Women with a low satiety phenotype show impaired appetite control and greater resistance to weight loss.

AbstractThis trial compared weight loss outcomes over 14-weeks in women showing low or high satiety responsiveness [low or high satiety phenotype (LSP, HSP)] measured by a standardized protocol. Food preferences and energy intake after low and high energy density (LED, HED) meals were also assessed. Ninety-six women (n = 52 analysed; 41.24 ± 12.54 years; 34.02 ± 3.58 kg/m2) engaged in one of two weight loss programs underwent LED and HED laboratory-test days during weeks 3 and 12. Preferences for LED and HED-foods (Leeds Food Preference Questionnaire) and ad libitum evening meal and snack energy intake (EI) were assessed in response to equi-caloric LED- and HED-breakfasts and lunches. Weekly questionnaires assessed control over eating and ease of adherence to the program. Satiety quotients based on subjective fullness ratings post-LED and HED breakfasts determined LSP (n=26) and HSP (n=26) by tertile splits. Results showed that the LSP lost less weight and had smaller reductions in waist circumference compared to HSP. The LSP showed greater preferences for HED-foods, and under HED-conditions, consumed more snacks (kcal) compared to HSP. Snack EI did not differ under LED-conditions. LSP reported less control over eating and reported more difficulty with program adherence. In conclusion, low satiety responsiveness is detrimental for weight loss. LED meals can improve self-regulation of EI in the LSP, which may be beneficial for longer-term weight control.</jats:p

Chronic or recurrent Campylobacter enteritis in primary immunodeficiency: A UK national case-series and review of the literature

Campylobacter infection is an important diagnosis to consider in primary immunodeficiency patients with chronic or recurrent diarrhea, particularly in those with very low diagnostic immunoglobulin levels. Macrolides, aminoglycosides, and/or carbapenems are promising treatment options for this potentially debilitating condition

Free-living energy balance behaviours are associated with greater weight loss during a weight loss programme

Introduction: Free-living movement (physical activity [PA] and sedentary behavior [SB]) and eating behaviors (energy intake [EI] and food choice) affect energy balance and therefore have the potential to influence weight loss (WL). This study explored whether free-living movement and/or eating behaviors measured early (week 3) in a 14-week WL programme or their change during the intervention are associated with WL in women. Methods: In the study, 80 women (M ± SD age: 42.0 ± 12.4 years) with overweight or obesity [body mass index (BMI): 34.08 ± 3.62 kg/m2] completed a 14 week WL program focused primarily on diet (commercial or self-led). Body mass (BM) was measured at baseline, and again during week 2 and 14 along with body composition. Free-living movement (SenseWear Armband) and eating behavior (weighed food diaries) were measured for 1 week during week 3 and 12. Hierarchical multiple regression analyses examined whether early and early-late change in free-living movement and eating behavior were associated with WL. The differences in behavior between clinically significant weight losers (CWL; ≥5% WL) and non-clinically significant weight losers (NWL; ≤ 3% WL) were compared. Results: The energy density of food consumed [β = 0.45, p < 0.001] and vigorous PA [β = −0.30, p < 0.001] early in the intervention (regression model 1) and early-late change in light PA [β = −0.81 p < 0.001], moderate PA [β = −1.17 p < 0.001], vigorous PA [β = −0.49, p < 0.001], total energy expenditure (EE) [β = 1.84, p < 0.001], and energy density of food consumed [β = 0.27, p = 0.01] (regression model 2) significantly predicted percentage change in BM. Early in the intervention, CWL consumed less energy dense foods than NWL [p = 0.03]. CWL showed a small but significant increase in vigorous PA, whereas NWL showed a slight decrease in PA [p = 0.04]. Conclusion: Both early and early-late change in free-living movement and eating behaviors during a 14 week WL program are predictors of WL. These findings demonstrate that specific behaviors that contribute to greater EE (e.g., vigorous PA) and lower EI (e.g., less energy-dense foods) are related to greater WL outcomes. Interventions targeting these behaviors can be expected to increase the effectiveness of WL programs

Changes in Grauer's gorilla (Gorilla beringei graueri) and other primate populations in the Kahuzi-Biega National Park and Oku Community Reserve, the heart of Grauer's gorilla global range

