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Objective Doxorubicin is a valuable chemotherapeutic drug; however, it is associated with a high risk of cardiotoxicity. Several institutions and organizations have developed guidelines for risk factor assessment, monitoring and prevention strategies against chemotherapy-induced cardiotoxicity. This review aimed to assess the quality of current practice guidelines, using the Appraisal of Guidelines for Research and Evaluation II (AGREE II). This tool was used to compare the recommendations with regards to their strength and evidence recommendations were based on. Data Sources This review identified guidelines in literature from January 1960 to February 6, 2022, through a systematic search that included PubMed, EMBASE, MEDLINE, Cochrane Database and Google Scholar. The quality, consistency and the strength of supporting evidence was evaluated using the AGREE II method. Data Summary Eight guidelines met the inclusion criteria and 144 recommendations were extracted from these guidelines. The results from the AGREE II evaluation showed that the total assessment scores of guidelines ranged from 2 to 5, indicating the guidelines need modifications. The recommendations were evaluated according to the references used, and it was found that 12 (11%) recommendations had high evidence, 36 (33%) had moderate evidence, 38 (35.19%) had low and 22 (20.37%) had insufficient evidence. Recommendations for risk factors assessment, prophylaxis of cardiotoxicity, management of cardiotoxicity and monitoring of cardiotoxicity were quite varied amongst the different guidelines evaluated. Conclusions All studied guidelines need modifications as per the AGREE II evaluating tool. Several shortcomings were identified, including a lack of evidence-based studies supporting the recommendations in the guidelines.

Background Doxorubicin induces acute and chronic cardiotoxicity. This study is aimed to evaluate the efficacy and safety of vitamin E and levocarnitine (EL) as cardioprotective agents against acute doxorubicin cardiotoxicity in female adult breast cancer patients. Methods A prospective, randomized controlled study was conducted in patients treated with doxorubicin and cyclophosphamide (AC). Patients were randomly assigned to EL plus AC or AC alone for the duration of 4 cycles. Cardiac enzymes (B-type natriuretic peptide, creatine kinase, troponin I (Trop)) and cardiac events were monitored during treatment to evaluate the cardioprotective efficacy of EL. Results Seventy-four patients were recruited and received four cycles of chemotherapy. The intervention group ( n = 35) showed a significant reduction in both the B-type natriuretic peptide and creatine kinase cardiac enzymes compared to the control group ( n = 39). The median (IQR) change for BNP was 0.80 (0.00–4.00) for IG versus 1.80 (0.40–3.60) for CG groups ( p Conclusion This study supports the addition of EL as prophylaxis against acute doxorubicin cardiotoxicity and it was also very well tolerated by a majority of the patients. The co-administration of EL at higher doxorubicin (240 mg/m2) dose should be further investigated.

Background: Greater access and prolonged exposure to ART may inevitably lead to more treatment failure and increase the need for third-line ART (TLART) in a resource-limited setting. Objective: To describe characteristics and resistance patterns of adult patients initiated on TLART in three districts of the North West province. Method: All-inclusive retrospective descriptive investigation. Demographics and clinical variables were recorded from adult patient health records (2002-2017) and analysed. Results: 21 Patients (17 females, 4 males) with median (IQR) age of 34 years (30.2-37.8) at HIV diagnosis and 45 years (39.5-47) at TLART initiation were included. Median duration (days) from HIV diagnosis to first-line ART initiation was 101 (37-367), treatment duration on first-line, second-line and between second-line failure and TLART initiation were: 1 269 (765-2 343); 1 512 (706-2096) and 71 (58-126) days respectively. High-level resistance most prevalent were: nelfinavir/r (85.7%), indinavir/r (80.9%), lopinavir/r (76.2%), emtricitabine and lamivudine (95.2%), nevirapine (76.2%) and efavirenz (71.4%). Resistance to 3 major PI mutations in 95% of patients and cross resistance were documented extensively. Conclusion: This study support the need for earlier resistance testing. It firstly reported on time duration post diagnosis on various ART regimens and secondly resistance patterns of adults before TLART was initiated in these districts. Keywords: HIV; Human immunodeficiency virus; third-line antiretroviral therapy; drug resistance patterns; salvage therapy.

