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Biomedical subjects

P Garner

Publications and source records attributed to P Garner.

At least 37 records · Page 2Linked to original sources

Open general medical wards versus specialist psychiatric units for acute psychoses.

BACKGROUND: As international healthcare policy has moved away from treating people with severe mental illness in large inpatient psychiatric institutions, beds for people with acute psychiatric disorders are being established in specialised psychiatric units in general hospitals. In developing countries, however, limited resources mean that it is not always possible to provide discrete psychiatric units, either in general hospitals or in the community. An alternative model of admission, used in the Caribbean, is to treat the person with acute psychosis in a general hospital ward. OBJECTIVES: To compare the outcomes for people with acute psychoses who have been admitted to open medical wards with those admitted to conventional psychiatric units. SEARCH STRATEGY: The Cochrane Schizophrenia Group's study-based register was searched (November 2001). This register is compiled from searches of BIOSIS, CINAHL, The Cochrane Library, EMBASE, LILACS, MEDLINE, PsycINFO, PSYNDEX, Sociofile, and many conference proceedings. SELECTION CRITERIA: All relevant randomised or quasi-randomised trials, allocating anyone thought to be suffering from an acute psychotic episode to either acute management on general medical wards, or acute management in a specialist psychiatric unit. The primary outcomes of interest were length of stay in hospital and relapse. DATA COLLECTION AND ANALYSIS: Studies were reliably selected, assessed for quality, and their data would have been extracted. Homogeneous data were to have been synthesised. For binary data, the risk ratios (RR) and 95% confidence intervals (CI) were to have been calculated on an-intention-to-treat basis. If possible, the number needed to treat/harm statistic (NNT/H) was to have been calculated. For continuous data, weighted mean differences (WMD) were to have been calculated and only data from valid scales would have been reported in this review. MAIN RESULTS: We identified no relevant randomised trials. REVIEWER'S CONCLUSIONS: The Caribbean practice of treating people with severe mental illness on general medical wards has been influenced by socio-economic factors rather than evidence from randomised trials. This practice affords an opportunity for a well designed, well conducted and reported randomised trial, now impossible in many other settings.

Acute Disease↗

Amodiaquine-artesunate versus amodiaquine for uncomplicated Plasmodium falciparum malaria in African children: a randomised, multicentre trial.

BACKGROUND: Increasing drug resistance limits the choice of efficacious chemotherapy against Plasmodium falciparum malaria in Africa. Amodiaquine still retains efficacy against P falciparum in many African countries. We assessed the safety, treatment efficacy, and effect on gametocyte carriage of adding artesunate to amodiaquine in three randomised trials in Kenya, Sénégal, and Gabon. METHODS: We enrolled 941 children (400 in Kenya, 321 in Sénégal, and 220 in Gabon) who were 10 years or older and who had uncomplicated P falciparum malaria. Patients were randomly assigned amodiaquine (10 mg/kg per day for 3 days) plus artesunate (4 mg/kg per day for 3 days) or amodiaquine (as above) and placebo (for 3 days). The primary endpoints were parasitological cure rates at days 14 and 28. Analysis was by intention to treat and by an evaluability method. FINDINGS: Both regimens were well tolerated. Six patients in the amodiaquine-artesunate group and five in the amodiaquine group developed early, drug-induced vomiting, necessitating alternative treatment. By intention-to-treat analysis, the day-14 cure rates for amodiaquine-artesunate versus amodiaquine were: 175/192 (91%) versus 140/188 (74%) in Kenya (D=16.7% [95% CI 9.3-24.1], p<0.0001), 148/160 (93%) versus 147/157 (94%) in Sénégal (-1.1% [-6.7 to 4.5], p=0.7), and 92/94 (98%) versus 86/96 (90%) in Gabon (8.3% [1.5-15.1], p=0.02). The corresponding rates for day 28 were: 123/180 (68%) versus 75/183 (41%) in Kenya (27.3% [17.5-37.2], p<0.0001), 130/159 (82%) versus 123/156 (79%) in Sénégal (2.9% [-5.9 to 11.7], p=0.5), and 80/94 (85%) versus 70/98 (71%) in Gabon (13.7% [2.2-25.2], p=0.02). Similar rates were obtained by evaluability analysis. INTERPRETATION: The combination of artesunate and amodiaquine improved treatment efficacy in Gabon and Kenya, and was equivalent in Sénégal. Amodiaquine-artesunate is a potential combination for use in Africa. Further investigations to assess the potential effect on the evolution of drug resistance, disease transmission, and safety of amodiaquine-artesunate are warranted.

