Risk factors, prevention and treatment of weight gain associated with the use of antidepressants and antipsychotics: a state-of-the-art clinical review.

INTRODUCTION: People with severe mental illness have poor cardiometabolic health. Commonly used antidepressants and antipsychotics frequently lead to weight gain, which may further contribute to adverse cardiovascular outcomes. AREAS COVERED: We searched MEDLINE up to April 2023 for umbrella reviews, (network-)meta-analyses, trials and cohort studies on risk factors, prevention and treatment strategies of weight gain associated with antidepressants/antipsychotics. We developed 10 clinical recommendations. EXPERT OPINION: To prevent, manage, and treat antidepressant/antipsychotic-related weight gain, we recommend i) assessing risk factors for obesity before treatment, ii) monitoring metabolic health at baseline and regularly during follow-up, iii) offering lifestyle interventions including regular exercise and healthy diet based on patient preference to optimize motivation, iv) considering first-line psychotherapy for mild-moderate depression and anxiety disorders, v)choosing medications based on medications' and patient's weight gain risk, vi) choosing medications based on acute vs long-term treatment, vii) using effective, tolerated medications, viii) switching to less weight-inducing antipsychotics/antidepressants where possible, ix) using early weight gain as a predictor of further weight gain to inform the timing of intervention/switch options, and x) considering adding metformin or glucagon-like peptide-1 receptor agonists, or topiramate(second-line due to potential adverse cognitive effects) to antipsychotics, or aripiprazole to clozapine or olanzapine.

Global and risk-group stratified well-being and mental health during the COVID-19 pandemic in adults: Results from the international COH-FIT Study.

International studies measuring wellbeing/multidimensional mental health before/ during the COVID-19 pandemic, including representative samples for >2 years, identifying risk groups and coping strategies are lacking. COH-FIT is an online, international, anonymous survey measuring changes in well-being (WHO-5) and a composite psychopathology P-score, and their associations with COVID-19 deaths/restrictions, 12 a-priori defined risk individual/cumulative factors, and coping strategies during COVID-19 pandemic (26/04/2020-26/06/2022) in 30 languages (representative, weighted non-representative, adults). T-test, χ2, penalized cubic splines, linear regression, correlation analyses were conducted. Analyzing 121,066/142,364 initiated surveys, WHO-5/P-score worsened intra-pandemic by 11.1±21.1/13.2±17.9 points (effect size d=0.50/0.60) (comparable results in representative/weighted non-probability samples). Persons with WHO-5 scores indicative of depression screening (<50, 13% to 32%) and major depression (<29, 3% to 12%) significantly increased. WHO-5 worsened from those with mental disorders, female sex, COVID-19-related loss, low-income country location, physical disorders, healthcare worker occupations, large city location, COVID-19 infection, unemployment, first-generation immigration, to age=18-29 with a cumulative effect. Similar findings emerged for P-score. Changes were significantly but minimally related to COVID-19 deaths, returning to near-pre-pandemic values after >2 years. The most subjectively effective coping strategies were exercise and walking, internet use, social contacts. Identified risk groups, coping strategies and outcome trajectories can inform global public health strategies.

Effects of antipsychotic treatment on cardio-cerebrovascular related mortality in schizophrenia: A subanalysis of a systematic review and meta-analysis with meta-regression of moderators.

