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J C Craig

Publications and source records attributed to J C Craig.

At least 37 records · Page 2Linked to original sources

Temporal factors in tactile spatial acuity: evidence for RA interference in fine spatial processing.

We investigated the extent to which subjects' ability to perceive the fine spatial structure of a stimulus depends on its temporal properties (namely the frequency at which it vibrates). Subjects were presented with static or vibrating gratings that varied in spatial period (1-8 mm) and vibratory frequency (5-80 Hz) and judged the orientation of the gratings, presented either parallel or perpendicular to the long axis of the finger. We found that the grating orientation threshold (GOT)-the spatial period at which subjects can reliably discriminate the orientation of the grating-increased as the vibratory frequency of the gratings increased. As the spatial modulation of SA1 and RA afferent fibers has been found to be independent of vibratory frequency, the frequency dependence of spatial acuity cannot be attributed to changes in the quality of the peripheral signal. Furthermore, we found GOTs to be relatively independent of stimulus amplitude, so the low spatial acuity at high flutter frequencies does not appear to be due to an inadequacy in the strength of the afferent response at those frequencies. We hypothesized that the RA signal, the strength of which increases with vibratory frequency, interfered with the spatially modulated signal conveyed by SA1 fibers. Consistent with this hypothesis, we found that adapting RA afferent fibers improved spatial acuity, as gauged by GOTs, at the high flutter frequencies.

Afferent Pathways↗

Non-corticosteroid treatment for nephrotic syndrome in children.

BACKGROUND: Eighty to ninety per cent of children with steroid-sensitive nephrotic syndrome (SSNS) have relapses. About half relapse frequently and are at risk of the adverse effects of corticosteroids. Non-corticosteroid immunosuppressive agents are used to prolong periods of remission in children who relapse frequently. However these non-corticosteroid agents also have significant potential adverse effects. Currently there is no consensus as to the most appropriate second line agent in children who are steroid sensitive, but who continue to relapse. OBJECTIVES: To evaluate the benefits and harms of non-corticosteroid immunosuppressive agents in relapsing SSNS in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, EMBASE, reference lists of articles, abstracts from proceedings and contact with known investigators. Search date: August 2004 SELECTION CRITERIA: RCTs or quasi-RCTs were included if they were undertaken in children with relapsing SSNS, if they compared non-corticosteroid agents with placebo, prednisone or no treatment, different doses and/or durations of the same non-corticosteroid agent, different non-corticosteroid agents and outcome data at six months. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Twenty trials involving 923 children were identified. Cyclophosphamide (three trials: RR 0.44, 95% CI 0.26 to 0.73) and chlorambucil (two trials: RR 0.13, 95% CI 0.03 to 0.57) significantly reduced the relapse risk at six to twelve months compared with prednisone alone. In the single chlorambucil versus cyclophosphamide trial, there was no observed difference in relapse risk at two years (RR 1.31, 95% CI 0.80 to 2.13). Cyclosporin was as effective as cyclophosphamide (one trial: RR 1.07, 95% CI 0.48 to 2.35) and chlorambucil (one trial: RR 0.82, 95% CI 0.44 to 1.53) but the effect was not sustained when cyclosporin was ceased. During treatment, levamisole (three trials: RR 0.60, 95% CI 0.45 to 0.79) was more effective than steroids alone but the effect was not sustained. Mizoribine (one trial) and azathioprine (two trials) were no more effective than placebo or prednisone alone in maintaining remission. AUTHORS' CONCLUSIONS: Eight week courses of cyclophosphamide or chlorambucil and prolonged courses of cyclosporin and levamisole reduce the risk of relapse in children with relapsing SSNS compared with corticosteroids alone. Clinically important differences in efficacy among these agents are possible and further comparative trials are still needed.

Adolescent↗

Corticosteroid therapy for nephrotic syndrome in children.

