Association of the Sweet-Liking Phenotype and Craving for Alcohol With the Response to Naltrexone Treatment in Alcohol Dependence: A Randomized Clinical Trial

Identification of moderators of the response to naltrexone hydrochloride treatment for alcohol dependence could improve clinical care for patients with alcohol use disorders. To investigate the preliminary finding that the sweet-liking (SL) phenotype interacts with a high level of craving for alcohol and is associated with an improved response to naltrexone in alcohol dependence. This 12-week double-blind, randomized, placebo-controlled clinical trial was conducted from February 1, 2010, to April 30, 2012, in an academic outpatient medical center. Eighty actively drinking patients were randomized by the SL (n = 22) or the sweet-disliking (SDL) (n = 58) phenotype and by pretreatment high (n = 40) or low (n = 40) craving for alcohol, with high craving defined as greater than the median. Patients and staff were blinded to categorization. Patients were excluded for unstable medical or psychiatric illness, including dependence on drugs other than nicotine. Four patients (2 in the placebo arm and 2 in the naltrexone arm) stopped medication therapy because of adverse effects. Data were analyzed from January 15, 2013, to May 15, 2016, based on intention to treat. Oral naltrexone hydrochloride, 50 mg/d, or daily placebo with weekly to biweekly brief counseling. The a priori hypothesis tested SL/SDL phenotype, pretreatment craving, and their interaction as moderators of frequency of abstinent and heavy drinking days during treatment, assessed with the timeline follow-back method. Eighty patients were randomized (57 men [71%]; 23 women [29%]; mean [SD] age, 47.0 [8.6] years). A nonsignificant effect of naltrexone on heavy drinking was noted (4.8 fewer heavy drinking days; Cohen d = 0.45; 95% CI, -0.01 to 0.90; F1,67 = 3.52; P = .07). The SL phenotype moderated the effect of naltrexone on heavy drinking (6.1 fewer heavy drinking days; Cohen d = 0.58; 95% CI, 0.12-1.03; F1,67 = 5.65; P = .02) and abstinence (10.0 more abstinent days; Cohen d = 0.57; 95% CI, 0.11-1.02; F1,67 = 5.36; P = .02), and high craving moderated heavy drinking (7.1 fewer heavy drinking days; Cohen d = 0.66; 95% CI, 0.20-1.11; F1,67 = 7.37; P = .008). The combination of the SL phenotype and high craving was associated with a strong response to naltrexone, with 17.1 fewer heavy drinking days (Cohen d = 1.07; 95% CI, 0.58-1.54; F1,67 = 19.33; P < .001) and 28.8 more abstinent days (Cohen d = 0.72; 95% CI, 0.25-1.17; F1,67 = 8.73; P = .004) compared with placebo. The SL phenotype and a high craving for alcohol independently and particularly in combination are associated with a positive response to naltrexone. The SL/SDL phenotype and a high craving for alcohol merit further investigation as factors to identify patients with alcohol dependence who are responsive to naltrexone. clinicaltrials.gov Identifier: NCT01296646

Moderate physical activity may prevent cartilage loss in women with knee osteoarthritis : data from the Osteoarthritis Initiative

All authors have completed the ICMJE uniform disclosure form at http://www.icmje.org/coi_disclosure.pdf and declare: data acquisition in this study was funded by the Osteoarthritis Initiative, a public–private partnership comprised of five contracts (N01-AR-2-2258; N01-AR-2-2259;N01-AR-2-2260; N01-AR-2-2261; N01-AR-2-2262) funded by the National Institutes of Health, a branch of the Department of Health and Human Services, and conducted by the Osteoarthritis Initiative study Investigators. Private funding partners of the OAI include Merck Research Laboratories, Novartis Pharmaceuticals Corporation, GlaxoSmithKline, and Pfizer, Inc. Private sector funding for the Osteoarthritis Initiative is managed by the Foundation for the National Institutes of Health. The image analysis in this study was partly funded by the FNIH OA Biomarkers Consortium, with grants, direct and in -kind contributions, provided by: AbbVie; Amgen Inc.; Arthritis Foundation; Bioiberica S.A.; DePuy Mitek, Inc.; Flexion Therapeutics, Inc.; GlaxoSmithKline; Merck KGaA; Rottapharm | Madaus; Sanofi; and Stryker. Other parts of funding were provided by a direct grant from Merck KGaA, by a contract with the University of Pittsburgh (Pivotal OAI MRI Analyses [POMA]: NIH/NHLBI Contract No. HHSN2682010000 21C), by a vendor contract from the OAI coordinating center at University of California, San Francisco (N01-AR-2-2258), and by an ancillary study to the OAI held by the Division of Rheumatology, Feinberg School of Medicine, Northwestern University (R01 AR52918). This research has also received funding from the European Union Seventh Framework Programme (FP7-PEOPLE-2013-ITN; KNEEMO) under grant agreement number 607510. AGC is supported by a National Health and Medical Research Council (NHMRC) of Australia Early Career Fellowship (Neil Hamilton Fairley Clinical Fellowship No.1121173). The sponsors were not involved in the design and conduct of this particular study, in the analysis and interpretation of the data, and in the preparation, review, or approval of the manuscript.Peer reviewedPostprin

Divine intervention? A Cochrane review on intercessory prayer gone beyond science and reason