Grauer's gorillas (Gorilla beringei graueri) have declined drastically across their range in eastern Democratic Republic of Congo (DRC). Survey data analysed in 2016 estimated a 77% decline in numbers between the mid- 1990s and 2016 and predicted that Kahuzi-Biega National Park (KBNP), and the contiguous Oku Community Reserve (OCR) held much of the global population. An estimate of 3800 Grauer's gorillas was made across its range at that time. Here, we publish the most extensive survey of Grauer's gorilla numbers to date, using nest counts from 230 line transects across KBNP and OCR to derive more accurate estimates of both gorilla and chimpanzee numbers. Gorilla numbers were estimated from line transects at 1,571 (95% confidence interval [CI]: 824–2,993) within KBNP and at 2,244 (95% CI: 1,471–3,422) in OCR. Eastern chimpanzee (Pan troglodytes schweinfurthii) numbers were estimated at 2,500 (95% CI: 1,804–3,462) in KBNP and 687 (95% CI: 472–999) in OCR. Estimates of total numbers for the survey area were 5,252 (95% CI: 3,687–7,481) Grauer's gorillas and 4,275 (95% CI: 3,322–5,502) eastern chimpanzees. Chimpanzee numbers were not significantly different from the estimates in the mid-1990s but the gorillas had significantly declined, mostly in KBNP. Modeled densities of these apes indicated that distances to mines, villages, or roads significantly explained part of the distribution of these apes, with higher densities also found in more rugged and remote sites. Other primates have all declined in this region, likely due to bushmeat hunting, especially the Endangered Ulindi River Red Colobus Piliocolobus lulindicus. These results confirm the negative impact of insecurity on Grauer's gorilla but indicate that the population declines may not be as great as previously feared. Using our revised gorilla density estimate we revise the original estimate of global numbers from 3,800 to 6,800 individuals

A National Survey of Hereditary Angioedema and Acquired C1 Inhibitor Deficiency in the United Kingdom

Background: Detailed demographic data on people with hereditary angioedema (HAE) and acquired C1 inhibitor deficiency in the United Kingdom are relatively limited. Better demographic data would be beneficial in planning service provision, identifying areas of improvement, and improving care./ Objective: To obtain more accurate data on the demographics of HAE and acquired C1 inhibitor deficiency in the United Kingdom, including treatment modalities and services available to patients./ Methods: A survey was distributed to all centers in the United Kingdom that look after patients with HAE and acquired C1 inhibitor deficiency to collect these data./ Results: The survey identified 1152 patients with HAE-1/2 (58% female and 92% type 1), 22 patients with HAE with normal C1 inhibitor, and 91 patients with acquired C1 inhibitor deficiency. Data were provided by 37 centers across the United Kingdom. This gives a minimum prevalence of 1:59,000 for HAE-1/2 and 1:734,000 for acquired C1 inhibitor deficiency in the United Kingdom. A total of 45% of patients with HAE were on long-term prophylaxis (LTP) with the most used medication being danazol (55% of all patients on LTP). Eighty-two percent of patients with HAE had a home supply of acute treatment with C1 inhibitor or icatibant. A total of 45% of patients had a supply of icatibant and 56% had a supply of C1 inhibitor at home./ Conclusions: Data obtained from the survey provide useful information about the demographics and treatment modalities used in HAE and acquired C1 inhibitor deficiency in the United Kingdom. These data are useful for planning service provision and improving services for these patients

A low energy dense diet in the context of a weight management program improves appetite control in overweight and obese women

Background: Low energy density foods (LED) reduce energy intake (EI); whether this effect is sustained over time and during weight loss is unknown. Objective: This trial examined the effects of LED compared to high energy density (HED) meals on appetite, EI and control over eating in the laboratory and during a weight management program that encourages unrestricted intake of LED foods [Slimming World, UK (SW)] compared to a self-led Standard Care program [NHS weight loss plan (SC)]. Methods: Overweight and obese women (n=96;age:41.03±12.61 years; BMI:34.00±3.61 kg/m2) were recruited from SW- or SC-program. Primary outcomes included appetite, food preferences (liking and wanting for LED and HED foods), cravings and evening meal EI (LED, HED) in response to calorie-matched LED (≤0.8 kcal/g) and HED (≥2.5 kcal/g) breakfast and lunch meals. Probe day tests were conducted at weeks 3 and 4 and repeated at weeks 12 and 13 in a within-day cross-over design. Secondary outcomes including body weight and program experience were measured from week 1 to 14 in a parallel-group design. Dietary compliance was monitored using weighed food diaries at weeks 3 and 12. Results: Intention-to-treat (ITT) and completers-analyses showed SW lost more weight compared to SC [ITT:-5.9% (95%CI:-4.7, -7.2) versus -3.5% (-2.3,-4.8), p<0.05; completers:-6.2% (-4.8,-7.6) versus 3.9% (-2.5,-5.2), p<0.05]. SW reported greater control over eating and more motivation to continue the program compared to SC. LED meals increased sensations of fullness and reduced hunger on probe days (p<0.001). Total-day-EI was 1057±73 kcal less (95% CI:912, 1203;36%) under LED compared to HED (p<.001). Liking for LED and HED foods and wanting for HED foods were lower pre-lunch under LED compared to HED conditions and liking decreased to a greater extent after the LED-lunch. SW reported fewer cravings under LED compared to HED conditions (p<0.05). On probe days, appetite and EI outcomes did not differ between weeks 3 and 12 or SW- and SC-groups. Conclusion: LED meals improve appetite control in women attempting weight loss and the effect is sustainable. Consumption of LED meals likely contributed to weight loss in the SW-program.ClinicalTrials.gov #NCT02012426

Clinical development of new drug-radiotherapy combinations.

