Analog filtering methods improve leading edge timing performance of multiplexed SiPMs.

Multiplexing many SiPMs to a single readout channel is an attractive option to reduce the readout complexity of high performance time of flight (TOF) PET systems. However, the additional dark counts and shaping from each SiPM cause significant baseline fluctuations in the output waveform, degrading timing measurements using a leading edge threshold. This work proposes the use of a simple analog filtering network to reduce the baseline fluctuations in highly multiplexed SiPM readouts. With 16 SiPMs multiplexed, the FWHM coincident timing resolution for single [Formula: see text] mm LYSO crystals was improved from 401 ± 4 ps without filtering to 248 ± 5 ps with filtering. With 4 SiPMs multiplexed, using an array of [Formula: see text] mm LFS crystals the mean time resolution was improved from 436 ± 6 ps to 249 ± 2 ps. Position information was acquired with a novel binary positioning network. All experiments were performed at room temperature with no active temperature regulation. These results show a promising technique for the construction of high performance multiplexed TOF PET readout systems using analog leading edge timing pickoff.

Clinical and economic evaluation of laparoscopic surgery compared with medical management for gastro-oesophageal reflux disease: 5-year follow-up of multicentre randomised trial (the REFLUX trial).

BACKGROUND: Despite promising evidence that laparoscopic fundoplication provides better short-term relief of gastro-oesophageal reflux disease (GORD) than continued medical management, uncertainty remains about whether benefits are sustained and outweigh risks. OBJECTIVE: To evaluate the long-term clinical effectiveness, cost-effectiveness and safety of laparoscopic surgery among people with GORD requiring long-term medication and suitable for both surgical and medical management. DESIGN: Five-year follow-up of a randomised trial (with parallel non-randomised preference groups) comparing a laparoscopic surgery-based policy with a continued medical management policy. Cost-effectiveness was assessed alongside the trial using a NHS perspective for costs and expressing health outcomes in terms of quality-adjusted life-years (QALYs). SETTING: Follow-up was by annual postal questionnaire and selective hospital case notes review; initial recruitment in 21 UK hospitals. PARTICIPANTS: Questionnaire responders among the 810 original participants. At entry, all had documented evidence of GORD and symptoms for > 12 months. Questionnaire response rates (years 1-5) were from 89.5% to 68.9%. INTERVENTIONS: Three hundred and fifty-seven participants were recruited to the randomised comparison (178 randomised to surgical management and 179 randomised to continued medical management) and 453 to the preference groups (261 surgical management and 192 medical management). The surgeon chose the type of fundoplication. MAIN OUTCOME MEASURES: Primary: disease-specific outcome measure (the REFLUX questionnaire); secondary: Short Form questionnaire-36 items (SF-36), European Quality of Life-5 Dimensions (EQ-5D), NHS resource use, reflux medication, complications. RESULTS: The randomised groups were well balanced. By 5 years, 63% in the randomised surgical group and 13% in the randomised medical management group had received a total or partial wrap fundoplication (85% and 3% in the preference groups), with few perioperative complications and no associated deaths. At 1 year (and 5 years) after surgery, 36% (41%) in the randomised surgical group - 15% (26%) of those who had surgery - were taking proton pump inhibitor medication compared with 87% (82%) in the randomised medical group. At each year, differences in the REFLUX score significantly favoured the randomised surgical group (a third of a SD; p< 0.01 at 5 years). SF-36 and EQ-5D scores also favoured surgery, but differences attenuated over time and were generally not statistically significant at 5 years. The worse the symptoms at trial entry, the larger the benefit observed after surgery. Those randomised to medical management who subsequently had surgery had low baseline scores that markedly improved after surgery. Following fundoplication, 3% had surgical treatment for a complication and 4% had subsequent reflux-related operations - most often revision of the wrap. Dysphagia, flatulence and inability to vomit were similar in the two randomised groups. The economic analysis indicated that surgery was the more cost-effective option for this patient group. The incremental cost-effectiveness ratio for surgery in the base case was £7028 per additional QALY; these findings were robust to changes in approaches and assumptions. The probability of surgery being cost-effective at a threshold of £20,000 per additional QALY was > 0.80 for all analyses. CONCLUSIONS: After 5 years, laparoscopic fundoplication continues to provide better relief of GORD symptoms with associated improved health-related quality of life. Complications of surgery were uncommon. Despite being initially more costly, a surgical policy is highly likely to be cost-effective. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15517081. FUNDING: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 17, No. 22. See the HTA programme website for further project information.

Minimal access surgery compared with medical management for gastro-oesophageal reflux disease: five year follow-up of a randomised controlled trial (REFLUX).