Amodiaquine↗

Artemether-lumefantrine for treating uncomplicated falciparum malaria.

BACKGROUND: Artemether-lumefantrine is being promoted by the World Health Organization for treating uncomplicated malaria. It is expensive. We sought evidence of its superiority over existing treatment regimens. OBJECTIVES: To compare artemether-lumefantrine with other antimalarial drugs for treating uncomplicated falciparum malaria. SEARCH STRATEGY: We searched the Cochrane Infectious Diseases Group specialized trials register (April 2002), the Cochrane Controlled Trials Register (Issue 2, 2002), MEDLINE (1966 to April 2002), EMBASE (1988 to April 2002), conference proceedings, and reference lists of articles. We contacted experts in malaria research and the pharmaceutical company that manufactures artemether-lumefantrine. SELECTION CRITERIA: Randomized and quasi-randomized trials comparing artemether-lumefantrine administered orally with standard treatment regimens (single drug or combination). DATA COLLECTION AND ANALYSIS: Two reviewers independently applied inclusion criteria to potentially relevant trials, assessed trial quality, and extracted data. Parasitaemia on day 28 (day 42 for sulfadoxine-pyrimethamine and day 63 for mefloquine) was the primary outcome. Adverse event information was collected from the studies. MAIN RESULTS: Eight trials (2117 participants) met the inclusion criteria. In the four studies against single agents, failure rates for artemether-lumefantrine tended to be higher in comparisons against sulfadoxine-pyrimethamine, halofantrine, and mefloquine. This difference was statistically significant for mefloquine. When compared with chloroquine, artemether-lumefantrine was better in two studies, but the failure rate for chloroquine at these sites was over 50%. All single agent studies used four doses of artemether-lumefantrine. In comparisons against combination treatment, three trials tested artemether-lumefantrine against mefloquine-artesunate and showed that artemether-lumefantrine was inferior for day 28 cure (Relative Risk 6.33, 95% confidence interval 3.08 to 13.01). If this comparison is confined to the two trials where participants received six doses, artemether-lumefantrine was associated with higher cure rates, but this was not statistically significant (Relative Risk 4.20, 95% confidence interval 0.55 to 31.93). REVIEWER'S CONCLUSIONS: Artemether-lumefantrine is more effective than chloroquine in chloroquine resistant areas. Artemether-lumefantrine is less effective than mefloquine or mefloquine combined with artesunate. We found no evidence to confirm or refute whether artemether-lumefantrine was better than sulfadoxine-pyrimethamine.

Antimalarials↗

In vitro stability of alpha-helical peptide nucleic acids (alphaPNAs).

Alpha-helical peptide nucleic acids (alphaPNAs) are synthetic molecules that merge the alpha-helix secondary structure of peptides with the codified Watson-Crick base pairing capability of nucleic acids. It is now demonstrated that alphaPNAs made up of either L- or D-amino acids are resistant to degradation by the proteases present in human serum. The increased stability of alphaPNAs towards proteases may be attributable to the presence of unnatural nucleoamino acid residues [-NHCH(CH(2)OCH(2)B)CO-, where B=thymine or cytosine] since the replacement of these amino acids by serine yields a control peptide that does break down in human serum. The stability of alphaPNAs towards proteases makes them attractive candidates for further development as antisense agents.

Amino Acid Sequence↗

Reduced osmolarity oral rehydration solution for treating dehydration due to diarrhoea in children: systematic review.

