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Biomedical subjects

Z A Bhutta

Publications and source records attributed to Z A Bhutta.

At least 19 recordsLinked to original sources
PubMed2006

Multiple-micronutrient supplementation for women during pregnancy.

BACKGROUND: Multiple-micronutrient deficiencies often coexist in low- to middle-income countries. They are exacerbated in pregnancy due to the increased demands, leading to potentially adverse effects on the mother. Substantive evidence regarding the effectiveness of multiple-micronutrient supplements (MMS) during pregnancy is not available. OBJECTIVES: To evaluate the benefits to mother and infant of multiple-micronutrient supplements in pregnancy and assess the risk of excess supplementation and potential adverse interactions between micronutrients. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (30 December 2005). SELECTION CRITERIA: All prospective randomised controlled trials evaluating micronutrient supplementation during pregnancy and its effects on the pregnancy outcome. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed trial quality and extracted the data. MAIN RESULTS: Nine trials (15,378 women) are included. When compared with supplementation of two or less micronutrients or no supplementation or a placebo, multiple-micronutrient supplementation resulted in a statistically significant decrease in the number of low birthweight babies (relative risk (RR) 0.83; 95% confidence interval (CI) 0.76 to 0.91), small-for-gestational-age babies (RR 0.92; 95% CI 0.86 to 0.99) and in maternal anaemia (RR 0.61; CI 0.52 to 0.71). However, these differences lost statistical significance when multiple-micronutrient supplementation was compared with iron folic acid supplementation alone. No statistically significant differences were shown for the outcomes of preterm births and perinatal mortality in any of the comparisons. A number of prespecified clinically important outcomes could not be assessed due to insufficient or non-available data from the included trials. These include placental abruption, congenital anomalies including neural tube defects, premature rupture of membranes, pre-eclampsia, miscarriage, maternal mortality, neurodevelopmental delay, very preterm births, cost of supplementation, side-effects of supplements, maternal wellbeing or satisfaction and nutritional status of children. AUTHORS' CONCLUSIONS: The evidence provided in this review is insufficient to suggest replacement of iron and folate supplementation with a multiple-micronutrient supplement. A reduction in the number of low birthweight and small-for-gestational-age babies and maternal anaemia has been found with a multiple-micronutrient supplement against supplementation with two or less micronutrients or none or a placebo, but analyses revealed no added benefit of multiple-micronutrient supplements compared with iron folic acid supplementation. These results are limited by the small number of studies available. There is also insufficient evidence to identify adverse effects and to say that excess multiple-micronutrient supplementation during pregnancy is harmful to the mother or the fetus. Further research is needed to find out the beneficial maternal or fetal effects and to assess the risk of excess supplementation and potential adverse interactions between the micronutrients.

Dietary Supplements↗
PubMed2006

Pyridoxine (vitamin B6) supplementation in pregnancy.

BACKGROUND: Vitamin B6 plays vital roles in numerous metabolic processes in the human body, such as nervous system development and functioning. It has been associated with some benefits in non-randomised studies, such as higher Apgar scores, higher birthweights, and reduced incidence of pre-eclampsia and preterm birth. Recent studies also suggest a protection against certain congenital malformations. OBJECTIVES: To evaluate the clinical effects of vitamin B6 supplementation during pregnancy and/or labour. SEARCH STRATEGY: We searched the Cochrane Pregnancy and Childbirth Group Trials Register (30 December 2005). SELECTION CRITERIA: We included randomised controlled trials comparing vitamin B6 administration in pregnancy and/or labour with: placebos, no supplementations, or supplements not containing vitamin B6. DATA COLLECTION AND ANALYSIS: Two authors independently extracted data and assessed trials for methodological quality. We used relative risk and weighted mean difference with 95% confidence intervals. MAIN RESULTS: Five trials (1646 women) were included. Four trials used blinding. One had adequate method of randomisation and allocation concealment; four did not report this. Three trials had large losses to follow up. Vitamin B6 as oral capsules or lozenges resulted in decreased risk of dental decay in pregnant women (capsules: relative risk (RR) 0.84; 95% confidence interval (CI) 0.71 to 0.98; one trial, n = 371; lozenges: RR 0.68; 95% CI 0.56 to 0.83; one trial, n = 342). A small trial showed reduced mean birthweights with vitamin B6 supplementation (weighted mean difference -0.23 kg; 95% CI -0.42 to -0.04; n = 33; one trial). We did not find any statistically significant differences in the risk of eclampsia (capsules: n = 1242; three trials; lozenges: n = 944; one trial), pre-eclampsia (capsules n = 1197; two trials; lozenges: n = 944; one trial) or low Apgar scores at one minute (oral pyridoxine: n = 45; one trial), between supplemented and non-supplemented groups. No differences were found in Apgar scores at one or five minutes, or breastmilk production between controls and women receiving oral (n = 24; one trial) or intramuscular (n = 24; one trial) loading doses of pyridoxine at labour. AUTHORS' CONCLUSIONS: There were few trials, reporting few clinical outcomes and mostly with unclear trial methodology and inadequate follow up. There is not enough evidence to detect clinical benefits of vitamin B6 supplementation in pregnancy and/or labour other than one trial suggesting protection against dental decay. Future trials assessing this and other outcomes such as orofacial clefts, cardiovascular malformations, neurological development, preterm birth, pre-eclampsia and adverse events are required.