OBJECTIVES: To determine the long term clinical effectiveness of laparoscopic fundoplication as an alternative to drug treatment for chronic gastro-oesophageal reflux disease (GORD). DESIGN: Five year follow-up of multicentre, pragmatic randomised trial (with parallel non-randomised preference groups). SETTING: Initial recruitment in 21 UK hospitals. PARTICIPANTS: Responders to annual questionnaires among 810 original participants. At entry, all had had GORD for >12 months. INTERVENTION: The surgeon chose the type of fundoplication. Medical therapy was reviewed and optimised by a specialist. Subsequent management was at the discretion of the clinician responsible for care, usually in primary care. MAIN OUTCOME MEASURES: Primary outcome measure was self reported quality of life score on disease-specific REFLUX questionnaire. Other measures were health status (with SF-36 and EuroQol EQ-5D questionnaires), use of antireflux medication, and complications. RESULTS: By five years, 63% (112/178) of patients randomised to surgery and 13% (24/179) of those randomised to medical management had received a fundoplication (plus 85% (222/261) and 3% (6/192) of those who expressed a preference for surgery and for medical management). Among responders at 5 years, 44% (56/127) of those randomised to surgery were taking antireflux medication versus 82% (98/119) of those randomised to medical management. Differences in the REFLUX score significantly favoured the randomised surgery group (mean difference 8.5 (95% CI 3.9 to 13.1), P<0.001, at five years). SF-36 and EQ-5D scores also favoured surgery, but were not statistically significant at five years. After fundoplication, 3% (12/364) had surgical treatment for a complication and 4% (16) had subsequent reflux-related operations-most often revision of the wrap. Long term rates of dysphagia, flatulence, and inability to vomit were similar in the two randomised groups. CONCLUSIONS: After five years, laparoscopic fundoplication continued to provide better relief of GORD symptoms than medical management. Adverse effects of surgery were uncommon and generally observed soon after surgery. A small proportion had re-operations. There was no evidence of long term adverse symptoms caused by surgery. TRIAL REGISTRATION: Current Controlled Trials ISRCTN15517081.

Surveillance of female patients with inherited bleeding disorders in United States Haemophilia Treatment Centres.

Inherited bleeding disorders are especially problematic for affected girls and women due to the monthly occurrence of menstrual periods and the effects on reproductive health. Although heavy menstrual bleeding (HMB) is the most common manifestation, females with inherited bleeding disorders (FBD) experience other bleeding symptoms throughout the lifespan that can lead to increased morbidity and impairment of daily activities. The purpose of this article is to describe the utility of a female-focused surveillance effort [female Universal Data Collection (UDC) project] in the United States Haemophilia Treatment Centres (HTCs) and to describe the baseline frequency and spectrum of diagnoses and outcomes. All FBD aged 2 years and older receiving care at selected HTCs were eligible for enrollment. Demographic data, diagnoses and historical data regarding bleeding symptoms, treatments, gynaecological abnormalities and obstetrical outcomes were analysed. Analyses represent data collected from 2009 to 2010. The most frequent diagnoses were type 1 von Willebrand's disease (VWD) (195/319; 61.1%), VWD type unknown (49/319; 15.4%) and factor VIII deficiency (40/319; 12.5%). HMB was the most common bleeding symptom (198/253; 78.3%); however, 157 (49.2%) participants reported greater than four symptoms. Oral contraceptives were used most frequently to treat HMB (90/165; 54.5%), followed by desmopressin [1-8 deamino-D-arginine vasopressin (DDAVP)] (56/165; 33.9%). Various pregnancy and childbirth complications were reported, including bleeding during miscarriage (33/43; 76.7%) and postpartum haemorrhage (PPH) (41/109; 37.6%). FBD experience multiple bleeding symptoms and obstetrical-gynaecological morbidity. The female UDC is the first prospective, longitudinal surveillance in the US focusing on FBD and has the potential to further identify complications and reduce adverse outcomes in this population.

Early life stage salinity tolerance of wild and hatchery-reared juvenile pink salmon Oncorhynchus gorbuscha.

Salinity tolerance in wild (Glendale) and hatchery (Quinsam) pink salmon Oncorhynchus gorbuscha (average mass 0·2 g) was assessed by measuring whole body [Na(+)] and [Cl⁻] after 24 or 72 h exposures to fresh water (FW) and 33, 66 or 100% sea water (SW). Gill Na(+), K(+)-ATPase activity was measured following exposure to FW and 100% SW and increased significantly in both populations after a 24 h exposure to 100% SW. Whole body [Na(+)] and whole body [Cl⁻] increased significantly in both populations after 24 h in 33, 66 and 100% SW, where whole body [Cl⁻] differed significantly between Quinsam and Glendale populations. Extending the seawater exposure to 72 h resulted in no further increases in whole body [Na(+)] and whole body [Cl⁻] at any salinity, but there was more variability among the responses of the two populations. Per cent whole body water (c. 81%) was maintained in all groups of fish regardless of salinity exposure or population, indicating that the increase in whole body ion levels may have been related to maintaining water balance as no mortality was observed in this study. Thus, both wild and hatchery juvenile O. gorbuscha tolerated abrupt salinity changes, which triggered an increase in gill Na(+), K(+)-ATPase within 24 h. These results are discussed in terms of the preparedness of emerging O. gorbuscha for the marine phase of their life cycle.