OBJECTIVES: To compare reduced osmolarity oral rehydration solution with standard World Health Organization oral rehydration solution in children with acute diarrhoea. DESIGN: Systematic review of randomised controlled trials. STUDIES: 15 randomised controlled trials including 2397 randomised patients. OUTCOMES: The primary outcome was unscheduled intravenous infusion; secondary outcomes were stool output, vomiting, and hyponatraemia. RESULTS: In a meta-analysis of nine trials for the primary outcome, reduced osmolarity rehydration solution was associated with fewer unscheduled intravenous infusions compared with standard WHO rehydration solution (odds ratio 0.61, 95% confidence interval 0.47 to 0.81). Three trials reported that no patients required unscheduled intravenous infusion. Trials reporting secondary outcomes suggested that in the reduced osmolarity rehydration solution group, stool output was lower (standardised mean difference in the log scale -0.214 (95% confidence interval -0.305 to -0.123; 13 trials) and vomiting was less frequent (odds ratio 0.71, 0.55 to 0.92; six trials). Six trials sought presence of hyponatraemia, with events in three studies, but no significant difference between the two arms. CONCLUSION: In children admitted to hospital with dehydration associated with diarrhoea, reduced osmolarity rehydration solution is associated with reduced need for unscheduled intravenous infusions, lower stool volume, and less vomiting compared with standard WHO rehydration solution.

Administration, Oral↗

Reduced osmolarity oral rehydration solution for treating dehydration caused by acute diarrhoea in children.

BACKGROUND: Oral rehydration solution (ORS) has reduced childhood deaths from diarrhoea in many countries. Recent studies suggest that the currently recommended formulation of ORS recommended by the World Health Organization (WHO) may not be optimal, and solutions that contain lower concentrations of sodium and glucose may be more effective. OBJECTIVES: In children with acute diarrhoea, to compare reduced osmolarity glucose-based oral rehydration salt solution with international WHO formulation. SEARCH STRATEGY: The Cochrane Collaboration Trials Register, MEDLINE, and EMBASE were searched. Additional trials were identified by hand searching. Content experts were contacted. SELECTION CRITERIA: Randomised controlled trials comparing reduced osmolarity ORS solution with the WHO formulation. Outcomes sought were unscheduled intravenous fluid infusion therapy and measures of clinical illness. DATA COLLECTION AND ANALYSIS: Data were extracted by two reviewers. We tested for heterogeneity using the chi-square statistic, conducted sensitivity analysis by allocation concealment, and the regression approach to assess funnel plot asymmetry from selective trial publication. MAIN RESULTS: The primary outcome was reported in 12 trials. In a meta-analysis of nine trials, reduced osmolarity ORS was associated with fewer unscheduled infusions compared with standard WHO ORS (Mantel Haenzel odds ratio 0.61, 95% confidence interval 0.47 to 0.81) with no evidence for heterogeneity between trials. No unscheduled intravenous fluid infusion therapy was required in any participant in three trials. Thirteen trials reported stool output, and data suggested less stool output in the reduced osmolarity ORS group. Vomiting was less frequent in the reduced osmolarity group in the six trials reporting this. Six trials sought hyponatraemia, with events in three studies, but no obvious difference between the two arms. REVIEWER'S CONCLUSIONS: In children admitted to hospital with diarrhoea, reduced osmolarity ORS when compared to WHO ORS is associated with fewer unscheduled intravenous infusions, smaller stool volume post randomisation, and less vomiting. No additional risk of developing hyponatraemia when compared with WHO ORS was detected.

Bicarbonates↗

Strategies for integrating primary health services in middle- and low-income countries: effects on performance, costs and patient outcomes.