Dietary Supplements↗
PubMed2006

Enhanced detection rate of typhoid fever in children in a periurban slum in Karachi, Pakistan using polymerase chain reaction technology.

OBJECTIVE: Yield of blood culture in clinically suspected cases of typhoid fever is low, whereas indirect serological diagnostic tests are unreliable. Hence, polymerase chain reaction (PCR)-based detection of Salmonella enterica Serovar typhi was used as an aid for diagnosis of typhoid fever in addition to other diagnostic tests. Two periurban communities in Karachi were selected for an epidemiological study of typhoid fever. The aim of the study was to assess whether PCR increased the detection rate of typhoid fever in children in the community. MATERIAL AND METHODS: Children aged 2 to 14 years presenting with fever lasting for three or more days were selected. PCR using Hashimoto's protocol based on ViaB gene sequence was used in addition to blood culture and other serological tests. RESULTS: Of the 214 children included in the study, blood culture was found positive for S. enterica S. typhi in 26 (12.4%) cases, whereas 24 children (11.7%) were diagnosed as suffering from typhoid fever when the PCR-based method was used. Both tests were positive in only 10 (4.9%) children. The number of children found positive for either test was 40. PCR increased the rate of detection of typhoid fever by 51%. CONCLUSION: The sensitivity, specificity, +ve and -ve predictive values of PCR in this study were 40%, 93%, 45% and 92%, respectively.

Adolescent↗
PubMed2006

Profile and factors determining outcome in a cohort of cystic fibrosis patients seen at the Aga Khan University Hospital, Karachi, Pakistan.

Cystic fibrosis is the most common potentially lethal autosomal recessive, genetic disease associated with pulmonary and pancreatic insufficiency. It is caused by variations in the CFTR (cystic fibrosis transmembrane regulator) gene. The most common mutation in the CFTR gene designated DeltaF508, is found in only 33 per cent of CF patients in Pakistan. The variability in presentation and clinical severity of disease may be a function of genotypic-phenotypic factors. Our aim was to attempt to define the disease in this region and to lay the ground work for future mutational analysis. This study was a retrospective chart review was conducted to identify cystic fibrosis patients seen at the Aga Khan University Hospital over a 10-year period. Our study identified 56 patients diagnosed by a pilocarpine iontophoresis sweat test. A chart review was then done to look at the various clinical profiles. 58.3 per cent of our patients presented in the first 6 months of life supporting the hypothesis that CF may be a severe disease in Asians with an earlier age of presentation. Most of the patients (80.6 per cent) presented with pulmonary problems while 83.9 per cent had failure to thrive. The most frequently isolated pathogen was Pseudomonas aeruginosa in 87.5 per cent of the patients tested. 70 per cent of the patients died in the first year of life. The clinical parameters studied suggest a severe form of CF in Pakistani patients and provides a foundation for future studies to define genotype/phenotype correlations of the specific mutations involved in Pakistani CF patients.

Child↗
PubMed2005

Fluoroquinolones for treating typhoid and paratyphoid fever (enteric fever).

