Concise gene signature for point‐of‐care classification of tuberculosis

There is an urgent need for new tools to combat the ongoing tuberculosis (TB) pandemic. Gene expression profiles based on blood signatures have proved useful in identifying genes that enable classification of TB patients, but have thus far been complex. Using real‐time PCR analysis, we evaluated the expression profiles from a large panel of genes in TB patients and healthy individuals in an Indian cohort. Classification models were built and validated for their capacity to discriminate samples from TB patients and controls within this cohort and on external independent gene expression datasets. A combination of only four genes distinguished TB patients from healthy individuals in both cross‐validations and on separate validation datasets with very high accuracy. An external validation on two distinct cohorts using a real‐time PCR setting confirmed the predictive power of this 4‐gene tool reaching sensitivity scores of 88% with a specificity of around 75%. Moreover, this gene signature demonstrated good classification power in HIV (+) populations and also between TB and several other pulmonary diseases. Here we present proof of concept that our 4‐gene signature and the top classifier genes from our models provide excellent candidates for the development of molecular point‐of‐care TB diagnosis in endemic areas

Young women and limits to the normalisation of condom use: a qualitative study

Encouraging condom use among young women is a major focus of HIV/STI prevention efforts but the degree to which they see themselves as being at risk limits their use of the method. In this paper, we examine the extent to which condom use has become normalised among young women. In-depth interviews were conducted with 20 year old women from eastern Scotland (N = 20). Purposive sampling was used to select a heterogeneous group with different levels of sexual experience and from different social backgrounds. All of the interviewees had used (male) condoms but only three reported consistent use. The rest had changed to other methods, most often the pill, though they typically went back to using condoms occasionally. Condoms were talked about as the most readily available contraceptive method, and were most often the first contraceptive method used. The young women had ingrained expectations of use, but for most, these norms centred only on their new or casual partners, with whom not using condoms was thought to be irresponsible. Many reported negative experiences with condoms, and condom dislike and failure were common, lessening trust in the method. Although the sexually transmitted infection (STI) prevention provided by condoms was important, this was seen as additional, and secondary, to pregnancy prevention. As the perceived risks of STIs lessened in relationships with boyfriends, so did condom use. The promotion of condoms for STI prevention alone fails to consider the wider influences of partners and young women's negative experiences of the method. Focusing on the development of condom negotiation skills alone will not address these issues. Interventions to counter dislike, method failure, and the limits of the normalisation of condom use should be included in STI prevention efforts

Stories of Hell and Healing: Internet Users’ Construction of Benzodiazepine Distress and Withdrawal

Abstract Benzodiazepines are a group of drugs used mainly as sedatives, hypnotics, antiepileptics, and muscle relaxants. Consumption is recommended for 2 to 4 weeks only, due to fast onset of dependency and potentially distressing withdrawal symptoms. Few peer-review studies have drawn on the user experiences and language to appreciate firsthand experiences of benzodiazepine withdrawal or discontinuation syndrome. We looked extensively at patient stories of benzodiazepine withdrawal and recovery on Internet support sites and YouTube. Our analysis indicated that users employ rich metaphors to portray the psychologically disturbing and protracted nature of their suffering. We identified seven major themes: hell and isolation, anxiety and depression, alienation, physical distress, anger and remorse, waves and windows, and healing and renewal. By posting success stories, ex-users make known that “healing” can be a long, unpredictable process, but distress does lessen, and recovery can happen

Which antidepressants have demonstrated superior efficacy? A review of the evidence

A review of published evidence of superior efficacy of a particular antidepressant in major depressive disorder may assist clinicians in making considered treatment choices. To identify such candidates, an international group of experts met to assess published evidence (identified through searches in Medline and Embase databases and discussions with experts in the field) from randomized, controlled trials and meta-analyses comparing two antidepressants under conditions of fair comparison. Criteria were defined to judge the strength of evidence. Two pivotal studies in moderate-to-severe major depressive disorder that demonstrate superiority on the primary efficacy measure, or alternatively one pivotal study supported by consistent results from meta-analyses, was considered to constitute evidence for definite superiority. Three antidepressants met these criteria: clomipramine, venlafaxine, and escitalopram. Three antidepressants were found to have probable superiority: milnacipran, duloxetine, and mirtazapine. Only escitalopram was found to have definite superiority in the treatment of severe depression; probable superiority was identified for venlafaxine and possible superiority for milnacipran and clomipramine. This review of published data found evidence that only a very few antidepressants are shown to be more effective than other

