Randomised controlled trial to assess acceptability of phenobarbital for childhood epilepsy in rural India

BACKGROUND: The use of phenobarbital for childhood epilepsy is controversial because of reported behavioural side-effects; however, whether this research can validly be extrapolated to developing countries is not clear. We undertook a randomised comparison of phenobarbital and phenytoin to assess the acceptability and efficacy of phenobarbital as monotherapy for childhood epilepsy in rural India. METHODS: Between August, 1995, and February, 1996, 109 unselected children aged 2-18 years with partial and generalised tonic-clonic epilepsy were identified by population screening. 15 families declined to take part. 94 children were randomly allocated treatment with phenobarbital (1.5 mg/kg daily for 2 weeks; maintenance dose 3.0 mg/kg daily; n = 47) or phenytoin (2.5 mg/kg daily then 5.0 mg/kg daily; n = 47). Children were followed up for 12 months. The primary outcome measure was the frequency of behavioural side-effects; behaviour was assessed by the Conners parent rating scale for children aged 6 years and older, and by the preschool behaviour screening questionnaire (BSQ) for those aged 2-5 years, at 12 months or at withdrawal from treatment. Analysis was by intention to treat. FINDINGS: The mean log-transformed scores on the behaviour rating scales did not differ significantly between the phenobarbital and phenytoin groups (Conners 2.64 [SD 0.71] vs 2.65 [0.89], p = 0.97; n = 32 in each group: BSQ 2.12 [1.31] vs 2.18 [1.02], p = 0.94; n = 4 vs 3). The odds ratio for behavioural problems (phenobarbital vs phenytoin) was 0.51 (95% CI 0.16-1.59). There was no excess in parental reports of side-effects for phenobarbital. We found no difference in efficacy between the study drugs (adjusted hazard ratio for time to first seizure from randomisation 0.97 [0.28-3.30]). INTERPRETATION: This evidence supports the acceptability of phenobarbital as a first-line drug for childhood epilepsy in rural settings in developing countries.     

Randomised comparison of thalidomide versus placebo in toxic epidermal necrolysis

BACKGROUND: Toxic epidermal necrolysis (TEN) is associated with a 30% death rate. Tumour necrosis factor alpha (TNF-alpha) has been implicated in the pathogenesis of TEN. Thalidomide is a potent inhibitor of TNF-alpha action. We did a double-blind, randomised, placebo-controlled study of thalidomide in TEN. METHODS: The patients received a 5-day course of thalidomide 400 mg daily or placebo. The main endpoint was the progression of skin detachment after day 7. Secondary endpoints were the severity of the disease, evaluated with the simplified acute physiology score (SAPS), and the mortality. TNF-alpha and interleukin 6 were measured. FINDINGS: The study was stopped because there was excess mortality in the thalidomide group--ten of 12 patients died compared with three of ten in the placebo group (Fisher's exact test with Katz's approximation, relative risk=2.78, p=0.03). After adjustment for SAPS, mortality remained significantly higher in the thalidomide group than in the placebo group (exact logistic regression mid-p=0.007; 95% CI for odds ratio 2.7 to infinity). Plasma TNF-alpha concentration was higher in the thalidomide group than the placebo group on day 2, though the difference was not significant (Wilcoxon rank-sum test p=0.07). INTERPRETATION: Even though few patients were included, our data suggest that thalidomide is detrimental in TEN, possibly because of a paradoxical enhancement of TNF-alpha production.     

Randomised comparison on the treatment of falciparum malaria with dihydroartemisinin and piperaquine

In 1988, 50 cases each of falciparum malaria were treated by dihydroartemisin (360 mg in 5 days and 480 mg in 7 days respectively), and compared randomly with piperaquine phosphate group. The results showed that the plasmodium of falciparal malaria in Dong Fang County, Hainan province, is much more resistant to piperaquine phosphate, in the 51 cases treated by piperaquine, 33.3% were sensitive, 19.0% were RI, 21.6% were RII, and 25.5% were RIII. The effect of dihydroartemisinin (both 5 days and 7 days therapy) were obviously better than that of pipera quine, fever subsidence time and parasite clearance time were similar and parasite recrudescence rate showed no obvious difference in these two groups too.     

