Medical students' attitudes towards and views of general practice careers in Singapore: a cross-sectional survey and qualitative analysis.

BACKGROUND: Like many other countries, Singapore needs to support its ageing population by attracting more doctors into general practice (GP) and family medicine (FM). To achieve this requires a better understanding of what attracts or deters medical students. We conducted a cross-sectional survey among medical students in Singapore. METHODS: An online survey was distributed to students from all three medical schools to understand their likelihood of choosing primary care careers, what they valued in their careers, their attitude towards different aspects of general practice and family medicine relative to other medical fields, and the positive and negative perceptions of primary care held by themselves, their lecturers, and clinical mentors. They were able to elaborate the negativity encountered in the open-ended questions. Quantitative data was analyzed with descriptive statistics, principal component analysis, and linear regression; qualitative data was analyzed thematically. RESULTS: The survey was completed by 391 students. Slightly over half indicated a likelihood of choosing a career in primary care. For their own careers, the students valued job satisfaction and career development opportunities the most. They perceived careers in primary care as being most likely to offer reasonable hours and close patient relationships, but least likely to offer career advancement potential relative to other medical fields. Their likelihood of choosing primary care careers was significantly predicted by what they value in their own career and their attitudes toward GP/FM relative to other medical fields, but not by the perceptions of GP/FM by others. Free-text responses illustrated how students encounter derogatory comments about GP/FM: the work being "mundane and repetitive", the careers non-competitive, and the doctors poor in clinical competence. CONCLUSION: While the shortage of primary care doctors is a global issue, our findings highlight the value of situating inquiries in localized contexts. Medical curriculum should emphasize the critical role of primary care in the healthcare system and primary care doctors should be given due recognition to build a strong and motivated primary care workforce to serve the future healthcare needs of the population.

Teledermatology in Primary Care in Singapore: Experiences of Family Doctors and Specialists.

Most teledermatology studies focus on patients' satisfaction; fewer focus on the experiences of healthcare professionals. This qualitative study explored healthcare professionals' perceptions of teledermatology used for linking public primary care clinics with the specialist dermatology centre in Singapore. Semi-structured in-depth interviews were conducted with 25 family physicians and dermatologists. Six themes were identified: satisfaction with the service; perceived patient benefits; rationale for introducing teledermatology; educational impact; challenges of virtual consultations; and desirable service refinements for the future. Family physicians and dermatologists were positive about the service, but highlighted a need to streamline referral processes and improve the quality of transmitted images. Reduced need for referral to the specialist centre could be achieved by expanding the polyclinic's pharmacopoeia and treatment modalities. This study highlights the benefits of telemedicine for patient, professionals, and healthcare organizations, and these are reassuring given the widespread and rapid introduction of telemedicine through necessity during the COVID-19 pandemic.

A mobile swabbing booth to address Singapore GPs' concerns about swabber protection: human-centred design during the COVID-19 pandemic.

BACKGROUND: During the COVID-19 pandemic, the Ministry of Health asked Singapore's private general practitioners (GPs) to perform swab testing in their clinics, but some GPs had concerns about swabber protection. Our aim was to develop a swabbing booth to address these concerns. METHODS: We developed a prototype with potential GP users using a human-centred design approach and piloted it with 10 GP clinics. The pilot was then extended to 170 GP clinics around Singapore. These GPs were then surveyed on user satisfaction. RESULTS: Ninety-three GPs (54%) responded. The majority (75%) practiced in public residential estates in small practices (mean 1.95 doctors). 86% requested the booth to enhance swabber protection. 74% "would recommend" or "would strongly recommend" the booth to colleagues. 79% continue to use the booth to conduct swab tests. 92% liked that it offered swabber protection. 71% liked that the booth created a separate space for swabbing and 64% liked its ease of disinfection. 47% started swabbing only after receiving the booth and 58% said the booth was "important" or "very important" to their decision to participate in swab testing. However, 34% disliked that it took up too much space and the most frequently critiqued area was the gloves. CONCLUSION: The human-centred design approach generated a product that had high user satisfaction, addressed GPs' concerns of swabber protection and increased GPs' participation in swab testing. The booth may be useful where GPs are concerned about swabber protection and space is limited.