To further explore the role of different antipsychotic treatments for cardio-cerebrovascular mortality, we performed several subgroup, sensitivity and meta-regression analyses based on a large previous meta-analysis focusing on cohort studies assessing mortality relative risk (RR) for cardio-cerebrovascular disorders in people with schizophrenia, comparing antipsychotic treatment versus no antipsychotic. Quality assessment through the Newcastle-Ottawa Scale (NOS) and publication bias was measured. We meta-analyzed 53 different studies (schizophrenia patients: n = 2,513,359; controls: n = 360,504,484) to highlight the differential effects of antipsychotic treatment regimens on cardio-cerebrovascular-related mortality in incident and prevalent samples of patients with schizophrenia. We found first generation antipsychotics (FGA) to be associated with higher mortality in incident samples of schizophrenia (oral FGA [RR=2.20, 95 %CI=1.29-3.77, k = 1] and any FGA [RR=1.70, 95 %CI=1.20-2.41, k = 1]). Conversely, second generation antipsychotics (SGAs) and clozapine were associated with reduced cardio-cerebrovascular-related mortality, in prevalent samples of schizophrenia. Subgroup analyses with NOS score ≥7 (higher quality) demonstrated a significantly increased cardio-cerebrovascular disorder-related mortality, among those exposed to FGAs vs SGAs. Meta-regression analyses demonstrated a larger association between antipsychotics and decreased risk of mortality with longer follow-up, recent study year, and higher number of adjustment variables. Overall, this subanalysis of a systematic review contributes to the evolving understanding of the complex role of antipsychotic treatment for cardio-cerebrovascular mortality in schizophrenia, paving the way for more targeted interventions and improved patient outcomes.

Markers of Intestinal Permeability and Inflammation in Enterally Fed Children with Cerebral Palsy.

Cerebral palsy (CP) results in non-progressive damage to the central nervous system, leading to functional disorders of the gastrointestinal tract and requiring enteral nutrition via gastrostomy in some patients. The aim of the study was to assess the impact of enteral nutrition on intestinal inflammation expressed by stool calprotectin and intestinal permeability determined by fecal zonulin and IFABP, and to determine whether CP affects these parameters. The study group consisted of 30 children with CP, fed enterally (Cerebral Palsy Enteral Nutrition-CPEN), and two reference groups: 24 children with CP, fed orally with a standard diet (CPC-Cerebral Palsy Controls) and 24 healthy children (HC-healthy controls). The differences between these groups and between the combined CP groups (CPG and CPEN + CPC) and HC were analyzed. Fecal zonulin, calprotectin, and intestinal fatty acid-binding protein 2 (IFABP2) levels were determined by ELISA. The concentrations of fecal calprotectin and zonulin were significantly higher in the CPEN group than in the CPC group (p = 0.012, p = 0.025). When comparing the CPG (n = 53) with the HC group (n = 24), statistically significant differences were observed for calprotectin (p = 0.000018, higher in the CPG) and IFABP (p = 0.021, higher in HC). Enteral nutrition was associated in our cohort with increased fecal calprotectin and zonulin. Children with cerebral palsy presented with increased fecal calprotectin but not increased intestinal permeability expressed by stool zonulin.

One- versus Two-Minute Intercostal Nerve Cryoanalgesia in Children Undergoing Surgery for Funnel Chest Deformity.

An inherent defect of the sternum and ribs results in the formation of a funnel-shaped anterior chest wall. The gold standard of surgical correction is the minimally invasive Nuss procedure, which might cause severe pain and carries the risk of sensory disturbances and chronic discomfort. Integrating cryoanalgesia with standard multimodal analgesia improves the outcomes of this procedure. Based on histological results, it was hypothesised that the time of cryo-application can be reduced from the current standard period of two minutes. The goal of this study was to evaluate the efficacy of a one-minute application compared with the routine two-minute method in the same patient, considering the subjective perception of pain and sensory disturbances. A total of 33 patients were included in this prospective study. The results show that the assessment of pain severity and sensory disturbances did not differ significantly in terms of the time of cryo-application during first 14 days after the surgical procedure. The one-minute cryo-application time for intraoperative intercostal nerve cryoablation prior to the Nuss procedure seems to be as safe and effective as the routinely used two-minute application time in regards to pain severity, sensory disturbances, and the risk of chronic pain development. Intercostal nerve cryoanalgesia is an essential element of multimodal analgesia.

Quality of life of caregivers of patients on home enteral nutrition.

