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Rationale Preclinical and clinical data suggest that pregnenolone may be a promising therapeutic in schizophrenia. Pregnenolone is neuroprotective and enhances learning and memory, myelination, and microtubule polymerization. Treatment with pregnenolone elevates allopregnanolone (a neurosteroid that enhances GABA A receptor responses) and pregnenolone sulfate (a positive NMDA receptor modulator). Pregnenolone could thus potentially mitigate GABA dysregulation and/or NMDA receptor hypofunction in schizophrenia via metabolism to other neurosteroids. Objective The objective of this study is to conduct a randomized controlled trial of adjunctive pregnenolone in schizophrenia. Methods Following a placebo lead-in, 120 participants were randomized to pregnenolone or placebo for 8 weeks (Institute for Mental Health, Singapore). Primary endpoints were changes in MATRICS Consensus Cognitive Battery (MCCB) composite scores (cognitive symptoms), UCSD Performance-based Skills Assessment—Brief (UPSA-B) composite scores (functional capacity), and Scale for Assessment of Negative Symptoms (SANS) total scores (negative symptoms). A modified intent-to-treat analysis approach was utilized. Results No significant changes compared to placebo were demonstrated in composite MCCB scores. In contrast, participants randomized to pregnenolone ( n  = 56) demonstrated greater improvements in functional capacity (UPSA-B composite changes) compared to placebo ( n  = 55), p  = 0.03. Pregnenolone was also superior to placebo in the communication subscale of the UPSA-B ( p  < 0.001). Serum pregnenolone changes post-treatment were correlated with UPSA-B composite score changes in females ( r s  = 0.497, p  < 0.042, n  = 17) but not in males. Mean total SANS scores were very low at baseline and did not improve further post-treatment. Pregnenolone was well-tolerated. Conclusions Pregnenolone improved functional capacity in participants with schizophrenia, but did not improve cognitive symptoms over an 8-week treatment period. Neurosteroid changes correlated with functional improvements in female participants. Neurosteroid interventions may exhibit promise as new therapeutic leads for schizophrenia.

The use of brain-computer interface in neurofeedback therapy for attention deficit hyperactivity disorder (ADHD) is a relatively new approach. We conducted a randomized controlled trial (RCT) to determine whether an 8-week brain computer interface (BCI)-based attention training program improved inattentive symptoms in children with ADHD compared to a waitlist-control group, and the effects of a subsequent 12-week lower-intensity training. We randomized 172 children aged 6-12 attending an outpatient child psychiatry clinic diagnosed with inattentive or combined subtypes of ADHD and not receiving concurrent pharmacotherapy or behavioral intervention to either the intervention or waitlist-control group. Intervention involved 3 sessions of BCI-based training for 8 weeks, followed by 3 training sessions per month over the subsequent 12 weeks. The waitlist-control group received similar 20-week intervention after a wait-time of 8 weeks. The participants' mean age was 8.6 years (SD = 1.51), with 147 males (85.5%) and 25 females (14.5%). Modified intention to treat analyzes conducted on 163 participants with at least one follow-up rating showed that at 8 weeks, clinician-rated inattentive symptoms on the ADHD-Rating Scale (ADHD-RS) was reduced by 3.5 (SD 3.97) in the intervention group compared to 1.9 (SD 4.42) in the waitlist-control group (between-group difference of 1.6; 95% CI 0.3 to 2.9 p = 0.0177). At the end of the full 20-week treatment, the mean reduction (pre-post BCI) of the pooled group was 3.2 (95% CI 2.4 to 4.1). The results suggest that the BCI-based attention training program can improve ADHD symptoms after a minimum of 24 sessions and maintenance training may sustain this improvement. This intervention may be an option for treating milder cases or as an adjunctive treatment.