Waist-to-height ratios in relation to BMI z-scores in three ethnic groups from a representative sample of New Zealand children aged 5-14 years.

Waist-to-height ratio (WHtR) is purported to offer a simpler index of health risk than body mass index (BMI) in children as it requires no adjustment for age or sex. Little is known regarding the usefulness of WHtR in different ethnic groups. The aim of this study was to compare the WHtR cutpoints associated with BMI definitions of overweight and obesity in a nationally representative sample of New Zealand children. Height, weight and waist circumference were measured in 3006 children (51.5% male) aged 5-14 years (n=1107 Maori, n=985 Pacific and n=924 New Zealand European and Others (NZEO)). A WHtR >0.5 was more common in Pacific (43.4%) and Maori (33.1%) children than in NZEO children (20.8%, P<0.001), with 25.6% of children overall being above this cutoff. Although ethnicity influenced the relationship between BMI and WHtR (P<0.01), differences were clinically insignificant as illustrated by the similarity in WHtR values for a given BMI (WHtR of 0.47 in Maori, 0.46 in Pacific and 0.48 in European boys at the 85th BMI percentile). The present results suggest that having WHtR values >0.5 should be equally useful in evaluating cardiovascular health risks in groups of Maori, Pacific and NZEO children.

Osteoporosis and gait and balance disturbances in older sarcopenic obese New Zealanders.

UNLABELLED: Bone, muscle, and fat may affect gait and balance in older adults. Osteoporosis was prevalent in low muscle mass participants and related to gait and balance deficits. Low muscle combined with high fat mass had more functional deficits and poorer bone health, which has implications for falls risk and fractures. INTRODUCTION: Decreasing bone density and muscle mass and increasing fat mass may act synergistically to affect gait and balance in older adults. METHODS: One hundred eighty-three older adults (age 72.7 +/- 6 years, range 56-93; body mass index 28.2 +/- 4.9, range 16.6-46.0) were recruited from a New Zealand falls prevention intervention trial. Total and appendicular skeletal muscle mass (ASM), percent fat, and bone mineralization were assessed by dual energy X-ray absorptiometry and used to characterize normal lean (NL, n = 51), sarcopenic (SS, n = 18), sarcopenic obese (SO, n = 29), and obese (OO, n = 85) phenotypes. Functional performance was assessed using timed up and go, chair stand, single leg stand, and step test. Regression models were adjusted for age, sex, medications, and physical activity. RESULTS: Femoral neck osteoporosis was present in 22% SS, 17% SO, 12% NL, and 7% OO. Femoral neck osteoporosis with low ASM predicted poor chair stand performance (beta -3.3, standard error 1.6, p = 0.04). SO scored lowest on the chair stand (p = 0.03) and step test (p = 0.03). Higher ASM predicted faster timed up and go performance (p = 0.001). CONCLUSIONS: Osteoporosis was prevalent in low ASM groups (SS and SO) and related to gait and balance deficits, particularly in the SO. This has implications for falls risk, fractures, and interventions.

The effect of adiposity measured by dual-energy X-ray absorptiometry on lung function.

Respiratory function is impaired in obesity but there are limitations with body mass index and skin-fold thickness in assessing this effect. The present authors hypothesised that the regional distribution of body fat and lean mass, as measured by dual-energy X-ray absorptiometry (DXA), might be more informative than conventional measurements of total body fat. In total, 107 subjects (55 female, 51.4%) aged 20-50 yrs with no respiratory disease were recruited. Respiratory function tests, anthropometric measurements and a DXA scan were performed. Partial correlation and linear regression analyses were used to explore the effect of adiposity and lean body mass on respiratory function. The majority of respiratory function parameters were significantly correlated with DXA and non-DXA measurements of body fat. Neither thoracic nor abdominal fat had a greater effect. There were some differences in the effect of adiposity between the sexes. Respiratory function was negatively associated with lean body mass in females but positively associated in males. This disappeared after adjustment in females but remained in males. The effects of thoracic and abdominal body fat on respiratory function are comparable but cannot be separated from one another.

New postnatal urinary incontinence: obstetric and other risk factors in primiparae.