BACKGROUND: Fluoroquinolones are recommended as first-line therapy for typhoid and paratyphoid fever, but how they compare with other cheaper antibiotics and different fluoroquinolones is unclear. OBJECTIVES: To evaluate fluoroquinolone antibiotics for treating enteric fever in children and adults compared with other antibiotics, different fluoroquinolones, and different treatment durations of the same fluoroquinolone. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group Specialized Register (August 2004), CENTRAL (The Cochrane Library Issue 3, 2004), MEDLINE (1966 to August 2004), EMBASE (1974 to August 2004), LILACS (1982 to August 2004), conference proceedings, reference lists, and contacted researchers. SELECTION CRITERIA: Randomized controlled trials of fluoroquinolones in people with blood or bone marrow culture-confirmed enteric fever. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed the methodological quality of trials and extracted data. We calculated the odds ratio (OR) for dichotomous data with 95% confidence intervals. We analysed norfloxacin separately. MAIN RESULTS: Thirty-three trials met the inclusion criteria; 22 had unclear allocation concealment, and 29 were not blinded. Three trials exclusively included children, and two studied outpatients. The main analysis examined clinical failure, microbiological failure, and relapse. Compared with chloramphenicol, fluoroquinolones were not statistically significantly different for clinical (544 participants) or microbiological failure (378 participants) in adults; they reduced clinically diagnosed relapse in adults (OR 0.14, 0.04 to 0.50; 467 participants, 6 trials), but this was not statistically significant in participants with blood culture-confirmed relapse (121 participants, 2 trials). Compared with co-trimoxazole, we detected no statistically significant difference (82 participants, 2 trials). Among adults, fluoroquinolones reduced clinical failure compared with ceftriaxone (OR 0.08, 0.01 to 0.45; 120 participants, 3 trials), but showed no difference for microbiological failure or relapse. We detected no statistically significant difference between fluoroquinolones and cefixime (80 participants, 1 trial) or azithromycin (152 participants, 2 trials). In trials of hospitalized children, fluoroquinolones were not statistically significantly different from ceftriaxone (60 participants, 1 trial, involving norfloxacin) or cefixime (82 participants, 1 trial). Norfloxacin had more clinical failures than other fluoroquinolones (417 participants, 5 trials). Trials comparing different durations of fluoroquinolone treatment showed no statistically significant differences (693 participants, 8 trials). AUTHORS' CONCLUSIONS: Many trials were small, and methodological quality varied widely. Although enteric fever most commonly affects children, trials in this group were particularly sparse. Insufficient data in all comparisons preclude any firm conclusions to be made regarding superiority of fluoroquinolones over first-line antibiotics in children and adults.

Adult↗
PubMed2004

Beyond Bellagio: addressing the challenge of sustainable child health in developing countries.

Despite the hype and ostensible investments in child survival strategies, the state of child health in much of the developing world is alarming. Not only are global investments and support programmes for child health by the development agencies declining, but commensurate support for maternal and child health by poor countries themselves is poor. In order to make a meaningful contribution to maternal and child health and survival, a multi-pronged approach is needed which not only focuses on the proximal determinants of child health but also some of the underlying factors governing the status of women in society and expenditures on health and development.

Child↗
PubMed2002

Genetic diversity of Salmonella enterica serovar Paratyphi A from different geographical regions in Asia.

AIMS: Subtyping of Salmonella Paratyphi A isolates from India, Pakistan, Indonesia and Malaysia was carried out by pulsed-field gel electrophoresis (PFGE) to assess the extent of genetic diversity of these isolates from different endemic countries. METHODS AND RESULTS: A total of 39 human isolates of Salmonella Paratyphi A from Pakistan, India, Indonesia and Malaysia were studied using PFGE analysis following digestion of chromosomal DNA with XbaI. Seven isolates from Pakistan were resistant to ampicillin, tetracycline and cotrimoxazole. It was noted that Salmonella Paratyphi A isolates obtained from outbreaks in India had limited genetic diversity and probably belonged to closely related clones. Significant genetic homogeneity was observed among antimicrobial-resistant isolates from Pakistan and antimicrobial-sensitive isolates from Pakistan and Indonesia, respectively. CONCLUSIONS: PFGE was a useful subtyping technique to differentiate Salmonella Paratyphi A from different endemic countries. However, it fails to differentiate the antimicrobial-resistant and -sensitive strains. SIGNIFICANCE AND IMPACT OF THE STUDY: The findings of the present study verify the usefulness of PFGE in characterizing and comparing strains of Salmonella Paratyphi A. Our study suggests that a limited number of clones are responsible for paratyphoid fever in these countries.

Asia↗
PubMed2000

Multidrug-resistant strains of Salmonella enterica serotype typhi are genetically homogenous and coexist with antibiotic-sensitive strains as distinct, independent clones.