Določanje benzodiazepinov v urinu preko benzofenonskih derivatov z uporabo tekočinske kromatografije sklopljene s tandemsko masno spektrometrijo

The aim of this study was to validate a new method for determining benzodiazepines in urine via their benzophenone derivatives, based on liquid chromatography-tandem mass spectrometry (LC-MS/MS). Selected benzodiazepines were analysed after acid hydrolysis of urine and extraction by ethyl acetate in the presence of an internal standard. Samples were analysed using electrospray ionization LC-MS/MS in a multiple reaction monitoring mode. The chromatographic run time on a reversed phase C18 analytical column was set for 9 min. This method was validated in 21 patients receiving methadone. Benzodiazepines intake was established in two out of three patients. LC-MS/MS results were also compared with the rapid immunoassay and the methods showed good agreement. However, in three cases benzodiazepines were detected by LC-MS/MS, but not by the immunoassay. The sensitivity of the developed LC-MS/MS method is comparable to or even higher than of previously reported methods, which makes it suitable as a confi rmatory method.Razvili smo selektivno in občutljivo metodo za določanje nekaterih benzodiazepinov v urinu preko določanja njihovih benzofenonov. Metoda temelji na tekočinski kromatografi ji, sklopljeni s tandemsko masno spektrometrijo (LC-MS/MS). Izbrane benzodiazepine smo analizirali po kisli hidrolizi urinskih vzorcev in ekstrakciji z etilacetatom v prisotnosti internega standarda. Vzorce smo analizirali z elektrorazprševalno ionizacijo z MRM načinom detekcije. Čas kromatografske ločbe na reverznofazni (C18) analitski koloni je bil 9 min. Metoda je bila validirana in preizkušena na 21 pacientih, ki so prejemali metadonsko terapijo. Pri dveh tretjinah primerov je bil vnos benzodiazepinov tudi potrjen. Vzorce smo testirali tudi s hitro imunokemijsko metodo in rezultate primerjali z rezultati pridobljenimi z LC-MS/MS metodo. Ugotovili smo dobro ujemanje med rezultati pridobljenimi z obe a metodama. Kljub temu smo v treh primerih določili prisotnost benzodiazepinov z LC-MS/MS metodo, ki je z imunokemijsko metodo nismo. Občutljivost razvite metode je primerljiva ali celo boljša od predhodno opisanih metod, zato jo lahko uporabimo kot potrditveno metodo

“I’m Not Waving, I’m Drowning”: An Autoethnographical Exploration of Biographical Disruption and Reconstruction During Recovery From Prescribed Benzodiazepine Use

Benzodiazepines are group of drugs used mainly as sedatives, hypnotics, muscle relaxants, and anti-epileptics. Tapering off benzodiazepines is, for some users, a painful, traumatic, and protracted process. In this article, I use an autoethnographic approach, adopting the metaphor of water, to examine heuristically my experience of iatrogenic illness and recovery. I draw on personal journals and blog entries and former users’ narratives to consider the particular form of biographical disruption associated with benzodiazepines and the processes involved in identity reconstruction. I emphasize the role of the online community in providing benzodiazepine users such as myself with a co-cultural community through which to share a voice and make sense of our experiences. I explain how the success stories of former users provided me with the hope that I, the “medical victim,” could become the “victor” and in the process construct a new life and fresh identity

Adding 5-hydroxytryptamine receptor type 3 antagonists may reduce drug-induced nausea in poor insight obsessive-compulsive patients taking off-label doses of selective serotonin reuptake inhibitors: a 52-week follow-up case report

