A Systematic Review and Meta-Analysis of the Clinical Use of Megestrol Acetate for Cancer-Related Anorexia/Cachexia.

Cancer-related anorexia/cachexia is known to be associated with worsened quality of life and survival; however, limited treatment options exist. Although megestrol acetate (MA) is often used off-label to stimulate appetite and improve anorexia/cachexia in patients with advanced cancers, the benefits are controversial. The present meta-analysis aimed to better elucidate the clinical benefits of MA in patients with cancer-related anorexia/cachexia. A systematic search of PubMed, EMBASE, OVID Medline, Clinicaltrials.gov, and Google Scholar databases found 23 clinical trials examining the use of MA in cancer-related anorexia. The available randomized, controlled trials were appraised using Version 2 of the Cochrane risk-of-bias tool (RoB 2) and they had moderate-to-high risk of bias. A total of eight studies provided sufficient data on weight change for meta-analysis. The studies were divided into high-dose treatment (>320 mg/day) and low-dose treatment (≤320 mg/day). The overall pooled mean change in weight among cancer patients treated with MA, regardless of dosage was 0.75 kg (95% CI = −1.64 to 3.15, τ2 = 9.35, I2 = 96%). Patients who received high-dose MA tended to have weight loss rather than weight gain. There were insufficient studies to perform a meta-analysis for the change in tricep skinfold, midarm circumference, or quality of life measures. MA was generally well-tolerated, except for a clear thromboembolic risk, especially with higher doses. On balance, MA did not appear to be effective in providing the symptomatic improvement of anorexia/cachexia in patients with advanced cancer.

Biomarkers of immune tolerance in kidney transplantation: an overview.

Kidney failure, one of the most prevalent diseases in the world and with increasing incidence, is associated with substantial morbidity and mortality. Currently available modes of kidney replacement therapy include dialysis and kidney transplantation. Though kidney transplantation is the preferred and ideal mode of kidney replacement therapy, this modality, however, is not without its risks. Kidney transplant recipients are constantly at risk of complications associated with immunosuppression, namely, opportunistic infections (e.g., Epstein-Barr virus and cytomegalovirus infections), post-transplant lymphoproliferative disorder, and complications associated with immunosuppressants (e.g., calcineurin inhibitor- and corticosteroid-associated new onset diabetes after transplantation and calcineurin inhibitor-associated nephrotoxicity). Transplantation tolerance, an acquired state in which immunocompetent recipients have developed donor-specific unresponsiveness, may be the Holy Grail in enabling optimal allograft survival and obviating the risks associated with immunosuppression in kidney transplant recipients. This review aims to discuss the biomarkers available to predict, identify, and define the transplant immune tolerant state and various tolerance induction strategies. Regrettably, pediatric patients have not been included in any tolerance studies and this should be the focus of future studies.

Obsessive-Compulsive Disorders and Functional Urinary Disorders: A Fortuitous Association?

Although psychological factors are known to affect bladder and bowel control, the occurrence of functional urinary disorders in patients with psychiatric disorders has not been well-studied or described. A higher prevalence of functional lower urinary tract disorders have also been reported amongst patients with obsessive-compulsive (OC) disorders. A systematic literature search of PubMed, EMBASE, OVID Medline, PsycINFO, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), Clinicaltrials.gov and Google Scholar databases found five observational studies on the topic. Unfortunately, as only one study had a (healthy) control group, a meta-analytic approach was not possible. Overall, patients with OC symptoms appeared to have increased occurrence of functional urinary symptoms, e.g., overactive bladder, increase in urgency, frequency, incontinence and enuresis. This was even more common amongst patients with Pediatric Autoimmune Neuropsychiatric Disorder Associated with Streptococcal Infections (PANDAS) or Pediatric Acute-onset Neuropsychiatric Syndrome (PANS) as opposed to patients with OCD alone. Several biological and behavioural mechanisms and treatment approaches were discussed. However, as the current evidence base was significantly limited and had moderate to serious risk of bias, no strong inferences could be drawn. Further well-designed cohort studies are necessary to better elucidate the observed associations and their management.

Effects of Astaxanthin Supplementation on Skin Health: A Systematic Review of Clinical Studies.

Astaxanthin (AST), a naturally-occurring keto-carotenoid found in several species of bacteria and microalgae, has demonstrated diverse biological activities in vitro and in vivo. There is growing commercial interest in the application of astaxanthin in nutraceuticals and cosmeceuticals, due to its purported photoprotective, DNA repair, antioxidant, and anti-inflammatory benefits. This systematic review therefore aimed to summarize current clinical evidence on the effects of astaxanthin supplementation on skin health. Using the following combinations of broad Major Exploded Subject Headings (MesH) terms or text words [astaxanthin OR AST OR ASX OR carotenoid OR xanthophyll] AND [skin OR derm*], a comprehensive search of PubMed, EMBASE, Medline, Clinicaltrials.gov, and Google Scholar databases found a total of eleven clinical studies. There were six randomized, placebo-controlled, double-blind trials, while the rest were prospective, open-label studies. In many of the randomized, controlled trials reviewed, AST supplementation improved skin texture, appearance (wrinkles), and moisture content at the end of the study period. AST also appeared to protect against UV-induced skin damage. No serious adverse events were reported in any of the studies. However, most available studies had a relatively small sample size and were conducted on healthy Japanese females. Many of the studies were also funded by commercial entities, with potential conflicts of interests. This was difficult to account for in our analyses. Overall, there is some clinical data to support the benefits of astaxanthin supplementation (in the range of 3 to 6 mg/d) on skin health, especially for photoaged skin.