Randomised comparison of ceftazidime and imipenem as initial monotherapy for febrile episodes in neutropenic cancer patients

With the availability of new, broad-spectrum antibiotics, initial therapy with a single agent has become an alternative to classic combinations in the management of febrile, neutropenic cancer patients. The aims of this study were to compare the efficacy of ceftazidime and imipenem as empirical monotherapy of febrile episodes in neutropenic patients, and to examine the frequency with which second-line antibiotics (amikacin, vancomycin, or both) were required. A prospective clinical trial was carried out in a single centre. Eligible patients with solid tumours or lymphoma were randomised to receive monotherapy with ceftazidime or imipenem. In the event of no response, amikacin and/or vancomycin were added in 48-72 h intervals (sequentially, or according to clinical or microbiological data). Efficacy was evaluable for 111 assessable episodes. Median neutrophil count at entry was 100 cells/microliters and median duration of neutropenia was 4 days. Febrile episodes were classified as microbiologically (34%) or clinically documented (42%), and fever of unknown origin (24%). Gram-negative infections (57%) predominated over gram-positive isolates (30%). The overall success rate with monotherapy (69% versus 70%), or with modification (20% versus 23%) were equivalent for ceftazidime and imipenem (P = 0.75). The mortality in this series was 5%. Single-agent therapy with either ceftazidime or imipenem is effective for the empirical treatment of febrile episodes in neutropenic patients with solid tumours. Early addition of amikacin and/or vancomycin resolves most failures of the first step.     

A comparison of active and simulated chiropractic manipulation as adjunctive treatment for childhood asthma

BACKGROUND: Chiropractic spinal manipulation has been reported to be of benefit in nonmusculoskeletal conditions, including asthma. METHODS: We conducted a randomized, controlled trial of chiropractic spinal manipulation for children with mild or moderate asthma. After a three-week base-line evaluation period, 91 children who had continuing symptoms of asthma despite usual medical therapy were randomly assigned to receive either active or simulated chiropractic manipulation for four months. None had previously received chiropractic care. Each subject was treated by 1 of 11 participating chiropractors, selected by the family according to location. The primary outcome measure was the change from base line in the peak expiratory flow, measured in the morning, before the use of a bronchodilator, at two and four months. Except for the treating chiropractor and one investigator (who was not involved in assessing outcomes), all participants remained fully blinded to treatment assignment throughout the study. RESULTS: Eighty children (38 in the active-treatment group and 42 in the simulated-treatment group) had outcome data that could be evaluated. There were small increases (7 to 12 liters per minute) in peak expiratory flow in the morning and the evening in both treatment groups, with no significant differences between the groups in the degree of change from base line (morning peak expiratory flow, P=0.49 at two months and P=0.82 at four months). Symptoms of asthma and use of 3-agonists decreased and the quality of life increased in both groups, with no significant differences between the groups. There were no significant changes in spirometric measurements or airway responsiveness. CONCLUSIONS: In children with mild or moderate asthma, the addition of chiropractic spinal manipulation to usual medical care provided no benefit.     

Randomised double blind comparison of terbinafine and itraconazole for treatment of toenail tinea infection. Seventh Lamisil German Onychomycosis Study Group