Examining the Trends in Online Health Information-Seeking Behavior About Chronic Obstructive Pulmonary Disease in Singapore: Analysis of Data From Google Trends and the Global Burden of Disease Study.

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally, and timely health care seeking is imperative for its prevention, early detection, and management. While online health information-seeking behavior (OHISB) is increasingly popular due to widespread internet connectivity, little is known about how OHISB for COPD has changed in comparison with the COPD disease burden, particularly at a country-specific level. OBJECTIVE: This study aimed to examine the trends in OHISB for COPD and how that compared with the estimates of COPD disease burden in Singapore, a highly wired country with a steadily increasing COPD disease burden. METHODS: To examine the trends in OHISB for COPD, we performed Prais-Winsten regression analyses on monthly search volume data for COPD from January 2004 to June 2020 downloaded from Google Trends. We then conducted cross-correlational analyses to examine the relationship between annualized search volume on COPD topics and estimates of COPD morbidity and mortality reported in the Global Burden of Disease study from 2004 to 2017. RESULTS: From 2004 to 2020, the trend in COPD search volume was curvilinear (ß=1.69, t194=6.64, P<.001), with a slope change around the end of 2006. There was a negative linear trend (ß=-0.53, t33=-3.57, P=.001) from 2004 to 2006 and a positive linear trend (ß=0.51, t159=7.43, P<.001) from 2007 to 2020. Cross-correlation analyses revealed positive associations between COPD search volume and COPD disease burden indicators: positive correlations between search volume and prevalence, incidence, years living with disability (YLD) at lag 0, and positive correlations between search volume and prevalence, YLD at lag 1. CONCLUSIONS: Google search volume on COPD increased from 2007 to 2020; this trend correlated with the upward trajectory of several COPD morbidity estimates, suggesting increasing engagement in OHISB for COPD in Singapore. These findings underscore the importance of making high-quality, web-based information accessible to the public, particularly COPD patients and their carers.

Improving access to care for people who inject drugs: Qualitative evaluation of project ITTREAT-An integrated community hepatitis C service.

Achieving hepatitis C virus (HCV) elimination by 2030 requires an increased linkage to care for people who inject drugs (PWID). Project ITTREAT was established to mitigate barriers to HCV care by providing an integrated service within a local drug and alcohol treatment centre. This study aimed to explore the experiences of clients and staff involved in Project ITTREAT and assess the facilitators and barriers to a community-based HCV service. Between October 2014 and April 2016, drug and alcohol treatment attendees were interviewed using one-to-one semi-structured interviews. Drug and alcohol treatment staff took part in focus groups. All data were recorded, transcribed verbatim and analysed using thematic content analysis. Fifteen drug and alcohol treatment attendees with current/previous HCV infection were interviewed, and 15 staff members contributed across two focus groups. Drug and alcohol treatment staff and attendees reported that Project ITTREAT facilitated access to HCV care by mitigating previous negative hospital-based experiences. Other key facilitators were positive narratives around HCV care, and drug and alcohol treatment attendees being well engaged in their drug/alcohol recovery. Barriers included a lack of stability in drug and alcohol treatment attendees, negative discourse around testing/treatment and stigma associated with attending the drug and alcohol treatment to access HCV treatment in some who had successfully achieved drug rehabilitation. Our findings indicate the positive impact of an integrated and personalized community-based service delivered by a dedicated hepatitis nurse. This played a crucial role in reducing barriers to HCV care for PWID. Our work also highlights areas for future investment including non-DAT-based community services and increasing awareness of new treatments amongst this cohort.

"At a loss of what to do": a qualitative analysis of parents' online discussion forums about their administration of asthma inhalers to their young children.

