Worldwide trends in population-based survival for children, adolescents, and young adults diagnosed with leukaemia, by subtype, during 2000-14 (CONCORD-3): analysis of individual data from 258 cancer registries in 61 countries.

BACKGROUND: Leukaemias comprise a heterogenous group of haematological malignancies. In CONCORD-3, we analysed data for children (aged 0-14 years) and adults (aged 15-99 years) diagnosed with a haematological malignancy during 2000-14 in 61 countries. Here, we aimed to examine worldwide trends in survival from leukaemia, by age and morphology, in young patients (aged 0-24 years). METHODS: We analysed data from 258 population-based cancer registries in 61 countries participating in CONCORD-3 that submitted data on patients diagnosed with leukaemia. We grouped patients by age as children (0-14 years), adolescents (15-19 years), and young adults (20-24 years). We categorised leukaemia subtypes according to the International Classification of Childhood Cancer (ICCC-3), updated with International Classification of Diseases for Oncology, third edition (ICD-O-3) codes. We estimated 5-year net survival by age and morphology, with 95% CIs, using the non-parametric Pohar-Perme estimator. To control for background mortality, we used life tables by country or region, single year of age, single calendar year and sex, and, where possible, by race or ethnicity. All-age survival estimates were standardised to the marginal distribution of young people with leukaemia included in the analysis. FINDINGS: 164 563 young people were included in this analysis: 121 328 (73·7%) children, 22 963 (14·0%) adolescents, and 20 272 (12·3%) young adults. In 2010-14, the most common subtypes were lymphoid leukaemia (28 205 [68·2%] patients) and acute myeloid leukaemia (7863 [19·0%] patients). Age-standardised 5-year net survival in children, adolescents, and young adults for all leukaemias combined during 2010-14 varied widely, ranging from 46% in Mexico to more than 85% in Canada, Cyprus, Belgium, Denmark, Finland, and Australia. Individuals with lymphoid leukaemia had better age-standardised survival (from 43% in Ecuador to ≥80% in parts of Europe, North America, Oceania, and Asia) than those with acute myeloid leukaemia (from 32% in Peru to ≥70% in most high-income countries in Europe, North America, and Oceania). Throughout 2000-14, survival from all leukaemias combined remained consistently higher for children than adolescents and young adults, and minimal improvement was seen for adolescents and young adults in most countries. INTERPRETATION: This study offers the first worldwide picture of population-based survival from leukaemia in children, adolescents, and young adults. Adolescents and young adults diagnosed with leukaemia continue to have lower survival than children. Trends in survival from leukaemia for adolescents and young adults are important indicators of the quality of cancer management in this age group. FUNDING: Children with Cancer UK, the Institut National du Cancer, La Ligue Contre le Cancer, Centers for Disease Control and Prevention, Swiss Re, Swiss Cancer Research foundation, Swiss Cancer League, Rossy Family Foundation, US National Cancer Institute, and the American Cancer Society.

Missing cases of injury death: use of quantitative methods and case reviews to inform future improvements in case definition.

BACKGROUND: Knowledge of fatal injuries is required to inform prevention activities. Where hospital patients with an injury principal diagnosis (PDx) died and were certified to a medical underlying cause of death (UCoD), there is the potential to underestimate injury mortality. We sought to characterise injury/non-injury (NI) mismatches between PDx and UCoD by identifying which subgroups had small/large mismatches, and to understand why mismatches had occurred using informative examples. METHOD: Hospital records (n=10 234) with a PDx of injury were linked to the mortality collection using a unique personal identifier. Percentages UCoD coded to a NI were tabulated, for three follow-up periods and by selected variables. Additionally, we reviewed a sample of 70 records for which there was a mismatch. RESULTS: %NIs were 39%, 66% and 77% for time from injury to death of <1 week, <90 days and <1 year, respectively. Variations in %NI were found for all variables. Illustrative examples of 70 medical UCoD deaths showed that for 12 cases the injury event was unequivocally judged to have resulted in premature death. A further 16 were judged as injury deaths using balance of probability arguments. CONCLUSION: There is variation in rates of mismatch between PDx of injury and UCoD of NI. While legitimate reasons exist for mismatches in certain groups, a material number of injury deaths are not captured using UCoD alone; a new operational definition of injury death is needed. Early solutions are proposed. Further work is needed to investigate operational definitions with acceptable false positive and negative detection rates.

A salutary childbirth education program: Health promoting by design. A discussion paper.

Pregnancy is an ideal time to focus on health promotion. Many women and their partners attend childbirth education classes to prepare themselves for pregnancy, birth and parenting. However, rather than promoting health, these classes have been criticized for preparing women and their partners for a medicalized birth, which has become the norm in many well-resourced countries. This paper describes the development of a childbirth education program using the theory of salutogenesis. While much has been written about the theory, few have attempted to operationalize the theory for health service delivery, particularly in the maternity care context. The aim of the program was to move individuals participating in the program towards greater health on the health-ease/dis-ease continuum by increasing their sense of coherence, focusing on generalized resistance resources and strengthening the key components comprehensibility, manageability and meaningfulness. This paper describes the development of the program.