OBJECTIVE: To compare the efficacy and tolerability of terbinafine and itraconazole in the treatment of toenail tinea unguium. DESIGN: Multicentre, double blind, parallel group study. SETTING: 17 university hospitals, one army hospital, and five dermatology practices. PATIENTS: 195 patients with clinically suspected toenail tinea and growth of dermatophytes in baseline culture; data on 86 patients in the terbinafine group and 84 patients in the itraconazole group were fully evaluated for efficacy. INTERVENTIONS: Daily dose of 250 mg terbinafine or 200 mg itraconazole for 12 weeks, with follow up for a further 40 weeks. MAIN OUTCOME MEASURES: Mycological cure (negative results on microscopy and culture) and clinical improvement (length and area of unaffected nail) at week 52 or at discontinuation of treatment. RESULTS: At the end of the study mycological cure rates were 81% (70 out of 86) for terbinafine and 63% (53 out of 84) for itraconazole (2P < 0.01). Negative culture was achieved in 92% (79 out of 86) in the terbinafine group and 67% (56 out of 84) in the itraconazole group (2P < 0.0001). Length of unaffected nail was 9.44 mm in the terbinafine group and 7.85 mm in the itraconazole group (2P < 0.05). CONCLUSION: Terbinafine is more effective than itraconazole in the treatment of toenail tinea infection.     

Randomised comparison of combined step-down prednisolone, methotrexate and sulphasalazine with sulphasalazine alone in early rheumatoid arthritis

BACKGROUND: The value of intensive combination therapy in early rheumatoid arthritis is unproven. In a multicentre, double-blind, randomised trial (COBRA), we compared the combination of sulphasalazine (2 g/day), methotrexate (7.5 mg/week), and prednisolone (initially 60 mg/day, tapered in 6 weekly steps to 7.5 mg/day) with sulphasalazine alone. METHODS: 155 patients with early rheumatoid arthritis (median duration 4 months) were randomly assigned combined treatment (76) or sulphasalazine alone (79). Prednisolone and methotrexate were tapered and stopped after 28 and 40 weeks, respectively. The main outcomes were the pooled index (a weighted change score of five disease activity measures) and the Sharp/Van der Heijde radiographic damage score in hands and feet. Independent health-care professionals assessed the main outcomes without knowledge of treatment allocation. FINDINGS: At week 28, the mean pooled index was 1.4 (95% CI 1.2-1.6) in the combined treatment group and 0.8 (0.6-1.0) in the sulphasalazine group (p < 0.0001). At this time, 55 (72%) and 39 (49%) patients, respectively, were improved according to American College of Rheumatology criteria. The clinical difference between the groups decreased and was no longer significant after prednisolone was stopped, and there were no further changes after methotrexate was stopped. At 28 weeks, the radiographic damage score had increased by a median of 1 (range 0-28) in the combined-therapy group and 4 (0-44) in the sulphasalazine group (p < 0.0001). The increases at week 56 (2 [0-43] vs 6 [0-54], p = 0.004), and at week 80 (4 [0-80] vs 12 [0-72], p = 0.01) were also significant. Further analysis suggests that combined therapy immediately suppressed damage progression, whereas sulphasalazine did so less effectively and with a lag of 6 to 12 months. There were fewer withdrawals in the combined therapy than the sulphasalazine group (6 [8%] vs 23 [29%]), and they occurred later. INTERPRETATION: This combined-therapy regimen offers additional disease control over and above that of sulphasalazine alone that persists for up to a year after corticosteroids are stopped. Although confirmatory studies and long-term follow-up are needed, this approach may prove useful in the treatment of early rheumatoid arthritis.     

Sensitivity testing of ciprofloxacin for Pseudomonas aeruginosa

The presence and distribution of the most important highly repetitive DNA sequences of rye in cultivated and wild species of the genus Secale were investigated using fluorescence in situ hybridization. Accurate identification of individual chromosomes in the most commonly recognized species or subspecies of the genus Secale (S. cereale, S. ancestrale, S. segetale, S. afghanicum, S. dighoricum, S. montanum, S. montanum ssp. kuprijanovii, S. africanum, S. anatolicum, S. vavilovii, and S. silvestre) was achieved using three highly repetitive rye DNA sequences (probes pSc119.2, pSc74, and pSc34) and the 5S ribosomal DNA sequence pTa794. It is difficult to superimpose trends in the complexity of repetitive DNA during the evolution of the genus on conclusions from other cytogenetic and morphological assays. However, there are two clear groups. The first comprises the self-pollinated annuals S. silvestre and S. vavilovii that have few repeated nucleotide sequences of the main families of 120 and 480 bp. The second group presents amplification and interstitialization of the repeated nucleotide sequences and includes the perennials S. montanum, S. anatolicum, S. africanum, and S. kuprijanovii, as well as the annual and open-pollinated species S. cereale and its related weedy forms. The appearance of a new locus for 5S rRNA in S. cereale and S. ancestrale suggests that cultivated ryes evolved from this wild weedy species.     