Objective: The difficulties adults have using inhaler devices is well documented but much less is known about how parents administer inhaler devices to young children and the difficulties experienced. The purpose of this article is to explore the underlying concepts and practical issues that parents encounter in administering inhaled asthma medications to their young children.Methods: This is a qualitative study using applied thematic analysis on parental written discourses from asynchronous online discussion forums on the topic of administration and use of asthma inhaler devices to young children.Results: "At a loss of what to do" summarizes the experiences parents described when administering inhaler devices to their young children. Parents describe the problems, the situations, the emotions, the decisions, and the confusion they face. They struggle with their child's resistance and the associated conflict, describing their own and their child's distress. Results highlight the coping strategies used in administration, how parents decide whether to use coercive measures or not, their help-seeking endeavors, together with the assurance they give to themselves and others after administration.Conclusion: The online discussions highlight parents' distress, lack of preparedness, and understanding of administering inhaler devices to young children. While the prevalence of the problem cannot be estimated from our data, it illustrates a need for some healthcare professionals to review their own knowledge and skills in administration of inhaled medication to younger patients, and their provision of patient and family centered care.

Demographic predictors of wellbeing in Carers of people with psychosis: secondary analysis of trial data.

BACKGROUND: Carers of people with psychosis are at a greater risk of physical and mental health problems compared to the general population. Yet, not all carers will experience a decline in health. This predicament has provided the rationale for research studies exploring what factors predict poor wellbeing in carers of people with psychosis. Our study builds on previous research by testing the predictive value of demographic variables on carer wellbeing within a single regression model. METHODS: To achieve this aim, we conducted secondary analysis on two trial data sets that were merged and recoded for the purposes of this study. RESULTS: Contrary to our hypotheses, only carer gender and age predicted carer wellbeing; with lower levels of carer wellbeing being associated with being female or younger (aged under 50). However, the final regression model explained only 11% of the total variance. CONCLUSIONS: Suggestions for future research are discussed in light of the limitations inherent in secondary analysis studies. Further research is needed where sample sizes are sufficient to explore the interactive and additive impact of other predictor variables.

Perspectives on public involvement in health research from Singapore: The potential of a supported group model of involvement.

BACKGROUND: Singapore is an international research hub, with an emphasis on translational clinical research. Despite growing evidence of the positive impact of public involvement (PPI) in research, it remains rare in Singapore. AIMS: To investigate Singaporean public perspectives around the rationale, role and scope for being involved in health research To identify the potential, challenges, facilitators and strategies for implementing PPI in Singapore. DESIGN: Semi-structured qualitative interviews with members of the public, analysed using thematic framework analysis. RESULTS: Twenty people participated. Four main themes emerged: potential benefits; challenges; facilitators; and strategies for implementation. Whilst initially unfamiliar with the concept, all interviewees recognized potential benefits for the research itself and those involved, including researchers. PPI was seen to offer opportunities for public empowerment and strengthening of relationships and understanding between the public, academics and health professionals, resulting in more impactful research. Challenges included a Singaporean culture of passive citizenship and an education system that inculcates deferential attitudes. Facilitators comprised demographic and cultural changes, including trends towards greater individual openness and community engagement. Implementation strategies included formal government policies promoting involvement and informal community-based collaborative approaches. CONCLUSION: Given the socio-political framework in Singapore, a community-based approach has potential to address challenges to PPI and maximize impact. Careful consideration needs to be given to issues of resource and support to enable members of the public to engage in culturally sensitive and meaningful ways that will deliver research best placed to effectively address patient needs.

Search strategies to identify observational studies in MEDLINE and Embase.

