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Randomised control trial of tongue acupuncture versus sham acupuncture in improving functional outcome in cerebral palsy.

BACKGROUND: Traditional Chinese medicine (TCM) has been used historically in the treatment of cerebral palsy (CP). We investigated the efficacy of acupuncture in improving the motor function of children with CP. METHODS: A randomised control trial was conducted to assess the effect of tongue acupuncture (TAC) in 33 CP children. The subjects were randomised to treatment (n = 22) with TAC or control (n = 11). Clinical outcome was evaluated using the gross motor function measure (GMFM) and the pediatric evaluation of disability inventory (PEDI). RESULTS: The increase in mean GMFM score was significantly greater in the treatment than in the control group (p = 0.042). CONCLUSION: An improvement in motor function of CP subjects is seen following a short course of acupuncture.

Acupuncture Therapy↗

A pilot randomised controlled trial of eccentric exercise to prevent hamstring injuries in community-level Australian Football.

Hamstring injuries are the most common injury sustained by Australian Football players. Eccentric training has been proposed as a potential preventative strategy. This pilot randomised controlled trial (RCT) evaluated the effectiveness of a pre-season eccentric training program for preventing hamstring injuries at the community level of Australian Football. Seven amateur clubs (n=220 players) were recruited. Players were randomised within clubs to the intervention (eccentric exercise) or control (stretching) groups and randomisation was stratified according to previous history of hamstring injury. Five exercise sessions were completed over a 12-week period, three during the pre-season and two during the first 6 weeks of the season. Compliance was recorded and players were monitored for the season to collect injury and participation data. There was no difference between the control (n=106) or intervention (n=114) groups with respect to baseline characteristics. Only 46.8% of all players completed at least two program sessions. Compliance was poorest for the intervention group. Intention-to-treat analysis suggested that players in the intervention group were not at reduced risk of hamstring injury (RR 1.2, 95% CI: 0.5, 2.8). When only control and intervention group players who participated in at least the first two sessions were analysed, 4.0% of intervention and 13.2% of control group players sustained a hamstring injury (RR 0.3, 95% CI: 0.1, 1.4; p=0.098). The findings suggest that a simple program of eccentric exercise could reduce the incidence of hamstring injuries in Australian Football but widespread implementation of this program is not likely because of poor compliance.

Adolescent↗

Safety and effectiveness of nurse telephone consultation in out of hours primary care: randomised controlled trial. The South Wiltshire Out of Hours Project (SWOOP) Group.

OBJECTIVE: To determine the safety and effectiveness of nurse telephone consultation in out of hours primary care by investigating adverse events and the management of calls. DESIGN: Block randomised controlled trial over a year of 156 matched pairs of days and weekends in 26 blocks. One of each matched pair was randomised to receive the intervention. SETTING: One 55 member general practice cooperative serving 97 000 registered patients in Wiltshire. SUBJECTS: All patients contacting the out of hours service or about whom contact was made during specified times over the trial year. INTERVENTION: A nurse telephone consultation service integrated within a general practice cooperative. The out of hours period was 615 pm to 1115 pm from Monday to Friday, 1100 am to 1115 pm on Saturday, and 800 am to 1115 pm on Sunday. Experienced and specially trained nurses received, assessed, and managed calls from patients or their carers. Management options included telephone advice; referral to the general practitioner on duty (for telephone advice, an appointment at a primary care centre, or a home visit); referral to the emergency service or advice to attend accident and emergency. Calls were managed with the help of decision support software. MAIN OUTCOME MEASURES: Deaths within seven days of a contact with the out of hours service; emergency hospital admissions within 24 hours and within three days of contact; attendance at accident and emergency within three days of a contact; number and management of calls in each arm of the trial. RESULTS: 14 492 calls were received during the specified times in the trial year (7308 in the control arm and 7184 in the intervention arm) concerning 10 134 patients (10.4% of the registered population). There were no substantial differences in the age and sex of patients in the intervention and control groups, though male patients were underrepresented overall. Reasons for calling the service were consistent with previous studies. Nurses managed 49.8% of calls during intervention periods without referral to a general practitioner. A 69% reduction in telephone advice from a general practitioner, together with a 38% reduction in patient attendance at primary care centres and a 23% reduction in home visits was observed during intervention periods. Statistical equivalence was observed in the number of deaths within seven days, in the number of emergency hospital admissions, and in the number of attendances at accident and emergency departments. Conclusions Nurse telephone consultation produced substantial changes in call management, reducing overall workload of general practitioners by 50% while allowing callers faster access to health information and advice. It was not associated with an increase in the number of adverse events. This model of out of hours primary care is safe and effective.