Randomised double-masked placebo-controlled trial of a treatment for congenital nystagmus

Several therapies have been developed for congenital nystagmus (CN) but without placebo-controlled trials. We investigated a treatment which combined two therapies that had been advocated by several authors and were reported to improve visual acuity (VA). A placebo treatment was designed to mimic the time, attention, 'high tech' apparatus, and the explanation used in the experimental treatment. To each group, 38 subjects with CN were randomly allocated. Their VA and contrast sensitivity (CS) were assessed three times before undergoing treatment for 6 weeks and then once more. An improvement in VA occurred, however, this was not significantly different in the two groups. The improvement in CS was greater in the experimental than in the control group, but the difference failed to reach significance in most statistical tests. We conclude that putative therapies for CN should be assumed to be placebos until proven otherwise with randomized controlled trials.     

Individual and group psychotherapy of childhood aggression: A comparison of outcomes and processes.

The purpose of this study was to compare outcomes and processes of a therapeutic intervention to reduce children's aggressive behavior, delivered in individual and group formats. Children in 15 small groups (n?=?71) and 15 individual treatment children were compared in a pre–post experimental and control design. The Achenbach self-report behavior checklist and teachers' evaluations were used to measure outcomes. To assess outcome results further, the process of change was qualitatively analyzed. In addition, the therapeutic processes were compared using Hill's counselor and client verbal response modes system. Results concerning outcomes indicated reduced aggression of treated children compared with wait-list children, with no differential impact of the format of treatment. The analyses of stages of change supported the similarity in outcomes. Results concerning process variables indicated differences in both therapist and client verbal responses. In therapists' responses, directives were used more in groups and self-disclosure was used more in individual therapy. In clients' responses, most variables were more frequently used in individual therapy. Experiencing was more frequent in group therapy, and there was no difference in insight and simple responses… (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Randomised trial of laparoscopic versus open cholecystectomy for acute and gangrenous cholecystitis

BACKGROUND: Laparoscopic cholecystectomy (LC) has become the treatment of choice for elective cholecystectomy, but controversy persists over use of this approach in the treatment of acute cholecystitis. We undertook a randomised comparison of the safety and outcome of LC and open cholecystectomy (OC) in patients with acute cholecystitis. METHODS: 63 of 68 consecutive patients who met criteria for acute cholecystitis were randomly assigned OC (31 patients) or LC (32 patients). The primary endpoints were hospital mortality and morbidity, length of hospital stay, and length of sick leave from work. Analysis was by intention to treat. Suspected bile-duct stones were investigated by preoperative endoscopic retrograde cholangiography (LC group) or intraoperative cholangiography (OC group). FINDINGS: The two randomised groups were similar in demographic, physical, and clinical characteristics. 48% of the patients in the OC group and 59% in the LC group were older than 60 years. 13 patients in each group had gangrene or empyema, and one in each group had perforation of the gallbladder causing diffuse peritonitis. Five (16%) patients in the LC group required conversion to OC, in most because severe inflammation distorted the anatomy of Calot's triangle. There were no deaths or bile-duct lesions in either group, but the postoperative complication rate was significantly (p=0.0048) higher in the OC than in the LC group: seven (23%) patients had major and six (19%) minor complications after OC, whereas only one (3%) minor complication occurred after LC. The postoperative hospital stay was significantly shorter in the LC than the OC group (median 4 [IQR 2-5] vs 6 [5-8] days; p=0.0063). Mean length of sick leave was shorter in the LC group (13.9 vs 30.1 days; 95% CI for difference 10.9-21.7). INTERPRETATION: Even though LC for acute and gangrenous cholecystitis is technically demanding, in experienced hands it is safe and effective. It does not increase the mortality rate, and the morbidity rate seems to be even lower than that in OC. However, a moderately high conversion rate must be accepted.     