OBJECTIVE: To identify obstetric and other risk factors for urinary incontinence that occurs during pregnancy or after childbirth. DESIGN: Questionnaire survey of women. SETTING: Maternity units in Aberdeen (Scotland), Birmingham (England) and Dunedin (New Zealand). POPULATION: A total of 3405 primiparous women with singleton births delivered during 1 year. METHODS: Questionnaire responses and obstetric case note data were analysed using multivariate analysis to identify associations with urinary incontinence. MAIN OUTCOME MEASURES: Urinary incontinence at 3 months after delivery first starting in pregnancy or after birth. RESULTS: The prevalence of urinary incontinence was 29%. New incontinence first beginning after delivery was associated with older maternal age (oldest versus youngest group, OR 2.02, 95% CI 1.35-3.02) and method of delivery (caesarean section versus spontaneous vaginal delivery, OR 0.28, 95% CI 0.19-0.41). There were no significant associations with forceps delivery (OR 1.18, 95% CI 0.92-1.51) or vacuum delivery (OR 1.16, 95% CI 0.83-1.63). Incontinence first occurring during pregnancy and still present at 3 months was associated with higher maternal body mass index (BMI>25, OR 1.68, 95% CI 1.16-2.43) and heavier babies (birthweight in top quartile, OR 1.56, 95% CI 1.12-2.19). In these women, caesarean section was associated with less incontinence (OR 0.39, 95% CI 0.27-0.58) but incontinence was not associated with age. CONCLUSIONS: Women have less urinary incontinence after a first delivery by caesarean section whether or not that first starts during pregnancy. Older maternal age was associated with new postnatal incontinence, and higher BMI and heavier babies with incontinence first starting during pregnancy. The effect of further deliveries may modify these findings.

Children who experience their first fracture at a young age have high rates of fracture.

Rate of fracture was examined according to age at first fracture in 313 New Zealand children (145 girls, 168 boys) under l3 years of age (95.4% of a consecutive series of children treated at one hospital for a recent confirmed fracture at any site). In their lifetimes they had experienced 468 separate fracture events, over half (54.7%) occurring in the 32.3% of children breaking bones on more than one occasion. Children experiencing a first fracture before 4 years of age had 36.7 (95%CI 30.7-44.1) fractures per l00 years of exposure: this was a significantly higher rate than that of children experiencing their first fracture later in life. Thus, using the <4.0 year age group as a reference, we found that rate ratios (adjusted for gender) for groups that had suffered the first fracture at later ages were: first fracture between 4.0 and 6.99 years, 0.77 (95%CI 0.58-1.03); first fracture between 7.0 and 9.99 years, 0.63 (95%CI 0.42-0.94); first fracture between 10.0 and 12.99 years, 0.48 (95% CI 0.32-0.72). Asthma was over-represented (31% seen, 25% expected), and a high proportion of the sample (32.9%) used corticosteroid medications; however, neither characteristic affected age at first fracture. In contrast, the large number (n= 42) of youngsters (13.4% of the sample) reporting adverse reactions to milk were younger at first fracture than children without reactions to milk (P<0.05). We conclude that children experiencing their first fracture at a young age have high rates of fracture and should be targeted for advice to improve their bone strength.

Open retropubic colposuspension for urinary incontinence in women.

