Association of Multimorbidity With Frailty in Older Adults for Elective Non-Cardiac Surgery.

Introduction Frailty is associated with adverse surgical outcomes. While existing studies describe the prevalence of multimorbidity and frailty in the community, the surgical population may have more severe disease and significant surgical stress. This study aims to describe the distribution of frailty and multimorbidity in the older surgical population and examine if specific comorbidities are more strongly associated with frailty. Methods This is a single-centre retrospective cohort study using an electronic database in the preoperative evaluation clinic, conducted in Singapore General Hospital, Singapore. All patients above 70 years old going for elective non-cardiac surgery were included. Demographics and comorbidities were analysed for their association with frailty according to the Edmonton Frail Scale. Results A total of 1396 out of 1398 patients were analyzed. The overall incidence of frailty was 27.8% and multimorbidity was 63.4%. Factors independently associated with frailty were age (adjusted Odds Ratio [aOR] = 1.07), female gender (aOR = 1.67), type 2 diabetes mellitus (aOR = 1.69), chronic kidney disease (aOR = 1.47), end-stage renal failure (aOR = 3.58), history of cerebrovascular accident or transient ischemic attack (aOR = 1.87), moderate anaemia (aOR = 2.11), dementia (aOR = 6.38), depression (aOR = 3.82), and peptic ulcer disease (aOR = 1.98). The presence of multi-morbidity was significantly associated with frailty, with overall increasing strength of association. Conclusion As the number of comorbidities increases, the odds of frailty increase. Only a small proportion of those with multimorbidity accumulate enough biological deficits to develop frailty, putting them at higher risk than with solely multimorbidity or frailty. Dementia and depression are comorbidities with strong associations that have yet to see coordinated interventional efforts in the preoperative setting.

A Systematic Review of the Effect of Probiotic Supplementation on Schizophrenia Symptoms.

BACKGROUND: Derangements of the gut microbiome have been linked to increased systemic inflammation and central nervous system disorders, including schizophrenia. This systematic review thus aimed to investigate the hypothesis that probiotic supplementation improves schizophrenia symptoms. METHODS: By using the keywords (probiotic OR gut OR microbiota OR microbiome OR yogurt OR yoghurt OR lactobacillus OR bifidobacterium) AND (schizophrenia OR psychosis), a preliminary search of the PubMed, Medline, Embase, Google Scholar, ClinicalTrials.gov, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), and Cochrane Field for Complementary Medicine databases yielded 329 papers published in English between January 1, 1960 and May 1, 2018. Attempts were made to search grey literature as well. RESULTS: Three clinical studies were reviewed, comparing the use of probiotics to placebo controls. Applying per-protocol analysis and a fixed-effects model, there was no significant difference in schizophrenia symptoms between the group that received probiotic supplementation and the placebo group post-intervention as the standardized mean difference was -0.0884 (95% CI -0.380 to 0.204, p = 0.551). Separate analyses were performed to investigate the effect of probiotic supplementation on positive or negative symptoms of schizophrenia alone. In both instances, no significant difference was observed as well. CONCLUSION: Based on current evidence, limited inferences can be made regarding the efficacy of probiotics in schizophrenia. Although probiotics may have other benefits, for example to regulate bowel movement and ameliorate the metabolic effects of antipsychotic medications, the clinical utility of probiotics in the treatment of schizophrenia patients remains to be validated by future clinical studies.

Selective Serotonin Reuptake Inhibitors and Persistent Pulmonary Hypertension of the Newborn: An Update Meta-Analysis.

BACKGROUND: Persistent pulmonary hypertension of the newborn (PPHN) is a serious condition associated with substantial mortality and morbidity. Previous studies have suggested a possible link between maternal selective serotonin reuptake inhibitor (SSRI) use and the risk of PPHN. This study aimed to provide an up-to-date review and meta-analysis of the topic. METHODS: Using the search terms [SSRI OR SSRIs OR selective serotonin reuptake inhibitors OR antidepressant OR Prozac OR fluoxetine OR Lexapro OR escitalopram] AND [pregnancy OR maternal OR newborn OR persistent pulmonary hypertension OR PPHN OR neonat* OR fet*], a preliminary search on the PubMed, Medline, EMBASE, Web of Science, and Google Scholar database yielded 7327 articles published in English between January 1, 1960 and October 1, 2017. RESULTS: A total of 9 cohort and case-control studies, with a total of 7,540,265 subjects were systematically reviewed. Random-effects meta-analysis of eight studies revealed a significantly increased risk of PPHN with maternal SSRI use during pregnancy, with a pooled OR of 1.516 (95% confidence interval: 1.035-1.997, p < 0.001). Overall, the absolute increase in risk of PPHN with SSRI use appears small, with an absolute risk difference of 0.619 per 1000 livebirths and a number needed to harm of 1615 women. CONCLUSIONS: Current evidence suggests that there were significantly greater odds of PPHN with SSRI use during pregnancy. However, the clinical significance of this association remains modest and likely outweighed by the potential benefits of treatment of perinatal depression. The risk of PPHN associated with SSRI therapy might not warrant the recommendation to withdraw antidepressant therapy, as evidence from other studies show that untreated perinatal depression presents additional adverse maternal and fetal outcomes. Given the increasing prevalence of maternal depression and consequent use of antidepressant medications, further research with robust longitudinal or randomized, controlled studies and mechanistic investigations are needed.