BACKGROUND: Home enteral nutrition (HEN) patients often rely heavily on caregivers (CGs), whose quality of life (QoL) is significantly impacted. This study aimed to identify potentially modifiable factors influencing the QoL of CGs of HEN patients. METHODS: A multicentre, cross-sectional study was conducted in three home nutrition centers from Jan 2021 to Jan 2022. We enrolled 90 CGs of HEN patients, collecting data on QoL (WHOQOL-BREF), depression (Beck Depression Inventory), CG burden (Zarit Burden Interview), sleep quality (Pittsburgh Sleep Quality Index), stress (Perceived Stress Scale), life satisfaction (Satisfaction With Life Scale) and financial status. RESULTS: The mean age of CGs was 54.53 years, with 76% being female. 19% of CGs rated their QoL as poor, and 57% had depression. Multivariate regression analysis showed that financial satisfaction (ß = 0.14, p < 0.01) and depression (ß = -0.03, p < 0.001) were significant predictors of QoL (R2 = 0.6). Depression correlated with CG burden (r = 0.54, p < 0.001), poor sleep quality (r = 0.47, p < 0.001), stress (r = 0.68, p < 0.001), and financial satisfaction (r = -0.39, p = 0.001). The average monthly income per person was $663.3 and 51.2% of CGs were not satisfied with their financial situation. Lower income was correlated with stress (r = -0.298, p = 0.023). CG burden was associated with financial satisfaction (r = -0.373, p < 0.001), quality of sleep (r = 0.296, p = 0.005) depression (r = 0.54, p < 0.001), stress (r = 0.5, p < 0.001) and satisfaction with life (r = -0.389, p < 0.001). CONCLUSIONS: CGs of HEN patients face substantial challenges impacting their QoL, particularly financial stress and depression. Addressing these issues through comprehensive support systems is crucial to improve CG well-being and, subsequently, patient care outcomes.

Gut microbiome dynamics and predictive value in hospitalized COVID-19 patients: a comparative analysis of shallow and deep shotgun sequencing.

The COVID-19 pandemic caused by SARS-CoV-2 has led to a wide range of clinical presentations, with respiratory symptoms being common. However, emerging evidence suggests that the gastrointestinal (GI) tract is also affected, with angiotensin-converting enzyme 2, a key receptor for SARS-CoV-2, abundantly expressed in the ileum and colon. The virus has been detected in GI tissues and fecal samples, even in cases with negative results of the reverse transcription polymerase chain reaction in the respiratory tract. GI symptoms have been associated with an increased risk of ICU admission and mortality. The gut microbiome, a complex ecosystem of around 40 trillion bacteria, plays a crucial role in immunological and metabolic pathways. Dysbiosis of the gut microbiota, characterized by a loss of beneficial microbes and decreased microbial diversity, has been observed in COVID-19 patients, potentially contributing to disease severity. We conducted a comprehensive gut microbiome study in 204 hospitalized COVID-19 patients using both shallow and deep shotgun sequencing methods. We aimed to track microbiota composition changes induced by hospitalization, link these alterations to clinical procedures (antibiotics administration) and outcomes (ICU referral, survival), and assess the predictive potential of the gut microbiome for COVID-19 prognosis. Shallow shotgun sequencing was evaluated as a cost-effective diagnostic alternative for clinical settings. Our study demonstrated the diverse effects of various combinations of clinical parameters, microbiome profiles, and patient metadata on the precision of outcome prognostication in patients. It indicates that microbiological data possesses greater reliability in forecasting patient outcomes when contrasted with clinical data or metadata. Furthermore, we established that shallow shotgun sequencing presents a viable and cost-effective diagnostic alternative to deep sequencing within clinical environments.

The Link between Inflammation, Lipid Derivatives, and Microbiota Metabolites in COVID-19 Patients: Implications on Eating Behaviors and Nutritional Status.

Extreme inflammation that continues even after infections can lead to a cytokine storm. In recent times, one of the most common causes of cytokine storm activation has been SARS-CoV-2 infection. A cytokine storm leads to dysregulation and excessive stimulation of the immune system, producing symptoms typical of post-COVID syndrome, including chronic fatigue, shortness of breath, joint pain, trouble concentrating (known as "brain fog"), and even direct organ damage in the heart, lungs, kidneys, and brain. This work summarizes the current knowledge regarding inflammation and the cytokine storm related to SARS-CoV-2 infection. Additionally, changes in lipid metabolism and microbiota composition under the influence of inflammation in COVID-19, along with the possible underlying mechanisms, are described. Finally, this text explores potential health implications related to changes in eating behaviors and nutritional status in COVID-19 patients. Although research on the cytokine storm is still ongoing, there is convincing evidence suggesting that severe immune and inflammatory responses during the acute phase of COVID-19 may lead to long-term health consequences. Understanding these links is key to developing treatment strategies and supporting patients after infection.

