Adherence with NICE guidance on lifestyle advice for people with schizophrenia: a survey

Background Substantial weight gain is common in people taking antipsychotics. NICE recommends these patients are offered physical health screening and intervention. The STEPWISE trial is currently evaluating a lifestyle education programme in addition to usual care. However, it is difficult to define what constitutes “usual care”. Aims To define “usual care” for lifestyle management in people with schizophrenia, schizoaffective disorder and first episode psychosis in STEPWISE study sites. Method Ten NHS Mental Health Trusts participated in a bespoke survey based on NICE guidance. Results Eight trusts reported offering lifestyle education programmes. Nine Trusts reported offering smoking cessation support. Reported recording of biomedical measures varied. Conclusions No consistent lifestyle education programme is currently offered across UK NHS Mental Health Trusts. The survey benchmarks ‘usual care’ for the STEPWISE study on which changes can be measured

Psychological distress among Plains Indian mothers with children referred to screening for Fetal Alcohol Spectrum Disorders

<p>Abstract</p> <p>Background</p> <p>Psychological distress (PD) includes symptoms of depression and anxiety and is associated with considerable emotional suffering, social dysfunction and, often, with problematic alcohol use. The rate of current PD among American Indian women is approximately 2.5 times higher than that of U.S. women in general. Our study aims to fill the current knowledge gap about the prevalence and characteristics of PD and its association with self-reported current drinking problems among American Indian mothers whose children were referred to screening for fetal alcohol spectrum disorders (FASD).</p> <p>Methods</p> <p>Secondary analysis of cross-sectional data was conducted from maternal interviews of referred American Indian mothers (n = 152) and a comparison group of mothers (n = 33) from the same Plains culture tribes who participated in an NIAAA-funded epidemiology study of FASD. Referred women were from one of six Plains Indian reservation communities and one urban area who bore children suspected of having an FASD. A 6-item PD scale (PD-6, Cronbach's alpha = .86) was constructed with a summed score range of 0-12 and a cut-point of 7 indicating serious PD. Multiple statistical tests were used to examine the characteristics of PD and its association with self-reported current drinking problems.</p> <p>Results</p> <p>Referred and comparison mothers had an average age of 31.3 years but differed (respectively) on: education (<high school: 47.4%, 9.1%), PD-6 mean scores (3.57, 1.48), current prevalence of serious PD (19.1%, 0.0%), and a current drinking problem (31.6%, 12.1%). Among referred mothers, those with a current drinking problem had a significantly higher mean PD-6 score. Having PD, serious PD, and 2 specific scale items significantly increased the odds that a referred mother would have a current drinking problem.</p> <p>Conclusions</p> <p>Psychological distress among referred mothers is significantly associated with having a self-reported drinking problem. FASD prevention requires multi-level prevention efforts that provide real opportunities for educational attainment and screening and monitoring of PD and alcohol use during the childbearing years. Mixed methods studies are needed to illuminate the social and cultural determinants at the base of the experience of PD and to identify the strengths and protective factors of unaffected peers who reside within the same communities.</p

Chemogenetic silencing of NaV1.8 positive sensory neurons reverses chronic neuropathic and bone cancer pain in FLEx PSAM4-GlyR mice

Drive from peripheral neurons is essential in almost all pain states, but pharmacological silencing of these neurons to effect analgesia has proved problematic. Reversible gene therapy using long-lived chemogenetic approaches is an appealing option. We used the genetically-activated chloride channel PSAM4-GlyR to examine pain pathways in mice. Using recombinant AAV9-based delivery to sensory neurons, we found a reversal of acute pain behavior and diminished neuronal activity using in vitro and in vivo GCaMP imaging upon activation of PSAM4-GlyR with varenicline. A significant reduction in inflammatory heat hyperalgesia and oxaliplatin-induced cold allodynia was also observed. Importantly, there was no impairment of motor coordination, but innocuous von Frey sensation was inhibited. We generated a transgenic mouse that expresses a CAG-driven FLExed PSAM4-GlyR downstream of the Rosa26 locus that requires Cre recombinase to enable the expression of PSAM4-GlyR and tdTomato. We used NaV1.8 Cre to examine the role of predominantly nociceptive NaV1.8+ neurons in cancer-induced bone pain (CIBP) and neuropathic pain caused by chronic constriction injury (CCI). Varenicline activation of PSAM4-GlyR in NaV1.8-positive neurons reversed CCI-driven mechanical, thermal, and cold sensitivity. Additionally, varenicline treatment of mice with CIBP expressing PSAM4-GlyR in NaV1.8+ sensory neurons reversed cancer pain as assessed by weight-bearing. Moreover, when these mice were subjected to acute pain assays, an elevation in withdrawal thresholds to noxious mechanical and thermal stimuli was detected, but innocuous mechanical sensations remained unaffected. These studies confirm the utility of PSAM4-GlyR chemogenetic silencing in chronic pain states for mechanistic analysis and potential future therapeutic use.Significance StatementChronic pain is a massive problem. Peripheral nerve block is effective in many chronic pain conditions, demonstrating the importance of peripheral drive in chronic pain. We used chemogenetic tools based on the modified ligand-gated chloride channel PSAM4-GlyR to silence dorsal root ganglion neurons in vitro and in vivo This approach reduces pain-like behavior in acute and chronic pain models, including resistant pain conditions like neuropathic pain or cancer-induced bone pain. We generated a mouse line that expresses PSAM4-GlyR in a Cre-dependent manner, providing a useful research tool to address not only the role of nociceptive sensory neurons in pain states but also the function of genetically defined sets of neurons throughout the nervous system in normal and pathological conditions