BACKGROUND: Systematic reviews are essential for decision-making. Systematic reviews on observational studies help answer research questions on aetiology, risk, prognosis, and frequency of rare outcomes or complications. However, identifying observational studies as part of systematic reviews efficiently is challenging due to poor and inconsistent indexing in literature databases. Search strategies that include a methodological filter focusing on study design of observational studies might be useful for improving the precision of the search performance. OBJECTIVES: To assess the sensitivity and precision of a search strategy with a methodological filter to identify observational studies in MEDLINE and Embase. SEARCH METHODS: We searched MEDLINE (1946 to April 2018), Embase (1974 to April 2018), CINAHL (1937 to April 2018), the Cochrane Library (1992 to April 2018), Google Scholar and Open Grey in April 2018, and scanned reference lists of articles. SELECTION CRITERIA: Studies using a relative recall approach, i.e. comparing sensitivity or precision of a search strategy containing a methodological filter to identify observational studies in MEDLINE and Embase against a reference standard, or studies that compared two or more methodological filters. DATA COLLECTION AND ANALYSIS: Two review authors independently screened articles, extracted relevant information and assessed the quality of the search strategies using the InterTASC Information Specialists' Sub-Group (ISSG) Search Filter Appraisal Checklist. MAIN RESULTS: We identified two eligible studies reporting 18 methodological filters. All methodological filters in these two studies were developed using terms from the reference standard records.The first study evaluated six filters for retrieving observational studies of surgical interventions. The study reported on six filters: one Precision Terms Filter (comprising terms with higher precision while maximum sensitivity was maintained) and one Specificity Terms Filter (comprising terms with higher specificity while maximum sensitivity was maintained), both of which were adapted for MEDLINE, for Embase, and for combined MEDLINE/Embase searches. The study reported one reference standard consisting of 217 articles from one systematic review of which 83.9% of the included studies were case seriesThe second study reported on 12 filters for retrieving comparative non-randomised studies (cNRSs) including cohort, case-control, and cross-sectional studies. This study reported on 12 filters using four different approaches: Fixed method A (comprising of a fixed set of controlled vocabulary (CV) words), Fixed method B (comprising a fixed set of CV words and text words (TW)), Progressive method (CV) (a random choice of study design-related CV terms), and Progressive method (CV or TW) (a random choice of study design-related CV terms, and title and abstracts-based TWs). The study reported four reference standards consisting of 89 cNRSs from four systematic reviews.The six methodological filters developed from the first study reported sensitivity of 99.5% to 100% and precision of 16.7% to 21.1%. The Specificity Terms Filter for combined MEDLINE/Embase was preferred because it had higher precision and equal sensitivity to the Precision Terms Filter. The 12 filters from the second study reported lower sensitivity (48% to 100%) and much lower precision (0.09% to 4.47%). The Progressive method (CV or TW) had the highest sensitivity.There were methodological limitations in both included studies. The first study used one surgical intervention-focused systematic review thus limiting the generalizability of findings. The second study used four systematic reviews but with less than 100 studies. The external validation was performed only on Specificity Terms Filter from the first study Both studies were published 10 years ago and labelling and indexing of observational studies has changed since then. AUTHORS' CONCLUSIONS: We found 18 methodological filters across two eligible studies. Search strategies from the first study had higher sensitivity and precision, underwent external validation and targeted observational studies. Search strategies from the second study had lower sensitivity and precision, focused on cNRSs, and were not validated externally. Given this limited and heterogeneous evidence, and its methodological limitations, further research and better indexation are needed.

Researchers' perspectives on public involvement in health research in Singapore: The argument for a community-based approach.

BACKGROUND: Singapore is becoming a world-class research hub, promoting the advancement of patient care through translational clinical research. Despite growing evidence internationally of the positive impact of public involvement (PPI), in Singapore PPI remains unusual beyond patient participation as subjects in studies. OBJECTIVE: To explore health researchers' understandings of the principles, role and scope of PPI, and to identify barriers and opportunities for implementation in Singapore. DESIGN: Semi-structured qualitative interviews between April and July 2018. Data were analysed using thematic framework analysis. RESULTS: Whilst most participants (n = 20) expressed a lack of experience of PPI, the interview process provided an opportunity for reflection through which it emerged as a beneficial strategy. Interviewees highlighted both utilitarian and ethical reasons for implementing PPI, particularly around increasing the relevance and efficiency of research. In addition to those challenges to PPI documented in the existing literature, participants highlighted others specific to the Singaporean context that make PPI at an individual level unlikely to be successful, including the socio-political environment and prevailing social and professional hierarchies. They also identified asset-based strategies to overcome these, in particular, a more community-oriented approach. CONCLUSION: The cultural reluctance of individuals to question perceived authority figures such as researchers may be overcome by adopting an approach to PPI that is closer to family and local community values, and which facilitates patients and the public collectively engaging in research. Further work is needed to explore the views of patients and the public in Singapore, and the implications for other Asian communities.