Improvement in the Spatial Distribution of Pain, Somatic Symptoms, and Depression After a Weight Loss Intervention.

Weight loss is known to improve pain localized to weight-bearing joints but it is not known how weight loss affects the spatial distribution of pain and associated somatic symptoms like fatigue. We sought to determine if weight loss using a low-calorie diet improves pain, affect, and somatic symptoms commonly associated with chronic pain conditions in an observational study. We also documented changes in inflammatory markers in serum before and after weight loss. Participants were 123 obese individuals undergoing a 12- to 16-week calorie restriction weight loss intervention. The spatial distribution of pain, symptom severity (eg, fatigue, sleep difficulties), depression, and total fibromyalgia scale scores were measured before and after weight loss. Pain (P = . 022), symptom severity (P = .004), depression (P < .001), and fibromyalgia scores (P = .004) improved after weight loss; men showed greater improvement than women on somatic symptoms and fibromyalgia scores (both P < .01). Those who lost at least 10% of body weight showed greater improvement than those who lost <10%. Levels of the regulatory cytokine interleukin-10 increased after the intervention (P = .002). Weight loss may improve diffuse pain and comorbid symptoms commonly seen in chronic pain participants. PERSPECTIVE: This article presents the effect of a weight loss intervention on characteristics of chronic pain, including the spatial distribution of pain and comorbid somatic symptoms. Weight loss appeared to produce larger improvements in somatic symptoms for men.

Impact of weight loss on waist circumference and the components of the metabolic syndrome.

OBJECTIVE: Central adiposity is a component of the metabolic syndrome (MetS). Little is known about the impact of medical weight loss and decreased waist circumference (WC) on the MetS. Our objective was to assess the impact of changes in WC on blood pressure, lipids and glycemia. RESEARCH DESIGN AND METHODS: We studied 430 obese patients enrolled in a 2-year, intensive, behavioral, weight management program. We report results for participants who completed 6-month and 2-year follow-up. RESULTS: Participants were 49±9 years of age (mean±SD), 56% were women and 85% were white. Baseline body mass index (BMI) was 41±6 kg/m2 and baseline WC was 120±14 cm. At 6 months, BMI decreased by 6±3 kg/m2 and WC by 14±9 cm. Relative change in WC was defined as the 6-month or 2-year WC minus the baseline WC divided by the baseline WC. Systolic blood pressure decreased by 8 mm Hg for the tertile of participants with the largest relative decrease in WC and by 2 mm Hg for those with the smallest relative decrease in WC (p=0.025). Similar patterns of improvement were observed in total cholesterol (-29 vs -12 mg/dL, p=0.017), low-density lipoprotein-cholesterol (-19 vs -4 mg/dL, p=0.033), and glycated hemoglobin (-1.2 vs -0.3%, p=0.006). At 2 years, BMI decreased by 5±4 kg/m2 and WC by 11±11 cm and similar patterns of improvements were seen in components of the MetS. At both 6 months and 2 years, larger relative decreases in WC were associated with greater improvements in lipids and glycemia independent of sex. CONCLUSIONS: In obese people, greater relative decreases in WC with medical weight loss are associated with greater improvements in components of the MetS independent of sex.

Feasibility of a brief, intensive weight loss intervention to improve reproductive outcomes in obese, subfertile women: a pilot study.

OBJECTIVE: To evaluate the feasibility of a brief, intensive weight loss intervention (IWL) to improve reproductive outcomes in obese subfertile women. DESIGN: Pilot study of IWL versus standard-of-care nutrition counseling (SCN). SETTING: Single-site, academic institution. PATIENT(S): Obese women (body mass index, 35-45 kg/m2) with anovulatory subfertility. INTERVENTION(S): Women were rigorously prescreened to rule out secondary causes of subfertility. Eligible women were randomized to IWL or SCN. IWL consisted of 12 weeks of very-low-energy diet (800 kcal/day) + 4 weeks of a low-calorie conventional food-based diet (CFD) to promote 15% weight loss. SCN consisted of 16 weeks of CFD to promote ≥5% weight loss. Women were transitioned to weight maintenance diets and referred back to reproductive endocrinology for ovulation induction. MAIN OUTCOME MEASURE(S): Feasibility of recruitment, randomization, intervention implementation, and retention. RESULT(S): Thirty-nine women were screened; 25 (64%) were eligible to participate, and 14 of those eligible (56%) agreed to be randomized, seven in each group. One withdrew from the IWL group and two from the SCN group. Percent weight loss was greater in the IWL group than in the SCN group (13% ± 5% vs. 4% ± 4%). Three of six women in the IWL group conceived and delivered term pregnancies. No pregnancies occurred in the SCN group. CONCLUSION(S): After rigorous screening, 44% of eligible women completed the study. IWL was associated with greater percentage weight loss and improvements in insulin sensitivity. CLINICAL TRIAL REGISTRATION: NCT01894074.