BACKGROUND: In nephrotic syndrome protein leaks from the blood to the urine through the glomeruli resulting in hypoproteinaemia and generalised oedema. While the majority of children with nephrotic syndrome respond to corticosteroids, 70% experience a relapsing course. Corticosteroid usage has reduced the mortality rate to around 3%, however they have known serious adverse effects. OBJECTIVES: To determine the benefits and harms of corticosteroid regimens in preventing relapse in children with steroid sensitive nephrotic syndrome (SSNS). SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Renal Group Specialised Register, MEDLINE and EMBASE without language restriction, reference lists of articles, abstracts from conference proceedings and contact with known investigators. Date of most recent search: October 2004 SELECTION CRITERIA: Randomised controlled trials performed in children (three months to 18 years) in their initial or subsequent episode of SSNS, comparing different durations, total doses or other dose strategies using any corticosteroid agent, with outcome data at six months or more. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using a random effects model and results expressed as relative risk (RR) with 95% confidence intervals (CI).Meta-regression was used to explore potential between-study differences due to baseline risk of relapse, study quality and interventions. MAIN RESULTS: Nineteen trials were identified. Six trials comparing two months of prednisone with three months or more in the first episode showed longer duration significantly reduced the risk of relapse at 12 to 24 months (RR 0.70; 95% CI 0.58 to 0.84). There was an inverse linear relationship between treatment duration and risk of relapse (RR = 1.26 - 0.112 duration; P = 0.03). There was a significant reduction in the number of frequent relapsers and the mean relapse rate/patient/year. Deflazacort was significantly more effective in maintaining remission than prednisone in children who frequently relapsed (RR 0.44; 95% CI 0.25 to 0.78). There were no increases in adverse events. AUTHORS' CONCLUSIONS: Children in their first episode of SSNS should be treated for at least three months with an increase in benefit being demonstrated for up to seven months of treatment For a baseline risk for relapse following the first episode of 60% with two months of prednisone, daily prednisone for four weeks followed by alternate-day therapy for six months would reduce the number of children relapsing by 33%. Deflazacort deserves further study for frequent relapsers.

Adolescent↗

Antibiotics for acute pyelonephritis in children.

BACKGROUND: Urinary tract infection (UTI) is one of the most common bacterial infection in infants. The most severe form of UTI is acute pyelonephritis, which results in significant acute morbidity and may cause permanent renal damage. Published guidelines recommend treatment of acute pyelonephritis initially with intravenous (IV) therapy followed by oral therapy for seven to 14 days though there is no consensus on the duration of either IV or oral therapy. OBJECTIVES: To determine the benefits and harms of different antibiotic regimens for the treatment of acute pyelonephritis in children. SEARCH STRATEGY: We searched the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists of articles and abstracts from conference proceedings without language restriction. Date of most recent search: June 2004. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing different antibiotic agents, routes, frequencies or durations of therapy in children aged 0 to 18 years with proven UTI and acute pyelonephritis were selected. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or weight mean difference (WMD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: Eighteen trials (2612 children) were eligible for inclusion. No significant differences were found in persistent renal damage at six months (one trial, 306 infants: RR 1.45, 95% CI 0.69 to 3.03) or in duration of fever (WMD 0.80, 95% CI -4.41 to - 6.01) between oral cefixime therapy (14 days) and IV therapy (three days) followed by oral therapy (10 days). Similarly no significant differences in persistent renal damage (three trials, 315 children: RR 0.99, 95% CI 0.72 to 1.37) were found between IV therapy (3-4 days) followed by oral therapy and IV therapy for 7-14 days. In addition no significant differences in efficacy were found between daily and thrice daily administration of aminoglycosides (one trial, 179 children, persistent symptoms at three days: RR 1.98, 95% CI 0.37 to 10.53). AUTHORS' CONCLUSIONS: These results suggest that children with acute pyelonephritis can be treated effectively with oral cefixime or with short courses (2-4 days) of IV therapy followed by oral therapy. If IV therapy is chosen, single daily dosing with aminoglycosides is safe and effective. Trials are required to determine the optimal total duration of therapy and if other oral antibiotics can be used in the initial treatment of acute pyelonephritis.

Acute Disease↗

Oral retinoids for the prevention of skin cancers in solid organ transplant recipients: a systematic review of randomized controlled trials.

BACKGROUND: The increased incidence of skin cancers after solid organ transplantation is well recognized. Skin cancers developing in transplant recipients are more aggressive in behaviour. Therapeutic options to reduce and/or delay the development of cutaneous neoplasms are therefore of interest. OBJECTIVES: The objective of this review was to summarize the available medical literature from randomized controlled trials on the use of oral retinoids as a preventive agent for skin cancers in the solid organ transplant population. METHODS: Three electronic databases were searched for relevant trials: MEDLINE (1966-October 2003), EMBASE (1980-week 44, 2003) and the Cochrane Controlled Trials Register (third quarter 2003). Randomized or quasi-randomized controlled clinical trials on subjects of any age or ethnic background who had received a solid organ transplant (cardiac, renal, liver, etc.) were evaluated. All titles and abstracts found by the search strategy were independently reviewed by two researchers for inclusion into the review. RESULTS: Eighty-one abstracts were identified through the electronic databases for consideration. Review of the abstracts identified three eligible trials. One cross-over trial involving 23 subjects treated with acitretin 25 mg daily for 12 months reported 46 squamous cell carcinomas (SCCs) developing in six subjects during acitretin treatment vs. 65 SCCs developing in 15 subjects during the drug-free period. Another trial involving 44 subjects treated with acitretin 30 mg daily or placebo for 6 months reported two of 19 subjects developing two SCCs in the treatment group vs. nine of 19 subjects developing 18 new skin cancers (15 SCCs, one Bowen's disease, two basal cell carcinomas) in the placebo group. One dose comparison trial involving 26 renal transplant recipients treated with acitretin did not find a significant difference in numbers of skin cancers developing at the doses examined. The major limitation to the use of acitretin was poor tolerance due to adverse events. Headaches, rash, musculoskeletal symptoms and hyperlipidaemia were the most common causes of withdrawal from treatment. No alterations in renal or liver function were detected during the periods of treatment or follow-up. CONCLUSIONS: The available data from a small number of randomized controlled trials suggest that acitretin may have a role in the management of solid organ transplant recipients with skin cancers. Tolerability of the drug is a major factor limiting its use. Appropriate selection of patients may help improve the risk-benefit ratio.