AcrB drug-binding pocket substitution confers clinically relevant resistance and altered substrate specificity.

The incidence of multidrug-resistant bacterial infections is increasing globally and the need to understand the underlying mechanisms is paramount to discover new therapeutics. The efflux pumps of Gram-negative bacteria have a broad substrate range and transport antibiotics out of the bacterium, conferring intrinsic multidrug resistance (MDR). The genomes of pre- and posttherapy MDR clinical isolates of Salmonella Typhimurium from a patient that failed antibacterial therapy and died were sequenced. In the posttherapy isolate we identified a novel G288D substitution in AcrB, the resistance-nodulation division transporter in the AcrAB-TolC tripartite MDR efflux pump system. Computational structural analysis suggested that G288D in AcrB heavily affects the structure, dynamics, and hydration properties of the distal binding pocket altering specificity for antibacterial drugs. Consistent with this hypothesis, recreation of the mutation in standard Escherichia coli and Salmonella strains showed that G288D AcrB altered substrate specificity, conferring decreased susceptibility to the fluoroquinolone antibiotic ciprofloxacin by increased efflux. At the same time, the substitution increased susceptibility to other drugs by decreased efflux. Information about drug transport is vital for the discovery of new antibacterials; the finding that one amino acid change can cause resistance to some drugs, while conferring increased susceptibility to others, could provide a basis for new drug development and treatment strategies.

Barriers to Antenatal Care in an Urban Community in the Gambia: An In-depth Qualitative Interview Study.

This qualitative study investigated the barriers to obtaining access to antenatal care in a small, urban government-supported health centre in the Gambia. It thus addresses an important issue related to maternal health and the prevention of maternal deaths. In-depth interviews were conducted with 25 pregnant women, 13 healthcare workers and 9 male partners. Three areas were identified for study: recognition and acknowledgment of pregnancy, recognition of the need for care and practical barriers to attendance. Intentional concealment of early pregnancy was common to avoid adverse social consequences or for fear that malign interventions would cause a miscarriage. In the absence of symptoms many women considered it unnecessary to attend the antenatal clinic until well into the second trimester. Practical barriers to attendance included conflicting domestic demands and the attitude of some healthcare workers. Access to antenatal care in the Gambia throughout pregnancy should be considered in a stepwise fashion and barriers to care were identified at each stage. Interviews with male partners and health workers highlighted their key role.

Sexual healthcare professionals' views on HPV vaccination for men in the UK.

BACKGROUND: Human Papillomavirus (HPV) vaccination for men could prevent anal cancers amongst men who have sex with men (MSM). METHODS: An e-survey of attitudes towards vaccination for men in the UK was conducted in July-August 2014. RESULTS: Among 325 sexual health professionals, 14% were already vaccinating men against HPV, 83% recommended gender-neutral HPV vaccination and 65% recommended targeting MSM. Over 50% reported having poor knowledge about the use of HPV vaccine for MSM and the skills to identify MSM likely to benefit from HPV vaccination. CONCLUSIONS: Clear advice and guidelines on HPV vaccine use for men at sexual health clinics are required to ensure equitable opportunities for vaccination.

Expression of homologous RND efflux pump genes is dependent upon AcrB expression: implications for efflux and virulence inhibitor design.