We discuss in this commentary a recent Cochrane review of 10 randomised trials aimed at testing the religious belief that praying to a god can help those who are prayed for. The review concluded that the available studies merit additional research. However, the review presented a scientifically unsound mixture of theological and scientific arguments, and two of the included trials that had a large impact on the findings had problems that were not described in the review. The review fails to live up to the high standards required for Cochrane reviews

Efficacy and Safety of Baclofen for Alcohol Dependence: A Randomized, Double-Blind, Placebo-Controlled Trial

Recent clinical trials and case-reports indicate that baclofen, a GABAB agonist, may have efficacy for alcohol dependence. Baclofen has been shown to enhance abstinence, to reduce drinking quantity, to reduce craving, and to reduce anxiety in alcohol dependent individuals in two placebo-controlled trials in Italy. However, the clinical trial data with baclofen is limited. The purpose of the present study was to test the efficacy and tolerability of baclofen in alcohol dependence in the United States

Earthworm activity and availability for meadow birds is restricted in intensively managed grasslands

Earthworms are an important prey for the endangered meadow birds of northwest Europe. Although intensive grassland management with high manure inputs generally promotes earthworm abundance, it may reduce the effective food availability for meadow birds through desiccation of the topsoil, which causes earthworms to remain deeper in the soil. We studied the response of Red Worm Lumbricus rubellus, a detritivore, and Grey Worm Aporrectodea caliginosa, a geophage, to soil moisture profiles in the field and under experimental conditions. Surfacing earthworms were counted weekly in eight intensively managed grasslands (treated with high inputs of slurry by slit injection) with variable groundwater tables in the Netherlands. At each count, soil penetration resistance, soil moisture tension and groundwater level were measured, while air temperature and humidity were obtained from a nearby weather station. The response to variation in the vertical distribution of soil moisture was also experimentally studied in the two earthworm species. In the field, earthworms’ surfacing activity at night was negatively associated with soil moisture tension and positively by relative air humidity. Surprisingly, there was no effect of groundwater level; an important management variable in meadow bird conservation. Under experimental conditions, both L. rubellus and A. caliginosa moved to deeper soil layers (&gt;20 cm) in drier soil moisture treatments, avoiding the upper layer when moisture levels dropped below 30%. Synthesis and applications. We propose that in intensively managed grasslands with slurry application, topsoil desiccation reduces earthworm availability for meadow birds. This can be counteracted by keeping soil moisture tensions of the top soil above −15 kPa. We suggest that the late raising of groundwater tables in spring and the disturbance of the soil by slit injection of slurry increase topsoil desiccation. This decreases earthworm availability when it matters most for breeding meadow birds. Meadow bird conservation will benefit from revised manure application strategies that promote earthworm activity near or at the soil surface.</p

A Prologue to Nostalgia: Savoring Creates Nostalgic Memories that Foster Optimism

How are nostalgic memories created? We considered savoring as one process involved in the genesis of nostalgia. Whereas nostalgia refers to an emotional reflection upon past experiences, savoring is a process in which individuals deeply attend to and consciously capture a present experience for subsequent reflection. Thus, having savored an experience may increase the likelihood that it will later be reflected upon nostalgically. Additionally, to examine how cognitive and emotional processes are linked across time, we tested whether nostalgia for a previously savored experience predicts optimism for the future. Retrospective reports of having savored a positive event were associated with greater nostalgia for the event (Study 1). Retrospective reports of savoring a time period (college) were associated with greater nostalgia for that time period when participants were in a setting (alumni reunion event) that prompted thoughts of the time period (Study 2). Savoring an experience predicted nostalgia for the experience 4-9 months later (Study 3). Additionally, nostalgia was associated with greater optimism (Studies 2-3). Thus, savoring provides a foundation for nostalgic memories and an ensuing optimism

Comparison of treatment with insulin degludec and glargine U100 in patients with type 1 diabetes prone to nocturnal severe hypoglycaemia:The HypoDeg randomized, controlled, open-label, crossover trial

AIM: To investigate whether the long‐acting insulin analogue insulin degludec compared with insulin glargine U100 reduces the risk of nocturnal symptomatic hypoglycaemia in patients with type 1 diabetes (T1D). METHODS: Adults with T1D and at least one episode of nocturnal severe hypoglycaemia during the last 2 years were included in a 2‐year prospective, randomized, open, multicentre, crossover trial. A total of 149 patients were randomized 1:1 to basal‐bolus therapy with insulin degludec and insulin aspart or insulin glargine U100 and insulin aspart. Each treatment period lasted 1 year and consisted of 3 months of run‐in or crossover followed by 9 months of maintenance. The primary endpoint was the number of blindly adjudicated nocturnal symptomatic hypoglycaemic episodes. Secondary endpoints included the occurrence of severe hypoglycaemia. We analysed all endpoints by intention‐to‐treat. RESULTS: Treatment with insulin degludec resulted in a 28% (95% CI: 9%‐43%; P = .02) relative rate reduction (RRR) of nocturnal symptomatic hypoglycaemia at level 1 (≤3.9 mmol/L), a 37% (95% CI: 16%‐53%; P = .002) RRR at level 2 (≤3.0 mmol/L), and a 35% (95% CI: 1%‐58%; P = .04) RRR in all‐day severe hypoglycaemia compared with insulin glargine U100. CONCLUSIONS: Patients with T1D prone to nocturnal severe hypoglycaemia have lower rates of nocturnal symptomatic hypoglycaemia and all‐day severe hypoglycaemia with insulin degludec compared with insulin glargine U100