Acitretin↗

Antimicrobial agents for preventing peritonitis in peritoneal dialysis patients.

BACKGROUND: Peritoneal dialysis (PD) is used as substitutive treatment of renal function in a large proportion (15-50%) of the end-stage kidney disease (ESRD) population. The major limitation is peritonitis which leads to technique failure, hospitalisation and increased mortality. Oral, nasal, topical antibiotic prophylaxis, exit-site disinfectants and other antimicrobial interventions are used to prevent peritonitis. OBJECTIVES: The objective of this systematic review of randomised controlled trials (RCTs) was to evaluate what evidence supports the use of different antimicrobial approaches to prevent peritonitis in PD. SEARCH STRATEGY: The Cochrane CENTRAL Registry (issue 1, 2004), MEDLINE (1966-May 2003), EMBASE (1988-May 2003) and reference lists were searched for RCTs of antimicrobial agents in PD. SELECTION CRITERIA: Trials of the following agents were included: antibiotics by any route (oral, nasal, topical), exit-site disinfectants (chlorhexidine, povidone iodine, soap and water), vaccines, and ultraviolet germicidal devices. DATA COLLECTION AND ANALYSIS: Two reviewers extracted data on the number of patients with one or more episodes and rates of peritonitis and exit-site/tunnel infection, catheter removal, catheter replacement, technique failure, toxicity of antibiotic treatments, all-cause mortality. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Nineteen trials, enrolling 1949 patients met our inclusion criteria. Nasal mupirocin compared with placebo significantly reduced the exit-site and tunnel infection rate (one trial, 2716 patient months, RR 0.58, 95% CI 0.40 to 0.85) but not peritonitis rate (one trial, 2716 patient months, RR 0.84, 95% CI 0.44 to 1.60). Perioperative intravenous antibiotics compared with no treatment significantly reduced the risk of early peritonitis (four trials, 335 patients, RR 0.35, 95% CI 0.15 to 0.80) but not exit site and tunnel infection (three trials, 114 patients, RR 0.32, 95% CI 0.02 to 4.81). No intervention reduced the risk of catheter removal or replacement. REVIEWERS' CONCLUSIONS: This review demonstrates that nasal mupirocin reduces exit-site/tunnel infection but not peritonitis. Preoperative intravenous prophylaxis reduces early peritonitis but not exit-site/tunnel infection. No other antimicrobial interventions have proven efficacy. Given the large number of patients on PD and the importance of peritonitis, the lack of adequately powered RCTs to inform decision making about strategies to prevent peritonitis is striking.

Anti-Bacterial Agents↗

Catheter type, placement and insertion techniques for preventing peritonitis in peritoneal dialysis patients.

BACKGROUND: As many as 15-50% of end-stage kidney disease patients are on peritoneal dialysis (PD), but peritonitis limits its more widespread use. Several PD catheter-related interventions have been purported to reduce the risk of peritonitis in PD. OBJECTIVES: To evaluate the use of catheter-related interventions for the prevention of peritonitis in PD. SEARCH STRATEGY: The Cochrane Renal Group's specialised register (June 2004), The Cochrane CENTRAL Register of Controlled Trials (The Cochrane Library Issue 2 2004), MEDLINE (1966-April 2004), EMBASE (1988-April 2004) and reference lists were searched without language restriction SELECTION CRITERIA: Trials comparing different catheter insertion techniques, catheter types, use of immobilisation techniques or different break in periods were included. Trials of different PD sets were excluded. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using a random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (CI). MAIN RESULTS: Seventeen eligible trials (1089 patients) were identified, eight of surgical strategies of catheter insertion, eight of straight versus coiled catheters, one of single cuff versus double cuff catheters and one of an immobiliser device. The methodological quality was suboptimal. There were no significant differences with laparoscopy compared with laparotomy for peritonitis, the peritonitis rate, exit-site/tunnel infection or catheter removal/replacement. Standard insertion with resting but no subcutaneous burying of the catheter versus implantation and subcutaneous burying was not associated with a significant reduction in peritonitis rate, exit-site/tunnel infection rate or all-cause mortality. Midline compared to lateral insertion showed no significant difference in the risk of peritonitis or exit-site/tunnel infection. There was no significant difference in the risk of peritonitis, peritonitis rate, exit-site/tunnel infection, exit-site/tunnel infection rate or catheter removal/replacement between straight versus coiled intraperitoneal portion catheters. One trial compared single versus double cuffed catheters and showed no significant difference in the risk of peritonitis, exit-site/tunnel infection or catheter removal/replacement. One trial compared immobilisation versus no immobilisation of the PD catheter and showed no significant difference in the risk of peritonitis and exit-site/tunnel infection. No trials of different break-in periods were identified. REVIEWERS' CONCLUSIONS: No major advantages from any of the catheter-related interventions which have been purported to reduce the risk of PD peritonitis could be demonstrated in this review. The frequency and quality of available trials are suboptimal.