In countries with the best cancer outcomes, approximately 60% of patients receive radiotherapy as part of their treatment, which is one of the most cost-effective cancer treatments. Notably, around 40% of cancer cures include the use of radiotherapy, either as a single modality or combined with other treatments. Radiotherapy can provide enormous benefit to patients with cancer. In the past decade, significant technical advances, such as image-guided radiotherapy, intensity-modulated radiotherapy, stereotactic radiotherapy, and proton therapy enable higher doses of radiotherapy to be delivered to the tumour with significantly lower doses to normal surrounding tissues. However, apart from the combination of traditional cytotoxic chemotherapy with radiotherapy, little progress has been made in identifying and defining optimal targeted therapy and radiotherapy combinations to improve the efficacy of cancer treatment. The National Cancer Research Institute Clinical and Translational Radiotherapy Research Working Group (CTRad) formed a Joint Working Group with representatives from academia, industry, patient groups and regulatory bodies to address this lack of progress and to publish recommendations for future clinical research. Herein, we highlight the Working Group's consensus recommendations to increase the number of novel drugs being successfully registered in combination with radiotherapy to improve clinical outcomes for patients with cancer.National Institute for Health ResearchThis is the final version of the article. It first appeared from Nature Publishing Group via http://dx.doi.org/10.1038/nrclinonc.2016.7

Convalescent plasma in patients admitted to hospital with COVID-19 (RECOVERY): a randomised controlled, open-label, platform trial

SummaryBackground Azithromycin has been proposed as a treatment for COVID-19 on the basis of its immunomodulatoryactions. We aimed to evaluate the safety and efficacy of azithromycin in patients admitted to hospital with COVID-19.Methods In this randomised, controlled, open-label, adaptive platform trial (Randomised Evaluation of COVID-19Therapy [RECOVERY]), several possible treatments were compared with usual care in patients admitted to hospitalwith COVID-19 in the UK. The trial is underway at 176 hospitals in the UK. Eligible and consenting patients wererandomly allocated to either usual standard of care alone or usual standard of care plus azithromycin 500 mg once perday by mouth or intravenously for 10 days or until discharge (or allocation to one of the other RECOVERY treatmentgroups). Patients were assigned via web-based simple (unstratified) randomisation with allocation concealment andwere twice as likely to be randomly assigned to usual care than to any of the active treatment groups. Participants andlocal study staff were not masked to the allocated treatment, but all others involved in the trial were masked to theoutcome data during the trial. The primary outcome was 28-day all-cause mortality, assessed in the intention-to-treatpopulation. The trial is registered with ISRCTN, 50189673, and ClinicalTrials.gov, NCT04381936.Findings Between April 7 and Nov 27, 2020, of 16 442 patients enrolled in the RECOVERY trial, 9433 (57%) wereeligible and 7763 were included in the assessment of azithromycin. The mean age of these study participants was65·3 years (SD 15·7) and approximately a third were women (2944 [38%] of 7763). 2582 patients were randomlyallocated to receive azithromycin and 5181 patients were randomly allocated to usual care alone. Overall,561 (22%) patients allocated to azithromycin and 1162 (22%) patients allocated to usual care died within 28 days(rate ratio 0·97, 95% CI 0·87–1·07; p=0·50). No significant difference was seen in duration of hospital stay (median10 days [IQR 5 to >28] vs 11 days [5 to >28]) or the proportion of patients discharged from hospital alive within 28 days(rate ratio 1·04, 95% CI 0·98–1·10; p=0·19). Among those not on invasive mechanical ventilation at baseline, nosignificant difference was seen in the proportion meeting the composite endpoint of invasive mechanical ventilationor death (risk ratio 0·95, 95% CI 0·87–1·03; p=0·24).Interpretation In patients admitted to hospital with COVID-19, azithromycin did not improve survival or otherprespecified clinical outcomes. Azithromycin use in patients admitted to hospital with COVID-19 should be restrictedto patients in whom there is a clear antimicrobial indication

GWAS meta-analysis of intrahepatic cholestasis of pregnancy implicates multiple hepatic genes and regulatory elements

Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-specific liver disorder affecting 0.5–2% of pregnancies. The majority of cases present in the third trimester with pruritus, elevated serum bile acids and abnormal serum liver tests. ICP is associated with an increased risk of adverse outcomes, including spontaneous preterm birth and stillbirth. Whilst rare mutations affecting hepatobiliary transporters contribute to the aetiology of ICP, the role of common genetic variation in ICP has not been systematically characterised to date. Here, we perform genome-wide association studies (GWAS) and meta-analyses for ICP across three studies including 1138 cases and 153,642 controls. Eleven loci achieve genome-wide significance and have been further investigated and fine-mapped using functional genomics approaches. Our results pinpoint common sequence variation in liver-enriched genes and liver-specific cis-regulatory elements as contributing mechanisms to ICP susceptibility