Background Iron deficiency anaemia is a common disorder affecting up to 30% of pregnant women. Treatment guidelines for iron deficiency anaemia in pregnancy exist, which if adopted, may reduce the associated risks of maternal and fetal morbidity and mortality. However, multiple factors may impair adherence and absorption of oral iron, limiting the success of this first-line treatment. Methods To document the effectiveness of national (British Society of Haematology) guidelines for the treatment of iron deficiency anaemia (IDA) in pregnancy, with a focus on use of oral iron, we carried out a prospective cohort study. Aims were to assess the response, side effect and adherence to treatment and predictability of response using routine clinical and laboratory data. The study population consisted of pregnant women diagnosed with anaemia. Women were offered follow-up through a dedicated anaemia clinic in a secondary care maternity unit serving a multi-ethnic population in the midlands of England. First line treatment was ferrous sulphate 200 mg three time a day as recommended in earlier national guidelines. The response was assessed 2 to 4 weeks later by measuring the haemoglobin (Hb) concentration. A response was defined in 2 ways; (i) a 10 g/L increase in Hb; and (ii) a 10 g/L increase in Hb and/or gestationally adjusted threshold of the Hb. Education and advice were provided to women, with on-going follow-up at clinic appointments including an assessment of side effects. Following a response with oral iron, treatment was continued for a further 3 months when the women were again reviewed. Results The overall rate of haematological response to a first course of oral iron was 36.5% (10 g/L increase in Hb) and 55.2% (incorporating gestational threshold in Hb). The response rates at the completion of follow up, post-delivery, were 70.5% and 88.5% respectively. Responders to oral iron had lower median Hb at diagnosis (95 g/L) compared to non-responders (100 g/L). The responders median Hb was 113 g/l versus 103 g/L for non-responders at first follow-up and was Hb 122 g/L versus 110 g/L, respectively, at the end of the study visit 5. There is a statistically significant difference between responders and non-responders for the change in haemoglobin from baseline to visit 5 ( p  = 0.017). Non-responders reported more side effects than responders (95% versus 85%). Conclusion Oral iron treatment for IDA in pregnancy as advocated in national guidelines is challenging to deliver, even in the setting of a specialist anaemia clinic. The findings have implications for guideline recommendations and implementation, and identify research opportunities for diagnosing IDA in pregnancy, optimising the pathways of iron treatment.

Positive mindset (PM) is an important domain of health-related quality of life in Singapore, a multi-ethnic urban city state in Southeast Asia. We therefore developed and calibrated a novel item bank to measure and improve PM. We developed an initial candidate pool of 48 items from focus groups, in-depth interviews and existing instruments locally developed and validated for use in Singapore. We administered all items in English to a multi-stage sample stratified for age and gender, of subjects with and without medical conditions recruited from the community and a hospital, and calibrated their responses using Samejima's Graded Response Model. We evaluated a final 36-item bank with respect to Item Response Theory (IRT) model assumptions, model fit, differential item functioning (DIF), concurrent and known-groups validity. Among 493 participants (49.3% male, 41.6% above 50 years old, 33% Chinese, Malay and Indian), bifactor model analyses supported unidimensionality: explained common variance of the general factor was 0.86 and omega hierarchical was 0.97. Local independence was deemed acceptable: the average absolute residual correlations were <0.06 and 3.3% of the total item-pair residuals were flagged for local dependence. The overall model fit was adequate and provided good coverage of the PM construct (theta range: -3.6 to +2.4). Five items exhibited DIF with respect to ethnicity and gender, but were retained without modification of scores because they measured important aspects of PM. Scores correlated in the hypothesized direction with a self-reported measure of global health (Spearman's rho = -0.28, p<0.001) and discriminated between groups of participants with and without a self-reported diagnosis of a mood disorder (p = 0.007) adjusting for age, gender, ethnicity, education and marital status. The 36-item PM item bank demonstrated satisfactory psychometric properties for the English-speaking Singaporean population. IRT model assumptions were sufficiently met and scores showed concurrent and known-groups validity. Future studies to evaluate the validity of PM scores when items are administered adaptively are needed.