Thioguanine versus mercaptopurine for therapy of childhood lymphoblastic leukaemia: a comparison of haematological toxicity and drug metabolite concentrations

Stocks of the International Reference Preparation (IRP) for thromboplastin, human, plain, coded BCT/253 and held by the World Health Organization (WHO) are nearly exhausted and must be replaced. For practical reasons the choice of the replacement candidate was restricted to two available human recombinant preparations which were coded as X/95 and Y/95 and calibrated in an international collaborative study involving 19 laboratories from Europe, Australia, Canada and Argentina. To minimize the differences between routes of calibration, the two candidates were calibrated against the existing WHO-IRP from human, rabbit and bovine origin and the final ISI was the resultant average value. On the basis of predefined criteria (i.e., within- and between-laboratory precision of the calibration and the conformity to the calibration model), X/95 was the preferred candidate. The assigned ISI (SE of the mean) value is 0.940 (0.0060) and the interlaboratory coefficient of variation 4.7%.     

Comparison of two regimens for ciprofloxacin treatment of enteric infections

An understanding of the functional significance of the newly identified estrogen receptor (ER beta) in the brain will require definition of its expression pattern and relationship to ER alpha. Using an antibody generated against the C-terminus of rat ER beta, we report the presence of ER beta immunoreactivity in the lateral septum, medial amygdala, hippocampus and paraventricular nucleus (PVN) of ovariectomized rats. Double labelling studies in the PVN revealed that approximately 35% of oxytocin neurons located principally in the medial and lateral parvocellular divisions of the caudal PVN were immunoreactive for ER beta while vasopressin, somatostatin and magnocellular oxytocin neurons exhibited no ER beta staining with this antibody. No ER alpha immunoreactive cells were identified in the caudal PVN. These observations provide direct evidence for the differential expression of ER sub-types within neurons and indicate that ER beta may be of physiological significance in the regulation of hypothalamic parvocellular oxytocin neurons by estrogen.     

A comparison of trauma-focused and present-focused group therapy for survivors of childhood sexual abuse: A randomized controlled trial.

This randomized controlled trial compared trauma-focused group psychotherapy (TFGT) with present-focused group psychotherapy (PFGT) and a waitlist condition for 166 survivors of childhood sexual abuse who were at risk for HIV infection. Primary outcomes included risk for HIV infection (based on sexual revictimization, drug and alcohol use, and risky sex) and posttraumatic stress disorder (PTSD) symptoms. It was hypothesized that TFGT would be superior to the PFGT and waitlist conditions and that receiving either treatment (combining both TFGT and PFGT) would be superior to no treatment (waitlist condition). Intention-to-treat analyses for HIV risk found that all conditions reduced risk; however, there was no effect for condition on HIV risk. Intention-to-treat analyses for PTSD symptoms found a reduction for all conditions. There was no advantage for either TFGT or PFGT in reducing PTSD symptoms; however, there was an effect for treatment compared with the waitlist condition. On secondary outcomes, there was a greater reduction in anger for TFGT compared with PFGT, and when comparing treatment with the waitlist condition, there was a greater reduction in hyperarousal, reexperiencing, anger, and impaired self-reference for the treatment condition. Adequate dose analyses generally confirmed the intention-to-treat findings and additionally found that treatment led to reductions in depression, dissociation, and sexual concerns. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Long-term results of the Stamey bladder neck suspension: direct comparison with the Marshall-Marchetti-Krantz procedure