Adolescent↗

Procalcitonin-guided antibiotic use versus a standard approach for acute respiratory tract infections in primary care: study protocol for a randomised controlled trial and baseline characteristics of participating general practitioners [ISRCTN73182671].

BACKGROUND: Acute respiratory tract infections (ARTI) are among the most frequent reasons for consultations in primary care. Although predominantly viral in origin, ARTI often lead to the prescription of antibiotics for ambulatory patients, mainly because it is difficult to distinguish between viral and bacterial infections. Unnecessary antibiotic use, however, is associated with increased drug expenditure, side effects and antibiotic resistance. A novel approach is to guide antibiotic therapy by procalcitonin (ProCT), since serum levels of ProCT are elevated in bacterial infections but remain lower in viral infections and inflammatory diseases. The aim of this trial is to compare a ProCT-guided antibiotic therapy with a standard approach based on evidence-based guidelines for patients with ARTI in primary care. METHODS/DESIGN: This is a randomised controlled trial in primary care with an open intervention. Adult patients judged by their general practitioner (GP) to need antibiotics for ARTI are randomised in equal numbers either to standard antibiotic therapy or to ProCT-guided antibiotic therapy. Patients are followed-up after 1 week by their GP and after 2 and 4 weeks by phone interviews carried out by medical students blinded to the goal of the trial. Exclusion criteria for patients are antibiotic use in the previous 28 days, psychiatric disorders or inability to give written informed consent, not being fluent in German, severe immunosuppression, intravenous drug use, cystic fibrosis, active tuberculosis, or need for immediate hospitalisation. The primary endpoint is days with restrictions from ARTI within 14 days after randomisation. Secondary outcomes are antibiotic use in terms of antibiotic prescription rate and duration of antibiotic treatment in days, days off work and days with side-effects from medication within 14 days, and relapse rate from the infection within 28 days after randomisation. DISCUSSION: We aim to include 600 patients from 50 general practices in the Northwest of Switzerland. Data from the registry of the Swiss Medical Association suggests that our recruited GPs are representative of all eligible GPs with respect to age, proportion of female physicians, specialisation, years of postgraduate training and years in private practice.

Adult↗

Collaboration in maternity care: a randomised controlled trial comparing community-based continuity of care with standard hospital care.

OBJECTIVE: To test whether a new community-based model of continuity of care provided by midwives and obstetricians improved maternal clinical outcomes, in particular a reduced caesarean section rate. DESIGN: Randomised controlled trial. SETTING: A public teaching hospital in metropolitan Sydney, Australia. Sample 1089 women randomised to either the community-based model (n = 550) or standard hospital-based care (n = 539) prior to their first antenatal booking visit at an Australian metropolitan public hospital. MAIN OUTCOME MEASURES: Data were collected on onset and outcomes of labour, antenatal, intrapartum and postnatal complications, antenatal admissions to hospital and neonatal mortality and morbidity. RESULTS: There was a significant difference in the caesarean section rate between the groups, 13.3% (73/550) in the community-based group and 17.8% in the control group (96/539). This difference was maintained after controlling for known contributing factors to caesarean section (OR = 0.6, 95% CI 0.4-0.9, P = 0.02). There were no other significant differences in the events during labour and birth. Eighty babies (14.5%) from the community-based group and 102 (18.9%) from the control group were admitted to the special care nursery, but this difference was not significant (OR 0.75, 95% CI 0.5-1.1, P = 0.12). Eight infants died during the perinatal period (four from each group), for an overall perinatal mortality rate of 7.3 per 1000 births. CONCLUSION: Community-based continuity of maternity care provided by midwives and obstetricians resulted in a significantly reduced caesarean section rate. There were no other differences in clinical outcomes.