BACKGROUND: Urinary incontinence is a common and potentially debilitating problem. Open retropubic colposuspension is a surgical treatment which involves lifting the tissues near the bladder neck and proximal urethra in the area behind the anterior pubic bones to correct deficient urethral closure. OBJECTIVES: To assess the effects of open retropubic colposuspension for the treatment of urinary incontinence. SEARCH STRATEGY: We searched the Cochrane Incontinence Group specialised register (searched 30 June 2004)and reference lists of relevant articles. We contacted investigators to locate extra studies. SELECTION CRITERIA: Randomised or quasi-randomised controlled trials in women with symptoms or urodynamic diagnoses of stress or mixed incontinence that included open retropubic colposuspension surgery in at least one trial group. DATA COLLECTION AND ANALYSIS: Studies were evaluated for methodological quality and appropriateness for inclusion and data extracted by two of the reviewers. Trial data were analysed by intervention. Where appropriate, a summary statistic was calculated. MAIN RESULTS: This review included 39 trials involving a total of 3301 women. Overall cure rates were 68.9% to 88.0% for open retropubic colposuspension. Two small studies suggest lower failure rates after open retropubic colposuspension than conservative treatment. Similarly, one trial suggests lower failure rates after open retropubic colposuspension compared to anticholinergic treatment. Evidence from six trials showed a lower failure rate for subjective cure after open retropubic colposuspension than after anterior colporrhaphy. Such benefit was maintained over time (RR of failure 0.51; 95% CI 0.34 to 0.76 before the first year, RR 0.43; 95% CI 0.32 to 0.57 at one to five years, RR 0.49; 95% CI 0.32 to 0.75 in periods beyond 5 years). In comparison with needle suspensions there was a lower failure rate after colposuspension in the first year after surgery (RR 0.66; 95% CI 0.42 to 1.03), after the first year (RR 0.48; 95% CI 0.33 to 0.71), and beyond five years (RR 0.32; 95% CI 15 to 0.71). Evidence from twelve trials in comparison with suburethral slings found no significant difference in failure rates in all time periods assessed. Patient-reported failure rates in short-, medium- and long-term follow-up showed no significant difference between open and laparoscopic retropubic colposuspension, but with wide confidence intervals. In two trials failure was less common after Burch (RR 0.38 95% CI 0.18 to 0.76) than after the Marshall Marchetti Krantz procedure at one to five year follow-up. There were few data at any other follow-up time.In general, the evidence available does not show a higher morbidity or complication rate with open retropubic colposuspension, compared to the other open surgical techniques, although pelvic organ prolapse is more common than after anterior colporrhaphy and sling procedures. AUTHORS' CONCLUSIONS: The evidence available indicates that open retropubic colposuspension is an effective treatment modality for stress urinary incontinence especially in the long term. Within the first year of treatment, the overall continence rate is approximately 85-90%. After five years, approximately 70% patients can expect to be dry. Newer minimal access procedures like tension free vaginal tape look promising in comparison with open colposuspension but their long-term performance is not known and closer monitoring of its adverse event profile must be done. Laparoscopic colposuspension should allow speedier recovery but its relative safety and effectiveness is not known yet.

Do young New Zealand Pacific Island and European children differ in bone size or bone mineral?

Although Pacific Island adults have been shown to have larger bones and greater bone mineral density than caucasians, no previous studies have been undertaken to determine whether differences are present in prepubertal children. Forty-one Pacific Island children (both parents of Pacific Island descent) and 38 European children, aged 3 to 7 years, living in New Zealand were studied. Heights and weights were determined by simple anthropometry and body mass index (BMI, kg/m2) was calculated. Body composition, bone size, and bone mineral content (BMC, g) were measured by dual energy X-ray absorptiometry (DXA) of the total body and the non-dominant forearm. Compared to European children, in data adjusted for age and gender, Pacific Island children had significantly greater (P < 0.05) BMC in the total body (12%), the ultradistal radius (16%), and the 33% radius (8%), and also greater total body bone area (10%). Bone mineral density (BMD, g/cm2) was higher only at the ultradistal radius (11%). However, after adjustment for body weight, in particular lean mass, no differences were seen between Pacific Island and European children in any bone measure. The larger bone area and BMC of young Pacific Island children can be explained by their greater height and weight. Therefore, this study has shown that prepubertal Pacific Island children do not have greater bone size or BMC for their weight.

Oral vitamin D3 and calcium for secondary prevention of low-trauma fractures in elderly people (Randomised Evaluation of Calcium Or vitamin D, RECORD): a randomised placebo-controlled trial.

BACKGROUND: Elderly people who have a fracture are at high risk of another. Vitamin D and calcium supplements are often recommended for fracture prevention. We aimed to assess whether vitamin D3 and calcium, either alone or in combination, were effective in prevention of secondary fractures. METHODS: In a factorial-design trial, 5292 people aged 70 years or older (4481 [85%] of whom were women) who were mobile before developing a low-trauma fracture were randomly assigned 800 IU daily oral vitamin D3, 1000 mg calcium, oral vitamin D3 (800 IU per day) combined with calcium (1000 mg per day), or placebo. Participants who were recruited in 21 UK hospitals were followed up for between 24 months and 62 months. Analysis was by intention-to-treat and the primary outcome was new low-energy fractures. FINDINGS: 698 (13%) of 5292 participants had a new low-trauma fracture, 183 (26%) of which were of the hip. The incidence of new, low-trauma fractures did not differ significantly between participants allocated calcium and those who were not (331 [12.6%] of 2617 vs 367 [13.7%] of 2675; hazard ratio (HR) 0.94 [95% CI 0.81-1.09]); between participants allocated vitamin D3 and those who were not (353 [13.3%] of 2649 vs 345 [13.1%] of 2643; 1.02 [0.88-1.19]); or between those allocated combination treatment and those assigned placebo (165 [12.6%] of 1306 vs 179 [13.4%] of 1332; HR for interaction term 1.01 [0.75-1.36]). The groups did not differ in the incidence of all-new fractures, fractures confirmed by radiography, hip fractures, death, number of falls, or quality of life. By 24 months, 2886 (54.5%) of 5292 were still taking tablets, 451 (8.5%) had died, 58 (1.1%) had withdrawn, and 1897 (35.8%) had stopped taking tablets but were still providing data for at least the main outcomes. Compliance with tablets containing calcium was significantly lower (difference: 9.4% [95% CI 6.6-12.2]), partly because of gastrointestinal symptoms. However, potentially serious adverse events were rare and did not differ between groups. INTERPRETATION: The findings do not support routine oral supplementation with calcium and vitamin D3, either alone or in combination, for the prevention of further fractures in previously mobile elderly people.