Objective Doxorubicin, a component of the anthracycline group, is a highly effective in the treatment of hematologic and solid malignancies. Because of the cardiotoxic adverse effects, use is limited. Antioxidants may negate this anthracycline-induced cardiotoxicity, although the literature is not conclusive with regards to the cardioprotective benefits of antioxidants. This review assessed and mapped evidence of the efficacy of vitamin E and levocarnitine against doxorubicin-induced cardiotoxicity in adult cancer patients. Data Sources This review was based on the Arksey and O’Malley methodology. Potentially relevant literature in English published between January 1960 and April 2021 was identified through a database search. Oxford Quality Scoring System and AMSTR2 were used to assess the quality of trials and systematic reviews respectively, as well as the risks of potential bias. Data Summary Nineteen of the 10 268 (0.2%) articles from the initial search were included in the final analysis (12 clinical trials and 7 systematic reviews). Vitamin E was included in seven prospective clinical trials. Levocarnitine was included in five clinical trials as an individual agent and a single trial as a combination treatment. No trials could be found investigating the combination of vitamin E and levocarnitine in humans. Conclusions This review found that levocarnitine trials showed some cardioprotective effects but the results from vitamin E trials were controversial and inconclusive. Most of the trials reviewed had some shortcomings. Further investigations are therefore needed to determine the efficacy of vitamin E and levocarnitine in preventing doxorubicin-induced cardiotoxicity in adult cancer patients.

Background: The high incidence of adverse drug reactions (ADRs) in children is of global concern. Enhancing the reporting of ADRs could contribute to making safer medicines available to children. Aim: To assess parents’ awareness of reporting ADRs and their knowledge on the reporting procedures in South Africa. Setting: South African parents with online access. Method: A quantitative descriptive study was conducted based on an anonymous voluntarily web-based self-administered questionnaire that was distributed through Facebook® and LinkedIn™ to parents in South Africa. Results: The questionnaire was completed voluntarily by 206 respondents. The majority of participants (70.9%) were aware of the term ADR. Significant associations between not being aware of the term ADR and single marital status, lower education level, not having private medical aid and accessing public clinics for medical services were found. The majority (66.5%) of participants did report an ADR to a healthcare professional whilst only 15% reported it to a product manufacturer. More than half of the participants (58.7%) knew how to report ADRs whilst 72.8% knew what type of ADRs to report. Almost a third (32.5%) did not know where more information on ADR reporting could be found or how ADRs could be reported (31.5%). Conclusion: The majority of the respondents were aware of the term ADR, indicative of a good knowledge basis on which ADRs to report and the importance of reporting ADRs. However, gaps in the respondents’ knowledge were identified which highlighted specific groups of individuals to be targeted to increase ADR awareness and improve the knowledge on the reporting process.

The study aimed to determine factors associated with changes in bone mineral density (BMD) and bone resorption markers over two years in black postmenopausal women living with human immunodeficiency virus (HIV) on antiretroviral therapy (ART). Women (n = 120) aged &gt, 45 years were recruited from Potchefstroom, South Africa. Total lumbar spine and left femoral neck (LFN) BMD were measured with dual energy X-ray absorptiometry. Fasting serum C-Telopeptide of Type I collagen (CTx), vitamin D and parathyroid hormone were measured. Vitamin D insufficiency levels increased from 23% at baseline to 39% at follow up. In mixed linear models serum CTx showed no change from baseline to end (p = 0.363, effect size = 0.09). Total and LFN BMD increased significantly over two years, but effect sizes were small. No significant change in spine BMD over time was detected (p = 0.19, effect size = 0.02). Age was significantly positively associated with CTx over time, and negatively with total and LFN BMD. Physical activity (PA) was positively associated with LFN BMD (p = 0.008). Despite a decrease in serum vitamin D, BMD and CTx showed small or no changes over 2 years. Future studies should investigate PA interventions to maintain BMD in women living with HIV.

