (ie post-saline SAC 5 - 10 ng/dl). Imaging studies revealed normal adrenal glands in one patient, unilateral adrenal enlargement in three patients, and unilateral adrenal masses in two patients. Only one of these latter two patients was shown to have an adrenal adenoma on histological examination. In this series, there appears to be fewer cases of the APA subtype of PH than expected. It remains to be seen whether the distribution of PH subtypes in Jamaica is actually different from elsewhere. This, and the cost-effectiveness of different approaches to screening, identification and management of patients suspected of having PH in Jamaica are areas for further study.

Prospective evaluation and characteristics of patients with suspected primary hyperaldosteronism / Evaluación prospectiva y características de los pacientes con sospecha de hiperaldosteronismo primario

Primary hyperaldosteronism (PH), resulting in hypokalaemic hypertension, may be due to an aldosterone-producing adenoma (APA) or bilateral zona glomerulosa hyperplasia. Six patients with suspected PH were identified at the University Hospital of the West Indies and standardized screening was carried out. Plasma renin activity (PRA) and serum aldosterone concentrations (SAC) were measured, followed by confirmatory intravenous saline suppression test. The patients were all women, of median age 48 years (interquartile range, IQR: 41-51.7 years). They tended to be overweight with suboptimal blood pressure control. Median serum potassium was 3.1 mmol/L (IQR 2.7 - 3.3 mmol/l) and kaliuresis was elevated or inappropriately normal. All individuals had suppressed PRA (< 0.6 ng/ml/hr) and elevated SAC (> 30 ng/dl), with SAC/PRA ratios > 50. Five patients had confirmed PH (ie post-saline SAC > 10 ng/dl); PH could not be definitely excluded in the sixth patient (ie post-saline SAC 5 - 10 ng/dl). Imaging studies revealed normal adrenal glands in one patient, unilateral adrenal enlargement in three patients, and unilateral adrenal masses in two patients. Only one of these latter two patients was shown to have an adrenal adenoma on histological examination. In this series, there appears to be fewer cases of the APA subtype of PH than expected. It remains to be seen whether the distribution of PH subtypes in Jamaica is actually different from elsewhere. This, and the cost-effectiveness of different approaches to screening, identification and management of patients suspected of having PH in Jamaica are areas for further study.

El hiperaldosteronismo primario (HP), que trae como resultado hipertensión hipocalémica, puede tener por causa un adenoma productor de aldosterona (APA) o una hiperplasia bilateral de la zona glomerulosa. Seis pacientes con sospecha de HP fueron identificados en el Hospital Universitario de West Indies, y se llevó a cabo un tamizaje estandarizado. Se realizaron mediciones de la actividad de renina plasmática (ARP) y las concentraciones de aldosterona en suero (CAS), seguidas de una prueba confirmatoria de supresión con salina por vía intravenosa. Los pacientes fueron en su totalidad mujeres, con una edad mediana de 48 años (rango intercuartil, IQR: 41­51.7 años). Tenían tendencia al sobrepreso y un control subóptimo de la presión sanguínea. La mediana de potasio sérico fue 3.1 mmol/L (IQR 2.7­3.3 mmol/l) y la caliuresis fue elevada o inadecuadamente normal. Todos los indi-viduos presentaron ARP suprimida (< 0.6 ng/ml/hr) y CAS elevada (> 30 ng/dl), coproporciones CAS/ARP> 50. A cinco pacientes les fue confirmado HP (ie CAS post-salina > 10 ng/dl); el HP no pudo ser definitivamente excluido en el sexto paciente (ie CAS post-salina 5 ­ 10 ng/dl). Estudios de imagen revelaron glándulas suprarrenales normales en un paciente, agrandamiento suprarrenal unilateral en tres pacientes, y masas suprarrenales unilaterales en dos pacientes. Solamente uno de estos dos últimos pacientes mostró tener un adenoma adrenal al realizarse el examen histológico. En esta serie, parece haber menos casos del subtipo APA de HP que lo esperado. Queda por ver si la distribución de los subtipos de HP en Jamaica es en realidad diferente de la de otras partes. Esto, al igual que el costo-efectividad de los diferentes métodos de tamizaje, identificación y tratamiento de pacientes con sospecha de HP en Jamaica, son áreas que requieren ulterior investigación.

Predicted declines in sickle allele frequency in Jamaica using empirical data.