A prospective pilot study of gut microbiome in cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

A recent systematic review indicated that gut-microbiota-brain axis contributes to growth and rupture of intracranial aneurysms. However, gaps were detected in the role of intestinal microbiome in cerebral vasospasm (CVS) after aneurysmal subarachnoid hemorrhage (aSAH). This is the first pilot study aiming to test study feasibility and identify differences in gut microbiota between subjects with and without CVS following aSAH. A prospective nested case-control pilot study with 1:1 matching was conducted recruiting subjects with aSAH: cases with CVS; and controls without CVS based on the clinical picture and structured bedside transcranial Doppler (TCD). Fecal samples for microbiota analyses by means of 16S rRNA gene amplicon sequencing were collected within the first 96 h after ictus. Operational taxonomic unit tables were constructed, diversity metrics calculated, phylogenetic trees built, and differential abundance analysis (DAA) performed. At baseline, the groups did not differ significantly in basic demographic and aneurysm-related characteristics (p > 0.05). Alpha-diversity (richness and Shannon Index) was significantly reduced in cases of middle cerebral artery (MCA) vasospasm (p < 0.05). In DAA, relative abundance of genus Acidaminococcus was associated with MCA vasospasm (p = 0.00013). Two butyrate-producing genera, Intestinimonas and Butyricimonas, as well as [Clostridium] innocuum group had the strongest negative correlation with the mean blood flow velocity in anterior cerebral arteries (p < 0.01; rho = - 0.63; - 0.57, and - 0.57, respectively). In total, 16 gut microbial genera were identified to correlate with TCD parameters, and two intestinal genera correlated with outcome upon discharge. In this pilot study, we prove study feasibility and present the first preliminary evidence of gut microbiome signature associating with CVS as a significant cause of stroke in subjects with aSAH.

Evaluating the Impact of Probiotic Therapy on the Endocannabinoid System, Pain, Sleep and Fatigue: A Randomized, Double-Blind, Placebo-Controlled Trial in Dancers.

Emerging research links the endocannabinoid system to gut microbiota, influencing nociception, mood, and immunity, yet the molecular interactions remain unclear. This study focused on the effects of probiotics on ECS markers-cannabinoid receptor type 2 (CB2) and fatty acid amide hydrolase (FAAH)-in dancers, a group selected due to their high exposure to physical and psychological stress. In a double-blind, placebo-controlled trial (ClinicalTrials.gov NCT05567653), 15 dancers were assigned to receive either a 12-week regimen of Lactobacillus helveticus Rosell-52 and Bifidobacterium longum Rosell-17 or a placebo (PLA: n = 10, PRO: n = 5). There were no significant changes in CB2 (probiotic: 0.55 to 0.29 ng/mL; placebo: 0.86 to 0.72 ng/mL) or FAAH levels (probiotic: 5.93 to 6.02 ng/mL; placebo: 6.46 to 6.94 ng/mL; p > 0.05). A trend toward improved sleep quality was observed in the probiotic group, while the placebo group showed a decline (PRO: from 1.4 to 1.0; PLA: from 0.8 to 1.2; p = 0.07841). No other differences were noted in assessed outcomes (pain and fatigue). Probiotic supplementation showed no significant impact on CB2 or FAAH levels, pain, or fatigue but suggested potential benefits for sleep quality, suggesting an area for further research.

Insights into the Mechanisms of Action of Akkermansia muciniphila in the Treatment of Non-Communicable Diseases.

