Impact of overweight and obesity on life expectancy, quality-adjusted life years and lifetime costs in the adult population of Ghana

Introduction: Prior studies have revealed the increasing prevalence of obesity and its associated health effects among ageing adults in resource poor countries. However, no study has examined the long-term and economic impact of overweight and obesity in sub-Saharan Africa. Therefore, we quantified the long-term impact of overweight and obesity on life expectancy (LE), quality-adjusted life years (QALYs) and total direct healthcare costs. Methods: A Markov simulation model projected health and economic outcomes associated with three categories of body mass index (BMI): healthy weight (18.5≤BMI 2) in simulated adult cohorts over a 50-year time horizon from age fifty. Costs were estimated from government and patient perspectives, discounted 3% annually and reported in 2017 US$. Mortality rates from Ghanaian lifetables were adjusted by BMI-specific all-cause mortality HRs. Published input data were used from the 2014/2015 Ghana WHO Study on global AGEing and adult health data. Internal and external validity were assessed. Results: From age 50 years, average (95$619 (95% CI: 616 to 622), US$1298 (95$2057 (95% CI: 2043 to 2071) for healthy weight, overweight and obesity, respectively. QALYs and costs were lower in males. Conclusion: Overweight and obesity have substantial health and economic impacts, hence the urgent need for cost-effective preventive strategies in the Ghanaian population

Correction: Exome Sequencing of Phenotypic Extremes Identifies CAV2 and TMC6 as Interacting Modifiers of Chronic Pseudomonas aeruginosa Infection in Cystic Fibrosis

Discovery of rare or low frequency variants in exome or genome data that are associated with complex traits often will require use of very large sample sizes to achieve adequate statistical power. For a fixed sample size, sequencing of individuals sampled from the tails of a phenotype distribution (i.e., extreme phenotypes design) maximizes power and this approach was recently validated empirically with the discovery of variants in DCTN4 that influence the natural history of P. aeruginosa airway infection in persons with cystic fibrosis (CF; MIM219700). The increasing availability of large exome/genome sequence datasets that serve as proxies for population-based controls affords the opportunity to test an alternative, potentially more powerful and generalizable strategy, in which the frequency of rare variants in a single extreme phenotypic group is compared to a control group (i.e., extreme phenotype vs. control population design). As proof-of-principle, we applied this approach to search for variants associated with risk for age-of-onset of chronic P. aeruginosa airway infection among individuals with CF and identified variants in CAV2 and TMC6 that were significantly associated with group status. These results were validated using a large, prospective, longitudinal CF cohort and confirmed a significant association of a variant in CAV2 with increased age-of-onset of P. aeruginosa airway infection (hazard ratio = 0.48, 95% CI=[0.32, 0.88]) and variants in TMC6 with diminished age-of-onset of P. aeruginosa airway infection (HR = 5.4, 95% CI=[2.2, 13.5]) A strong interaction between CAV2 and TMC6 variants was observed (HR=12.1, 95% CI=[3.8, 39]) for children with the deleterious TMC6 variant and without the CAV2 protective variant. Neither gene showed a significant association using an extreme phenotypes design, and conditions for which the power of an extreme phenotype vs. control population design was greater than that for the extreme phenotypes design were explored

Results of paclitaxel (day 1 and 8) and carboplatin given on every three weeks in advanced (stage III-IV) non-small cell lung cancer

BACKGROUND: Both paclitaxel (P) and carboplatin (C) have significant activity in non-small cell lung cancer (NSCLC). The weekly administration of P is active, dose intense, and has a favorable toxicity profile. We retrospectively reviewed the data of 51 consecutive patients receiving C and day 1 and 8 P chemotherapy (CT) regimen in advanced stage NSCLC to evaluate the efficacy and toxicity. METHODS: Patients treated in our institutions having pathologically proven NSCLC, no CNS metastases, adequate organ function and performance status (PS) ECOG 0–2 were given P 112.5 mg/m(2 )intravenously (IV) over 1 hour on day 1 and 8, followed by C AUC 5 IV over 1 hour, repeated in every three weeks. PC was given for maximum of 6 cycles. RESULTS: Median age was 58 (age range 39–77) and 41 patients (80%) were male. PS was 0/1/2 in 29/17/5 patients and stage was IIIA/IIIB/IV in 3/14/34 patients respectively. The median number of cycles administered was 3 (1–6). Seven patients (14%) did not complete the first 3 cycles either due to death, progression, grade 3 hypersensitivity reactions to P or lost to follow up. Best evaluable response was partial response (PR) in 45% and stable disease (SD) in 18%. Twelve patients (24%) received local RT. Thirteen patients (25%) received 2nd line CT at progression. At a median follow-up of 7 months (range, 1–20), 25 (49%) patients died and 35 patients (69%) progressed. Median overall survival (OS) was 11 ± 2 months (95% CI; 6 to 16), 1-year OS ratio was 44%. Median time to progression (TTP) was 6 ± 1 months (95% CI; 4 to 8), 1-year progression free survival (PFS) ratio was 20%. We observed following grade 3 toxicities: asthenia (10%), neuropathy (4%), anorexia (4%), anemia (4%), hypersensitivity to P (2%), nausea/vomiting (2%), diarrhea (2%) and neutropenia (2%). Two patients (4%) died of febrile neutropenia. Doses of CT were reduced or delayed in 12 patients (24%). CONCLUSIONS: P on day 1 and 8 and C every three weeks is practical and fairly well tolerated outpatient regimen. This regimen seems to be comparably active to regimens given once in every three weeks