OBJECTIVES: Enterobacteriaceae have multiple efflux pumps that confer intrinsic resistance to antibiotics. AcrB mediates clinically relevant multidrug resistance and is required for virulence and biofilm formation, making it an attractive target for the design of inhibitors. The aim of this study was to assess the viability of single transporters as a target for efflux inhibition using Salmonella Typhimurium as the model pathogen. METHODS: The expression of resistance-nodulation-division (RND) efflux pump genes in response to the inactivation of single or multiple homologues was measured using real-time RT-PCR. Phenotypes of mutants were characterized by measuring antimicrobial susceptibility, dye accumulation and the ability to cause infection in vitro. RESULTS: The expression of all RND efflux pump genes was increased when single or multiple acr genes were inactivated, suggesting a feedback mechanism that activates the transcription of homologous efflux pump genes. When two or three acr genes were inactivated, the mutants had further reduced efflux, altered susceptibility to antimicrobials (including increased susceptibility to some, but conversely and counterintuitively, decreased susceptibility to some others) and were more attenuated in the tissue culture model than mutants lacking single pumps were. CONCLUSIONS: These data indicate that it is critical to understand which pumps an inhibitor is active against and the effect of this on the expression of homologous systems. For some antimicrobials, an inhibitor with activity against multiple pumps will have a greater impact on susceptibility, but an unintended consequence of this may be decreased susceptibility to other drugs, such as aminoglycosides.

The effects of expressive writing on lung function, quality of life, medication use, and symptoms in adults with asthma: a randomized controlled trial.

OBJECTIVES: Asthma is a chronic condition affecting 300 million people worldwide. Management involves adherence to pharmacological treatments such as corticosteroids and ß-agonists, but residual symptoms persist. As asthma symptoms are exacerbated by stress, one possible adjunct to pharmacological treatment is expressive writing (EW). EW involves the disclosure of traumatic experiences which is thought to facilitate cognitive and emotional processing, helping to reduce physiological stress associated with inhibiting emotions. A previous trial reported short-term improvements in lung function. This study aimed to assess whether EW can improve lung function, quality of life, symptoms, and medication use in patients with asthma. METHODS: Adults (18-45 years) diagnosed as having asthma requiring regular inhaled corticosteroids were recruited from 28 general practices in South East England (n = 146). In this double-blind randomized controlled trial, participants were allocated either EW or nonemotional writing instructions and asked to write for 20 minutes for 3 consecutive days. Lung function (forced expired volume in 1 second [FEV1]% predicted), quality of life (Mark's Asthma Quality of Life Questionnaire), asthma symptoms (Wasserfallen Symptom Score Questionnaire), and medication use (inhaled corticosteroids and ß-agonist) were recorded at baseline, 1, 3, 6, and 12 months. RESULTS: Hierarchical linear modeling indicated no significant main effects between time and condition on any outcomes. Post hoc analyses revealed that EW improved lung function by 14% for 12 months for participants with less than 80% FEV1% predicted at baseline (ß = 0.93, p = .002) whereas no improvement was observed in the control condition (ß = 0.10, p = .667). CONCLUSIONS: EW seems to be beneficial for patients with moderate asthma (<80% FEV1% predicted). Future studies of EW require stratification of patients by asthma severity. TRIAL REGISTRATION: ISRCTN82986307.

Mind and body therapy for fibromyalgia.