This comprehensive review delineates the extensive roles of Akkermansia muciniphila in various health domains, spanning from metabolic and inflammatory diseases to neurodegenerative disorders. A. muciniphila, known for its ability to reside in the mucous layer of the intestine, plays a pivotal role in maintaining gut integrity and interacting with host metabolic processes. Its influence extends to modulating immune responses and potentially easing symptoms across several non-communicable diseases, including obesity, diabetes, inflammatory bowel disease, and cancer. Recent studies highlight its capacity to interact with the gut-brain axis, suggesting a possible impact on neuropsychiatric conditions. Despite the promising therapeutic potential of A. muciniphila highlighted in animal and preliminary human studies, challenges remain in its practical application due to stability and cultivation issues. However, the development of pasteurized forms and synthetic mediums offers new avenues for its use in clinical settings, as recognized by regulatory bodies like the European Food Safety Authority. This narrative review serves as a crucial resource for understanding the broad implications of A. muciniphila across different health conditions and its potential integration into therapeutic strategies.

Untargeted metabolomics in gastric and colorectal cancer patients - preliminary results.

Introduction: Recent years, microbiota-associated aspects have been analysed in multiple disorders regarding cancers. Existing evidence pints that gut microorganisms might take part in tumour origin and therapy efficacy. Nevertheless, to date, data on faecal metabolomics in cancer patients is still strongly limited. Therefore, we aimed to analyse gut untargeted metabolome in gastrointestinal cancer patients (i.e., gastric and colorectal cancer). Patients and methods: There were 12 patients with either gastric (n=4) or colorectal cancer (n=8) enrolled and 8 analysed (n=4 each). Stool samples were collected prior to anti-cancer treatments. Untargeted metabolomics analyses were conducted by means of mass spectrometry. Results: A plethora of metabolites in cancer patients we analysed were noted, with higher homogenity in case of gastric cancer patients. We found that the level of Deoxyguanosine,m/z 266.091,[M-H]-, Uridine,m/z 245.075,[M+H]+, Deoxyguanosine,m/z 268.104,[M]+, 3-Indoleacetic acid,m/z 176.07,[M+H]+, Indoxyl,m/z 132.031,[M-H]-, L-Phenylalanine,m/z 164.073,[M-H]-, L-Methionine,m/z 150.058,[M+NH4]+, was significantly higher in colorectal cancer patients and Ethyl hydrogen malonate,m/z 133.031,[M+H]+ in gastric cancer. Conclusion: The overall insights into untargeted metabolomics showed that most often higher levels of analysed metabolites were detected in colorectal cancer patients compared to gastric cancer patients. The link between gut metabolome and both local and distal metastasis might exist, however it requires confirmation in further multi-centre studies regarding larger sample size.

Prognostic Value of Postneoadjuvant Chemotherapy Neutrophil-to-Lymphocyte Ratio in Patients undergoing Radical Cystectomy.

Background: Neutrophil-to-lymphocyte ratio (NLR), a widely assessed biomarker in most common diseases, is typically evaluated before treatment initiation. However, data on NLR in the post-treatment setting is limited. Therefore, we assessed the NLR calculated after neoadjuvant chemotherapy (NAC) initiation in patients with bladder cancer (BC). We hypothesised that changes in blood cells after NAC could be a marker of tumour response and long-term survival. Materials and Methods: Our study included 214 patients who underwent NAC followed by radical cystectomy (RC) in two urological departments, wherein post-NAC NLR was used to categorize patients into the low (NLR ≤ 1.75) and high (NLR > 1.75) groups. Results: Logistic regression analysis indicated that a post-NAC NLR ≥ 1.75 is a good biomarker for pathologic response (odds ratio (OR), 0.045; p <0.001), emphasizing its ability to predict patient survival. The HRs for overall survival and cancer-specific survival were 2.387 (p = 0.048) and 2.342 (p < 0.001), respectively. Conclusions: We believe that post-NAC NLR can be used for patient stratification after NAC. Consequently, the post-NAC NLR may serve as a guide for the decision-making process regarding RC versus bladder-preserving strategies.

No Impact of Enteral Nutrition on Fecal Short-Chain Fatty Acids in Children with Cerebral Palsy.