Background Corticosteroid injections can be performed blind (landmark-guided) or with image guidance, and this may account for variable clinical outcomes. The objective of this study was to assess the effectiveness and safety of image-guided versus blind corticosteroid injections in improving pain and function among adults with shoulder pain. Methods MEDLINE, the Cochrane Controlled Trials Register and EMBASE were searched to May 2010. Additional studies were identified by searching bibliographies of shortlisted articles. Search items included blind, landmark, anatomical, clinical exam, image-guided, ultrasound, fluoroscopy, steroid injection, frozen shoulder, random allocation, randomized controlled trial (RCT) and clinical trial. Randomized controlled studies comparing image-guided versus blind (landmark-guided) corticosteroid shoulder injections that examined pain, function and/or adverse events were included. Independent extraction was done by two authors using a form with pre-specified data fields, including risk of bias appraisal. Conflicts were resolved by discussion. The decision to pool data was based on assessment of clinical design homogeneity. When warranted, studies were pooled under a random-effects model. Results Two RCTs for pain, function and adverse events (n = 101) met eligibility criteria. No serious threats to validity were found. Both trials compared ultrasound-guided versus landmark-guided injections and were judged similar in clinical design. Low to moderate heterogeneity was observed: shoulder pain I 2 = 60%, function I 2 = 22%. A meta-analysis demonstrated greater improvement with ultrasound-guided injections at 6 weeks after injection in both pain (mean difference = 2.23 [95% CI: 1.27, 3.18]), as assessed with a 0 to 10 visual analogue scale, and shoulder function (standardised mean difference = 1.09 [95% CI: 0.61, 1.57]) as assessed with shoulder function scores. Although more adverse events (all mild) were reported with landmark-guided injections, the difference was not statistically significant (risk ratio = 0.20 [95% CI: 0.04, 1.13]). This review was only based on two moderate-sized trials. Blinding of patients was not performed in both trials, causing some risk of bias in outcome assessment since primary endpoints were wholly or partially patient-reported. Conclusion There is a paucity of RCTs on image-guided versus landmark-guided corticosteroid shoulder injections examining pain, function and adverse events. In this review, patients who underwent image-guided (ultrasound) injections had statistically significant greater improvement in shoulder pain and function at 6 weeks after injection. Image-guided (ultrasound) corticosteroid injections potentially offer a significantly greater clinical improvement over blind (landmark-guided) injections in adults with shoulder pain. However, this apparent benefit requires confirmation from further studies (adequately-powered and well-executed RCTs).

The increasing focus of healthcare systems worldwide on long-term care highlights the need for culturally sensitive Health-Related Quality of Life instruments to accurately capture perceived health of various populations. Such instruments require a contextualized conceptual framework of health domains, which is lacking in some socio-cultural contexts. We developed a comprehensive and culturally sensitive conceptual framework of health domains relevant to the Singaporean population. We recruited Singaporeans/ permanent residents, English/ Chinese-speaking, with/ without chronic illnesses to participate in focus group discussions (FGDs) and in-depth interviews (IDIs). We elicited health areas participants perceived to be important for them to be happy and satisfied with life. To encourage spontaneous emergence of themes, we did not specify any aspect beyond the broad domains of Physical, Mental, and Social health so as not to limit the emergence of new themes. Themes from the transcripts were distilled through open coding (two independent coders), then classified into more abstract domains (each transcript coded independently by two coders from a pool of six coders). From October 2013 to August 2014, 121 members of the general public participated in 18 FGDs and 13 IDIs (44.6% males, mean age: 53.3 years 77% Chinese, 9% Malay, 12% Indian, 63% with chronic illness) while 13 healthcare workers participated as patient-proxies in three FGDs. Thematic analysis identified 27 domains. The 15 physical domains included physical appearance, energy, physical fitness, and health and resistance to illness. The nine mental domains included emotions, self-esteem, and personal freedom. The three social domains were social contact, social relationships, and social roles. This conceptual framework reflected physical, mental, and social dimensions of well-being, suggesting that the Singapore population's views on health support the World Health Organization's definition of health as \"a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity\".

Caregivers of technology-dependent children face considerable responsibilities. This study examined the association of 2 child-related stressors—functional status and use of mechanical ventilator—with 2 domains of family caregiver well-being—depressive symptoms (Center for Epidemiologic Studies Depression Scale [CES-D]) and health-related quality of life (HRQOL) and family function (PedsQL Family Impact Module). The secondary objective was to determine whether these associations were moderated by caregiver-perceived social support. Structured interviews were conducted with 88 primary family caregivers of technology-dependent children in Singapore. Hierarchical multiple regression was used to assess the primary and secondary objectives. A total of 44.3% of caregivers were at high risk of clinical depression. Moderately poor child functional status was associated with more caregiver depressive symptoms. Perceived social support moderated this association. Family caregivers of technology-dependent children have high levels of depressive symptoms and relatively poor HRQOL and family functioning. Enhancing caregivers’ social support is important for their well-being.