Catheterization↗

Interventions for primary vesicoureteric reflux.

BACKGROUND: Vesicoureteric reflux (VUR) results in urine passing, in a retrograde manner, up the ureter. Urinary tract infections (UTIs) have been considered to be the main cause of permanent renal parenchymal damage in children with reflux. Therefore management of these children has been directed at preventing infection by antibiotic prophylaxis and/or surgical correction of reflux. However controversy remains as to the optimum strategies for management of children with primary VUR. OBJECTIVES: To evaluate the benefits and harms of the different treatment options for primary VUR. SEARCH STRATEGY: Published and unpublished randomised controlled trials (RCTs) were identified from the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, reference lists of articles and abstracts from conference proceedings. SELECTION CRITERIA: RCTs were included if they compared any treatments of VUR including surgery (open and closed techniques), antibiotic prophylaxis of any duration, non-invasive techniques such as bladder training and any combination of therapies. DATA COLLECTION AND ANALYSIS: Two reviewers independently searched the literature, determined trial eligibility, assessed quality, extracted and entered data. For dichotomous outcomes, results were expressed as relative risk (RR) and 95% confidence intervals (CI). Data were pooled using the random effects model. MAIN RESULTS: Ten trials involving 964 evaluable children comparing long-term antibiotics and surgical correction of VUR with antibiotics (seven trials), antibiotics with no treatment (one trial) and different materials for endoscopic correction of VUR (two trials) were identified. Risk of UTI by 1-2 and 5 years was not significantly different between surgical and medical groups (by 2 years RR 1.07, 95% CI 0.55 to 2.09; by 5 years RR 0.99; 95% CI 0.79 to 1.26). Combined treatment resulted in a 60% reduction in febrile UTI by 5 years (RR 0.43, 95% CI 0.27 to 0.70) but no concomitant significant reduction in risk of new or progressive renal damage at 5 years (RR 1.05, 95% CI 0.85 to 1.29). In one small study no significant differences in risk for UTI or renal damage were found between antibiotic prophylaxis and no treatment. REVIEWERS' CONCLUSIONS: It is uncertain whether the identification and treatment of children with VUR confers clinically important benefit. The additional benefit of surgery over antibiotics alone is small at best. Assuming a UTI rate of 20% for children with VUR on antibiotics for five years, nine reimplantations would be required to prevent one febrile UTI, with no reduction in the number of children developing any UTI or renal damage.

Antibiotic Prophylaxis↗

Corticosteroid therapy for nephrotic syndrome in children.