Comparison of baseline drinking practices, knowledge, and attitudes of adult s residing in communities taking part in the FAS prevention study in South Africa

Foetal Alcohol Syndrome (FAS) has been identified as among the most serious consequences associated with hazardous and harmful drinking in the Western Cape province, South Africa. Community surveys were conducted in two wine growing regions in this province to assess drinking behaviour, guide interventions and serve as a baseline for assessing the impact of population-level interventions. As part of a cross-sectional comparative study interviews were conducted with 384 and 209 randomly selected adults in the prevention (PC) and comparison communities (CC) respectively. Over 80% of respondents resided in urban areas, except inthe CC, where 61% of males resided on farms. Symptoms of hazardous or harmful drinking were reported by 16.0% of females and 32.5% of males in the PC, while 19.3% of females and 56.2% of males in the CC reported such drinking. Over two-thirds of respondents indicated that it was equally harmful for a woman to drink during any of the trimesters of pregnancy, but more than 30% of the women interviewed had never had a health worker speak to them about the effects of drinking during pregnancy. Over 10% had never heard of fetal alcohol syndrome. The findings reinforce the need for interventions to address hazardous/harmful use of alcohol inboth communities and also to address gaps in knowledge regarding the effects of drinking during pregnancy.Key Words: Alcohol, epidemiology, pregnancy, South Afric

A comprehensive mental health care system for Native Americans in New Mexico. A report of the Native American Mental Health Planning Project.

This is a comprehensive report of a seven-month study contracted through the State Division of Mental Health to the University of New Mexico, Department of Psychiatry/Center on Alcoholism, Substance Abuse and Addictions (CASAA). A select committee of representatives from New Mexico tribes, appropriate state and federal agencies, private entities, and consumers provided input for the project. The final plan is based on the collection and triangulation of a variety of sources. The primary sources utilized in this document included: 1) literature review; 2) indirect measure of the magnitude of alcohol, drug abuse, and mental health needs using selected measures from current census data; 3) extensive survey of current agencies providing services; 4) clinical programming survey to select from optional mental health care delivery system models and a prioritization of services needed; 5) ideas, visions, suggestions and recommendations of selected committees; and 6) private interviews and focus group discussions with tribal members, service workers, and tribal leaders. The plan provides information on: 1) epidemiology of mental health problems; 2) programmatic issues for mental health services; 3) needs assessment studies and findings; 4) system and program design; 5) program development and management; 6) physical plant requirements; 7) management information system; and 8) ten-year implementation process. Based on the findings of this planning effort, a system of comprehensive mental health care for American Indians was proposed. This continuum of care extends from the tribal communities, to regional centers of care, and to a centralized facility

Maternal nutritional status as a contributing factor for the risk of fetal alcohol spectrum disorders

Compare nutritional status of 57 South African mothers of children with fetal alcohol spectrum disorders (FASD) with 148 mothers of controls

Replacing the Z-phenyl Ring in Tamoxifen® with a para-Connected NCN Pincer-Pt-Cl Grouping by Post-Modification

