Wide versus narrow excision margins for high-risk, primary cutaneous melanomas: long-term follow-up of survival in a randomised trial.

BACKGROUND: The necessary margin of excision for cutaneous melanomas greater than 2 mm in thickness is controversial. At a median follow-up of 5 years, findings from our previously published randomised trial of narrow (1 cm) versus wide (3 cm) excision margins in patients with thick cutaneous melanomas showed that narrow margins were associated with an increased frequency of locoregional relapse, but no significant difference in overall survival was apparent. We now report a long-term survival analysis of that trial. METHODS: We did a randomised, open-label multicentre trial in 59 hospitals--57 in the UK, one in Poland, and one in South Africa. Patients with one primary localised cutaneous melanoma greater than 2 mm in Breslow thickness on the trunk or limbs (excluding palms or soles) were randomly assigned (1:1) centrally to receive surgery with either a 1 cm or 3 cm excision margin following an initial surgery. The randomisation lists were generated with random permuted blocks and stratified by centre and extent of initial surgery. The endpoints of this analysis were overall survival and melanoma-specific survival. Analyses were done in the intention-to-treat population. This trial was not registered because it predated mandatory trial registration. FINDINGS: Between Dec 16, 1992, and May 22, 2001, we randomly assigned 900 patients to surgery with either a 1 cm excision margin (n=453) or a 3 cm excision margin (n=447). At a median follow-up of 8·8 years (106 months [IQR 76-135], 494 patients had died, with 359 of these deaths attributed to melanoma. 194 deaths were attributed to melanoma in the 1 cm group compared with 165 in the 3 cm group (unadjusted hazard ratio [HR] 1·24 [95% CI 1·01-1·53]; p=0·041). Although a higher number of deaths overall occurred in the 1 cm group compared with the 3 cm group (253 vs 241), the difference was not significant (unadjusted HR 1·14 [95% CI 0·96-1·36]; p=0·14). Surgical complications were reported in 35 (8%) patients in the 1 cm excision margin group and 65 (15%) patients in the 3 cm group. INTERPRETATION: Our findings suggest that a 1 cm excision margin is inadequate for cutaneous melanoma with Breslow thickness greater than 2 mm on the trunk and limbs. Current guidelines advise a 2 cm margin for melanomas greater than 2 mm in thickness but only a 1 cm margin for thinner melanomas. The adequacy of a 1 cm margin for thinner melanomas with poor prognostic features should be addressed in future randomised studies. FUNDING: Cancer Research UK, North Thames National Health Service Executive, Northern and Yorkshire National Health Service Executive, British United Provident Association Foundation, British Association of Plastic Surgeons, the Meirion Thomas Cancer Research Fund, and the National Institute for Health and Research Biomedical Research Centre at The Royal Marsden NHS Foundation Trust.

Effect of a behavioural intervention in obese pregnant women (the UPBEAT study): a multicentre, randomised controlled trial.

BACKGROUND: Behavioural interventions might improve clinical outcomes in pregnant women who are obese. We aimed to investigate whether a complex intervention addressing diet and physical activity could reduce the incidence of gestational diabetes and large-for-gestational-age infants. METHODS: The UK Pregnancies Better Eating and Activity Trial (UPBEAT) is a randomised controlled trial done at antenatal clinics in eight hospitals in multi-ethnic, inner-city locations in the UK. We recruited pregnant women (15-18 weeks plus 6 days of gestation) older than 16 years who were obese (BMI ≥30 kg/m(2)). We randomly assigned participants to either a behavioural intervention or standard antenatal care with an internet-based, computer-generated, randomisation procedure, minimising by age, ethnic origin, centre, BMI, and parity. The intervention was delivered once a week through eight health trainer-led sessions. Primary outcomes were gestational diabetes (diagnosed with an oral glucose tolerance test and by criteria from the International Association of Diabetes in Pregnancy Study Groups) and large-for-gestational-age infants (≥90th customised birthweight centile). Analysis was by intention to treat. This trial is registered with Current Controlled Trials, ISCRTN89971375. Recruitment and pregnancy outcomes are complete but childhood follow-up is ongoing. FINDINGS: Between March 31, 2009, and June 2, 2014, we assessed 8820 women for eligibility and recruited 1555, with a mean BMI of 36·3 kg/m(2) (SD 4·8). 772 were randomly assigned to standard antenatal care and 783 were allocated the behavioural intervention, of which 651 and 629 women, respectively, completed an oral glucose tolerance test. Gestational diabetes was reported in 172 (26%) women in the standard care group compared with 160 (25%) in the intervention group (risk ratio 0·96, 95% CI 0·79-1·16; p=0·68). 61 (8%) of 751 babies in the standard care group were large for gestational age compared with 71 (9%) of 761 in the intervention group (1·15, 0·83-1·59; p=0·40). Thus, the primary outcomes did not differ between groups, despite improvements in some maternal secondary outcomes in the intervention group, including reduced dietary glycaemic load, gestational weight gain, and maternal sum-of-skinfold thicknesses, and increased physical activity. Adverse events included neonatal death (two in the standard care group and three in the intervention group) and fetal death in utero (ten in the standard care group and six in the intervention group). No maternal deaths were reported. Incidence of miscarriage (2% in the standard care group vs 2% in the intervention group), major obstetric haemorrhage (1% vs 3%), and small-for-gestational-age infants (≤5th customised birthweight centile; 6% vs 5%) did not differ between groups. INTERPRETATION: A behavioural intervention addressing diet and physical activity in women with obesity during pregnancy is not adequate to prevent gestational diabetes, or to reduce the incidence of large-for-gestational-age infants. FUNDING: National Institute for Health Research, Guys and St Thomas' Charity, Chief Scientist Office Scotland, Tommy's Charity.