BACKGROUND: In nephrotic syndrome protein leaks from the blood to the urine through the glomeruli resulting in hypoproteinaemia and generalised oedema. Children with untreated nephrotic syndrome frequently die from infections. The majority of children with nephrotic syndrome respond to corticosteroids. However about 70% of children experience a relapsing course with recurrent episodes of oedema and proteinuria. Corticosteroid usage has reduced the mortality rate in childhood nephrotic syndrome to around 3%, with infection remaining the most important cause of death. However corticosteroids have known adverse effects such as obesity, poor growth, hypertension, diabetes mellitus, osteoporosis and adrenal suppression. The original treatment schedules for childhood nephrotic syndrome were developed in an ad hoc manner. The optimal doses and durations of corticosteroid therapy that are most beneficial and least harmful have not been clarified. OBJECTIVES: The aim of this review was to determine the benefits and harms of different corticosteroid regimens in preventing relapse in children with steroid sensitive nephrotic syndrome (SSNS). SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library, Issue 2, 2002), Cochrane Renal Group Specialised Register (July 2002), MEDLINE (1966 - July 2002) and EMBASE (1980 - July 2002) without language restriction, reference lists of articles, abstracts from conference proceedings and contact with known investigators in the area. SELECTION CRITERIA: Randomised controlled trials were included if they were carried out in children (aged three months to 18 years) in their initial or subsequent episode of SSNS, if they compared different durations, total doses or other dose strategies using prednisone or other corticosteroid agent and if they had outcome data at six months or more. DATA COLLECTION AND ANALYSIS: Two reviewers independently reviewed all eligible studies for inclusion, assessed study quality and extracted data. The principle outcome measure was the number of children with and without relapse after six and 12-24 months. Secondary outcomes sought included the number of children who developed frequently relapsing nephrotic syndrome and adverse events. A random effects model was used to estimate summary effect measures (relative risk (RR), risk difference (RD)) after testing for heterogeneity. Meta-regression was used to explore potential between-study differences due to the baseline risk of relapse, study quality and types of interventions used. MAIN RESULTS: Nineteen trials have been included in this review. A meta-analysis of six trials, which compared two months of prednisone with three months or more in the first episode, showed that the longer duration significantly reduced the risk of relapse at 12 - 24 months (RR 0.70; 95% CI 0.58 to 0.84) without an increase in adverse events. There was an inverse linear relationship between the duration of treatment and risk of relapse (RR = 1.26 - 0.112 duration; r(2) = 0.56; p = 0.03). The number of children who became frequent relapsers and the mean relapse rate/patient/year were also significantly reduced without increase in serious adverse events. In children with frequently relapsing nephrotic syndrome, deflazacort was significantly more effective in maintaining remission than prednisone (RR 0.44; 95% CI 0.25 to 0.78). REVIEWERS' CONCLUSIONS: Children in their first episode of SSNS should be treated for at least three months with an increase in benefit being demonstrated for up to seven months of treatment. In a population with a baseline risk for relapse following the first episode of 60% with two months of prednisone, daily prednisone for four weeks followed by alternate day therapy for six months would be expected to reduce the number of children experiencing a relapse by about 33%. In children who relapse frequently, deflazacort deserves further study.

Adolescent↗

Effects of nonsteroidal anti-inflammatory drugs on postoperative renal function in adults with normal renal function.

BACKGROUND: Nonsteroidal anti-inflammatory drugs (NSAIDs) can play a major role in the management of acute pain in the peri-operative period. However, there are conflicting views on whether NSAIDs are associated with adverse renal effects. OBJECTIVES: The primary objective of this review was to determine the effects of NSAIDs on postoperative renal function in adults with normal preoperative renal function. SEARCH STRATEGY: Electronic searches for relevant randomised and quasi-randomised controlled trials in Cochrane Central Register of Controlled Trials, MEDLINE and EMBASE were performed. Attempts were also made to identify trials from citation lists of relevant trials, review articles and clinical practice guidelines. Handsearching of conference abstracts published in major anaesthetic journals was also performed. (Search date: 7 February 2003) SELECTION CRITERIA: The inclusion criteria were randomised or quasi-randomised comparisons of individual NSAIDs with either each other or placebo for treatment of postoperative pain, with relevant postoperative renal outcome measures, in adult surgical patients with normal renal function. DATA COLLECTION AND ANALYSIS: The data was extracted independently by two reviewers. The primary outcome measure was creatinine clearance within the first two days after surgery. Secondary outcome measures included serum creatinine, urine volume, urinary sodium level, urinary potassium level, fractional excretion of sodium, fractional excretion of potassium, need for dialysis and need for diuretic or dopamine treatment for renal insufficiency. Weighted mean differences for continuous outcomes and relative risk for dichotomous outcomes were estimated. MAIN RESULTS: Nineteen trials ( n = 1204) fulfilled the selection criteria for this review. NSAIDs reduced creatinine clearance by 16 ml/min (95%CI 5 to 28) and potassium output by 38 mmol/day (95%CI 19 to 56) on the first day after surgery compared to placebo. There was no significant difference in serum creatinine on the first day (0 umol/L, 95%CI -5 to 4) compared to placebo. No significant reduction in urine volume during the early postoperative period was found. There was no significant difference in serum creatinine in the early postoperative period between patients receiving diclofenace and ketorolac (or indomethacin). No cases of postoperative renal failure requiring dialysis were described. The trials were homogeneous for the primary outcome. REVIEWERS' CONCLUSIONS: NSAIDs caused a clinically unimportant transient reduction in renal function in the early postoperative period in patients with normal preoperative renal function. NSAIDs should not be withheld from adults with normal preoperative renal function because of concerns about postoperative renal impairment.

Adult↗

Antifungal agents for preventing fungal infections in solid organ transplant recipients.