Factors associated with participant retention in a clinical, intensive, behavioral weight management program.

BACKGROUND: We sought to identify factors associated with participant retention in a 2-year, physician-lead, multidisciplinary, clinical weight management program that employs meal replacements to produce weight loss and intensive behavioral interventions and financial incentives for weight loss maintenance. We studied 270 participants enrolled in 2010 and 2011. Sociodemographic factors, health insurance, distance traveled, body mass index, comorbidities, health-related quality-of-life, and depression were explored as potential predictors of retention. RESULTS: Mean age was 49 ± 8 years and BMI was 41 ± 5 kg/m(2). Retention was excellent at 3 months (90%) and 6 months (83%). Attrition was greatest after participants were transitioned to regular foodstuffs and fell to 67% at 12 months and 51% at 2 years. Weight decreased by 15 ± 12 kg and BMI decreased by 5.1 ± 4.0 kg/m(2) in 2-year completers. Older age, lower baseline BMI, and financial incentives for program participation were independently associated with retention. Fewer depressive symptoms at baseline were associated with retention. CONCLUSIONS: This multidisciplinary, clinical, weight management program demonstrated high retention and excellent outcomes. Older age at baseline, less extreme obesity, and financial incentives were associated with program retention.

Very-low-energy diet for type 2 diabetes: an underutilized therapy?

BACKGROUND: Current approaches to the management of type 2 diabetes focus on the early initiation of novel pharmacologic therapies and bariatric surgery. OBJECTIVE: The purpose of this study was to revisit the use of intensive, outpatient, behavioral weight management programs for the management of type 2 diabetes. DESIGN: Prospective observational study of 66 patients with type 2 diabetes and BMI ≥ 32 kg/m² who enrolled in a program designed to produce 15% weight reduction over 12 weeks using total meal replacement and low- to moderate-intensity physical activity. RESULTS: Patients were 53 ± 7 years of age (mean ± SD) and 53% were men. After 12 weeks, BMI fell from 40.1 ± 6.6 to 35.1 ± 6.5 kg/m². HbA1c fell from 7.4% ± 1.3% to 6.5% ± 1.2% (57.4 ± 12.3 to 47.7 ± 12.9 mmol/mol) in patients with established diabetes: 76% of patients with established diabetes and 100% of patients with newly diagnosed diabetes achieved HbA1c <7.0% (53.0 mmol/mol). Improvement in HbA1c over 12 weeks was associated with higher baseline HbA1c and greater reduction in BMI. CONCLUSIONS: An intensive, outpatient, behavioral weight management program significantly improved HbA1c in patients with type 2 diabetes over 12 weeks. The use of such programs should be encouraged among obese patients with type 2 diabetes.

The impact of weight loss on health-related quality-of-life: implications for cost-effectiveness analyses.

PURPOSE: To assess the impact of weight loss on health-related quality-of-life (HRQL), to describe the factors associated with improvements in HRQL after weight loss, and to assess the relationship between obesity as assessed by body mass index (BMI) and HRQL before and after weight loss. METHODS: We studied 188 obese patients with BMI ≥ 32 kg/m(2) with one or more comorbidities or ≥35 kg/m(2). All patients had baseline and follow-up assessments of BMI and HRQL using the EuroQol (EQ-5D) and its visual analog scale (VAS) before and after 6 months of medical weight loss that employed very low-calorie diets, physical activity, and intensive behavioral counseling. RESULTS: At baseline, age was 50 ± 8 years (mean ± SD), BMI was 40. 0 ± 5.0 kg/m(2), EQ-5D-derived health utility score was 0.85 ± 0.13, and VAS-reported quality-of-life was 0.67 ± 0.18. At 6-month follow-up, BMI decreased by 7.0 ± 3.2 kg/m(2), EQ-5D increased by 0.06 [interquartile range (IQR) 0.06-0.17], and VAS increased by 0.14 (IQR 0.04-0.23). In multivariate analyses, improvement in EQ-5D and VAS were associated with lower baseline BMI, greater reduction in BMI at follow-up, fewer baseline comorbidities, and lower baseline HRQL. For any given BMI category, EQ-5D and VAS tended to be higher at follow-up than at baseline. CONCLUSION: Measured improvements in HRQL between baseline and follow-up were greater than predicted by the reduction in BMI at follow-up. If investigators use cross-sectional data to estimate changes in HRQL as a function of BMI, they will underestimate the improvement in HRQL associated with weight loss and underestimate the cost-utility of interventions for obesity treatment.