Adult↗

The feasibility of Whole Body Vibration in institutionalised elderly persons and its influence on muscle performance, balance and mobility: a randomised controlled trial [ISRCTN62535013].

BACKGROUND: Fatigue or lack of interest can reduce the feasibility of intensive physical exercise in nursing home residents. Low-volume exercise interventions with similar training effects might be an alternative. The aim of this randomised controlled trial was to investigate the feasibility of Whole Body Vibration (WBV) in institutionalised elderly, and its impact on functional capacity and muscle performance. METHODS: Twenty-four nursing home residents (15 female, 9 male; mean age 77.5 +/- 11.0 years) were randomised (stratification for age, gender and ADL-category) to 6 weeks static WBV exercise (WBV+, N = 13) or control (only static exercise; N = 11). Outcome measures were exercise compliance, timed up-and-go, Tinetti-test, back scratch, chair sit-and-reach, handgrip strength and linear isokinetic leg extension. RESULTS: At baseline, WBV+ and control groups were similar for all outcome variables. Twenty-one participants completed the program and attended respectively 96% and 86% of the exercise sessions for the WBV+ and control groups. Training-induced changes in timed up-and-go and Tinetti-test were better for WBV+ compared to control (p = 0.029 for timed up-and-go, p = 0.001 and p = 0.002 for Tinetti body balance and total score respectively). In an alternative analysis (Worst Rank Score & Last Observation Carried Forward) the differences in change remained significant on the Tinetti body balance and total score. No other significant differences in change between both groups were observed. CONCLUSION: In nursing home residents with limited functional dependency, six weeks static WBV exercise is feasible, and is beneficial for balance and mobility. The supplementary benefit of WBV on muscle performance compared to classic exercise remains to be explored further.

Aged↗

Randomised controlled trial of prevention of falls in people aged > or =75 with severe visual impairment: the VIP trial.

OBJECTIVES: To assess the efficacy and cost effectiveness of a home safety programme and a home exercise programme to reduce falls and injuries in older people with low vision. DESIGN: Randomised controlled trial. SETTING: Dunedin and Auckland, New Zealand. PARTICIPANTS: 391 women and men aged > or =75 with visual acuity of 6/24 or worse who were living in the community; 92% (361 of 391) completed one year of follow-up. INTERVENTIONS: Participants received a home safety assessment and modification programme delivered by an occupational therapist (n = 100), an exercise programme prescribed at home by a physiotherapist plus vitamin D supplementation (n = 97), both interventions (n = 98), or social visits (n = 96). MAIN OUTCOME MEASURES: Numbers of falls and injuries resulting from falls, costs of implementing the home safety programme. RESULTS: Fewer falls occurred in the group randomised to the home safety programme but not in the exercise programme (incidence rate ratios 0.59 (95% confidence interval 0.42 to 0.83) and 1.15 (0.82 to 1.61), respectively). However, within the exercise programme, stricter adherence was associated with fewer falls (P = 0.001). A conservative analysis showed neither intervention was effective in reducing injuries from falls. Delivering the home safety programme cost NZ650 dollars (234 pounds sterling, 344 euros, US432 dollars) (at 2004 prices) per fall prevented. CONCLUSION: The home safety programme reduced falls and was more cost effective than an exercise programme in this group of elderly people with poor vision. The Otago exercise programme with vitamin D supplementation was not effective in reducing falls or injuries in this group, possibly due to low levels of adherence. Trial registration number ISRCTN15342873.

Accidental Falls↗

Treatment of uncomplicated malaria with artemisinin derivatives. A systematic review of randomised controlled trials.

This systematic review of randomised or pseudorandomised trials was aimed at summarising the effectiveness and safety of artemisinin drugs for treating uncomplicated falciparum malaria. Ninety-three potentially eligible studies were identified and 38 met the inclusion criteria. Most data are from Southeast Asian areas of mefloquine-resistant falciparum malaria, Thailand in particular. Artemisinin drugs achieve high cure rates at follow-up in all endemic areas represented by the studies included provided that the duration of treatment is adequate. Combination with mefloquine improves sustained parasite clearance and is effective in multidrug resistant areas. Provided the dose of both drugs is adequate, the combination can shorten the duration of treatment. There is no evidence from randomised trials that any artemisinin derivative is better than the others. Data from just over 4,300 patients are included for analysis in this review. Despite the large amount of clinical research that has been done, variation in study design, quality and comparisons make synthesis of the data problematic. It is extremely difficult to draw clear conclusions from the existing database.