BACKGROUND: Invasive fungal infections (IFIs) are important causes of morbidity and mortality in solid organ transplant recipients. OBJECTIVES: This study aims to systematically identify and summarise the effects of antifungal prophylaxis in solid organ transplant recipients. SEARCH STRATEGY: The Cochrane Central Register of Controlled Trials (Issue 3, 2003), MEDLINE (1966-June 2003), and EMBASE (1980-June 2003) were searched. Reference lists, abstracts of conference proceedings and scientific meetings (1998-2003) were handsearched. Authors of included studies and pharmaceutical manufacturers were contacted. SELECTION CRITERIA: Randomised controlled trials (RCTs) in all languages comparing the prophylactic use of any antifungal agent or regimen with placebo, no antifungal, or another antifungal agent or regimen. DATA COLLECTION AND ANALYSIS: Two reviewers independently applied selection criteria, performed quality assessment, and extracted data using an intention-to-treat approach. Differences were resolved by discussion. Data were synthesised using the random effects model and expressed as relative risk (RR) with 95% confidence intervals (95% CI). MAIN RESULTS: Fourteen unique trials with 1497 randomised participants were included. Antifungal prophylaxis did not reduce mortality (RR 0.90, 95% CI 0.57 to 1.44). In liver transplant recipients, a significant reduction in IFIs was demonstrated for fluconazole (RR 0.28, 95% CI 0.13 to 0.57). Although less data were available for itraconazole and liposomal amphotericin B, indirect comparisons and one direct comparative trial suggested similar efficacy. Fluconazole prophylaxis did not significantly increase invasive infections or colonisation with fluconazole-resistant fungi. In renal and cardiac transplant recipients, neither ketoconazole nor clotrimazole significantly reduced invasive infections. Overall, the strength and precision of comparisons however were limited by a paucity of data. REVIEWERS' CONCLUSIONS: For liver transplant recipients, antifungal prophylaxis with fluconazole significantly reduces the incidence of IFIs with no definite mortality benefit. Given a 10% incidence of IFI, 14 liver transplant recipients would require fluconazole prophylaxis to prevent one infection. In transplant centres where the incidence of IFIs is high, or in situations where the individual risk is great, antifungal prophylaxis should be considered.

Antifungal Agents↗

Antibiotics for acute pyelonephritis in children.

BACKGROUND: Urinary tract infection (UTI) is one of the most common bacterial infection in infants. The most severe form of UTI is acute pyelonephritis, which results in significant acute morbidity and may cause permanent renal damage. Published guidelines recommend treatment of acute pyelonephritis initially with intravenous (IV) therapy followed by oral therapy for 7-14 days though there is no consensus on the duration of either IV or oral therapy. OBJECTIVES: To determine the benefits and harms of different antibiotic regimens for the treatment of acute pyelonephritis in children. SEARCH STRATEGY: We searched the Cochrane Register of Controlled Trials (Cochrane Library Issue 3, 2002), MEDLINE (1966 - September 2002), EMBASE (1988 -September 2002), reference lists of articles and abstracts from conference proceedings without language restriction. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing different antibiotic agents, routes, frequencies or durations of therapy in children aged 0-18 years with proven UTI and acute pyelonephritis were selected. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes or weight mean difference (WMD) for continuous data with 95% confidence intervals (CI). MAIN RESULTS: Sixteen trials involving 1872 children were eligible for inclusion. No significant differences were found in persistent renal damage at six months (one trial, 306 infants: RR 1.45, 95% CI 0.69 to 3.03) or in duration of fever (WMD 0.80, 95% CI -4.41 to - 6.01) between oral cefixime therapy (14 days) and IV therapy (three days) followed by oral therapy (10 days). Similarly no significant differences in persistent renal damage (three trials, 315 children: RR 0.99, 95% CI 0.72 to 1.37) were found between IV therapy (3-4 days) followed by oral therapy and IV therapy for 7-14 days. In addition no significant differences in efficacy were found between daily and thrice daily administration of aminoglycosides (one trial, 179 children, persistent symptoms at three days: RR 1.98, 95% CI 0.37 to 10.53). REVIEWER'S CONCLUSIONS: These results suggest that children with acute pyelonephritis can be treated effectively with oral cefixime or with short courses (2-4 days) of IV therapy followed by oral therapy. If IV therapy is chosen, single daily dosing with aminoglycosides is safe and effective. Trials are required to determine the optimal total duration of therapy and if other oral antibiotics can be used in the initial treatment of acute pyelonephritis.

Adolescent↗

Immunosuppressive agents for treating IgA nephropathy.