Non-glycosylated recombinant Locusta migratoria apolipophorin-III, apoLp-III, was expressed in E. coli and its physical-chemical properties were compared to those of the glycosylated native apoLp-III. Fluorescence quantum yield and acrylamide quenching studies indicated a slightly higher accessibility of the Trp residues in the recombinant apoLp-III. Far-UV CD spectroscopy indicated that the recombinant apoLp-III has a lower alpha-helical content than the glycosylated apoLp-III. Both proteins spontaneously formed discoidal recombinant lipoprotein particles when incubated with dimyristoylphosphatidylcholine (DMPC). Interaction with lipid promotes an increase in alpha-helical content. CD and fluorescence studies indicate that both proteins adopt the same conformation in the lipid-bound state. However, the kinetics of association of the recombinant protein with DMPC is 5-fold faster than that of the native protein. The results suggest that glycosylation inhibits the lipid binding activity by preventing the exposure of hydrophobic domains and/or decreasing the conformational flexibility of the protein.     

Evaluation of an intervention program for the control of an outbreak of shigellosis among institutionalized persons

After control measures were initiated to stop an outbreak of shigellosis in an institution for the developmentally disabled, there was a sharp decline in the number of cases of Shigella sonnei infection. Among ill residents, those treated with antibiotics had shorter mean duration of diarrhea (2.4 vs. 4.5 days, P < .01) and were less likely to have stool cultures positive for shigellae 2-4 weeks after onset of diarrhea (0/25 vs. 5/19; relative risk [RR] = undefined; P = .02). The attack rate was higher in villages where segregation of ill residents was not practiced (46/73 vs. 53/155; RR = 1.8; 95% confidence limits [CL], 1.4, 2.4). In individual housing units where ill residents were not segregated (preintervention), a correlation was found between mean duration of diarrhea and unit attack rates (r = .88; 95% CL, 0.29, 0.99). A study of all 305 residents 10 weeks after the intervention began revealed no positive stool cultures.     

Placental transfer of enrofloxacin and ciprofloxacin in rabbits

Placental transfer of enrofloxacin and ciprofloxacin was evaluated, using a rabbit in situ perfusion model. A two-step infusion program was carried out to obtain steady-state maternal plasma concentrations of these drugs. For each compound, the placenta in 5 rabbits was perfused for 200 minutes with Earle's enriched bicarbonate buffer at flow rate of 1.5 ml/min. To assess reliability of the model, most of the determinants of placental transfer (maternal and fetal pH, gas balance, heart status, rectal temperature, and protein binding) were controlled. In addition, the infusion program included administration of antipyrine, a commonly used indicator of placental exchange. Drug concentrations were measured in maternal plasma and perfusate by use of a high-performance liquid chromatographic assay. Plasma protein-binding estimation indicated no differences between the drugs. Placental clearance of the drugs was significantly (P < 0.01) different (0.88 +/- 0.13 ml/min for enrofloxacin and 0.06 +/- 0.02 ml/min for ciprofloxacin). These values accounted for 81 and 5%, respectively, of the placental clearance found for antipyrine. These results indicate that caution must be taken when enrofloxacin is to be used during pregnancy, and suggest the need to extend this type of experiment to species that can be exposed to these drugs used for therapeutic or prophylactic purposes.     

Randomised trial comparing the upright and supine positions for the second stage of labour

OBJECTIVE: To assess the maternal and neonatal effects of upright compared with recumbent positions during delivery, in terms of defined outcome variables. DESIGN: A randomised controlled trial. SETTING: St Monica's Nursing Home, a midwife based maternity unit in Cape Town, South Africa. PARTICIPANTS: Five hundred and seventeen women of low obstetrical risk assigned to deliver at the nursing home. RESULTS: The trial showed that women who adopted the upright posture for delivery experienced less pain. perineal trauma and fewer episiotomies than those who delivered in the supine position. CONCLUSION: The data suggest that in women of low obstetrical risk, choice of posture during delivery may be encouraged.