The antiendotoxin agent taurolidine potentially reduces ischemia/reperfusion injury through its metabolite taurine.

BACKGROUND: Cardiopulmonary bypass results in ischemia/reperfusion (I/R)-induced endotoxemia. We conducted a prospective randomized trial to investigate the effect of taurolidine, an antiendotoxin agent with antioxidant and membrane-stabilizing properties, on patients undergoing coronary artery bypass grafting (CABG). METHODS: A total of 60 patients undergoing CABG were randomized into 4 groups. St Thomas' Hospital cold crystalloid cardioplegia was used in groups A and B, and cold blood cardioplegia in groups C and D. Groups A and C received a placebo infusion of normal saline, whereas groups B and D were administered intravenous taurolidine. Arrhythmias induced by pro- and anti-inflammatory cytokines (interleukin [IL]-6 and IL-10), and I/R were assessed perioperatively. RESULTS: Administration of taurolidine in crystalloid cardioplegia patients resulted in a significant decrease in serum IL-6 and an increase in serum IL-10 at 24 hours postaortic unclamping compared to placebo (P < .0001). Although not statistically significant, this trend in serum IL-6 decrease was mirrored in the blood cardioplegia patients (P = .068). Taurolidine treatment also significantly decreased I/R-induced arrhythmias compared to placebo in the crystalloid cardioplegia patients (P < .003). There were fewer I/R-induced arrhythmias compared to placebo in the blood cardioplegia patients; the difference, however, was marginal and not statistically significant (P = .583). CONCLUSION: This study demonstrates that administration of taurolidine in CABG patients induces a potent anti-inflammatory response that is associated with a significant decrease in arrhythmias.

A descriptive study of Bruneian student nurses' perceptions of stress.

While much has been written about stress in nursing in the 'West', less research has been done on this issue in many 'Eastern' countries. This paper offers the findings of the first study of stress in student nurses in Brunei. The paper describes a study of 20 Brunei nursing students and their views about stress in nursing. A modified grounded theory approach was used in collecting and analysing data (and the 'modifications' are described). Findings were organised around the themes: stressors, moderators and outcomes [Carson, J., and Kuipers, E., 1998. Stress management interventions. In: Hardy, S., Carson, J., Thomas, B. (Eds.), Occupational Stress: Personal and Professional Approaches. Stanley Thornes, Cheltenham. pp. 157-174.]. Students often found their status as students caused them stress in the clinical setting: with other nurses, with doctors and even with patients. Academic related stressors included having to complete assignments and having to study in English. Various ways of moderating stress were reported including talking to 'trusted friends', engaging in sports or simply being quiet. Positive and negative outcomes of stress were identified: stress could lead to mental illness but, also, it could be motivating. This report concludes with a Weberian 'ideal type': a composite word-picture of the findings.

Triangulation in cross-cultural research of child development in Jamaica.

PIP: Triangulation is the use of multiple concepts and methods to study a single phenomenon. Ethnographic field studies and standardized measures of development were used in a study of long-term effects of perinatal cannabis (marijuana) use in Jamaica. The study was launched in 1983 in order to evaluate the effects of cannabis (or ganja, as it is called in Jamaica) consumption during pregnancy and lactation on infants from birth to school age in rural communities. Some researchers reported symptoms such as increased startles, high-pitched cry in the newborn, shortened gestation, and low birth weight. The project was based in St. Thomas, where ganja use is widespread. The ethnographic part involved home observations and interviews of each child in selected communities. The clinical component included monitoring 60 pregnant women (30 users and 30 nonusers) and their offspring from birth through age 5. The instruments for evaluation included the Brazelton Neonatal Assessment Scale (BNAS), the Bayley Scales of Infant Development (BSID), the McCarthy Scales of Children's Abilities (MSCA, for children aged 2 years 6 months to 8 years 6 months), and the Behavioral Style Questionnaire (BSQ, for temperament in 3 to 7 year olds). The MSCA and BSQ had to be adapted to local culture, partly because of different uses of words in the rural dialect and cultural experience. The MSCA modifications included the elimination of time limits, changes in language, and culturally correct alternative responses. Five of 72 items on the BSQ were modified. Most scores fell in the middle range of about 4, similar to the North American scores, except for the lower mean in the category of Threshold of Responsiveness, because of an unanticipated cultural difference. The adjustments made did not compromise the comparability of the findings.^ieng