Issues in data monitoring and interim analysis of trials.

OBJECTIVES: To address issues about data monitoring committees (DMCs) for randomised controlled trials (RCTs). DATA SOURCES: Electronic databases. Handsearching of selected books. Personal contacts with experts in the field. REVIEW METHODS: Systematic literature reviews of DMCs and small group processes in decision-making; sample surveys of: reports of RCTs, recently completed and ongoing RCTs and policies of major organisations involved in RCTs; case studies of four DMCs; and interviews with experienced DMC members. All focused on 23 prestated questions. RESULTS: Although still a minority, RCTs increasingly have DMCs. There is wide agreement that nearly all trials need some form of data monitoring. Central to the role of the DMC is monitoring accumulating evidence related to benefit and toxicity; variation in emphasis has been reflected in the plethora of names. DMCs for trials performed for regulatory purposes should be aware of any special requirements and regulatory consequences. Advantages were identified for both larger and smaller DMCs. There is general agreement that a DMC should be independent and multidisciplinary. Consumer and ethicist membership is controversial. The chair is recognised as being particularly influential, and likely to be most effective if he or she is experienced, understands both statistical and clinical issues, and is facilitating in style and impartial. There is no evidence available to judge suggested approaches to training. The review suggested that costs should be covered, but other rewards must be so minimal as to not affect decision-making. It is usual to have a minimum frequency of DMC meetings, with evidence that face-to-face meetings are preferable. It is common to have open sessions and a closed session. A report to a DMC should cover benefits and risks in a balanced way, summarised in an accessible style, avoiding excessive detail, and be as current as possible. Disadvantages of blinded analyses seem to outweigh advantages. Information about comparable studies should be included, although interaction with the DMCs of similar ongoing trials is controversial. A range of formal statistical approaches can be used, although this is only one of a number of considerations. DMCs usually reach decisions by consensus, but other approaches are sometimes used. The general, but not unanimous, view is that DMCs should be advisory rather than executive on the basis that it is the trial organisers who are ultimately responsible for the conduct of the trial. CONCLUSIONS: Some form of data monitoring should be considered for all RCTs, with reasons given where there is no DMC or when any member is not independent. An early DMC meeting is helpful, determining roles and responsibilities; planned operations can be agreed with investigators and sponsors/funders. A template for a DMC charter is suggested. Competing interests should be declared. DMC size (commonly three to eight people) is chosen to optimise performance. Members are usually independent and drawn from appropriate backgrounds, and some, particularly the chair, are experienced. A minimum frequency of meetings is usually agreed, with flexibility for more if needed. The DMC should understand and agree the statistical approach (and guidelines) chosen, with both the DMC statistician and analysis statistician competent to apply the method. A DMC's primary purpose is to ensure that continuing a trial according to its protocol is ethical, taking account of both individual and collective ethics. A broader remit in respect of wider ethical issues is controversial; arguably, these are primarily the responsibility of research ethics committees, trial steering committees and investigators. The DMC should know the range of recommendations or decisions open to it, in advance. A record should be kept describing the key issues discussed and the rationale for decisions taken. Errors are likely to be reduced if a DMC makes a thorough review of the evidence and has a clear understanding of how it should function, there is active participation by all members, differences are resolved through discussion and there is systematic consideration of the various decision options. DMCs should be encouraged to comment on draft final trial reports. These should include information about the data monitoring process and detail the DMC membership. It is recommended that groups responsible for data monitoring be given the standard name 'Data Monitoring Committee' (DMC). Areas for further research include: widening DMC membership beyond clinicians, trialists and statisticians; initiatives to train DMC members; methods of DMC decision-making; 'open' data monitoring; DMCs covering a portfolio of trials rather than single trials; DMC size and membership, incorporating issues of group dynamics; empirical study of the workings of DMCs and their decision-making, and which trials should or should not have a DMC.

Transabdominal pre-peritoneal (TAPP) vs totally extraperitoneal (TEP) laparoscopic techniques for inguinal hernia repair.