Randomised phase III trial of carboplatin plus etoposide vs split doses of cisplatin plus etoposide in elderly or poor-risk patients with extensive disease small-cell lung cancer: JCOG 9702

We compared the efficacy and the safety of a carboplatin plus etoposide regimen (CE) vs split doses of cisplatin plus etoposide (SPE) in elderly or poor-risk patients with extensive disease small-cell lung cancer (ED-SCLC). Eligibility criteria included: untreated ED-SCLC; age ⩾70 and performance status 0–2, or age <70 and PS 3. The CE arm received carboplatin area under the curve of five intravenously (IV) on day 1 and etoposide 80 mg m−2 IV on days 1–3. The SPE arm received cisplatin 25 mg m−2 IV on days 1–3 and etoposide 80 mg m−2 IV on days 1–3. Both regimens were given with granulocyte colony-stimulating factor support in a 21–28 day cycle for four courses. A total of 220 patients were randomised. Median age was 74 years and 74% had a PS of 0 or 1. Major grade 3–4 toxicities were (%CE/%SPE): leucopenia 54/51, neutropenia 95/90, thrombocytopenia 56/16, infection 7/6. There was no significant difference (CE/SPE) in the response rate (73/73%) and overall survival (median 10.6/9.9 mo; P=0.54). Palliation scores were very similar between the arms. Although the SPE regimen is still considered to be the standard treatment in elderly or poor-risk patients with ED-SCLC, the CE regimen can be an alternative for this population considering the risk–benefit balance

Exome Sequencing of Phenotypic Extremes Identifies <i>CAV2</i> and <i>TMC6</i> as Interacting Modifiers of Chronic <i>Pseudomonas aeruginosa</i> Infection in Cystic Fibrosis

<div><p>Discovery of rare or low frequency variants in exome or genome data that are associated with complex traits often will require use of very large sample sizes to achieve adequate statistical power. For a fixed sample size, sequencing of individuals sampled from the tails of a phenotype distribution (i.e., extreme phenotypes design) maximizes power and this approach was recently validated empirically with the discovery of variants in <i>DCTN4</i> that influence the natural history of <i>P</i>. <i>aeruginosa</i> airway infection in persons with cystic fibrosis (CF; MIM219700). The increasing availability of large exome/genome sequence datasets that serve as proxies for population-based controls affords the opportunity to test an alternative, potentially more powerful and generalizable strategy, in which the frequency of rare variants in a single extreme phenotypic group is compared to a control group (i.e., extreme phenotype vs. control population design). As proof-of-principle, we applied this approach to search for variants associated with risk for age-of-onset of chronic <i>P</i>. <i>aeruginosa</i> airway infection among individuals with CF and identified variants in <i>CAV2</i> and <i>TMC6</i> that were significantly associated with group status. These results were validated using a large, prospective, longitudinal CF cohort and confirmed a significant association of a variant in <i>CAV2</i> with increased age-of-onset of <i>P</i>. <i>aeruginosa</i> airway infection (hazard ratio = 0.48, 95% CI=[0.32, 0.88]) and variants in <i>TMC6</i> with diminished age-of-onset of <i>P</i>. <i>aeruginosa</i> airway infection (HR = 5.4, 95% CI=[2.2, 13.5]) A strong interaction between <i>CAV2</i> and <i>TMC6</i> variants was observed (HR=12.1, 95% CI=[3.8, 39]) for children with the deleterious <i>TMC6</i> variant and without the <i>CAV2</i> protective variant. Neither gene showed a significant association using an extreme phenotypes design, and conditions for which the power of an extreme phenotype vs. control population design was greater than that for the extreme phenotypes design were explored.</p></div