BACKGROUND: IgA nephropathy (IgAN) is a world-wide disease and the cause of end-stage renal failure (ESRF) in 15 to 20% of patients within 10 years and in 30 to 40% of individuals within 20 years from the apparent onset of disease. No specific treatment has yet been established but many approaches have been investigated. OBJECTIVES: To assess the benefits and harms of immunosuppressive treatment for IgAN. SEARCH STRATEGY: We searched The Cochrane Renal Group's specialized register (May 2003), Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library, Issue 3, 2002) MEDLINE (1966 - September 2002), EMBASE (1988 - September 2002) and handsearched reference lists of retrieved articles and conference proceedings. SELECTION CRITERIA: Randomized controlled trials (RCTs) and quasi-RCTs comparing treatment of IgAN with immunosuppressive agents against placebo, no treatment, other immunosuppressive or non-immunosuppressive agents. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals (CI). MAIN RESULTS: Thirteen eligible RCTs involving 623 patients were identified. All identified RCTs had a placebo, no treatment or warfarin/dipyridamole control group. Seven trials used steroids, three used alkylating agents/cyclosporin and three used combinations of steroids and alkylating agents/cyclosporin. No trial directly compared steroids versus alkylating agents/cyclosporin. Quality was sub-optimal. Steroids were associated with a lower risk of progression to ESRF (RR 0.44, 95% CI 0.25 to 0.80) and lower urinary protein excretion (WMD -0.49 g/24h, 95% CI -0.72 to -0.12). Urinary protein excretion was lower for patients treated with alkylating agents/cyclosporin compared to placebo/no treatment (WMD -0.94 g/24h, 95% CI -1.43 to -0.46). There was no significant reduction of urinary protein excretion with combination treatment of steroids and alkylating agents compared with placebo/no treatment. REVIEWER'S CONCLUSIONS: The optimal management of IgAN remains uncertain. The RCTs identified were small, of sub-optimal methodological quality and tended to only report favorable and surrogate outcomes without a thorough reporting of treatment harms. All outcomes favor the use of immunosuppressive interventions, with steroids appearing to be the most promising. Further study, in the form of RCTs, is necessary to ascertain which patients would benefit from these interventions, whether they are the ones with early signs of renal dysfunction or those with more advanced renal impairment.

Glomerulonephritis, IGA↗

Short versus standard duration oral antibiotic therapy for acute urinary tract infection in children.

BACKGROUND: The optimal duration of oral antibiotic therapy for urinary tract infection (UTI) in children has not been determined. A number of studies have compared single dose therapy to standard therapy for UTI, with mixed results. A course of antibiotics longer than a single dose but shorter than the usual 7-10 days might decrease the relapse rate and still provide some of the benefits of a shortened course of antibiotics. OBJECTIVES: The objective of this review was to assess the benefits and harms of short-course (2-4 days) compared to standard duration (7-14 days) oral antibiotic treatment for acute UTI in children. SEARCH STRATEGY: We searched the Cochrane Controlled Trials Register (Cochrane Library Issue 3, 2002) MEDLINE (1966 - September 2002) and EMBASE (1988 -September 2002) without language restriction. SELECTION CRITERIA: Randomised and quasi-randomised controlled trials comparing short-term (2-4 days) with standard (7-14 days) oral antibiotic therapy were selected if they studied children aged three months to 18 years with culture proven UTI. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) with 95% confidence intervals (95% CI). MAIN RESULTS: Ten trials were identified in which 652 children with lower tract UTI were evaluated. There was no significant difference in the frequency of positive urine cultures between the short (2-4 days) and standard duration oral antibiotic therapy (7-14 days) for UTI in children at 0-10 days after treatment (eight studies: RR 1.06; 95% CI 0.64 to 1.76) and at one to 15 months after treatment (10 studies: RR 0.95; 95% CI 0.70 to 1.29). There was no significant difference between short and standard duration therapy in the development of resistant organisms in UTI at the end of treatment (one study: RR 0.57, 95% CI 0.32 to 1.01) or in recurrent UTI (three studies: RR 0.39, 95% CI 0.12 to 1.29). REVIEWER'S CONCLUSIONS: A 2-4 day course of oral antibiotics appears to be as effective as 7-14 days in eradicating lower tract UTI in children.

Acute Disease↗

Haemoglobin and haematocrit targets for the anaemia of chronic renal disease.