Adult↗

Strategies for managing antidepressant-induced sexual dysfunction: systematic review of randomised controlled trials.

BACKGROUND: This review was undertaken to assess the effectiveness of management strategies for sexual dysfunction caused by antidepressant medication. METHODS: Electronic databases and reference lists were searched, and pharmaceutical companies and experts contacted to identify randomised controlled trials comparing management strategies for antidepressant-induced sexual dysfunction. RESULTS: Fifteen trials involving 904 people were included. One trial involving 75 people with sexual dysfunction due to sertraline assessed changing antidepressant. Switching to nefazodone was significantly less likely to result in the re-emergence of sexual dysfunction than restarting sertraline (RR 0.34, 95% CI 0.15 to 0.6). Meta-analysis of two trials involving 113 men with erectile dysfunction found that the addition of sildenafil resulted in less sexual dysfunction at endpoint on rating scales including the International Index of Erectile Function (IIEF) (WMD 19.36, 95% CI 15.00 to 23.72). Another trial found the addition of bupropion led to improved scores on the Changes in Sexual Functioning Questionnaire desire-frequency subscale (WMD 0.88, 95% CI 0.21 to 1.55). In a further study the addition of tadalafil was associated with greater improvement in the erectile function domain of the IIEF than placebo (WMD 8.10; 95% CI 4.62 to 11.68). Other augmentation strategies failed to show statistically significant improvements in sexual dysfunction compared with placebo. DISCUSSION: The currently available evidence is rather limited, with small numbers of trials assessing each strategy. However, while further randomised data is awaited, for men with antidepressant-induced erectile dysfunction, the addition of sildenafil appears to be an effective strategy.

Antidepressive Agents↗

Adherence therapy for people with schizophrenia. European multicentre randomised controlled trial.

BACKGROUND: There is equivocal evidence of the effectiveness of adherence therapy in improving treatment adherence and clinical outcomes for people with schizophrenia. AIMS: To evaluate the effectiveness of adherence therapy in improving quality of life for people with schizophrenia. METHOD: A 52-week, single-blind, multicentre randomised controlled trial of the effectiveness of adherence therapy. Participants were individually randomised to receive eight sessions of adherence therapy or health education. Assessments were undertaken at baseline and at 52-week follow-up. RESULTS: Adherence therapy was no more effective than health education in improving quality of life. CONCLUSIONS: This effectiveness trial provides evidence for the lack of effect of adherence therapy in people with schizophrenia with recent clinical instability, treated in ordinary clinical settings.

Adult↗

Anti-digoxin Fab fragments in cardiotoxicity induced by ingestion of yellow oleander: a randomised controlled trial.

BACKGROUND: Severe cardiac glycoside cardiotoxicity after ingestion of yellow oleander seeds is an important problem in rural areas of Sri Lanka. Currently, patients must be transferred to the capital for temporary cardiac pacing. We did a randomised controlled trial to investigate whether anti-digoxin Fab could reverse serious oleander-induced arrhythmias. METHODS: After a preliminary dose-finding study, 66 patients who presented to hospital with a serious cardiac arrhythmia were randomised to receive either 1200 mg of anti-digoxin Fab or a saline placebo. A 12-lead electrocardiogram, 3 min rhythm strip, and blood sample for measurement of electrolytes and cardiac glycosides were taken before treatment and at 12 timepoints thereafter. FINDINGS: 34 patients received anti-digoxin Fab and 32 received placebo. The presenting arrhythmia had resolved completely after 2 h in 15 antibody-treated patients and two controls (p<0.001); 24 and five patients, respectively, were in sinus rhythm at 8 h (p<0.001). Kaplan-Meier analysis of time to first reversal showed a significant response to anti-digoxin Fab. The heart rate increased in cases, from 49.1 per min at baseline to 66.8 at 2 h, but not in controls (50.6 per min at baseline to 51.5; p<0.001). Mean serum potassium concentrations decreased from 4.9 mmol/L to 4.1 mmol/L at 2 h in cases; no such decrease occurred in controls. INTERPRETATION: Anti-digoxin Fab fragments are a safe and effective treatment for serious cardiac arrhythmias induced by yellow oleander. Their use in small rural hospitals in Sri Lanka should minimise costly transfer of patients and reduce the numbers of deaths; however, further study will be required to confirm this reduction.