BACKGROUND: Mind-body interventions are based on the holistic principle that mind, body and behaviour are all interconnected. Mind-body interventions incorporate strategies that are thought to improve psychological and physical well-being, aim to allow patients to take an active role in their treatment, and promote people's ability to cope. Mind-body interventions are widely used by people with fibromyalgia to help manage their symptoms and improve well-being. Examples of mind-body therapies include psychological therapies, biofeedback, mindfulness, movement therapies and relaxation strategies. OBJECTIVES: To review the benefits and harms of mind-body therapies in comparison to standard care and attention placebo control groups for adults with fibromyalgia, post-intervention and at three and six month follow-up. SEARCH METHODS: Electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE (Ovid), EMBASE (Ovid), PsycINFO (Ovid), AMED (EBSCO) and CINAHL (Ovid) were conducted up to 30 October 2013. Searches of reference lists were conducted and authors in the field were contacted to identify additional relevant articles. SELECTION CRITERIA: All relevant randomised controlled trials (RCTs) of mind-body interventions for adults with fibromyalgia were included. DATA COLLECTION AND ANALYSIS: Two authors independently selected studies, extracted the data and assessed trials for low, unclear or high risk of bias. Any discrepancy was resolved through discussion and consensus. Continuous outcomes were analysed using mean difference (MD) where the same outcome measure and scoring method was used and standardised mean difference (SMD) where different outcome measures were used. For binary data standard estimation of the risk ratio (RR) and its 95% confidence interval (CI) was used. MAIN RESULTS: Seventy-four papers describing 61 trials were identified, with 4234 predominantly female participants. The nature of fibromyalgia varied from mild to severe across the study populations. Twenty-six studies were classified as having a low risk of bias for all domains assessed. The findings of mind-body therapies compared with usual care were prioritised.There is low quality evidence that in comparison to usual care controls psychological therapies have favourable effects on physical functioning (SMD -0.4, 95% CI -0.6 to -0.3, -7.5% absolute change, 2 point shift on a 0 to 100 scale), pain (SMD -0.3, 95% CI -0.5 to -0.2, -3.5% absolute change, 2 point shift on a 0 to 100 scale) and mood (SMD -0.5, 95% CI -0.6 to -0.3, -4.8% absolute change, 3 point shift on a 20 to 80 scale). There is very low quality evidence of more withdrawals in the psychological therapy group in comparison to usual care controls (RR 1.38, 95% CI 1.12 to 1.69, 6% absolute risk difference). There is lack of evidence of a difference between the number of adverse events in the psychological therapy and control groups (RR 0.38, 95% CI 0.06 to 2.50, 4% absolute risk difference).There was very low quality evidence that biofeedback in comparison to usual care controls had an effect on physical functioning (SMD -0.1, 95% CI -0.4 to 0.3, -1.2% absolute change, 1 point shift on a 0 to 100 scale), pain (SMD -2.6, 95% CI -91.3 to 86.1, -2.6% absolute change) and mood (SMD 0.1, 95% CI -0.3 to 0.5, 1.9% absolute change, less than 1 point shift on a 0 to 90 scale) post-intervention. In view of the quality of evidence we cannot be certain that biofeedback has a little or no effect on these outcomes. There was very low quality evidence that biofeedback led to more withdrawals from the study (RR 4.08, 95% CI 1.43 to 11.62, 20% absolute risk difference). No adverse events were reported.There was no advantage observed for mindfulness in comparison to usual care for physical functioning (SMD -0.3, 95% CI -0.6 to 0.1, -4.8% absolute change, 4 point shift on a scale 0 to 100), pain (SMD -0.1, CI -0.4 to 0.3, -1.3% absolute change, less than 1 point shift on a 0 to 10 scale), mood (SMD -0.2, 95% CI -0.5 to 0.0, -3.7% absolute change, 2 point shift on a 20 to 80 scale) or withdrawals (RR 1.07, 95% CI 0.67 to 1.72, 2% absolute risk difference) between the two groups post-intervention. However, the quality of the evidence was very low for pain and moderate for mood and number of withdrawals. No studies reported any adverse events.Very low quality evidence revealed that movement therapies in comparison to usual care controls improved pain (MD -2.3, CI -4.2 to -0.4, -23% absolute change) and mood (MD -9.8, 95% CI -18.5 to -1.2, -16.4% absolute change) post-intervention. There was no advantage for physical functioning (SMD -0.2, 95% CI -0.5 to 0.2, -3.4% absolute change, 2 point shift on a 0 to 100 scale), participant withdrawals (RR 1.95, 95% CI 1.13 to 3.38, 11% absolute difference) or adverse events (RR 4.62, 95% CI 0.23 to 93.92, 4% absolute risk difference) between the two groups, however rare adverse events may include worsening of pain.Low quality evidence revealed that relaxation based therapies in comparison to usual care controls showed an advantage for physical functioning (MD -8.3, 95% CI -10.1 to -6.5, -10.4% absolute change) and pain (SMD -1.0, 95% CI -1.6 to -0.5, -3.5% absolute change, 2 point shift on a 0 to 78 scale) but not for mood (SMD -4.4, CI -14.5 to 5.6, -7.4% absolute change) post-intervention. There was no difference between the groups for number of withdrawals (RR 4.40, 95% CI 0.59 to 33.07, 31% absolute risk difference) and no adverse events were reported. AUTHORS' CONCLUSIONS: Psychological interventions therapies may be effective in improving physical functioning, pain and low mood for adults with fibromyalgia in comparison to usual care controls but the quality of the evidence is low. Further research on the outcomes of therapies is needed to determine if positive effects identified post-intervention are sustained. The effectiveness of biofeedback, mindfulness, movement therapies and relaxation based therapies remains unclear as the quality of the evidence was very low or low. The small number of trials and inconsistency in the use of outcome measures across the trials restricted the analysis.