Efavirenz is a highly effective HIV-1 antiretroviral; however, it is also frequently associated with neuropsychiatric adverse events (NPAE) that include abnormal dreams, sleep disturbances, nervousness, anxiety, depression, and dizziness. The incidence of NPAEs upon initiation of treatment with efavirenz-containing medications is high, exceeding 50% in most studies. Although the NPAEs tend to decrease after the first month in many patients, they persist for long periods of time in others. Efavirenz-based treatment is generally well-tolerated in children, although some experience persistent concentration problems, as well as sleep disturbances, psychotic reactions, and seizures. In an effort to link basic with clinical research, parameters associated with efavirenz brain exposure are discussed, and factors that increase efavirenz levels are explored in depth as they are expected to contribute to NPAE risk. These include the role of modifiable and nonmodifiable risk factors such as diet, weight, and drug-drug interactions and sex, age, and ethnicity/pharmacogenetics. In addition to NPAEs, this review explores what is known about antiretroviral (ARV) drugs being used for recreational purposes. Although multiple ARV drugs are covered, special attention is devoted to efavirenz given that the majority of reports of NPAEs and illicit use of ARV drugs concern efavirenz. The evolving molecular mechanistic basis of NPAEs and abuse of efavirenz point to a complex and polymodal receptor pharmacology. Animal studies to date primarily point to a serotonergic mechanism of action. Recently emerging associations between HIV-associated neurocognitive disorder and efavirenz use, and possible contributions of the mitochondrial-immune-inflammatory-redox cascade are explored in the context of the signaling mechanisms that appear to be involved.

Despite some modest improvements described recently, anaemia remains a significant global public health concern affecting both developed and developing countries. It affects a quarter of the global population, including 293 million (47%) children who are younger than five years of age. A prevalence of 42% and 30% has been described in pregnant and non-pregnant women, respectively. Children and women of reproductive age are at high risk, partly because of physiological vulnerability, followed by the elderly. Africa and Asia are the most heavily affected regions, accounting for 85% of the absolute anaemia burden in highrisk groups. According to the World Health Organization global database on anaemia (1993–2005), this disorder was considered to be a moderate public health problem in South African preschool children, pregnant women and non-pregnant women of reproductive age. There has been an increased awareness of anaemia and its consequences on the health and development of women and children in the past few decades. The many underlying causes of the various types of anaemia seen in general practice means it is essential that practitioners’ clinical decisions be underpinned by a sound knowledge of the pathological processes involved. Thorough history-taking will guide practitioners to request specific tests to confirm or refute differential diagnoses. Management must be developed around the specific type of anaemia and the potential physical and psychological effects it may have on the individual.

The need for interprofessional education (IPE) in health science disciplines is a current global trend. However, despite international support and demand, IPE is still new to many health professions curricula in South Africa. Furthermore, while ample existing academic literature addresses commonly encountered barriers to IPE, there is still a need to investigate the dynamics and challenges associated with the process of implementing IPE at universities. IPE is not yet part of the formal curriculum at a faculty of health sciences at a South African Higher Education Institute, so a pilot project was conducted to investigate the experiences of an IPE process by students from different health professions toward informing the planning and implementation of IPE in the formal curriculum. To this effect, a multi-layered IPE project was piloted across pharmacy, nursing, social work, psychology, dietetics, and human movement sciences within this Faculty of Health Sciences. The aim of this research was to determine the dynamics between the different health professions by exploring and describing the students' experiences of the IPE process. Theoretical case studies were presented to third-year students, who were grouped into interprofessional teams from the six different health professions at the Higher Education Institute's health sciences faculty. Data were gathered from reflective journals over a five-week period and a questionnaire was administered at the end of the project. Data were analysed and evaluated based on the interprofessional learning domains listed in the IPE framework of the World Health Organization. All participating health professions students felt positive about the project and agreed that it provided them with valuable IPE experiences. However, their long-term participation and commitment presented difficulty in an already demanding curriculum. The interprofessional dynamics were influenced by the relevance of the scenarios presented in the case studies to the different professions, the students' personalities and their previous experiences. Although the nursing students took initial leadership, contributions from the other professions became more prominent as the case studies unfolded. The findings indicated that the inclusion of different health professions in an interprofessional team should be guided by the specific scenarios incorporated to simulate interprofessional cooperation. The availability of the students and their scope of practice at third-year level should also be taken into account.