Adult↗

The additional value of a night splint to eccentric exercises in chronic midportion Achilles tendinopathy: a randomised controlled trial.

AIM: To assess whether the use of a night splint is of added benefit on functional outcome in treating chronic midportion Achilles tendinopathy. METHODS: This was a single-blind, prospective, single centre, randomised controlled trial set in the Sports Medical Department, The Hague Medical Centre, The Netherlands. Inclusion criteria were: age 18-70 years, active participation in sports, and tendon pain localised at 2-7 cm from distal insertion. Exclusion criteria were: insertional disorders, partial or complete ruptures, or systemic illness. 70 tendons were included and randomised into one of two treatment groups: eccentric exercises with a night splint (night splint group, n = 36) or eccentric exercises only (eccentric group, n = 34). INTERVENTIONS: Both groups completed a 12-week heavy-load eccentric training programme. One group received a night splint in addition to eccentric exercises. At baseline and follow-up at 12 weeks, patient satisfaction, Victorian Institute of Sport Assessment-Achilles questionnaire (VISA-A) score and reported compliance were recorded by a single-blind trained researcher who was blinded to the treatment. RESULTS: After 12 weeks, patient satisfaction in the eccentric group was 63% compared with 48% in the night splint group. The VISA-A score significantly improved in both groups; in the eccentric group from 50.1 to 68.8 (p = 0.001) and in the night splint group from 49.4 to 67.0 (p<0.001). There was no significant difference between the two groups in VISA-A score (p = 0.815) and patient satisfaction (p = 0.261). CONCLUSION: A night splint is not beneficial in addition to eccentric exercises in the treatment of chronic midportion Achilles tendinopathy.

Achilles Tendon↗

The prevalence of myocardial ischemia six months after thrombolytic treatment of acute coronary episodes. A subset of a placebo controlled, randomised trial, the ASSET Study.

The purpose of this prospectively conducted study was to determine the prevalence of transient myocardial ischemia, evaluated from 24 h continuous ECG monitoring and exercise test, 6 months after inclusion in the Anglo Scandinavian Study of Early Thrombolysis (the ASSET trial, a randomised, placebo controlled study of alteplase for survival in patients with suspected acute myocardial infarction (AMI)), and to relate these findings to development of cardiac events. Of the 58 consecutively studied patients ischemic responses were found in 13 (45%) of 29 patients initially treated with placebo, and in 21 (72%) of 29 alteplase treated patients (P = 0.03). After another 6 months, i.e. 12 months after the acute event, two patients were dead, two had non-fatal reinfarctions and three had coronary artery by-pass surgery in the group with ischemic response; no events were recorded in patients without ischemia (P < 0.05). Alteplase treated patients more often had late myocardial ischemia, and cardiac events were found in patients with ischemia. Since the ASSET trial has demonstrated significantly higher short- and long-term survival rate in the alteplase treated group, it was indicated (1) that alteplase treated patients were better positioned for sustaining subsequent ischemia and thus cardiac events due to preservation of viable myocardial tissue, and (2) that late ischemia in the setting of initial alteplase treatment may convey other information than ischemia occurring in placebo treated patients.

Adrenergic beta-Antagonists↗

A randomised controlled trial to evaluate the effectiveness and cost-effectiveness of counselling patients with chronic depression.