OBJECTIVE: The goal of this study was to report the molecular analysis of antibiotic-sensitive and multidrug-resistant (MDR) strains of Salmonella typhi, using pulsed-field gel electrophoresis (PFGE), with a particular emphasis on the coexistence of these strains in a typhoid-endemic region of Karachi, Pakistan. METHODS: One hundred isolates of S. typhi in humans (50 MDR and 50 antibiotic-sensitive isolates) from sporadic cases of typhoid fever were analyzed by Vi-phage typing, antibiograms and PFGE. RESULTS: The MDR S. typhi strains were resistant to ampicillin, chloramphenicol, and trimethoprim-sulfamethoxazole. Analysis by PFGE showed that 50 MDR isolates of S. typhi had a single, homogenous PFGE profile, which was distinctly different from that of 50 antibiotic-sensitive isolates obtained in the same time frame from the same area. This latter group of isolates showed much greater diversity of PFGE profiles, as has been observed in other endemic regions. CONCLUSIONS: Multidrug-resistant and antibiotic-susceptible strains of S. typhi can coexist in endemic areas as epidemiologically independent pathogens and are not in competition for continued persistence and transmission.

Adolescent↗
PubMed2000

Therapeutic effects of oral zinc in acute and persistent diarrhea in children in developing countries: pooled analysis of randomized controlled trials.

BACKGROUND: Zinc deficiency is prevalent in children in developing countries. Supplemental zinc provides therapeutic benefits in diarrhea. OBJECTIVE: We sought to measure the effect of supplemental zinc given with oral rehydration therapy during recovery from acute or persistent diarrhea. DESIGN: We conducted pooled analyses including all available published and unpublished randomized controlled trials of the effects of supplementary oral zinc in children aged <5 y with acute or persistent diarrhea. We used Cox survival regression analysis to evaluate the overall effect of zinc on continuation of diarrhea and possible differential effects in subgroups divided by sex, age, weight-for-height, and initial plasma zinc concentration. Dichotomous outcomes were analyzed by logistic regression. To assess the effects of excluding studies without original data from the pooled analyses, effect-size was estimated for all studies by using random-effects models. RESULTS: Zinc-supplemented children had a 15% lower probability of continuing diarrhea on a given day (95% CI: 5%, 24%) in the acute-diarrhea trials and a 24% lower probability of continuing diarrhea (95% CI: 9%, 37%) and a 42% lower rate of treatment failure or death (95% CI: 10%, 63%) in the persistent-diarrhea trials. In none of the subgroup analyses were the 2 subgroups of each pair significantly different from each other; however, in persistent diarrhea there tended to be a greater effect in subjects aged <12 mo, who were male, or who had wasting or lower baseline plasma zinc concentrations. CONCLUSION: Zinc supplementation reduces the duration and severity of acute and persistent diarrhea.

Acute Disease↗
PubMed2000

Failure of short-course ceftriaxone chemotherapy for multidrug-resistant typhoid fever in children: a randomized controlled trial in Pakistan.

The precise duration of therapy of multidrug-resistant (MDR) typhoid with broad-spectrum cephalosporins is uncertain. We prospectively randomized 57 children with culture-proven MDR typhoid to receive treatment with intravenous ceftriaxone (CRO) (65 mg/kg of body weight/day) for 7 days (short course; n = 29) or 14 days (conventional; n = 28). The response to therapy, as evaluated by the serial monitoring of the typhoid morbidity score and bacteriological clearance, was comparable between groups. In contrast to the conventional therapy, 14% of the children receiving CRO for 7 days had a confirmed bacteriological relapse within 4 weeks of stopping therapy.

Ceftriaxone↗
PubMed2000

Clinical and bacteriologic efficacy of amoxycillin b.d. (45 mg/kg/day) versus amoxycillin t.d.s (40 mg/kg/day) in children with group A beta-hemolytic streptococcal tonsillopharyngitis.

This randomized, observer-blind, multicenter, parallel-group study compared the clinical and bacteriologic efficacy and safety of amoxycillin, 45 mg/kg/day b.d. and amoxycillin, 40 mg/kg/day t.d.s. after 7 days of treatment in 517 children with acute bacterial tonsillopharyngitis. At the end of treatment, a successful clinical response was recorded in more than 96% of patients in each of the treatment groups. A similar result was obtained at follow-up. Among those patients who were bacteriologically evaluable at the end of treatment, a successful bacteriologic response was achieved in more than 94% in each treatment group. Both treatments were well tolerated. Drug-related adverse events were recorded in just 12 patients (4.6%) in the b.d. group and six (2.4%) in the t.d.s. group. The study demonstrated that a twice-daily regimen of amoxycillin, 45 mg/kg/day, was as effective and as well tolerated as the standard three-times-daily regimen of amoxycillin, 40 mg/kg/day, in the treatment of acute bacterial tonsillopharyngitis in children.