BACKGROUND: The choice of approach to the laparoscopic repair of inguinal hernia is controversial. There is a scarcity of data comparing the laparoscopic transabdominal preperitoneal (TAPP) approach with the laparoscopic totally extraperitoneal (TEP) approach and questions remain about their relative merits and risks. OBJECTIVES: To compare the clinical effectiveness and relative efficiency of laparoscopic TAPP and laparoscopic TEP for inguinal hernia repair. SEARCH STRATEGY: We searched Medline Extra, Embase, Biosis, Science Citation Index, Cochrane Central Register of Controlled Trials (CENTRAL), Journals@ Ovid Full Text and the electronic version of the journal, Surgical Endoscopy. Recent conference proceedings by the following organisations were hand searched: Association of Endoscopic Surgeons of Great Britain & Ireland; International Congress of the European Association for Endoscopic Surgery; Scientific Session of the Society of American Gastrointestinal & Endoscopic Surgeons (SAGES); and the Italian Society of Endoscopic Surgery. In addition, specialists involved in research on the repair of inguinal hernia were contacted to ask for information about any further completed and ongoing trials, relevant websites were searched and reference lists of the all included studies were checked for additional reports. SELECTION CRITERIA: All published and unpublished randomised controlled trials and quasi-randomised controlled trials comparing laparoscopic TAPP with laparoscopic TEP for inguinal hernia repair were eligible for inclusion. Non-randomised prospective studies were also eligible for inclusion to provide further comparative evidence of complications and adverse events. DATA COLLECTION AND ANALYSIS: Statistical analyses were performed using the fixed 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: The search identified one RCT which reported no statistical difference between TAPP and TEP when considering duration of operation, haematoma, length of stay, time to return to usual activity and recurrence. The eight non-randomised studies suggest that TAPP is associated with higher rates of port-site hernias and visceral injuries whilst there appear to be more conversions with TEP. Vascular injuries and deep/mesh infections were rare and there was no obvious difference between the groups. No studies reporting economic evidence were identified. Very limited data were available on learning effects but these data suggest that operators become experienced at between 30 and 100 procedures. AUTHORS' CONCLUSIONS: There is insufficient data to allow conclusions to be drawn about the relative effectiveness of TEP compared with TAPP. Efforts should be made to start and complete adequately powered RCTs, which compare the different methods of laparoscopic repair.

Two-year changes in bone and body composition in young children with a history of prolonged milk avoidance.

No previous longitudinal studies of calcium intake, anthropometry and bone health in young children with a history of avoiding cow's milk have been undertaken. We report the 2-year changes of a group of 46 Caucasian children (28 girls, l8 boys) aged 8.1+/-2.0 years (mean +/- SD) who had low calcium intakes at baseline and were short in stature, with elevated body mass index, poor skeletons and lower Z scores for both areal bone mineral density (BMD, in grams per square centimeter) and volumetric density (bone mineral apparent density, BMAD, in grams per cubic centimeter), compared with a reference population of milk drinkers. At follow-up, adverse symptoms to milk had diminished and modest increases in milk consumption and calcium intake had occurred. Total body bone mineral content (BMC) and bone area assessed by dual energy X-ray absorptiometry had increased (P<0.05), and calcium intake from all sources was associated with both these measures (P<0.05). However, although some catch-up in height had taken place, the group remained significantly shorter than the reference population (Z scores -0.39+/-1.14), with elevated body mass index (Z scores 0.46+/-1.0). The ultradistal radius BMC Z scores remained low (-0.31+/-0.98). The Z scores for BMD had improved to lie within the normal range at predominantly cortical sites (33% radius, neck of femur and hip trochanter) but had worsened at predominantly trabecular sites (ultradistal radius and lumbar spine), where values lay below those of the reference group (P<0.05). Similarly, although volumetric BMAD Z scores at the 33% radius had normalized, BMAD Z scores at the lumbar spine remained below the reference population at follow-up (-0.67+/-1.12, P<0.001). Our results demonstrate persisting height reduction, overweight and osteopenia at the ultradistal radius and lumbar spine in young milk avoiders over 2 years of follow-up.

Five-year follow-up of a randomized trial to assess pain and numbness after laparoscopic or open repair of groin hernia.

BACKGROUND: Claims that laparoscopic groin hernia repair is followed by less persisting pain and numbness than open mesh repair were tested by follow-up within a multicentre randomized clinical trial. METHODS: Participants in the UK Medical Research Council Laparoscopic Groin Hernia Trial were followed up by means of self-completed postal questionnaires from 2 to 5 years after trial entry. The principal measures were pain (groin and testicular) and numbness (groin and thigh). RESULTS: Seven hundred and fifty (80.8 per cent) of the original 928 participants returned at least one questionnaire between 2 and 5 years; respondents were similar to the baseline randomized groups. Fewer respondents in the laparoscopic group had groin pain (absolute differences varied between 7.9 and 2.0 per cent, but were of marginal statistical significance); rates of testicular pain were similar in the two groups. Groin numbness was reported about half as commonly at all time points in the laparoscopic group (P < 0.001); there were no significant differences in thigh numbness. CONCLUSION: Laparoscopic surgery was associated with less long-term numbness and probably less pain in the groin.