Objectives: To investigate the differences between bone mineral density (BMD), lean and fat mass of human immunodeficiency virus (HIV-) positive and HIV-negative black women and to investigate factors associated with low BMD. Methods: Case-control study of black women (n = 565) aged 29–65 years from Potchefstroom, North West province, South Africa, based on secondary analysis of data. Total BMD, left femur neck of the hip (LFN BMD), spine BMD, total fat, fat-free tissue mass and percentage body fat (%BF) were measured by dual-energy X-ray absorptiometry. Results: HIV-negative women had significantly higher median BMD, %BF, appendicular skeletal mass (ASM), ASM index, body mass index (BMI) and waist circumference than HIV-positive women. When the groups were matched for age and BMI, only spine BMD was marginally lower in HIV-positive women. In the total group, age, smoking and HIV status were associated with lower BMD, while calcium intake was positively associated with BMD. Similar variables were associated with BMD in HIV-negative women, while age and educational status were associated with BMD in HIV-positive women. Conclusion: Low BMD was more common among HIV-positive than HIV-negative women. Older HIV-positive women with low educational status are particularly at risk

Background: South Africa has the highest number of patients on antiretroviral therapy (ART) globally. Various obstacles were identified that influence effective reporting of adverse drug reactions (ADRs) in resource-limited countries. This investigation aimed to identify, classify and analyse the prevalence of ART-related ADRs. Methods: This observational, quantitative and retrospective descriptive investigation utilised ADR forms completed by healthcare professionals in various healthcare facilities in the Tlokwe district, South Africa (January 2010 to December 2014). Descriptive and inferential analyses were carried out. Results: A total of 770 ART-related ADRs were included in the final analysis. The mean age was 40.1 (± 10.1%) years, with significantly higher ADRs reported in females (70.8%). In this study, 99% of the ADRs were reported by doctors. Abnormal fat distribution (58%), peripheral neuropathy (21.6%) and renal dysfunction (6.6%) were most frequently reported. Females presented with abnormal fat distribution and peripheral neuropathy at a significantly younger age (38.1 ± 4.6 vs. 43.4 ± 5.7 years, p < 0.0001 and 39.7 ± 1.1 vs. 45.1 ± 9.2 years, p < 0.001) respectively compared with males. Gender difference was practically significant (Cramer’s V = 0.3) for all three of the major reported ADRs. Conclusions: Gender was highly dependent among the major reported ADR categories, and women presented with abnormal fat distribution and peripheral neuropathy at a significantly earlier age than males. This retrospective analysis can serve as a platform for future ADR studies within this district. Sustainable and continuous efforts should be made to train and create more awareness among healthcare workers in this district. (Full text of the research articles are available online at www.medpharm.tandfonline.com/ojfp) S Afr Fam Pract 2018; DOI: 10.1080/20786190.2017.1364013

In South Africa, the pursuit of distributive justice is eminently permissible if not compelled by South African Competition Law and its unique responsiveness to issues of distributional equity and fairness. For example, in merger regulation the Competition Act permits consideration of equity issues such as empowerment, employment, and concern for small and medium-sized enterprises (SMEs). The Walmart/Massmart case illustrates how the competition authorities have implemented public interest provisions in merger control, while the Pioneer Foods settlement provides an example of crafting creative remedies to restore competition and at the same time pursue distributive justice. As we explain in more detail in the chapter, these two cases show how the competition authorities pursue equity issues such as empowerment, employment, and concern for small and medium-sized enterprises, as well as promote competition.