Adenoids↗
PubMed2000

Genetic analysis of cystic fibrosis in Pakistan: a preliminary report.

OBJECTIVE: Evaluation of the incidence of common delta F508 mutation in a cohort of Pakistani children with Cystic Fibrosis (CF). METHODOLOGY: The presence of the CFTR gene mutation at position 508 (delta F508) was evaluated in 15 consecutively presenting children with CF, proven by clinical features and an unequivocally positive sweat chloride test. The DNA from mononuclear cells was extracted and the delta F508 mutation assessed by the amplification refractory mutation system using the polymerase chain reaction. RESULTS: The delta F508 mutation was found in 9 cases (60%), of which 5 were homozygous for the disorder. CONCLUSION: In this preliminary study, the reported frequency of the delta F508 mutation in Pakistani children with CF is lower than the reported frequency among the Western Caucasian population. Further studies are needed to characterize the common genetic mutations in Pakistani children with CF.

Child↗
PubMed1999

Is management of neonatal respiratory distress syndrome feasible in developing countries? Experience from Karachi (Pakistan)

There is a marked paucity of data on the prevalence, management, and outcome of respiratory distress syndrome (RDS) among newborn infants born in developing countries. We reviewed the clinical profile, presentation, mode of therapy, and immediate and 12-month outcomes in 200 consecutive infants with documented RDS admitted to the Neonatal Intensive Care Unit at Aga Khan University Hospital, Karachi. One hundred fifty-six (79%) of these infants required assisted ventilation. Infants requiring ventilatory assistance had higher rates of maternal antenatal complications, were more frequently asphyxiated at birth, and were hypothermic on admission. The overall mortality was 39%, and a further 3 infants died in early infancy after discharge. The mean duration of hospitalization for ventilated survivors (n = 122) was 24.6 +/- 21.1 days, with an average cost of therapy per survivor of Rs 50,067 (US $1,391). While our experience from Karachi indicates that it is possible to provide successful respiratory support at comparatively low cost to newborn infants weighing >1,000 g with severe RDS, there is considerable room for improvement in outcome with the use of preventive measures such as antenatal steroids, appropriate intrapartal care, and attention to early stabilization after birth.

Developing Countries↗
PubMed1999

Prevention of diarrhea and pneumonia by zinc supplementation in children in developing countries: pooled analysis of randomized controlled trials. Zinc Investigators' Collaborative Group.

OBJECTIVES: This study assessed the effects of zinc supplementation in the prevention of diarrhea and pneumonia with the use of a pooled analysis of randomized controlled trials in children in developing countries. STUDY DESIGN: Trials included were those that provided oral supplements containing at least one half of the United States Recommended Daily Allowance (RDA) of zinc in children <5 years old and evaluated the prevention of serious infectious morbidity through household visits. Analysis included 7 "continuous" trials providing 1 to 2 RDA of elemental zinc 5 to 7 times per week throughout the period of morbidity surveillance and 3 "short-course" trials providing 2 to 4 RDA daily for 2 weeks followed by 2 to 3 months of morbidity surveillance. The effects on diarrhea and pneumonia were analyzed overall and in subgroups defined by age, baseline plasma zinc concentration, nutritional status, and sex. The analysis used random effects hierarchical models to calculate odds ratios (OR) and 95% CIs. RESULTS: For the zinc-supplemented children compared with the control group in the continuous trials, the pooled ORs for diarrheal incidence and prevalence were 0.82 (95% CI 0.72 to 0.93) and 0.75 (95% CI 0.63 to 0.88), respectively. Zinc-supplemented children had an OR of 0.59 (95% CI 0.41 to 0.83) for pneumonia. No significant differences were seen in the effects of the zinc supplement between the subgroups examined for either diarrhea or pneumonia. In the short-course trials the OR for the effects of zinc on diarrheal incidence (OR 0.89, 95% CI 0.62 to 1.28) and prevalence (OR 0.66, 95% CI 0.52 to 0.83) and pneumonia incidence (OR 0.74, 95% CI 0.40 to 1.37) were similar to those in the continuous trials. CONCLUSIONS: Zinc supplementation in children in developing countries is associated with substantial reductions in the rates of diarrhea and pneumonia, the 2 leading causes of death in these settings.

Child↗