Poor-insight obsessive-compulsive disorder (PI-OCD) is a severe form of OCD where the 'typically obsessive' features of intrusive, 'egodystonic' feelings and thoughts are absent. PI-OCD is difficult to treat, often requiring very high doses of serotonergic drugs as well as antipsychotic augmentation. When this occurs, unpleasant side effects as nausea are common, eventually further reducing compliance to medication and increasing the need for pharmacological alternatives. We present the case of a PI-OCD patient who developed severe nausea after response to off-label doses of the selective serotonin reuptake inhibitor (SSRI), fluoxetine. Drug choices are discussed, providing pharmacodynamic rationales and hypotheses along with reports of rating scale scores, administered within a follow-up period of 52 weeks. A slight reduction of fluoxetine dose, augmentation with mirtazapine and a switch from amisulpride to olanzapine led to resolution of nausea while preserving the anti-OCD therapeutic effect. Mirtazapine and olanzapine have already been suggested for OCD treatment, although a lack of evidence exists about their role in the course of PI-OCD. Both mirtazapine and olanzapine also act as 5-hydroxytryptamine receptor type 3 (5-HT3) blockers, making them preferred choices especially in cases of drug-induced nausea

Mechanistic and "natural" body metaphors and their effects on attitudes to hormonal contraception

A small, self-selected convenience sample of male and female contraceptive users in the United Kingdom (n = 34) were interviewed between 2006 and 2008 concerning their feelings about the body and their contraceptive attitudes and experiences. The interviewees were a sub-sample of respondents (n = 188) who completed a paper-based questionnaire on similar topics, who were recruited through a poster placed in a family planning clinic, web-based advertisements on workplace and university websites, and through direct approaches to social groups. The bodily metaphors used when discussing contraception were analyzed using an interpretative phenomenological analytical approach facilitated by Atlas.ti software. The dominant bodily metaphor was mechanistic (i.e.,"body as machine"). A subordinate but influential bodily metaphor was the "natural" body, which had connotations of connection to nature and a quasi-sacred bodily order. Interviewees drew upon this "natural" metaphorical image in the context of discussing their anxieties about hormonal contraception. Drawing upon a "natural," non-mechanistic body image in the context of contraceptive decision-making contributed to reluctance to use a hormonal form of contraception. This research suggests that clinicians could improve communication and advice about contraception by recognizing that some users may draw upon non-mechanistic body imagery

A Q-methodological study of 'smoking identities'

publication-status: Publishedtypes: ArticleIn contrast to the psychological literature on adolescent smoking, little research has investigated the social identities of adult smokers. This study aimed to identify shared ‘smoking identities’ amongst a sample of 64 British smokers from different socio-economic groups using Q-methodology. Participants were asked to sort 70 items concerning smoking and smokers according to their agreement/disagreement with them. The 64 Q-sorts were then subjected to a by-person factor analysis yielding six factors, with the first four interpretable factors being presented here. Each factor is understood to represent a distinct ‘identity position’. The first two, the ‘addicted’ smoker, and the ‘in control’ smoker, oriented around a biomedical model of smoking as an addictive health risk. The final two, the ‘no big deal’ smoker and the ‘proud’ smoker reflected alternative understandings and values. The identity positions also differed in the extent to which smoking was considered a core part of self-identity. Unpacking the ‘smoking identities’ of current smokers offers the opportunity to devise targeted health promotion.Economic and Social Research Counci

Environmental Factors in the Relapse and Recurrence of Inflammatory Bowel Disease:A Review of the Literature

The causes of relapse in patients with Crohn's disease (CD) and ulcerative colitis (UC) are largely unknown. This paper reviews the epidemiological and clinical data on how medications (non-steroidal anti-inflammatory drugs, estrogens and antibiotics), lifestyle factors (smoking, psychological stress, diet and air pollution) may precipitate clinical relapses and recurrence. Potential biological mechanisms include: increasing thrombotic tendency, imbalances in prostaglandin synthesis, alterations in the composition of gut microbiota, and mucosal damage causing increased permeability