Varenicline decreases alcohol consumption in heavy-drinking smokers

Rationale

Emerging evidence suggests that the ??4??2 form of the nicotinic acetylcholine receptor (nAChR) modulates the rewarding effects of alcohol. The nAChR ??4??2 subunit partial agonist varenicline (Chantix?), which is approved by the Food and Drug Administration for smoking cessation, also decreases ethanol consumption in rodents (Steensland et al., Proc Natl Acad Sci U S A 104:12518?C12523, 2007) and in human laboratory and open-label studies (Fucito et al., Psychopharmacology (Berl) 215:655?C663, 2011; McKee et al., Biol Psychiatry 66:185?C190 2009).

Objectives

We present a randomized, double-blind, 16-week study in heavy-drinking smokers (n?=?64 randomized to treatment) who were seeking treatment for their smoking. The study was designed to determine the effects of varenicline on alcohol craving and consumption. Outcome measures included number of alcoholic drinks per week, cigarettes per week, amount of alcohol craving per week, cumulative cigarettes and alcoholic drinks consumed during the treatment period, number of abstinent days, and weekly percentage of positive ethyl glucuronide and cotinine screens.

Results

Varenicline significantly decreases alcohol consumption (?? ²?=?35.32, p?Conclusions Varenicline can produce a sustained decrease in alcohol consumption in individuals who also smoke. Further studies are warranted to assess varenicline efficacy in treatment-seeking alcohol abusers who do not smoke and to ascertain the relationship between varenicline effects on smoking and drinking.     

Locomotor activation by theacrine, a purine alkaloid structurally similar to caffeine: involvement of adenosine and dopamine receptors

Purine compounds, such as caffeine, have many health-promoting properties and have proven to be beneficial in treating a number of different conditions. Theacrine, a purine alkaloid structurally similar to caffeine and abundantly present in Camellia kucha, has recently become of interest as a potential therapeutic compound. In the present study, theacrine was tested using a rodent behavioral model to investigate the effects of the drug on locomotor activity. Long Evans rats were injected with theacrine (24 or 48 mg/kg, i.p.) and activity levels were measured. Results showed that the highest dose of theacrine (48 mg/kg, i.p.) significantly increased locomotor activity compared to control animals and activity remained elevated throughout the duration of the session. To test for the involvement of adenosine receptors underlying theacrine's motor-activating properties, rats were administered a cocktail of the adenosine A₁ agonist, N⁶-cyclopentyladenosine (CPA; 0.1 mg/kg, i.p.) and A_2A receptor agonist 2-p-(2-carboxyethyl)phenethylamino-5′-N-ethylcarboxamidoadenosine (CGS-21680; 0.2 mg/kg, i.p.). Pre-treatment with theacrine significantly attenuated the motor depression induced by the adenosine receptor agonists, indicating that theacrine is likely acting as an adenosine receptor antagonist. Next, we examined the role of DA D₁ and D₂ receptor antagonism on theacrine-induced hyperlocomotion. Both antagonists, D₁R SCH23390 (0.1 or 0.05 mg/kg, i.p.) and D₂R eticlopride (0.1 mg/kg, i.p.), significantly reduced theacrine-stimulated activity indicating that this behavioral response, at least in part, is mediated by DA receptors. In order to investigate the brain region where theacrine may be acting, the drug (10 or 20 μg) was infused bilaterally into nucleus accumbens (NAc). Theacrine enhanced activity levels in a dose-dependent manner, implicating a role of the NAc in modulating theacrine's effects on locomotion. In addition, theacrine did not induce locomotor sensitization or tolerance after chronic exposure. Taken together, these findings demonstrate that theacrine significantly enhances activity; an effect which is mediated by both the adenosinergic and dopaminergic systems.     

Ablepharon-Macrostomia syndrome--extension of the phenotype

Ablepharon-Macrostomia syndrome (AMS) is a rare collection of findings characterized by absent or hypoplastic eyelids, fusion defects of the mouth with unfused lateral commissures, abnormal ears, ambiguous genitalia, skin differences including dry and coarse skin or redundant folds of skin, and developmental delay. Fewer than 20 patients have been reported to date. These include a parent and two children and a recent report of a father and daughter, therefore suggesting autosomal dominant inheritance. Here we present one additional sporadic case with an expanded phenotype. This patient has more significant hand and foot anomalies than previously reported.     