BACKGROUND: Anaemia affects 60-80% of patients with renal impairment, reduces quality of life and is a risk factor for early death. Treatment options are blood transfusion, erythropoietin (EPO) alpha or beta and darbepoetin alfa. Recently higher haemoglobin (Hb) and haematocrit targets have been widely advocated because of positive data from observational studies. However, higher targets may lead to access thrombosis and hypertension and are costly. OBJECTIVES: This review assesses the benefits and harms of low (Hb </= 100 g/L or HCT </= 30%) and high (Hb > 100 g/L or HCT > 30%) targets in pre- and post-dialysis patients receiving any treatment for anaemia. SEARCH STRATEGY: We searched The Cochrane Renal Group specialised register (September 2002), Cochrane Controlled Trials Register (The Cochrane Library, Issue 3, 2002) MEDLINE (1966 - September 2002), EMBASE (1988 - September 2002) and reference lists of retrieved articles. SELECTION CRITERIA: Randomised controlled trials (RCTs) and quasi-RCTs comparing low Hb/HCT targets (Hb</- 100 g/L) with high Hb/HCT targets (Hb > 100 g/dL) in patients with anaemia of chronic renal disease. DATA COLLECTION AND ANALYSIS: Two reviewers independently assessed trial quality and extracted data. Statistical analyses were performed using the random effects model and the results expressed as relative risk (RR) for dichotomous outcomes and weighted mean difference (WMD) for continuous outcomes, with 95% confidence intervals (95% CI). MAIN RESULTS: Fifteen trials were identified in which 2096 patients were included. Twelve trials (673 patients) compared placebo with EPO and three trials (1423 patients) compared two doses of EPO. Hb values of 100 g/L (obtained with low EPO doses) were associated with lower mortality compared to Hb values of 140 g/L or more (obtained with high EPO doses) in the population with chronic renal disease and cardiovascular impairment (two trials, 1379 patients: RR 0.82; 95% CI 0.68 to 0.99). Lower targets obtained with a placebo resulted in an increased risk for seizures (four trials, 219 patients: RR 5.25; 95% CI 1.13 to 24.34) as compared to higher targets reached with EPO treatment. Finally, there was a reduced risk for hypertensive episodes with lower Hb targets reached with a placebo as compared to higher targets reached with EPO (six trials, 387 patients: RR 0.50; 95% CI 0.33 to 0.76). Quality of life was not adequately evaluated in the studies. REVIEWER'S CONCLUSIONS: Lower Hb targets of 100 g/L were associated with a lower risk of death in the population with cardiovascular impairment and chronic renal disease as compared to Hb 140 g/L. Lower Hb targets (Hb < 100 g/L) were also significantly associated with an increased risk for seizures and a reduced risk of hypertension compared to Hb > 100 g/L. There is a need of more adequately powered, well-designed and reported trials in this area. In particular, randomised controlled trials comparing the benefits and harms of low (Hb < 100 g/L) versus intermediate (Hb 130 g/L) and high (Hb 140 g/L) targets in the pre-dialysis population with chronic renal disease are necessary. In fact, there is a large deficiency of trials in the pre-dialysis population. The new trials should focus on hard outcomes and also look at outcomes which were previously not studied adequately, such as seizures and quality of life, which is to be assessed with validated measures.

Anemia↗

Antibiotics and surgery for vesicoureteric reflux: a meta-analysis of randomised controlled trials.

AIMS: To evaluate the benefits and harms of treatments for vesicoureteric reflux in children. METHODS: Meta-analyses of randomised controlled trials using a random effects model. Main outcome measures were incidence of urinary tract infection (UTI), new or progressive renal damage, renal growth, hypertension, and glomerular filtration rate. RESULTS: Eight trials involving 859 evaluable children comparing long term antibiotics with surgical correction of reflux (VUR) and antibiotics (seven trials) and antibiotics compared with no treatment (one trial) were identified. Risk of UTI by 1-2 and 5 years was not significantly different between surgical and medical groups (relative risk (RR) by 2 years 1.07; 95% confidence interval (CI) 0.55 to 2.09, RR by 5 years 0.99; 95% CI 0.79 to 1.26). Combined treatment resulted in a 60% reduction in febrile UTI by 5 years (RR 0.43; 95% CI 0.27 to 0.70) but no concomitant significant reduction in risk of new or progressive renal damage at 5 years (RR 1.05; 95% CI 0.85 to 1.29). In one small study no significant differences in risk for UTI or renal damage were found between antibiotic prophylaxis and no treatment. CONCLUSION: It is uncertain whether the identification and treatment of children with VUR confers clinically important benefit. The additional benefit of surgery over antibiotics alone is small at best. Assuming a UTI rate of 20% for children with VUR on antibiotics for five years, nine reimplantations would be required to prevent one febrile UTI, with no reduction in the number of children developing any UTI or renal damage.

Adolescent↗

Short compared with standard duration of antibiotic treatment for urinary tract infection: a systematic review of randomised controlled trials.

AIMS: To compare the effectiveness of short course (2-4 days) with standard duration oral antibiotic treatment (7-14 days) for urinary tract infection (UTI). METHODS: Meta-analysis of randomised controlled trials using a random effects model. Ten trials were eligible, involving 652 children with lower tract UTI recruited from outpatient or emergency departments. Main outcome measures were UTI at the end of treatment, UTI during follow up (recurrent UTI), and urinary pathogens resistant to the treating antibiotic. RESULTS: There was no significant difference in the frequency of positive urine cultures between the short (2-4 days) and standard duration therapy (7-14 days) for UTI in children at 0-7 days after treatment (eight studies: RR 1.06; 95% CI 0.64 to 1.76) and at 10 days to 15 months after treatment (10 studies: RR 1.01; 95% CI 0.77 to 1.33). There was no significant difference between short and standard duration therapy in the development of resistant organisms in UTI at the end of treatment (one study: RR 0.57, 95% CI 0.32 to 1.01) or in recurrent UTI (three studies: RR 0.39, 95% CI 0.12 to 1.29). CONCLUSION: A 2-4 day course of oral antibiotics is as effective as 7-14 days in eradicating lower tract UTI in children.

Adolescent↗