South Africa has the highest burden of the human immunodeficiency virus (HIV) infection globally. Efavirenz (EFV), a frequently used drug against HIV infection, displays a relationship between drug concentration and pharmacodynamics effects clinically. However, haplotype-based genetic variation in drug metabolism in a pediatric sample has been little considered in a longitudinal long-term context. CYP2B6 plays a key role in variation of EFV plasma concentration through altered drug metabolism. We report here on a prospective clinical pharmacogenomics/pharmacokinetic study of Bantu-speaking children, importantly, over a period of 24 months post-initiation of EFV-based treatment in South Africa. We characterized the HIV-1-infected children (n = 60) for the CYP2B6 c.516G>T, c.785A>G, c.983T>C, and c.1459C>T single nucleotide polymorphisms (SNPs). These SNPs were determined using polymerase chain reaction/restricted fragment length polymorphism and SNaPshot genotyping. Longitudinal mid-dose EFV plasma concentrations were determined by LC-MS/MS and association analyses with genotypes and haplotypes at 1, 3, and 24 months were performed. The CYP2B6 c.516T/T genotype showed significantly higher EFV plasma concentrations (p T,–c.785A>G and c.983T>C. The haplotype T-G-T presented with significantly increased EFV plasma concentrations compared to the reference G-A-T haplotype at 1, 3, and 24 months (p = 0.009; p = 0.003; p = 0.001), suggesting that the T-G-T haplotype predisposes a risk of EFV plasma concentrations >4 μg/mL. The clinical implications of these pharmacogenomics observations for EFV toxicity and treatment resistance warrant further future research

Background: Tenofovir disoproxil fumarate (TDF) antiretroviral therapy is associated with disruption of the bone turnover process.Objectives: The objective of this study was to determine the association between tenofovir (TFV) plasma concentration and various bone turnover markers and compare these markers in HIV-infected women and HIV-uninfected controls.Method: A cross-sectional sub-study included 30 HIV-infected women on TDF and 30 HIV-uninfected matched participants. Serum calcium (SrCa), serum phosphate (SrP), C-terminal telopeptide (CTx), parathyroid hormone (PTH), alkaline phosphatase (ALP), C-reactive protein (CRP), vitamin D (VitD) and bone mineral density (BMD) were measured. Plasma TFV was assayed on HPLC-MS/MS. The statistical tests applied were Mann–Whitney test, unpaired t-test, analysis of covariance, regression and correlation analysis.Results: In HIV-infected women, no correlation existed between plasma TFV concentration and CTx, PTH, ALP, SrCa, SrP, VitD or BMD (p > 0.05). After adjusting for smoking and alcohol use, ALP (p < 0.001), CTx (p = 0.027) and PTH (p = 0.050) were significantly higher in HIV-infected compared to HIV-uninfected women. Women with TFV concentration ≥ 120 ng/mL had higher PTH concentrations (p = 0.037) compared to those with ≤ 100 ng/mL. Significant correlations between SrCa and PTH and SrCa and SrP including CTx and PTH (p < 0.05) were present in HIV-uninfected women while absent in HIV-infected counterparts (p > 0.05).Conclusion: The results indicate possible increased bone turnover at higher TFV concentrations. The normal regular bone turnover processes in HIV-infected women on TDF therapy are altered. Larger studies are warranted to confirm these results.