Invasive bacterial and fungal infections among hospitalized HIV-infected and HIV-uninfected children and infants in northern Tanzania

Objective To describe the contribution of paediatric HIV and of HIV co‐infections to admissions to a hospital in Moshi, Tanzania, using contemporary laboratory methods. Methods During 1 year, we enrolled consecutively admitted patients aged ≥2 months and <13 years with current or recent fever. All patients underwent standardized clinical history taking, a physical examination and HIV antibody testing; standard aerobic blood cultures and malaria film were also done, and hospital outcome was recorded. Early infant HIV diagnosis by HIV‐1 RNA PCR was performed on those aged <18 months. HIV‐infected patients also received serum cryptococcal antigen testing and had their CD4‐positive T‐lymphocyte count and percent determined. Results A total of 467 patients were enrolled whose median age was 2 years (range 2 months–13 years); Of those patients, 57.2% were female and 12.2% were HIV‐infected. Admission clinical diagnosis of HIV disease was made in 10.7% and of malaria in 60.4%. Of blood cultures, 5.8% grew pathogens; of these 25.9% were Salmonella enterica (including 6 Salmonella Typhi) and 22.2%Streptococcus pneumoniae. Plasmodium falciparum was identified on blood film of 1.3%. HIV infection was associated with S. pneumoniae (odds ratio 25.7, 95% CI 2.8, 234.0) bloodstream infection (BSI), but there was no evidence of an association with Escherichia coli or P. falciparum; Salmonella Typhi BSI occurred only among HIV‐uninfected participants. The sensitivity and specificity of an admission clinical diagnosis of malaria were 100% and 40.3%; and for an admission diagnosis of bloodstream infection, they were 9.1% and 86.4%, respectively. Conclusion Streptococcus pneumoniae is a leading cause of bloodstream infection among paediatric admissions in Tanzania and is closely associated with HIV infection. Malaria was over‐diagnosed clinically, whereas invasive bacterial disease was underestimated. HIV and HIV co‐infections contribute to a substantial proportion of paediatric febrile admissions, underscoring the value of routine HIV testing.     

Development of a multi-layered psychosocial care system for children in areas of political violence

Few psychosocial and mental health care systems have been reported for children affected by political violence in low- and middle income settings and there is a paucity of research-supported recommendations. This paper describes a field tested multi-layered psychosocial care system for children (focus age between 8-14 years), aiming to translate common principles and guidelines into a comprehensive support package. This community-based approach includes different overlapping levels of interventions to address varying needs for support. These levels provide assessment and management of problems that range from the social-pedagogic domain to the psychosocial, the psychological and the psychiatric domains. Specific intervention methodologies and their rationale are described within the context of a four-country program (Burundi, Sri Lanka, Indonesia and Sudan). The paper aims to contribute to bridge the divide in the literature between guidelines, consensus & research and clinical practice in the field of psychosocial and mental health care in low- and middle-income countries.     

Construction of titanium cranioplasty plate using craniectomy bone flap as template

In recent times a steady rise in cranioplasty operations has been noted because of increasing utilisation of decompressive craniectomy for trauma as well as stroke patients. A variety of techniques have been utilised for cranioplasty, with their own benefits and limitations. Titanium cranioplasty is one of the well-established and widely used techniques, with most centres utilising computer-assisted reconstruction for manufacture of titanium plates. In this paper we present a novel method for making titanium cranioplasty plates using the craniectomy bone flap as a template and the results of our experience. To date we have performed 51 cranioplasties using this method. The surgical results have been comparable to those obtained using the computer-assisted model technique. The construction cost for titanium cranioplasty plates using this method has been ￡360 cheaper per plate compared with the computer-assisted method. In addition, the CT workload and radiation exposure have been reduced.     

Marital Status Predicts Change in Distress and Well‐being in Women Newly Diagnosed With Breast Cancer and Their Peer Counselors

Abstract: We conducted a nonrandomized study matching 42 women newly diagnosed with breast cancer (sojourners) with 39 trained breast cancer survivors (navigators) who provided one‐on‐one peer counseling for 3–6 months. Because little is known about how marital status might impact participants in such an intervention, we tested whether being married/partnered buffered navigators and sojourners from distress at baseline and over time. We examined baseline and slopes over time for change in depression and trauma symptoms, and emotional well‐being. We were particularly concerned that being matched with a newly diagnosed breast cancer patient might trigger a re‐experiencing of trauma symptoms for the navigator, so we examined a re‐experiencing subscale. All participants completed baseline, 3‐, 6‐, and 12‐month assessments. Our hypotheses were tested in separate Analyses of Variance (married versus not) for the 39 sojourners and 34 navigators who provided baseline assessments, and the 29 sojourners and 24 navigators who were matched and provided at least one follow‐up. We found no significant baseline associations for navigators or sojourners. Being single/not married was associated with increasing depression symptoms over time in both navigators and sojourners compared with being married/partnered. By 12 months, these increases crossed above the clinical cut‐off for significant depression symptoms. Single status did not predict increasing trauma symptoms over time. However, being single/not married predicted a significant increase in navigators’ re‐experiencing of trauma symptoms. Over time, married sojourners increased significantly in emotional well‐being, whereas single/not married navigators did not differ from married navigators. In addition to providing ongoing training and emotional support to navigators, our findings indicate the importance of providing additional support for women who are not married or partnered.