Predominance of heavily calcified coccolithophores at low CaCO3 saturation during winter in the Bay of Biscay.

Coccolithophores are an important component of the Earth system, and, as calcifiers, their possible susceptibility to ocean acidification is of major concern. Laboratory studies at enhanced pCO(2) levels have produced divergent results without overall consensus. However, it has been predicted from these studies that, although calcification may not be depressed in all species, acidification will produce "a transition in dominance from more to less heavily calcified coccolithophores" [Ridgwell A, et al., (2009) Biogeosciences 6:2611-2623]. A recent observational study [Beaufort L, et al., (2011) Nature 476:80-83] also suggested that coccolithophores are less calcified in more acidic conditions. We present the results of a large observational study of coccolithophore morphology in the Bay of Biscay. Samples were collected once a month for over a year, along a 1,000-km-long transect. Our data clearly show that there is a pronounced seasonality in the morphotypes of Emiliania huxleyi, the most abundant coccolithophore species. Whereas pH and CaCO(3) saturation are lowest in winter, the E. huxleyi population shifts from <10% (summer) to >90% (winter) of the heavily calcified form. However, it is unlikely that the shifts in carbonate chemistry alone caused the morphotype shift. Our finding that the most heavily calcified morphotype dominates when conditions are most acidic is contrary to the earlier predictions and raises further questions about the fate of coccolithophores in a high-CO(2) world.

Redundancy in the periplasmic adaptor proteins AcrA and AcrE provides resilience and an ability to export substrates of multidrug efflux.

OBJECTIVES: The components of the AcrAB-TolC efflux pump function as a tripartite efflux system conferring resistance to multiple antibiotics and the individual components can also function in conjunction with other efflux pumps. This study aimed to establish whether redundancy exists between the homologous periplasmic adaptor proteins (PAPs) AcrA and AcrE and to measure the impact of this redundancy on antimicrobial resistance and the potential efficacy of inhibitor molecules. METHODS: The acrE gene was inactivated in Salmonella enterica serovar Typhimurium SL1344 and a ΔacrA mutant by insertion of the aph gene. The mutants were complemented with plasmids carrying acrA or acrE. The antimicrobial susceptibility of the mutants to various antimicrobials was determined and the accumulation or efflux of various substrates was measured. RESULTS: Inactivation of acrE alone had no phenotypic effect. However, the effect of inactivation of PAPs was additive; the acrA acrE mutant was more susceptible to certain antimicrobials and accumulated more Hoechst dye than single acrA, acrE or acrB mutants. In addition, the double mutant invaded human intestinal epithelial cells poorly. The phenotypic defects of the acrA acrE mutant were ameliorated by expression of either acrA or acrE, but the proteins exhibited some substrate specificity. CONCLUSIONS: These data show for the first time the level of redundancy between the PAPs AcrA and AcrE, and highlight the PAPs as excellent targets for inhibitor molecules that could be used to potentiate the action of clinical antimicrobials. However, the redundancy that exists between AcrA and AcrE means potential inhibitors must act on both targets to be effective.