Bacteria can impact the host organism through their metabolites, with short-chain fatty acids (SCFAs) being the most important, including acetate (C2), propionate (C3), butyrate (C4), valerate (C5n), and isovalerate (C5i). This study aimed to identify the impact of enteral nutrition on SCFAs in children with cerebral palsy and to test the hypothesis that the type of nutrition in cerebral palsy affects gut SCFA levels. Cerebral palsy is a heterogeneous syndrome resulting from non-progressive damage to the central nervous system. The study group included 30 children diagnosed with cerebral palsy, receiving enteral nutrition (Cerebral Palsy Enteral Nutrition (CPEN)) via gastrostomy. The first reference group (Cerebral Palsy Controls (CPCs)) consisted of 24 children diagnosed with cerebral palsy and fed orally on a regular diet. The second reference group (Healthy Controls (HCs)) consisted of 24 healthy children with no chronic disease and fed on a regular diet. Isolation and measurement of SCFAs were conducted using gas chromatography. Differences were observed in the median contents of isobutyric acid, valeric acid, and isovaleric acid between the CPC group, which had significantly higher levels of those acids than the HC group. No differences were found between the CPEN and CPC groups nor between the CPEN and HC groups. We conclude that enteral nutrition in cerebral palsy has no influence on the levels of SCFAs.

Gut Microbiome-How Does Two-Month Consumption of Fiber-Enriched Rolls Change Microbiome in Patients Suffering from MASLD?

BACKGROUND: The occurrence of metabolic dysfunction-associated steatotic liver disease (MASLD) is a growing global problem which commonly affects patients with co-existing diseases/conditions, such as type 2 diabetes and dyslipidemia. The effective treatment of MASLD is still limited; however, diet plays a significant role in its management. There are multiple beneficial properties of dietary fiber, including its ability to modify the gut microbiome. Therefore, the aim of this study was to determine the effect of the consumption of fiber-enriched rolls on the gut microbiome and microbial metabolites in patients suffering from MASLD. METHODS: The participants were recruited according to the inclusion criteria and were required to consume fiber-enriched rolls containing either 6 g or 12 g of fiber. There were three assessment timepoints, when the anthropometric and laboratory parameters were measured, and 16s on nanopore sequencing of the fecal microbiome was conducted. RESULTS: Firmicutes and Bacteroidetes were the most abundant phyla in the patients living with MASLD. It was demonstrated that the amount of short-chain fatty acids (SCFAs) changed after the consumption of fiber-enriched rolls; however, this was strongly associated with both the timepoint and the type of SCFAs-acetate and butyrate. Additionally, the high-fiber diet was related to the increase in phyla diversity (p = 0.006571). CONCLUSIONS: Overall, the introduction of an appropriate amount of fiber to the diet seems to be promising for patients suffering from MASLD due to its ability to create an improvement in gut microbiome-related aspects.

Association between symptoms of depression and inflammatory parameters in people aged over 90 years.

BACKGROUND: Old age is a period of life that presents many health and social challenges, resulting in a greater vulnerability to the development of mental disorders, including depression. There has been a growing interest in the relationship between depression and inflammatory factors, because of its potential clinical and therapeutic implications. Inflammatory processes, which were originally understood as a response to infection and trauma, appear to play an important role in the pathogenesis of depression in the elderly. The aim of the study was to analyse the relationship between the severity of depressive disorders and inflammatory parameters in people over 90 years of age. METHODS: The study was conducted in Poland in 2017. The study population consisted of long-lived individuals, both living at home and staying in residential care homes. The participants were 90 people of both sexes (69 women and 21 men), aged between 90 and 103 years (mean = 92.36; SD = 2.98). The study was conducted using the diagnostic survey method with a questionnaire technique. The Geriatric Depression Scale (GDS) was used to carry out the analysis. The levels of selected inflammatory factors were determined using relevant laboratory tests. RESULTS: In the study group, the highest percentage of people had symptoms of moderate depression (n = 36;40%), followed by those without depression (n = 35;38.9%). There was a weak negative correlation between GDS scores and fibrinogen levels (p ≤ 0.05). The logistic regression model showed no significant relationship between inflammatory parameters and the development of depressive disorders. CONCLUSIONS: Inflammatory parameters do not appear to predict the development of depressive disorders in people over 90 years of age.

The Iron Metabolism with a Specific Focus on the Functioning of the Nervous System.