BACKGROUND: Integration of primary health care is change to bring together inputs, organisation, management and delivery of particular service functions. Integration has been promoted in the health sector to improve the efficiency of health care delivery. The need for integration arose from perceptions that services were fragmented when delivered through separate vertical programmes. Integration is relevant to the health system at various levels, and this review is concerned with integration at the point of delivery. OBJECTIVES: To assess the effects of strategies to integrate primary health care services on producing a more coherent product and improving health care delivery and health status, in relation to service cost, outputs, impact and user acceptability. SEARCH STRATEGY: We searched the Cochrane Effective Practice and Organisation of Care Group specialised register (August 2000), MEDLINE (1966 to September 2000), EMBASE (1988 to September 2000), Socio Files (1974 to September 2000), Popline (1970 to September 2000), HealthStar (1975 to September 2000), Cinahl (1982 to September 2000); Cab Health (1972 to 1999), International Bibliography of the Social Sciences (1970 to 1999), and reference lists of articles. We also searched the Internet and World Health Organization (WHO) library database, hand searched relevant WHO publications and contacted experts in the field. SELECTION CRITERIA: Randomised trials, controlled before and after studies, and interrupted time series analyses of integration strategies in primary health care services. Health services in high-income countries were excluded. The primary outcomes were service outputs: productivity and coverage, impact, user acceptability and unit cost. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed study quality. MAIN RESULTS: Four studies were included. There was no consistent pattern of benefit. Integration had a clear positive effect on the outputs in only one study; in another it had similar effects to vertical programme delivery but greater effect than the control group. In the other two studies integration resulted in negative outputs in comparison with vertical programmes, although in one of these integration performed better than the control group. REVIEWER'S CONCLUSIONS: Few studies of good quality, large and with rigorous study design have been carried out to investigate the evidence to support integration as a style of service delivery. In fact, some studies found greater effects for vertical health care delivery. Policy makers and planners considering integration could introduce strategies, using rigorous study design, to allow further evaluation and increase the base of studies from which to draw evidence.

Clinical Trials as Topic↗

Directly observed therapy for treating tuberculosis.

BACKGROUND: Up to half the people with tuberculosis do not complete their treatment. Strategies to improve adherence to diagnostic and treatment regimens are therefore important. OBJECTIVES: To assess the effects of directly observed therapy by an appointed agent (health worker, community volunteer, or family member) on cure and treatment completion in people on treatment for tuberculosis. SEARCH STRATEGY: We searched The Cochrane Controlled Trials Register, the Cochrane Infectious Diseases Group specialized trials register, MEDLINE, EMBASE, LILACS, and reference lists of articles. We also contacted experts in the field. SELECTION CRITERIA: Randomized and quasi-randomized trials of direct observation of tablet swallowing compared with self treatment for tuberculosis. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. MAIN RESULTS: Four studies (n = 1603 participants) included. There was no difference detected between direct observation and self treatment for cure (Relative Risk [RR] 1.06, 95% confidence interval [CI] 0.98 to 1.14); and for cure plus treatment completion (RR 1.06, 95% CI 1.00 to 1.13). A stratified analysis by the appointed agent (health professional, lay health worker, or family/community member) did not reveal any important differences. One study conducted in an optimal setting in which patients were given a choice of supervisor did show modest benefit: cure (RR 1.13, 95% CI 1.04 to 1.24); cure plus treatment completion (RR 1.11, 95% CI 1.03 to 1.18). REVIEWER'S CONCLUSIONS: Randomized trials provide no evidence that directly observed therapy in low and middle income country settings improves cure or treatment completion rates in patients with tuberculosis.

Antitubercular Agents↗

Assessing the potential for bias in meta-analysis due to selective reporting of subgroup analyses within studies.

Subgroup analysis is frequently used to investigate heterogeneity in meta-analysis. Subgroup data are not always available, and researchers should record what data were available for each trial. If data were not available, and it is known that the subgroup data were collected, the potential for selective reporting should be considered. Bias due to selective publishing of reports is widely recognized in meta-analysis. In contrast, selective reporting within studies is little discussed but potentially important. We explored this problem by evaluating the effect of potential bias in subgroup analysis due to within-study selective reporting with an existing meta-analysis. The review addressed malaria chemoprophylaxis in pregnancy. The conclusion in the original review, that benefit is limited to primigravidae, was based on subgroup analysis using the three trials out of five which reported on subgroups. We developed a method of sensitivity analysis that imputes data for the missing subgroups to assess the robustness of the results and the conclusions drawn. In this particular example, our analysis indicates that the estimate of effect reported in the review is most likely to overestimate the true effect and the conclusion that benefit is limited to primigravidae may be false.