Enoxaparin: A cause of postoperative fever?

Enoxaparin (clexane) is a low-molecular-weight heparin commonly prescribed for the chemoprophylaxis of venous thromboembolism in postoperative hip or knee replacement or abdominal surgery patients. We herein report a case of persistent postoperative fever in a patient, likely due to enoxaparin use. Prompt resolution of the patient's fever was observed after discontinuation of subcutaneous enoxaparin for chemical thromboprophylaxis. Reliable incidence data are lacking. A comprehensive search of PubMed, MEDLINE and EMBASE databases, as well as grey literature, found only two prior single case reports on enoxaparin-related fever. The mechanism responsible for the febrile reaction is likely an idiosyncratic response. Enoxaparin is typically derived from bovine or porcine intestines and lungs, hence its potential to cause hypersensitivity reactions is perhaps unsurprising. Clinicians should be alert to this possibility.

A meta-analysis of cyclosporine treatment for Stevens-Johnson syndrome/toxic epidermal necrolysis.

BACKGROUND: Stevens-Johnson syndrome (SJS) and toxic epidermal necrolysis (TEN) are dermatologic emergencies with high morbidity and mortality risk. Cyclosporine, an immunomodulatory agent, is sometimes used off-label, and its role continues to be debated. This meta-analysis aimed to provide an update of current evidence and to clarify the role of cyclosporine in SJS/TEN treatment better. METHODS: Using the keywords [cyclosporine OR cyclosporine OR ciclosporin OR CsA] AND [Steven-Johnson OR SJS OR toxic epidermal OR epidermal necrolysis OR TEN OR hypersensitivity OR dermatologic OR burns], a preliminary search on the PubMed, Ovid, Web of Science, and Google Scholar Database yielded 615 papers published in English between January1, 1960 and July 1, 2017. The inclusion criteria for this review were: 1) published retrospective or prospective study (excluding single case reports); 2) patients with clinical diagnosis of SJS or TEN; 3) trial of cyclosporine treatment; and 4) available survival/mortality data. RESULTS: A total of 12 studies, with a total of 358 SJS/TEN patients were reviewed. Two studies were excluded from the meta-analysis as they did not report SCORe of toxic epidermal necrosis/predicted mortality data; one was excluded because of possible data irregularities. Meta-analysis of nine studies revealed a significant reduction in mortality risk with cyclosporine therapy (standardized mortality ratio 0.320; 95% CI: 0.119-0.522; P=0.002). Cyclosporine was also generally well tolerated with little adverse effects or increased infection, albeit the patients tended to be critically ill. Publication bias was observed in the funnel plot and Egger test (P=0.0467). CONCLUSION: Currently available evidence are predominantly open trials and retrospective studies with a significant risk of bias, perhaps owing to the rarity and life-threatening nature of the condition. Given its immunomodulatory actions, cyclosporine could be a potential treatment option for SJS/TEN in addition to best supportive measures. Further confirmation with robust randomized, controlled trials or larger case series is necessary and should be encouraged.

Use of Lactobacillus spp. to prevent recurrent urinary tract infections in females.