Distinguishing between typical Kawasaki disease and multisystem inflammatory syndrome in children (MIS-C) associated with SARS-CoV-2.

In recent months, there are increasing reports of a Kawasaki disease-like syndrome in children infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), termed 'Paediatric Multisystem Inflammatory Syndrome temporally associated with SARS-CoV-2 (PIMS-TS)' in the UK. Debate is ongoing regarding the nature of these pro-inflammatory syndromes. We herein propose that the platelet count may, at least in part, be able to help us differentiate between the two aforementioned syndromes. In a recent report, compared to a historical 'classical' Kawasaki disease (KD) cohort, patients with PIMS-TS had significantly lower platelet counts (188 vs 383 g/L, p < 0.0001). A possible explanation for this is their difference in underlying immunopathogenesis. In KD, the fundamental pathogenesis is thought to be immune complex-mediated, hence, the use of intravenous immunoglobulin (IVIg) which competes with the immunoglobulin Fc receptors (FcRs) on inflammatory cells, preventing the activation of these cells and thereby ameliorating the inflammatory response. If left untreated, these immune complexes activates the inflammatory cells (including monocytes and neutrophils), which also results in recruitment of platelets, resulting in the thrombocytosis we commonly see in KD. These immune complexes may also bind to platelets directly via FcRs on platelet membranes. In contrast, in viral-associated hyperinflammatory syndromes (e.g. PIMS-TS or MIS-C), there are mediators being secreted in the process of eradication of the virus (mainly to stimulate CD8+ cells to kill viral infected cells), which would inadvertently suppress bone marrow function and activate platelets, culminating in thrombocytopenia.

Yemen's Cholera Epidemic Is a One Health Issue.

Yemen has been faced with the worst cholera epidemic of modern times, with more than 1 million suspected cases and 3000 deaths at the time of writing. This problem is largely due to the longstanding civil war between pro-government forces and the Houthi armed movement, which has severely damaged already vulnerable sanitation and healthcare facilities and systems in the country. It is further compounded by a dire lack of basic amenities, chronic malnutrition, and unfavourable weather conditions. Another contributory component may be aerial transfer by cholera-infected chironomid insects. To contain the spread of cholera in Yemen, a nation-wide armistice should be negotiated, and national and local committees must be convened to coordinate efforts on the ground. Community isolation facilities with proper sanitation, reliable disposal systems, and a clean water supply should be set up to isolate and treat sick patients. The continuity of vaccination programmes should be ensured. Public health campaigns to educate local communities about good hygiene practices and nutrition are also necessary. The One Health paradigm emphasizes a multi-sectoral and transdisciplinary understanding and approach to prevent and mitigate the threat of communicable diseases. This paradigm is highly applicable to the ongoing cholera crisis in Yemen, as it demands a holistic and whole-of-society approach at the local, regional, and national levels. The key stakeholders and warring parties in Yemen must work towards a lasting ceasefire during these trying times, especially given the extra burden from the mounting severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) outbreak worldwide.

A systematic review of the clinical use of Withania somnifera (Ashwagandha) to ameliorate cognitive dysfunction.

Many developed countries are experiencing a rapidly "greying" population, and cognitive decline is common in the elderly. There is no cure for dementia, and pharmacotherapy options to treat cognitive dysfunction provide limited symptomatic improvements. Withania somnifera (Ashwagandha), a popular herb highly valued in Ayurvedic medicine, has often been used to aid memory and cognition. This systematic review thus aimed to evaluate the clinical evidence base and investigate the potential role of W. somnifera in managing cognitive dysfunction. Using the following keywords [withania somnifera OR indian ginseng OR Ashwagandha OR winter cherry] AND [brain OR cognit* OR mental OR dementia OR memory], a comprehensive search of PubMed, EMBASE, Medline, PsycINFO and Clinicaltrials.gov databases found five clinical studies that met the study's eligibility criteria. Overall, there is some early clinical evidence, in the form of randomized, placebo-controlled, double-blind trials, to support the cognitive benefits of W. somnifera supplementation. However, a rather heterogeneous study population was sampled, including older adults with mild cognitive impairment and adults with schizophrenia, schizoaffective disorder, or bipolar disorder. In most instances, W. somnifera extract improved performance on cognitive tasks, executive function, attention, and reaction time. It also appears to be well tolerated, with good adherence and minimal side effects.

Clinical Role of Aspirin in Mood Disorders: A Systematic Review.