OBJECTIVES: To examine the effectiveness and cost-effectiveness of short-term counselling in general practice for patients with chronic depression or combined depression and anxiety, compared with general practitioner (GP) care alone. DESIGN: A randomised controlled trial and economic evaluation with an initial assessment at randomisation and follow-ups at 6 and 12 months. SETTING: Nine general practices that were well-established participants of the Derbyshire counselling in general practice scheme, and already had a counsellor in the practice team. SUBJECTS: Patients were screened at GP practices, and asked to participate if they scored >/= 14 on the Beck Depression Inventory (BDI), had suffered depression or depression/anxiety for 6 months or more, were aged 18-70 and had no history of drug or alcohol abuse, psychoses or suicidal tendencies. INTERVENTIONS: The experimental group received usual GP treatment and were also referred to an experienced, well-qualified counsellor attached to their general practice. Of the eight counsellors, two practiced cognitive behavioural therapy (CBT) and six had a psychodynamic approach. The controls were referred back to their GP for routine treatment. There were no restrictions regarding the treatment that could be used, except that GPs could not refer controls to practice counsellors. OUTCOME MEASURES: The main outcome measure was the BDI. Others included the Brief Symptom Inventory, the Inventory of Interpersonal Problems and the Social Adjustment Scale. All tests were given at initial, 6- and 12-month assessments. Comprehensive costs were also estimated, and combined with changes in outcomes to examine between-group differences and whether counselling was more cost-effective than standard GP care. RESULTS: The trial recruited 181 patients. There was an overall significant improvement in the actual scores over time but no difference between groups or between CBT and psychodynamic counselling approaches at either 6 or 12 months. However, fewer experimental group patients were still 'cases' on the BDI than controls. This difference was statistically significant at 12 months and neared significance at 6 months (using logistic regression with the initial score as a covariate). In addition, most patients were very positive about the counselling and considered it helpful. Visual inspection of the outcomes suggested that more patients with mild or moderate depression at study entry had improved and ceased to be cases, and that more of these patients had become 'non-cases' in the experimental than the control group. However, a multiple regression analysis indicated no significant interactions between group and initial severity of depression. This could be partly due to there being no difference in outcome between the experimental and control group patients who were initially severely depressed and few of these patients ceasing to be cases at follow-up. There were no significant differences in the mean total costs, aggregate costs of services, or any of the service-group costs, except for primary care, between the experimental and control groups over time. The cost-burden to GP practices was significantly higher in the experimental than the control group at 6 months. CONCLUSIONS: Although patients were generally appreciative of the counselling received, there was only limited evidence of improved outcomes in those referred to counselling. Stricter referral criteria to exclude the severely depressed may have yielded more conclusive results. It is also difficult to estimate the effect of recruitment by screening rather than GP referral, which may limit the applicability of the results to routine clinical practice, and may have interfered with the normal working alliance established between the GP, patient and counsellor. A patient preference trial may, therefore, have been more appropriate. The results indicated that there were similar improvements for both CBT and psychodynamic counselling, but a

Adolescent↗

Multicentre randomised control trial comparing real time teledermatology with conventional outpatient dermatological care: societal cost-benefit analysis.

OBJECTIVES: Comparison of real time teledermatology with outpatient dermatology in terms of clinical outcomes, cost-benefits, and patient reattendance. DESIGN: Randomised controlled trial with a minimum follow up of three months. SETTING: Four health centres (two urban, two rural) and two regional hospitals. SUBJECTS: 204 general practice patients requiring referral to dermatology services; 102 were randomised to teledermatology consultation and 102 to traditional outpatient consultation. MAIN OUTCOME MEASURES: Reported clinical outcome of initial consultation, primary care and outpatient reattendance data, and cost-benefit analysis of both methods of delivering care. RESULTS: No major differences were found in the reported clinical outcomes of teledermatology and conventional dermatology. Of patients randomised to teledermatology, 55 (54%) were managed within primary care and 47 (46%) required at least one hospital appointment. Of patients randomised to the conventional hospital outpatient consultation, 46 (45%) required at least one further hospital appointment, 15 (15%) required general practice review, and 40 (39%) no follow up visits. Clinical records showed that 42 (41%) patients seen by teledermatology attended subsequent hospital appointments compared with 41 (40%) patients seen conventionally. The net societal cost of the initial consultation was pound132.10 per patient for teledermatology and pound48.73 for conventional consultation. Sensitivity analysis revealed that if each health centre had allocated one morning session a week to teledermatology and the average round trip to hospital had been 78 km instead of 26 km, the costs of the two methods of care would have been equal. CONCLUSIONS: Real time teledermatology was clinically feasible but not cost effective compared with conventional dermatological outpatient care. However, if the equipment were purchased at current prices and the travelling distances greater, teledermatology would be a cost effective alternative to conventional care.