Urinary tract infections (UTIs) are the most common bacterial infections seen in the community, especially amongst females. The widespread use of antibiotics has led to the increased occurrence of E. coli resistant isolates worldwide. A promising non-antibiotic approach is the use of probiotic lactobacilli strains. This paper hypothesizes that Lactobacillus spp. containing products are able to prevent recurrent urinary tract infections in females. Using the keywords [lactobacillus OR lactobacilli OR probiotic] and [urinary tract infection OR UTI OR cystitis], a preliminary search on the PubMed, Ovid, Google Scholar and ClinicalTrials.gov database yielded 1,647 papers published in English between 1-Jan-1960 and 1-May-2017. 9 clinical trials with a total of 726 patients were reviewed. Different lactobacilli strains (in either oral or suppository formulation) were utilized and they demonstrated varying efficacy in the prevention of recurrent UTIs. Using a random-effects model, pooled risk ratio of at least one recurrent UTI episode during the entire study duration was 0.684 (95% CI 0.438 to 0.929, p < 0.001), per-protocol analysis. However, key limitations include significant inter-study variability and the limited duration of follow-up of most studies. Our hypothesis on the chemoprophylactic effects of probiotics for UTIs is plausible and supported by current data. Lactobacillus rhamnosus GR1 and Lactobacillus reuteri RC14 were the most commonly studied lactobacilli strains. Further and more robust randomized controlled trials with standardized lactobacilli strains and formulation are required for confirmation of effects.

A meta-analysis of the use of probiotics to alleviate depressive symptoms.

INTRODUCTION: Some preclinical and clinical studies have demonstrated the positive impact of probiotic supplementation on depressive symptoms. This paper aims to provide an updated meta-analysis on the topic. METHODS: Using the keywords [probiotics OR gut OR microflora OR microbiome OR bacteria OR yeast OR yoghurt OR lactobacillus OR bifidobacterium] AND [mood OR depression OR MDD OR suicide], a preliminary search on the PubMed, Ovid, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR) and Cochrane Field for Complementary Medicine database yielded 917 papers published in English between 1-Jan-1960 and 1-June-2017. RESULTS: 10 clinical trials with a total of 1349 patients were reviewed, comparing the use of probiotics to placebo controls. There was no significant difference in mood between the treatment and placebo group post-intervention as the standardized mean difference (SMD) was -0.128 (95% CI -0.261 to 0.00463, P=0.059). A separate subgroup analysis of studies conducted in healthy versus depressed individuals found significant improvements in the moods of individuals with mild to moderate depressive symptoms (SMD -0.684, 95% CI -1.296 to -0.0712, P=0.029) and non-significant effects in healthy individuals (SMD -0.0999, 95% CI -0.235 to 0.0348, P=0.146). LIMITATIONS: Inter-study discrepancies with respect to probiotic dosing, bacterial strains and strain combinations limit the comparability of current clinical trials. Furthermore, majority of existing RCTs were conducted in healthy individuals, making it difficult to extrapolate the results to depressed individuals. CONCLUSION: Probiotic supplementation has an overall insignificant effect on mood. Future studies should be conducted on more patients with clinically diagnosed depression.

A meta-analysis of the association between Helicobacter pylori (H. pylori) infection and hyperemesis gravidarum.

BACKGROUND: Hyperemesis gravidarum remains a common, distressing, and significant yet poorly understood disorder during pregnancy. The association between maternal Helicobacter pylori (H. pylori) infection and hyperemesis gravidarum has been increasingly recognized and investigated. This study thus aimed to provide an updated review and meta-analysis of the topic. METHODS: Using the search terms (H. pyloriOR Helicobacter ORHelicobacter pyloriOR infection) AND (pregnancy OR emesis OR hyperemesis gravidarum OR nausea OR vomiting), a preliminary search on the PubMed, Ovid, Web of Science, Google Scholar, and WanFang database yielded 372 papers published in English between January 1st, 1960 and June 1st, 2017. RESULTS: A total of 38 cross-sectional and case-control studies, with a total of 10 289 patients were eligible for review. Meta-analysis revealed a significant association between H. pylori infection and hyperemesis gravidarum during pregnancy, with a pooled odds ratio of 1.348 (95% CI: 1.156-1.539, P < .001). Subgroup analysis found that serologic and stool antigen tests were comparable methods of detecting H. pylori as they yielded similar odds ratios. LIMITATIONS: Although the studies did not have high heterogeneity (I2  = 28%), publication bias was observed, and interstudy discrepancies in the diagnostic criteria adopted for hyperemesis gravidarum limit the reliability of findings. Also, 15 of the included studies were from the same country (Turkey), which could limit the generalizability of current findings. The prevalence of H. pylori infection varies throughout the world, and there may also be pathogenic differences as most strains of H. pylori in East Asia carry the cytotoxin-associated gene A gene. CONCLUSION: H. pylori infection was associated with an increased likelihood of hyperemesis gravidarum during pregnancy. Given the high prevalence of H. pylori infections worldwide, detecting H. pylori infection and the eradication of maternal H. pylori infection could be part of maternal hyperemesis gravidarum management. Further confirmation with robust longitudinal studies and mechanistic investigations are needed.

