Age-period-cohort modelling of non-Hodgkin's lymphoma incidence in a French region: a period effect compatible with an environmental exposure

<p>Abstract</p> <p>Background</p> <p>The incidence of non-Hodgkin's lymphoma (NHL) has risen steadily during the last few decades in all geographic regions covered by cancer registration for reasons that remain unknown. The aims of this study were to assess the relative contributions of age, period and cohort effects to NHL incidence patterns and therefore to provide clues to explain the increasing incidence.</p> <p>Methods</p> <p>Population and NHL incidence data were provided for the Doubs region (France) during the 1980-2005 period. NHL counts and person-years were tabulated into one-year classes by age (from 20 to 89) and calendar time period. Age-period-cohort models with parametric smooth functions (natural splines) were fitted to the data by assuming a Poisson distribution for the observed number of NHL cases.</p> <p>Results</p> <p>The age-standardised incidence rate increased from 4.7 in 1980 to 11.9 per 100,000 person-years at risk in 1992 (corresponding to a 2.5-fold increase) and stabilised afterwards (11.1 per 100,000 in 2005). Age effects showed a steadily increasing slope up to the age of 80 and levelled off for older ages. Large period curvature effects, both adjusted for cohort effects and non-adjusted (p < 10^-4and p < 10^-5, respectively), showed departure from linear periodic trends; period effects jumped markedly in 1983 and stabilised in 1992 after a 2.4-fold increase (compared to the 1980 period). In both the age-period-cohort model and the age-cohort model, cohort curvature effects were not statistically significant (p = 0.46 and p = 0.08, respectively).</p> <p>Conclusions</p> <p>The increased NHL incidence in the Doubs region is mostly dependent on factors associated with age and calendar periods instead of cohorts. We found evidence for a levelling off in both incidence rates and period effects beginning in 1992. It is unlikely that the changes in classification (which occurred after 1995) and the improvements of diagnostic accuracy could largely account for the 1983-1992 period-effect increase, giving way to an increased exposure to widely distributed risk factors including persistent organic pollutants and pesticides. Continued NHL incidence and careful analysis of period effects are of utmost importance to elucidate the enigmatic epidemiology of NHL.</p

Pooled analysis of WHO Surgical Safety Checklist use and mortality after emergency laparotomy

Background The World Health Organization (WHO) Surgical Safety Checklist has fostered safe practice for 10 years, yet its place in emergency surgery has not been assessed on a global scale. The aim of this study was to evaluate reported checklist use in emergency settings and examine the relationship with perioperative mortality in patients who had emergency laparotomy. Methods In two multinational cohort studies, adults undergoing emergency laparotomy were compared with those having elective gastrointestinal surgery. Relationships between reported checklist use and mortality were determined using multivariable logistic regression and bootstrapped simulation. Results Of 12 296 patients included from 76 countries, 4843 underwent emergency laparotomy. After adjusting for patient and disease factors, checklist use before emergency laparotomy was more common in countries with a high Human Development Index (HDI) (2455 of 2741, 89.6 per cent) compared with that in countries with a middle (753 of 1242, 60.6 per cent; odds ratio (OR) 0.17, 95 per cent c.i. 0.14 to 0.21, P <0001) or low (363 of 860, 422 per cent; OR 008, 007 to 010, P <0.001) HDI. Checklist use was less common in elective surgery than for emergency laparotomy in high-HDI countries (risk difference -94 (95 per cent c.i. -11.9 to -6.9) per cent; P <0001), but the relationship was reversed in low-HDI countries (+121 (+7.0 to +173) per cent; P <0001). In multivariable models, checklist use was associated with a lower 30-day perioperative mortality (OR 0.60, 0.50 to 073; P <0.001). The greatest absolute benefit was seen for emergency surgery in low- and middle-HDI countries. Conclusion Checklist use in emergency laparotomy was associated with a significantly lower perioperative mortality rate. Checklist use in low-HDI countries was half that in high-HDI countries.Peer reviewe

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone

Suppression of insulin secretion is associated with weight loss and altered macronutrient intake and preference in a subset of obese adults

PURPOSE: Hyperinsulinemia is a common feature of many obesity syndromes. We investigated whether suppression of insulin secretion, without dietary or exercise intervention, could promote weight loss and alter food intake and preference in obese adults. METHODS: Suppression of insulin secretion was achieved using octreotide-LAR 40 mg IM q28d for 24 weeks in 44 severely obese adults (89% female, 39% minority). Oral glucose tolerance testing was performed before and after treatment, indices of β-cell activity (CIRgp), insulin sensitivity (CISI), and clearance (CP/I AUC) were computed, and leptin levels, 3-day food records and carbohydrate-craving measurements were obtained. DEXA evaluations were performed pre- and post-therapy in an evaluable subgroup. RESULTS: For the entire cohort, significant insulin suppression was achieved with simultaneous improvements in insulin sensitivity, weight loss, and body mass index (BMI). Leptin, fat mass, total caloric intake, and carbohydrate craving significantly decreased. When grouped by BMI response, high responders (HR; ΔBMI < −3 kg/m(2)) and low responders (LR; ΔBMI between −3 and −0.5) exhibited higher suppression of CIRgp and IAUC than nonresponders (NR; ΔBMI > −0.5). CISI improved and significant declines in leptin and fat mass occurred only in HR and LR. Conversely, both leptin and fat mass increased in NR. Carbohydrate intake was markedly suppressed in HR only, while carbohydrate-craving scores decreased in HR and LR. For the entire cohort, ΔBMI correlated with ΔCISI, Δfat mass, and Δleptin. ΔFat mass also correlated with ΔIAUC and ΔCISI. CONCLUSIONS: In a subcohort of obese adults, suppression of insulin secretion was associated with loss of body weight and fat mass and with concomitant modulation of caloric intake and macronutrient preference