Bias↗

Effects of treatment for intestinal helminth infection on growth and cognitive performance in children: systematic review of randomised trials.

OBJECTIVE: To summarise the effects of anthelmintic drug treatment on growth and cognitive performance in children. DATA SOURCES: Electronic databases: Cochrane Infectious Diseases Group controlled trial register, Cochrane controlled trials register, Embase, and Medline. Citations of all identified trials. Contact with the World Health Organization and field researchers. REVIEW METHODS: Systematic review of randomised controlled trials in children aged 1-16 that compared anthelmintic treatment with placebo or no treatment. Assessment of validity and data abstraction conducted independently by two reviewers. MAIN OUTCOME MEASURES: Growth and cognitive performance. RESULTS: Thirty randomised controlled trials in more than 15 000 children were identified. Effects on mean weight were unremarkable, and heterogeneity was evident in the results. There were some positive effects on mean weight change in the trials reporting this outcome: after a single dose (any anthelmintic) the pooled estimates were 0.24 kg (95% confidence interval 0.15 kg to 0. 32 kg; fixed effects model assumed) and 0.38 kg (0.01 kg to 0.77 kg; random effects model assumed). Results from trials of multiple doses showed mean weight change in up to one year of follow up of 0.10 kg (0.04 kg to 0.17 kg; fixed effects) or 0.15 kg (0.00 to 0.30; random effects). At more than one year of follow up, mean weight change was 0.12 kg (-0.02 kg to 0.26 kg; fixed effects) and 0.43 (-0.61 to 1. 47; random effects). Results from studies of cognitive performance were inconclusive. CONCLUSIONS: There is some limited evidence that routine treatment of children in areas where helminths are common has effects on weight gain, but this is not consistent between trials. There is insufficient evidence as to whether this intervention improves cognitive performance.

Adolescent↗

Directly observed therapy and treatment adherence.

Direct observation of patients taking their medication is a strategy to improve completion rates for tuberculosis treatment, but the programmes to implement this approach consist of a complex array of inputs aimed at influencing adherence. Policy makers need a clear understanding of these inputs to succeed. We systematically identified and reviewed published reports of direct observation therapy (DOT) programmes and compared inputs with WHO's short-course DOT programme. DOT programmes frequently consist of more than the five elements of WHO's strategy, including incentives, tracing of defaulters, legal sanctions, patient-centred approaches, staff motivation, supervision, and additional external funds. Focusing on direct observation as a key factor in the promotion of adherence seems inappropriate. Multiple components might account for the success of DOT programmes, and WHO should make these explicit.

Antitubercular Agents↗

Cost-effectiveness of public-funded options for cataract surgery in Mysore, India.

BACKGROUND: In India 3.8 million people become blind due to cataracts every year. We assessed the cost-effectiveness of public-funded options for delivering cataract surgery in Mysore, Karnataka State, India. METHODS: Three types of delivery of cataract surgery were studied: mobile government camps, walk-in services at a state medical college hospital, and patients transported in from satellite clinics to a non-governmental hospital. We assessed outcomes in a systematic sample of patients operated on in 1996-97 by follow-up at home; average costs by provider derived from actual expenditures during the year. FINDINGS: Almost half the patients operated on in government camps were dissatisfied with the outcome (34/70, 49% [95% CI 36-61]). More than one third were blind in the operated eye (25/70, 36% [25-48]). User satisfaction was higher with other providers (medical college hospital 82% [63-94]; non-government hospital 85% [72-93]), and fewer patients remained blind. Camps were a low-cost option, but the poor outcomes reduced their cost-effectiveness to US$97 per patient. The state medical college hospital was least cost-effective, at US$176 per patient, and the non-governmental hospital was the most cost-effective at US$54 per patient. INTERPRETATION: The government of India should review its policy for government camp surgery, and consider alternatives, such as transporting patients to better permanent facilities. India and other developing countries should monitor outcomes in cataract surgery programmes, as well as throughput.

Blindness↗