Adolescent↗

A phase II randomised controlled trial of intensive insulin therapy in general intensive care patients.

OBJECTIVE: To determine the safety and efficacy of an intensive insulin regimen compared with a conventional insulin regimen in general intensive care unit patients. METHODS: A phase II, randomised controlled trial was conducted in 70 critically ill patients in a closed multidisciplinary ICU of a university-affiliated tertiary hospital. We assessed patient characteristics at baseline. Trial process measures included number of blood glucose measurements per day and number in target range, type and quantity of caloric intake, patient outcome and insulin dosing. The primary outcome was the median blood glucose concentration. Secondary outcome measures were incidence of hypoglycaemia (blood glucose level < 2.2 mmol/L), clinical sequelae of hypoglycaemia and hospital mortality. RESULTS: Thirty-five patients were randomised to each of the two groups. More blood glucose samples were taken per day in the intensive insulin group (16 versus 9), but the number of samples in the normoglycaemic range was 48.5%, compared with 79.8% within the target glucose range in the conventional insulin group. The median (interquartile range) blood glucose concentrations in the intensive and conventional insulin therapy groups were 5.4 (5.1-5.7) mmol/L and 7.9 (7.2-9.0) mmol/L, respectively (difference, 2.5 mmol/L; P < 0.0001). Five patients (14.3%) in the intensive insulin therapy group became hypoglycaemic versus none in the conventional insulin therapy group. There were no detected clinical sequelae of hypoglycaemia. CONCLUSION: The intensive insulin regimen was effective in achieving the target blood glucose concentration, with clear separation from the conventional insulin regimen. Although the incidence of hypoglycaemia was increased, there was no detectable harm.

Aged↗

Overcoming the limitations of current meta-analysis of randomised controlled trials.

For a meta-analysis to give definitive information, it should meet at least the minimum standards that would be expected of a well-designed, adequately powered, and carefully conducted randomised controlled trial. These minimum standards include both qualitative characteristics--a prospective protocol, comparable definitions of key outcomes, quality control of data, and inclusion of all patients from all trials in the final analysis--and quantitative standards--an assessment of whether the total sample is large enough to provide reliable results and the use of appropriate statistical monitoring guidelines to indicate when the results of the accumulating data of a meta-analysis are conclusive. We believe that rigorous meta-analyses undertaken according to these principles will lead to more reliable evidence about the efficacy and safety of interventions than either retrospective meta-analysis or individual trials.

Humans↗

Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial.

BACKGROUND: We have shown previously that lumpectomy with radiation therapy was more effective than lumpectomy alone for the treatment of ductal carcinoma in situ (DCIS). We did a double-blind randomised controlled trial to find out whether lumpectomy, radiation therapy, and tamoxifen was of more benefit than lumpectomy and radiation therapy alone for DCIS. METHODS: 1804 women with DCIS, including those whose resected sample margins were involved with tumour, were randomly assigned lumpectomy, radiation therapy (50 Gy), and placebo (n=902), or lumpectomy, radiation therapy, and tamoxifen (20 mg daily for 5 years, n=902). Median follow-up was 74 months (range 57-93). We compared annual event rates and cumulative probability of invasive or non-invasive ipsilateral and contralateral tumours over 5 years. FINDINGS: Women in the tamoxifen group had fewer breast-cancer events at 5 years than did those on placebo (8.2 vs 13.4%, p=0.0009). The cumulative incidence of all invasive breast-cancer events in the tamoxifen group was 4.1% at 5 years: 2.1% in the ipsilateral breast, 1.8% in the contralateral breast, and 0.2% at regional or distant sites. The risk of ipsilateral-breast cancer was lower in the tamoxifen group even when sample margins contained tumour and when DCIS was associated with comedonecrosis. INTERPRETATION: The combination of lumpectomy, radiation therapy, and tamoxifen was effective in the prevention of invasive cancer.

Antineoplastic Agents, Hormonal↗