Nearly 80% of women currently infected with HIV are of childbearing age. As women of childbearing age continue to be at risk of contracting HIV, there will be an increased need for choices about whether or not to have biological children. The purpose of this exploratory study was to investigate the influence of partners, physicians, and family members on pregnancy decisions, as well as the impact of HIV stigma on these decisions. Results indicated that most women chose not to become pregnant since learning their HIV diagnosis and the woman's age at the time of diagnosis is significantly associated with this decision. Additional factors included fear of transmitting HIV to their child, personal health-related concerns, and desire to have children. Women with a procreative inclination were more likely to choose to become pregnant which outweighed social support and personal health concerns. Implications and suggestions for future research are noted.

BackgroundEarly diagnosis of cognitive impairment allows timely intervention with pharmacological and non-pharmacological measures. However, current cognitive evaluation tools do not cater for multilingual populations.ObjectiveTo develop and validate a visual-based cognitive evaluation tool, the Visual Cognitive Assessment Test (VCAT), which can be administered to multilingual populations without the need for translation or adaptation.MethodWe designed a battery of tests to evaluate the domains of memory, executive function, visuospatial function, language and attention. Pilot testing of individual test items, followed by test refinement and development of a field version was performed. We subsequently validated VCAT for the diagnosis of mild cognitive impairment (MCI) and mild Alzheimer's disease (AD). Diagnostic performance was assessed by the area under the curve (AUC), sensitivity (Se) and specificity (Sp).ResultsVCAT was validated in a sample of 206 participants. The sample comprised 53.9% males; mean age (SD) was 67.8 (8.86) years; mean years of education was 10.5(6.0). AUC of VCAT for detection of cognitive impairment was found to be 93.3 (95% CI 90.1 to 96.4). Also, the Se and Sp of VCAT for the diagnosis of cognitive impairment (MCI and mild AD) were 85.6% and 81.1%, respectively. VCAT's diagnostic Se and Sp comparable to those of the Montreal Cognitive Assessment in the same cohort. Mean time-to-complete VCAT was 15.7±7.3 min.ConclusionsThe VCAT has good Se and Sp for the diagnosis of MCI and mild AD. The visual-based test paradigm allows easy application to multilingual populations without the need for translation or adaptation.

Health-related quality of life (HRQOL) instruments are sometimes used without explicit understanding of which HRQOL domains are important to a given population. In this study, we sought to elicit an importance hierarchy among 27 HRQOL domains (derived from the general population) via a best-worst scaling survey of the population in Singapore, and to determine whether these domains were consistently valued across gender, age, ethnicity, and presence of chronic illnesses. We conducted a community-based study that sampled participants with quotas for gender, ethnicity, age, presence of chronic illness, and interview language. For the best-worst scaling exercise, we constructed comparison sets according to a balanced incomplete block design resulting in 13 sets of questions, each with nine choice tasks. Each task involved three HRQOL domains from which participants identified the most and least important domain. We performed a standard analysis of best-worst object scaling design (Case 1) using simple summary statistics; 603 residents participated in the survey. The three most important domains of health were: \"the ability to take care of self without help from others\" (best-worst score (BWS): 636), \"healing and resistance to illness\" (BWS: 461), and \"having good relationships with family, friends, and others\" (BWS: 373). The 10 top-ranked domains included physical, mental, and social health. The three least important domains were: \"having a satisfying sex life\" (BWS: -803), \"having normal physical appearance\" (BWS: -461), and \"interacting with others (talking, shared activities, etc.)\" (BWS: -444). Generally, top-ranked domains were consistently valued across gender, age, ethnicity, and presence of chronic illness. We conclude that the 10 top-ranked domains reflect physical, mental, and social dimensions of well-being suggesting that the sampled population's views on health are consistent with the World Health Organization's definition of health, \"a state of complete physical, mental and social well-being and not merely the absence of disease or infirmity\".