Background: Tenofovir disoproxil fumarate (TDF) has been associated with kidney tubulardys function and reduced renal function. Limited studies were performed in Europe and Asia that related plasma tenofovir (TFV) concentration with renal function; no such studies to date have been performed on Africans. Objective: To investigate the correlation between plasma tenofovir (TFV) concentration and certain renal function markers in HIV-infected women on TDF antiretroviral therapy (ART).These markers were also compared to a HIV-uninfected control group. Methods: HIV-infected women ( n = 30) on TDF-based ART were matched with 30 controls forage and body mass index. Renal markers analysed were estimated glomerular filtration rate (eGFR), creatinine clearance (CrCl), serum creatinine, albuminuria, glucosuria, serum urea, serum uric acid, urine sodium and maximum tubular reabsorption of phosphate. Baseline eGFR and CrCl data were obtained retrospectively for the HIV-infected women. Plasma TFV was assayed using a validated HPLC-MS/MS method. Step wise regression, Mann–Whitney test, unpaired and paired t -tests were applied in the statistical analyses. Results: TFV concentration was independently associated with albuminuria (adjusted r 2 = 0.339; p = 0.001) in HIV-infected women. In the adjusted (weight) analysis, eGFR ( p = 0.038),CrCl ( p = 0.032) and albuminuria ( p = 0.048) were significantly higher in HIV-infected compared to the uninfected women, but eGFR was abnormally high in HIV-infected women. Both eGFR ( p < 0.001) and CrCl ( p = 0.008) increased from baseline to follow-up in HIV-infected women. Conclusion: Plasma TFV concentration was associated with increased albuminuria in HIV infected women in this sub-study. Both eGFR and CrCl were increased in HIV-infected women from baseline. These findings should be confirmed in larger studies, and hyperfiltration in HIV-infected women warrants further investigation.

Objective To investigate the influence of CYP2B6 516G>T polymorphism, as a covariate, and of interoccasion variability (IOV) on the oral clearance (CL/F) of efavirenz (EFV) in treatment-naïve black South African children over a period of 24 months post-antiretroviral therapy (ART) initiation. Methods HIV-infected black children (n = 60, aged 3–16 years), with no prior exposure to ART, eligible to commence ART and attending an outpatient clinic were enrolled into this study. Blood samples were taken at mid-dose interval at 1, 3, 6, 12, 18 and 24 months post-ART initiation. EFV plasma samples were determined with an adapted and validated LC/MS/MS method. Genotyping of the CYP2B6 G516T single nucleotide polymorphism (SNP) was performed using polymerase chain reaction–restriction fragment length polymorphism (PCR-RFLP). NONMEM was used for the population pharmacokinetic modelling. Results EFV concentrations below 1 μg/mL accounted for 18% (116/649), EFV concentrations >4 μg/mL accounted for 29.5% (192/649) and concentrations within the therapeutic range (1–4 μg/mL) represented 52.5% (341/649) of all the samples determined. The covariates age, weight and CYP2B6 G516Tgenotype were included in the final model with population estimates for CL/F determined as 2.46, 4.60 and 7.33 L/h for the T/T, G/T and G/G genotype groups respectively. Conclusions The inclusion of both age and weight to predict accurate EFV CL values for the respective genotype groups within this paediatric population was required, whereas the addition of gender and body surface area did not improve the predictions. The importance of introducing IOV in a PK model for a longitudinal study with sparsely collected data was again highlighted by this investigation. http://dx.doi.org/10.1007/s00228-011-1148-7

The aim of this study was to quantify the plasma efavirenz concentrations over 6 months in black HIV-1-infected South African children (3-14 years), from resource-limited households, attending an outpatient clinic. The children were antiretroviral treatment (ART) naive and received efavirenz in combination with two nucleoside reverse transcriptase inhibitors according to South African national guidelines. Two blood samples were taken between 12 and 20 h after the last efavirenz dose at 1 (n = 58), 3 (n = 54), and 6 (n = 54) months post-ART initiation. A total of 328 efavirenz mid-dose plasma samples from 58 patients was determined with a validated liquid chromatography tandem mass spectrometry method. Viral suppression (25 copies/ml) was achieved in 95% of the children after 6 months on ART. The median (range) plasma concentration at time points 1 and 2 were 2.06 (0.10-11.14) and 1.80 (0.14-10.70) microg/ml with respective mean (+/-SD) blood sampling times of 15.24 (2.03) and 16.91 (2.03) h post-evening dose. Efavirenz plasma samples within the therapeutic range of 1-4 microg/ml accounted for 58%; 17% were1 microg/ml and 25% were4 microg/ml over the 6 months. Efavirenz levels persistently4 microg/ml were recorded for 13 (23%) children and 3 (5%) children had persistent efavirenz levels1 microg/ml. Possible reasons for efavirenz plasma levels outside the accepted therapeutic range include genetic variation in drug metabolism, incorrect dosing, drug-drug interactions, and nonadherence. However, these need to be further explored and the importance of sequential plasma levels has been highlighted in this study.