Use of polymethylmethacrylate (PMMA) microspheres collagen to treat atrophic acne scars.

Acne scarring is a common and persistent sequela affecting many individuals worldwide, with significant physical and long-lasting psychological effects. Currently, the treatment options available for acne scars are mostly invasive and have several side effects. This paper explores the possibility of using polymethylmethacrylate (PMMA) collagen microspheres, a relatively underexplored technique hitherto, to treat common atrophic scars. PMMA-collagen is more popularly used in injectable wrinkle fillers. Preliminary research has shown that PMMA-collagen has a beneficial effect on atrophic scars while having the added advantage of being safe, tolerable and minimally invasive as well.

Managing childhood and adolescent attention-deficit/hyperactivity disorder (ADHD) with exercise: A systematic review.

BACKGROUND: Attention deficit hyperactivity disorder (ADHD) is one of the most common neuropsychiatric disorders affecting some 8-10% of children worldwide. Increasing research has shed light on the life course of the disorder, suggesting that majority of children with ADHD will continue to have persistent symptoms into adulthood. The mainstay of ADHD management has been pharmacologic and behavioural/psychological interventions, with little attention paid to exercise as a potential management strategy. A systematic review, examining both the short-term and long-term effects of exercise on children with ADHD, is timely and necessary to guide further research in this area. METHODS: Using the keywords [exercise OR physical OR activity OR sport] AND [attention deficit hyperactivity disorder OR ADHD OR ADDH], a preliminary search on the PubMed and Ovid database yielded 613 papers published in English between 1-Jan-1980 and 1-July-2016. Full articles were also reviewed for references of interest. RESULTS: A total of 30 studies were included in this systematic review. Both short-term and long-term studies support the clinical benefits of physical activity for individuals with ADHD. Cognitive, behavioural and physical symptoms of ADHD were alleviated in most instances, and the largest intervention effects were reported for mixed exercise programs. No adverse effects arising from physical exercise were reported in any of the studies, suggesting that exercise is a well-tolerated intervention. CONCLUSION: Physical activity, in particular moderate-to-intense aerobic exercise, is a beneficial and well-tolerated intervention for children and adolescents with ADHD. Future research should include more adequately-powered trials and investigate the ideal exercise prescription.

A meta-analysis of the use of rifaximin to prevent travellers' diarrhoea.

BACKGROUND: Travellers' diarrhoea affects tens of millions of people travelling to less developed countries or regions annually. There are positive reports of the use of rifaximin, a non-absorbed, gut-selective antibiotic to prevent travellers' diarrhoea. This study will critically review and analyse clinical trials on the subject. METHODS: Using the keywords [diarrhoea OR diarrhoea OR travel*] AND [rifaximin OR xifaxan OR xifaxanta OR normix OR rifagut], a preliminary search on the PubMed and Ovid databases yielded 411 papers published in English between 1 January 1988 and 1 July 2016. Of these, there were only five relevant clinical trials. RESULTS: The clinical trials were double-blind, placebo-controlled, randomized trials with a total of 879 subjects. The meta-analysis found significant reduction in risk of travellers' diarrhoea with rifaximin use compared to placebo (pooled RR 0.478, 95% CI: 0.375-0.610, and P < 0.001). For the entire travel and follow-up period, the risk of developing travellers' diarrhoea was significantly greater in individuals receiving the placebo than those receiving rifaximin (daily doses of 400-600 mg). Overall, rifaximin offered significant protection rates of 48-72%, with lower protection rates for Asian than Latin American countries. In terms of tolerability, similar rates of adverse events were reported for the rifaximin and placebo group ( P > 0.05), with no clinically significant or serious adverse events related to rifaximin use. CONCLUSIONS: There is good evidence supporting the use of rifaximin as a chemoprophylactic agent against travellers' diarrhoea, especially in individuals who are at high risk of severe complications from acute infectious diarrhoea. Rifaximin has an excellent tolerability/safety profile and demonstrated efficacy against diarrhoeagenic Escherichia coli and even enteroinvasive bacteria such Campylobacter species. Future studies should study the most effective dosing regimen for rifaximin chemoprophylaxis, as well as profile local antimicrobial resistance/susceptibility data in less developed regions to further guide rifaximin use.

Clinical Use of Curcumin in Depression: A Meta-Analysis.