Worldwide, depression and bipolar disorder affect a large and growing number of people. However, current pharmacotherapy options remain limited. Despite adequate treatment, many patients continue to have subsyndromal symptoms, which predict relapse in bipolar illness and often result in functional impairments. Aspirin, a common nonsteroidal anti-inflammatory drug (NSAID), has purported beneficial effects on mood symptoms, showing protective effects against depression in early cohort studies. This systematic review thus aimed to investigate the role of aspirin in mood disorders. Using the keywords (aspirin or acetylsalicy* or asa) and (mood or depress* or bipolar or mania or suicid*), a comprehensive search of PubMed, EMBASE, Medline, PsycINFO, Clinical Trials Register of the Cochrane Collaboration Depression, Anxiety and Neurosis Group (CCDANTR), Clinicaltrials.gov and Google Scholar databases found 13,952 papers published in English between 1 January 1988 and 1 May 2019. A total of six clinical studies were reviewed. There were two randomized, placebo-controlled, double-blind trials and populations drawn from two main cohort studies (i.e., the Geelong Osteoporosis Study and the Osteoarthritis Initiative study). Using a random-effects model, the pooled hazard ratio of the three cohort studies was 0.624 (95% confidence interval: 0.0503 to 1.198, p = 0.033), supporting a reduced risk of depression with aspirin exposure. Overall, the dropout rates were low, and aspirin appears to be well-tolerated with minimal risk of affective switch. In terms of methodological quality, most studies had a generally low risk of bias. Low-dose aspirin (80 to 100 mg/day) is safe, well-tolerated and potentially efficacious for improving depressive symptoms in both unipolar and bipolar depression. Due to its ability to modulate neuroinflammation and central nervous system processes, aspirin may also have valuable neuroprotective and pro-cognitive effects that deserve further exploration. Further randomized, controlled trials involving the adjunctive use of aspirin should be encouraged to confirm its therapeutic benefits.

Escitalopram-induced liver injury: A case report and review of literature.

BACKGROUND: Depression is a growing public health problem that affects over 350 million people globally and accounts for approximately 7.5% of healthy years lost due to disability. Escitalopram, one of the first-line medications for the treatment of depression, is a selective serotonin reuptake inhibitor and one of the most commonly prescribed antidepressant medications worldwide. Although thought to be generally safe and with minimal drug-drug interactions, we herein present an unusual case of cholestatic liver injury, likely secondary to escitalopram initiation. CASE SUMMARY: A 56-year-old Chinese lady presented with fever and cholestatic liver injury two weeks after initiation of escitalopram for the treatment of psychotic depression. Physical examination was unremarkable. Further investigations, including a computed tomography scan of the abdomen and pelvis and tests for hepatitis A, B and C and for autoimmune liver disease were unyielding. Hence, a diagnosis of escitalopram-induced liver injury was made. Upon stopping escitalopram, repeat liver function tests showed downtrending liver enzymes with eventual normalization of serum aspartate aminotransferase and alanine aminotransferase one-week post-discharge. CONCLUSION: Clinicians should be aware of the possibility of escitalopram-induced liver injury when initiating depressed patients on antidepressant treatment. This requires extra vigilance as most patients may remain asymptomatic. Measurement of liver function tests could be considered after initiation of antidepressant treatment, especially in patients with pre-existing liver disease.

Is there an association between Helicobacter pylori infection and irritable bowel syndrome? A meta-analysis.

BACKGROUND: Irritable bowel syndrome (IBS) is a prevalent and debilitating gastrointestinal condition. Research has reported persistent, low-grade mucosal inflammation and significant overlaps between patients with IBS and those with dyspepsia, suggesting a possible pathogenic role of Helicobacter pylori (H. pylori) in IBS. This study therefore aimed to provide the first systematic review and meta-analysis on the association between H. pylori infection and IBS. AIM: To investigate the association between H. pylori infection and IBS. METHODS: Using the keywords "H. pylori OR Helicobacter OR Helicobacter pylori OR infection" AND "irritable bowel syndrome OR IBS", a preliminary search of PubMed, Medline, Embase, Cochrane Database of Systematic Reviews, Web of Science, Google Scholar and WanFang databases yielded 2924 papers published in English between 1 January 1960 and 1 June 2018. Attempts were also made to search grey literature. RESULTS: A total of 13 clinical studies were systematically reviewed and nine studies were included in the final meta-analysis. Random-effects meta-analysis found a slight increased likelihood of H. pylori infection in patients with IBS, albeit this was not statistically significant (pooled odds ratio 1.47, 95% confidence interval: 0.90-2.40, P = 0.123). It must also be acknowledged that all of the available studies reported only crude odd ratios. H. pylori eradication therapy also does not appear to improve IBS symptoms. Although publication bias was not observed in the funnel plot, there was a high degree of heterogeneity amongst the studies included in the meta-analysis (I 2 = 87.38%). CONCLUSION: Overall, current evidence does not support an association between IBS and H. pylori infection. Further rigorous and detailed studies with larger sample sizes and after H. pylori eradication therapy are warranted.