Determination of plasma tenofovir (TFV) concentrations in small plasma volumes and in a short time period is most desirable in a clinical setting. The HPLC-MS/MS method was developed and validated for the determination of TFV. Plasma sample volumes of 10 μL were extracted by protein precipitation. Cimetidine, used as internal standard (ISTD) and TFV were separated on a C18 (Phenomenex Kinetex TM 30 mm × 2.1 mm, 2.6 μm) reversed phase column with a pre-column. The gradient mobile phase consisted of 10 mmol/L ammonium acetate in water and acetonitrile/methanol (50:50, v/v). TFV and ISTD retentiontimes were 0.27 and 0.90 minutes, respectively, with a run time of 2 minutes. Transition of the parent to the product ion of TFV (m/z 288.072→176.038) and ISTD (m/z 253.13→158.987) were monitored in positive ionization mode. Calibration curves were linear (average r2, 0.9958) over a TFV concentration range of 12.5-600 ng/mL. The mean recovery was 96.9%. Accuracy, inter and intra-assay of three quality controls and lower limit of quantification (12.5 ng/mL) were within the acceptable limit of

Anemia is a common complication of pediatric HIV infection and is associated with suboptimal cognitive performance and growth failure. Routine iron supplementation is not provided to South African HIV-infected children. We hypothesized that dietary iron intake without supplementation is sufficient to protect against iron deficiency (ID) in HIV-infected children receiving highly active antiretroviral therapy. In this prospective study, the difference between dietary intakes of iron-deficient children (soluble transferrin receptor >9.4 mg/L) and iron-sufficient children after 18 months on highly active antiretroviral therapy was examined. The association between iron intake and hemoglobin (Hb) concentration was also assessed. Longitudinal data collected for 18 months from 58 HIVinfected African children were assessed by generalized estimation equations, with adjustment for demographic information, dietary intakes, growth parameters, and CD4%. After adjustment for covariates, the longitudinal association between dietary iron intake and Hb concentration remained significant. This association shows that for every 1-mg increase in iron intake per day, Hb increases by 1.1 g/L (P < .001). Mean Hb increased significantly after 18 months of follow-up (106 ± 14 to 129 ± 14 g/L, P < .01), but soluble transferrin receptor also increased (7.7 ± 2.7 to 8.9 ± 3.0 mg/L, P < .01). The incidence of ID increased from 15.2% at baseline to 37.2% after 18 months. Children with animal protein intakes greater than >20 g/d had significantly lower odds for ID at 18 months than did children with lower intakes (odds ratio, 0.40; 95% confidence interval, 0.21-0.77). Dietary iron intake was insufficient to protect against ID, pointing to a need for low-dose iron supplementation for iron-deficient HIV-infected children and interventions to increase the consumption of animal protein. http://dx.doi.org/10.1016/j.nutres.2012.11.008 http://www.sciencedirect.com/science/article/pii/S0271531712002473 http://www.journals.elsevier.com/nutrition-research/

The interaction between verapamil, a P-glycoprotein (P-gp) inhibitor, with ritonavir and lopinavir/ritonavir (LPV/r) after acute and chronic treatment was investigated in rats. Rats were divided into 4 groups, viz. Group 1: ritonavir, 20 mg/kg/d (n=18), group 2: ritonavir, 20 mg/kg/d plus verapamil 5 mg/kg/d (n=18), group 3: LPV/r, 80 and 20 mg/kg/d (n=17) and group 4: LPV/r, 80 and 20 mg/kg/d plus verapamil 5 mg/kg/d (n=18). Blood samples were collected after decapitation on days 1, 7 and 21. Lopinavir and ritonavir plasma levels were simultaneous determined by a validated LC/MS/MS method. The lower limit of quantification for both ritonavir and lopinavir was 0.078 µg/ml. Verapamil significantly increased ritonavir plasma levels, administered as monotherapy, following acute (p