Systematic review of sacral nerve stimulation for faecal incontinence and constipation.

BACKGROUND AND METHOD: This systematic review assesses the efficacy and safety of sacral nerve stimulation (SNS) for faecal incontinence and constipation. Electronic databases and selected websites were searched for studies evaluating SNS in the treatment of faecal incontinence or constipation. Primary outcome measures included episodes of faecal incontinence per week (faecal incontinence studies) and number of evacuations per week (constipation studies). RESULTS: From 106 potentially relevant reports, six patient series and one crossover study of SNS for faecal incontinence, and four patient series and one crossover study of SNS for constipation, were included. After implantation, 41-75 per cent of patients achieved complete faecal continence and 75-100 per cent experienced improvement in episodes of incontinence. There were 19 adverse events among 149 patients. The small crossover study reported increased episodes of faecal incontinence when the implanted pulse generator was switched off. Case series of SNS for constipation reported an increased frequency of evacuation. There were four adverse events among the 20 patients with a permanent implant. The small crossover study reported a reduced number of evacuations when the pulse generator was switched off. CONCLUSION: SNS results in significant improvement in faecal incontinence in patients resistant to conservative treatment. Early data also suggest benefit in the treatment of constipation.

What are the long-term benefits of weight reducing diets in adults? A systematic review of randomized controlled trials.

BACKGROUND: Evidence is needed for the best long-term diet for weight loss, and improvement in cardiac risk and disease in obese adults. METHODS: We systematically reviewed randomized controlled trials (RCTs) in any language. We searched 13 databases and handsearched journals. Trials lasted 1 year or more. One investigator extracted the data and a second checked data extraction. Trial quality was assessed. RESULTS: Low fat diets (LFDs) produced significant weight losses up to 36 months (-3.55 kg; 95% CI, -4.54 to -2.55 kg). Blood pressure, lipids and fasting plasma glucose improved with these diets after 12 months. Four studies found that LFDs may prevent type 2 diabetes and reduce antihypertensive medication for up to 3 years. A very low calorie diet (VLCD, < 4.2 MJ day(-1)) was associated with the most weight loss after 12 months (-13.40 kg; 95% CI, -18.43 to -8.37 kg) in one small study with beneficial effects on asthma. There was no evidence that low carbohydrate protein sparing modified fasts (PSMFs) were associated with greater long-term weight loss than low calorie diets (LCDs, 4.2-6.7 MJ day(-1)) or VLCDs. PSMFs were, however, associated with greater lowering of fasting plasma glucose and HbA1c than LCDs. CONCLUSIONS: Little evidence supports the use of diets other than LFDs for weight reduction. With the increasing prevalence of morbid obesity, long-term follow-up in RCTs is needed to evaluate the effect of LCDs, VLCDs and PSMFs more fully.

What interventions should we add to weight reducing diets in adults with obesity? A systematic review of randomized controlled trials of adding drug therapy, exercise, behaviour therapy or combinations of these interventions.

BACKGROUND: Evidence is needed for the effectiveness of interventions given with reducing diets for obese adults: drug therapy, exercise, or behaviour therapy. METHODS: We systematically reviewed randomized controlled trials in any language. We searched 13 databases and handsearched journals. Trials lasted 1 year or more. One investigator extracted data and a second checked data extraction. Trial quality was assessed. RESULTS: Adding orlistat to diet was associated with weight change for up to 24 months (-3.26 kg, 95% CI, -4.15 to -2.37 kg), and statistically significant beneficial changes were found for total and LDL cholesterol, blood pressure and glycaemic control. Adding sibutramine to diet was associated with a 12 month weight change of -4.18 kg (95% CI, -5.14 to -3.21 kg), and statistically significant beneficial effects on high density lipoprotein cholesterol (HDL) and triglycerides (TGs), but an increase in diastolic blood pressure. Adding exercise to diet, or to diet and behaviour therapy, was associated with improved weight loss for up to 36 months and improvements in HDL, TGs and blood pressure. Adding behaviour therapy to diet, or to diet and sibutramine together, was associated with improved weight loss for up to 18 months. Adding drugs, exercise or behaviour therapy to dietary advice was each associated with similar weight change. CONCLUSIONS: Adding orlistat, sibutramine, exercise, or behaviour modification to dietary advice can improve long-term weight loss.