INTRODUCTION: There is growing interest in the use of curcumin, a plant polyphenol with potent anti-inflammatory, anti-oxidant, and neuroprotective properties, as a novel antidepressant. Clinical trials have yielded conflicting conclusions pertaining to its effectiveness in depression. A meta-analysis of the topic, which has not been done until now, is therefore necessary to summarize current evidence and generate hypotheses for further research. METHODS: Using the keywords [curcumin OR diferuloylmethane OR curcuminoid OR turmeric OR Indian saffron] AND [depression OR MDD OR suicide], a preliminary search on the PubMed, Ovid, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), and Cochrane Field for Complementary Medicine database yielded 2081 articles published in English between January 1, 1960, and August 1, 2016. RESULTS: Six clinical trials with a total of 377 patients were reviewed, comparing the use of curcumin to placebo. In patients with depression, the pooled standardized mean difference from baseline Hamilton Rating Scale for Depression scores (pooled standardized mean difference -0.344, 95% confidence interval -0.558 to -0.129; P = .002) support the significant clinical efficacy of curcumin in ameliorating depressive symptoms. Significant anti-anxiety effects were also reported in 3 of the trials. Notably, no adverse events were reported in any of the trials. Most trials had a generally low risk of bias, except for an open trial of curcumin and a single-blinded study. LIMITATIONS: Because of the small number of studies available, a funnel plot or sensitivity analysis was not possible. Evidence on the long-term efficacy and safety of curcumin is also limited as the duration of all available studies ranged from 4 to 8 weeks. CONCLUSIONS: Curcumin appears to be safe, well-tolerated, and efficacious among depressed patients. More robust randomized controlled trials with larger sample sizes and follow-up studies carried out over a longer duration should be planned to ascertain its benefits.

Clinical use of Hypericum perforatum (St John's wort) in depression: A meta-analysis.

INTRODUCTION: St John's wort is a popular herbal remedy recommended by Traditional Chinese Medicine (TCM) practitioners and licensed and widely prescribed for depression in many European countries. However, conflicting data regarding its benefits and risks exist, and the last large meta-analysis on St John's wort use for depression was done in 2008, with no updated meta-analysis available. METHODS: Using the keywords [St John's Wort OR Hypericum perforatum OR hypericin OR hyperforin OR johanniskraut OR] AND [depression OR antidepressant OR SSRI], a preliminary search (without language restriction) on the PubMed, Ovid, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group, Cochrane Field for Complementary Medicine, China National Knowledge Infrastructure and WanFang database yielded 5428 papers between 1-Jan-1960 and 1-May-2016. RESULTS: 27 clinical trials with a total of 3808 patients were reviewed, comparing the use of St John's wort and SSRI. In patients with depression, St John's wort demonstrated comparable response (pooled RR 0.983, 95% CI 0.924-1.042, p<0.001) and remission (pooled RR 1.013, 95% CI 0.892-1.134, p<0.001) rate, and significantly lower discontinuation/dropout (pooled OR 0.587, 95% CI 0.478-0.697, p<0.001) rate compared to standard SSRIs. The pooled SMD from baseline HAM-D scores (pooled SMD -0.068, 95% CI -0.127 to 0.021, p<0.001) also support its significant clinical efficacy in ameliorating depressive symptoms. LIMITATIONS: Evidence on the long-term efficacy and safety of St. John's wort is limited as the duration of all available studies ranged from 4 to 12 weeks. It is also unclear if St John's wort would be beneficial for patients with severe depression, high suicidality or suicide risk. CONCLUSION: For patients with mild-to-moderate depression, St John's wort has comparable efficacy and safety when compared to SSRIs. Follow-up studies carried out over a longer duration should be planned to ascertain its benefits.

Doll therapy for dementia sufferers: A systematic review.

Dementia affects more than 47.5 million people worldwide, and the number is expected to continue to increase as the population ages. Doll therapy is an emerging nonpharmacologic management strategy for patients with advanced dementia, especially in patients with challenging behaviours. A total of 12 published studies (mainly cohort and observational studies) were identified and discussed in this systematic review. In most instances, cognitive, behavioural and emotional symptoms were alleviated and overall wellbeing was improved with doll therapy, and dementia sufferers were found to be able to better relate with their external environment. Despite the relative paucity of empirical data and ethical concerns, we are of the opinion that doll therapy is effective for dementia care, is well-aligned with the ethos of person-centred care and should be applied in the management of dementia patients. Future research should include more robust randomized controlled trials.