Iron is the micronutrient with the best-studied biological functions. It is widely distributed in nature, and its involvement in the main metabolic pathways determines the great importance of this metal for all organisms. Iron is required for cellular respiration and various biochemical processes that ensure the proper functioning of cells and organs in the human body, including the brain. Iron also plays an important role in the production of free radicals, which can be beneficial or harmful to cells under various conditions. Reviews of iron metabolism and its regulation can be found in the literature, and further advances in understanding the molecular basis of iron metabolism are being made every year. The aim of this review is to systematise the available data on the role of iron in the function of the nervous system, especially in the brain. The review summarises recent views on iron metabolism and its regulatory mechanisms in humans, including the essential action of hepcidin. Special attention is given to the mechanisms of iron absorption in the small intestine and the purpose of this small but critically important pool of iron in the brain.

Regional differences in mortality risk and in attenuating or aggravating factors in schizophrenia: A systematic review and meta-analysis.

People with schizophrenia die prematurely, yet regional differences are unclear. PRISMA 2020-compliant systematic review/random-effects meta-analysis of cohort studies assessing mortality relative risk (RR) versus any control group, and moderators, in people with ICD/DSM-defined schizophrenia, comparing countries and continents. We conducted subgroup, meta-regression analyses, and quality assessment. The primary outcome was all-cause mortality. Secondary outcomes were suicide-, /natural-cause- and other-cause-related mortality. We included 135 studies from Europe (n = 70), North-America (n = 29), Asia (n = 33), Oceania (n = 2), Africa (n = 1). In incident plus prevalent schizophrenia, differences across continents emerged for all-cause mortality (highest in Africa, RR=5.98, 95 %C.I.=4.09-8.74, k = 1, lowest in North-America, RR=2.14, 95 %C.I.=1.92-2.38, k = 16), suicide (highest in Oceania, RR=13.5, 95 %C.I.=10.08-18.07, k = 1, lowest in North-America, RR=4.4, 95 %C.I.=4.07-4.76, k = 6), but not for natural-cause mortality. Europe had the largest association between antipsychotics and lower all-cause mortality/suicide (Asia had the smallest or no significant association, respectively), without differences for natural-cause mortality. Higher country socio-demographic index significantly moderated larger suicide-related and smaller natural-cause-related mortality risk in incident schizophrenia, with reversed associations in prevalent schizophrenia. Antipsychotics had a larger/smaller protective association in incident/prevalent schizophrenia regarding all-cause mortality, and smaller protective association for suicide-related mortality in prevalent schizophrenia. Additional regional differences emerged in incident schizophrenia, across countries, and secondary outcomes. Significant regional differences emerged for all-cause, cause-specific and suicide-related mortality. Natural-cause death was homogeneously increased globally. Moderators differed across countries. Global initiatives are needed to improve physical health in people with schizophrenia, local studies to identify actionable moderators.

Evaluation of the Efficacy of the 755 nm Picosecond Laser in Eliminating Pigmented Skin Lesions after a Single Treatment Based on Photographic Analysis with Polarised Light.

INTRODUCTION: Pigmentary changes can be bothersome and affect one's well-being. Laser therapy has been shown to effectively treat such skin discolouration. We aimed to assess the utility of a 755 nm alexandrite laser in pigmented lesions removal. MATERIALS AND METHODS: A total of 109 patients aged 44.17 ± 8.2 years were enrolled and underwent laser treatment of facial skin hyperpigmentation. The efficacy was analysed on the basis of photographic diagnosis using the VISIA Complexion Analysis System. The following measures were assessed: (1) score; (2) feature count; (3) comparison figure. RESULTS: A single laser treatment significantly improved the size and area of the lesion and decreased the number of lesion features. Parallelly, the overall skin condition significantly improved (p < 0.05). We found a statistical tendency of a higher feature count baseline, thus its change in men (p = 0.05 and 0.07, respectively), but failed to find any statistically significant associations (p > 0.05) between tested measures and skin phototypes and hyperpigmentation types. Age was also not correlated with the laser efficacy (p > 0.05). CONCLUSIONS: The use of the 755 nm laser is effective in reducing pigmented lesions.