A novel and robust screening method for the determination of the non-nucleoside reverse transcriptase inhibitor, efavirenz (EFV), in human saliva has been developed and validated based on high performance liquid chromatography tandem mass spectrometry (LC-MS/MS). Sample preparation of the saliva involved solid-phase extraction (SPE) on C18 cartridges. The analytes were separated by high performance liquid chromatography (Phenomenex Kinetex C18, 150mm×3mm internal diameter, 2.6μm particle size) and detected with tandem mass spectrometry in electrospray positive ionization mode with multiple reaction monitoring. Gradient elution with increasing methanol (MeOH) concentration was used to elute the analytes, at a flow-rate of 0.4mL/min. The total run time was 8.4min and the retention times for the internal standard (reserpine) was 5.4min and for EFV was 6.5min. The calibration curves showed linearity (r(2), 0.989-0.992) over the concentration range of 3.125-100μg/L. Mean intra- and inter-assay relative standard deviation, accuracy, mean extraction recovery, limit of detection (LOD) and limit of quantification (LOQ) were 0.46-9.43%, 80-120%, 60% (±7.95), 1.84 and 6.11μg/L respectively. The working range was defined as 6.25-100μg/L. This novel LC-MS/MS assay is suitable for reliable detection of low EFV concentrations in saliva and can be used as a screening tool for monitoring EFV compliance.

Purpose: The purpose of this pilot study was to investigate the effect of different size pinholes on visual acuity (VA) at near (0.4 m) while various factors were altered. The alterations made involved accommodation and illumination.Method: Four subjects were selected and their ages ranged from 7 to 14 years. Subjective refractions were performed and then near visual acuities were measured at 0.4 m under two different lighting conditions (460 lux and 1 lux) by adding stigmatic (or spherical) lenses of positive and negative powers in front of pinholes of diameters 1.5 mm and 2 mm.Results: The results showed that there was an improvement in VA in most, however, the size of the pinhole played a minor role. Low illumination did have a drastic effect on our results not only by decreasing the amount of lenses used for near that gave more positive results, but also when the pinhole was placed in front of the subjects. According to Borish, the pinhole does improve VA by a straight forward process of elimination produced by spherical aberrations of the eye. However, this did not seem to be the case in this study under conditions of low illumination.Conclusion: The pinhole effect offers improvement in VA at near by reducing the amount of blupresented to the retina. This study showed that alsubjects had an improvement in VA of at least twolines in high illumination. Pinhole size did not alte the results sufficiently thus suggesting that a pinhole, no matter the size, should increase the VA. However this was not the case when illumination was decreased.

This study addresses the role of psychofortigenic factors in maintaining quality of life in elderly people diagnosed with either rheumatoid arthritis or Alzheimer's disease. Opsomming Hierdie studie handel oor die rol wat psigofortigene faktore speel in die handhawing van lewenskwaliteit deur bejaardes wat gediagnoseer is met rumatoïede artritis of Alzheimer se siekte. *Please note: This is a reduced version of the abstract. Please refer to PDF for full text.

Potchefstroom experienced an outbreak of Neisseria meningitidis (N. meningitidis) during May-July 2003. An opportunity for obtaining valuable data arose when mass prophylactic treatment to approximately 28% of the Potchefstroom community was provided by the Department of Health, North-West Province. Opsomming ‘n Uitbraak van Neisseria meningitidis (N. meningitidis) gedurende Mei-Julie 2003 en die daaropvolgende verskaffing van massa-profilakse deur die Departement van Gesondheid, Noordwesprovinsie aan ongeveer 28% van die plaaslike gemeenskap het ‘n geleentheid geskep om waardevolle inligting in te win. *Please note: This is a reduced version of the abstract. Please refer to PDF for full text.