Post-modification of a series of NCN-pincer platinum(II) complexes [PtX(NCN-R-4)] (NCN = [C6H2(CH2NMe2)2-2,6]–, R = C(O)H, C(O)Me and C(O)Et), X = Cl– or Br–) at the para-position using the McMurry reaction was studied. The synthetic route towards two new [PtCl(NCN-R-4)] (R = C(O)Me and C(O)Et) complexes used above is likewise described. The utility and limitations of the McMurry reaction involving these pincer complexes was systematically evaluated. The predicted “homo-coupling” reaction of [PtBr(NCN-C(O)H-4)] led to the unexpected formation of 3,3′,5,5′-tetra[(dimethylamino)methyl]-4,4′-bis(platinum halide)-benzophenone (halide = Br or Cl), referred to hereafter as the bispincer-benzophenone complex 13. This material was further characterized using X-ray crystal structure determination. The applicability of the pincer complexes in the McMurry reaction is shown to open a route towards the synthesis of tamoxifen-type derivatives of which one phenyl ring of Tamoxifen® itself is replaced by an NCN arylplatinum pincer fragment. The newly synthesized derivatives can be used as potential candidates in anti-cancer drug screening protocols. Two NCN-arylpincer platinum tamoxifen type derivatives, 5 and 6, were successfully synthesized and of 5 the separation of the diastereomeric E-/Z-forms was achieved. Compound 6, which is the pivaloyl protected NCN pincer platinum hydroxy-Tamoxifen® derivative, was obtained as a mixture of E-/Z-isomers. The new derivatives were further analyzed and characterized with 1H-, 13C{1H}- and 195Pt{1H}-NMR, IR, exact mass MS and elemental analysis.This research was partly funded by the Council for Chemical Sciences of the Netherlands Organization for Scientific Research (NWO/CW) G.D.B., M.L

Tools for analysis and conditional deletion of subsets of sensory neurons [version 1; peer review: 4 approved]

Background: Somatosensation depends on primary sensory neurons of the trigeminal and dorsal root ganglia (DRG). Transcriptional profiling of mouse DRG sensory neurons has defined at least 18 distinct neuronal cell types. Using an advillin promoter, we have generated a transgenic mouse line that only expresses diphtheria toxin A (DTA) in sensory neurons in the presence of Cre recombinase. This has allowed us to ablate specific neuronal subsets within the DRG using a range of established and novel Cre lines that encompass all sets of sensory neurons. // Methods: A floxed-tdTomato-stop-DTA bacterial artificial chromosome (BAC) transgenic reporter line (AdvDTA) under the control of the mouse advillin DRG promoter was generated. The line was first validated using a Nav1.8Cre and then crossed to CGRPCreER (Calca), ThCreERT2, Tmem45bCre, Tmem233Cre, Ntng1Cre and TrkBCreER (Ntrk2) lines. Pain behavioural assays included Hargreaves’, hot plate, Randall-Selitto, cold plantar, partial sciatic nerve ligation and formalin tests. // Results: Motor activity, as assessed by the rotarod test, was normal for all lines tested. Noxious mechanosensation was significantly reduced when either Nav1.8 positive neurons or Tmem45b positive neurons were ablated whilst acute heat pain was unaffected. In contrast, noxious mechanosensation was normal following ablation of CGRP-positive neurons but acute heat pain thresholds were significantly elevated and a reduction in nocifensive responses was observed in the second phase of the formalin test. Ablation of TrkB-positive neurons led to significant deficits in mechanical hypersensitivity in the partial sciatic nerve ligation neuropathic pain model. // Conclusions: Ablation of specific DRG neuronal subsets using the AdvDTA line will be a useful resource for further functional characterization of somatosensory processing, neuro-immune interactions and chronic pain disorders

Combined adenocarcinoid and mucinous cystadenoma of the appendix: a case report

<p>Abstract</p> <p>Introduction</p> <p>Adenocarcinoid of the appendix is a rare malignant tumour with features of both adenocarcinoma and carcinoid, showing both epithelial and endocrine differentiation. Mucinous cystadenoma is the commonest of the benign neoplasms of the appendix, with an incidence of 0.6% in appendicectomy specimens. We report a rare combination of these tumours and discuss the latest treatment options. To the best of our knowledge, only six cases have been reported in the literature to date.</p> <p>Case presentation</p> <p>A 71-year-old Caucasian man presented to our department with a right iliac fossa mass associated with pain. Laparoscopy revealed an adenocarcinoid of the appendix in combination with mucinous cystadenoma. He underwent a radical right hemicolectomy with clear margins and lymph nodes.</p> <p>Conclusion</p> <p>Adenocarcinoids account for 2% of primary appendiceal malignancies. Most tumours are less than 2 cm in diameter and 20% of them metastasize to the ovaries. The mean age for presentation is 59 years and the 5-year survival rate ranges from 60% to 84%. Right hemicolectomy is generally advised if any of the following features are present: tumours greater than 2 cm, involvement of resection margins, greater than 2 mitoses/10 high-power fields on histology, extension of tumour beyond serosa. Chemotherapy mostly with 5-Fluorouracil and Leucovorin is advised for remnant disease after surgery. Cytoreductive surgery with intraperitoneal chemotherapy can offer improved survival for advanced peritoneal dissemination.</p