The high frequency of the sickle allele in some parts of Africa is understood to be a consequence of high malarial endemicity. One corollary of this is that the sickle allele frequency should be declining in populations of African ancestry that are no longer exposed to malaria. We have previously shown that there has been no change in sickle allele frequency in malaria-free Jamaica between two large-scale neonatal screening exercises conducted in 1973-1981 and 1995-2003. To evaluate the determinants of, and derive expected values for, sickle allele frequency in Jamaica, local empirical data were used to estimate the parameters of deterministic models of allele frequency decline. We found that although model predictions were broadly consistent with observed values in the 1973-1981 cohort, the predicted change in allele frequency between the two cohorts was larger than the observed, nonsignificant, reduction. Close agreement between predicted and observed values was only achieved by simulating a recent, marked increase in HbSS fitness. Thus, the "unexpected" persistence of the sickle allele in Jamaica may reflect the fact that the actual fitness among SS individuals is higher than that previously realized. If true, our models suggest that without substantial changes in current screening and counseling practice, there will be little "natural" reduction in sickle allele frequency for several hundred years. Better estimates of relative fitness will be helpful in refining these predictions and may aid in assigning health care priorities in Jamaica and the African Diaspora.

The frequency of the sickle allele in Jamaica has not declined over the last 22 years.

The 'malaria hypothesis' predicts that the frequency of the sickle allele, which is high in malaria-endemic African populations, should decline with each generation in populations of African descent living in areas where malaria is no longer endemic. In order to determine whether this has been the case in Jamaica, we compared haemoglobin electrophoresis results from two hospital-based screening programmes separated by more than 20 years (i.e. approximately one generation). The first comprised 100,000 neonates screened between 1973 and 1981, the second, 104,183 neonates screened between 1995 and 2003. The difference in frequency of the sickle allele was small (5.47% in the first cohort and 5.38% in the second screening cohort) and not significant (Z = 1.23, P = 0.22). The same was true of the sickle trait frequency (10.05% in the first cohort and 9.85% in the second, Z = 1.45, P = 0.15). These differences were smaller than predicted under simple deterministic models based on the malaria hypothesis, and suggest that these models may not capture important determinants of allele and trait frequency decline (or persistence) in contemporary populations. Refining the expectations for allele and trait frequency change for Jamaica and other similar populations is an area for future study.

SNP haplotypes in the angiotensin I-converting enzyme (ACE) gene: analysis of Nigerian family data using gamete competition models.

Gamete competition models were used to explore the relationships between 13 ACE gene polymorphisms and plasma ACE concentration in a set of Nigerian families. Several markers in the 5' and 3' regions of the gene were significantly associated with ACE concentration (P < 10(-4)). Multi-locus genotypes comprising different combinations of markers from the 5' UTR and the 3' region of the gene were also analysed; in addition to G2350A, in the 3' region, two markers from the 5' UTR (A-5466C and A-240T) were found to be associated with ACE concentration. These results are consistent with reports that have suggested the presence of at least two ACE-linked QTLs, and demonstrate the utility of gamete competition models in the exploratory investigation of the relationship between a quantitative trait and multiple variants in a small genomic region.

HIV serostatus and recovery from severe childhood malnutrition. A retrospective matched case-control study.

The world-wide epidemic of Human Immunodeficiency Virus/Acquired Immune Deficiency Syndrome (HIV/AIDS) has led to an increase in the number of HIV positive children, mainly through perinatal transmission. HIV/AIDS can lead to severe childhood malnutrition (SCM) and has been noted as an increasingly common cause of secondary SCM. In this context, it is important to make assessments of the appropriateness of current approaches to treatment of severe malnutrition in HIV positive children. A retrospective matched case-control study of ten HIV positive children admitted to the Tropical Metabolism Research Unit (TMRU) was conducted. There were few differences between cases and matched controls on admission to the ward. Oral candidiasis and lower respiratory tract infections appeared to occur more frequently, and serum globulin concentrations were significantly higher among HIV positive cases when compared to their controls. Despite the fact that the differences between cases and controls appeared to be small, four cases died; there were no deaths among the controls. The duration of the maintenance phase was approximately five days longer (p = 0.024) among cases than controls but the time between the end of the maintenance phase and discharge from the ward was not significantly longer for the cases. The results of this matched case-control study suggest that there are likely to be important differences between HIV positive and negative patients with SCM that influence risk of mortality and morbidity, particularly in the maintenance phase of treatment. Prospective studies will be required in order to explore these differences and to develop better approaches to the care of HIV positive children with SCM.