The longitudinal dynamics and natural history of clonal haematopoiesis.

Clonal expansions driven by somatic mutations become pervasive across human tissues with age, including in the haematopoietic system, where the phenomenon is termed clonal haematopoiesis1-4. The understanding of how and when clonal haematopoiesis develops, the factors that govern its behaviour, how it interacts with ageing and how these variables relate to malignant progression remains limited5,6. Here we track 697 clonal haematopoiesis clones from 385 individuals 55 years of age or older over a median of 13 years. We find that 92.4% of clones expanded at a stable exponential rate over the study period, with different mutations driving substantially different growth rates, ranging from 5% (DNMT3A and TP53) to more than 50% per year (SRSF2P95H). Growth rates of clones with the same mutation differed by approximately ±5% per year, proportionately affecting slow drivers more substantially. By combining our time-series data with phylogenetic analysis of 1,731 whole-genome sequences of haematopoietic colonies from 7 individuals from an older age group, we reveal distinct patterns of lifelong clonal behaviour. DNMT3A-mutant clones preferentially expanded early in life and displayed slower growth in old age, in the context of an increasingly competitive oligoclonal landscape. By contrast, splicing gene mutations drove expansion only later in life, whereas TET2-mutant clones emerged across all ages. Finally, we show that mutations driving faster clonal growth carry a higher risk of malignant progression. Our findings characterize the lifelong natural history of clonal haematopoiesis and give fundamental insights into the interactions between somatic mutation, ageing and clonal selection.

The multimodality cell segmentation challenge: toward universal solutions.

Cell segmentation is a critical step for quantitative single-cell analysis in microscopy images. Existing cell segmentation methods are often tailored to specific modalities or require manual interventions to specify hyper-parameters in different experimental settings. Here, we present a multimodality cell segmentation benchmark, comprising more than 1,500 labeled images derived from more than 50 diverse biological experiments. The top participants developed a Transformer-based deep-learning algorithm that not only exceeds existing methods but can also be applied to diverse microscopy images across imaging platforms and tissue types without manual parameter adjustments. This benchmark and the improved algorithm offer promising avenues for more accurate and versatile cell analysis in microscopy imaging.

Revisiting the beyond BMI paradigm in excess weight diagnosis and management: A call to action.

Adolphe Quételet, a 19th-century Belgian sociologist and statistician, pioneered the incorporation of statistics into social sciences. He initiated the development of anthropometry since he was interested in identifying the proportions of the 'ideal man'. He devised a ratio between weight and height, originally termed the Quételet Index, and today widely known and used as the body mass index or BMI. In 1835, he demonstrated that a normal curve accommodates the distribution of human traits articulating his reasoning on human variance around the average. Quételet's long-lasting legacy of the establishment of a simple measure to classify people's weight relative to an ideal for their height endures today with minor variations having dramatically influenced public health agendas. While being very useful, the limitations of the BMI are well known. Thus, revisiting the beyond BMI paradigm is a necessity in the era of precision medicine with morphofunctional assessment representing the way forward via incorporation of body composition and functionality appraisal. While healthcare systems were originally designed to address acute illnesses, today's demands require a radical rethinking together with an original reappraisal of our diagnosis and treatment approaches from a multidimensional perspective. Embracing new methodologies is the way forward to advance the field, gain a closer look at the underlying pathophysiology of excess weight, keep the spotlight on improving diagnostic performance and demonstrate its clinical validity. In order to provide every patient with the most accurate diagnosis together with the most appropriate management, a high degree of standardization and personalization is needed.

Diabetic Sarcopenia. A proposed muscle screening protocol in people with diabetes : Expert document.

OBJECTIVES: To propose the grounds for "diabetic sarcopenia" as a new comorbidity of diabetes, and to establish a muscle screening algorithm proposal to facilitate its diagnosis and staging in clinical practice. METHOD: A qualitative expert opinion study was carried out using the nominal technique. A literature search was performed with the terms "screening" or "diagnostic criteria" and "muscle loss" or "sarcopenia" and "diabetes" that was sent to a multidisciplinary group of 7 experts who, in a face-to-face meeting, discussed various aspects of the screening algorithm. RESULTS: The hallmark of diabetic sarcopenia (DS) is muscle mass atrophy characteristic of people with diabetes mellitus (DM) in contrast to the histological and physiological normality of muscle mass. The target population to be screened was defined as patients with DM with a SARC-F questionnaire > 4, glycosylated haemoglobin (HbA1C) ≥ 8.0%, more than 5 years since onset of DM, taking sulfonylureas, glinides and sodium/glucose cotransporter inhibitors (SGLT2), as well as presence of chronic complications of diabetes or clinical suspicion of sarcopenia. Diagnosis was based on the presence of criteria of low muscle strength (probable sarcopenia) and low muscle mass (confirmed sarcopenia) using methods available in any clinical consultation room, such as dynamometry, the chair stand test, and Body Mass Index (BMI)-adjusted calf circumference. DS was classified into 4 stages: Stage I corresponds to sarcopenic patients with no other diabetes complication, and Stage II corresponds to patients with some type of involvement. Within Stage II are three sublevels (a, b and c). Stage IIa refers to individuals with sarcopenic diabetes and some diabetes-specific impairment, IIb to sarcopenia with functional impairment, and IIc to sarcopenia with diabetes complications and changes in function measured using standard tests Conclusion: Diabetic sarcopenia has a significant impact on function and quality of life in people with type 2 diabetes mellitus (T2DM), and it is important to give it the same attention as all other traditionally described complications of T2DM. This document aims to establish the foundation for protocolising the screening and diagnosis of diabetic sarcopenia in a manner that is simple and accessible for all levels of healthcare.

Patterns, predictors, and patient-reported reasons for antidepressant discontinuation in the WHO World Mental Health Surveys.

BACKGROUND: Despite their documented efficacy, substantial proportions of patients discontinue antidepressant medication (ADM) without a doctor's recommendation. The current report integrates data on patient-reported reasons into an investigation of patterns and predictors of ADM discontinuation. METHODS: Face-to-face interviews with community samples from 13 countries (n = 30 697) in the World Mental Health (WMH) Surveys included n = 1890 respondents who used ADMs within the past 12 months. RESULTS: 10.9% of 12-month ADM users reported discontinuation-based on recommendation of the prescriber while 15.7% discontinued in the absence of prescriber recommendation. The main patient-reported reason for discontinuation was feeling better (46.6%), which was reported by a higher proportion of patients who discontinued within the first 2 weeks of treatment than later. Perceived ineffectiveness (18.5%), predisposing factors (e.g. fear of dependence) (20.0%), and enabling factors (e.g. inability to afford treatment cost) (5.0%) were much less commonly reported reasons. Discontinuation in the absence of prescriber recommendation was associated with low country income level, being employed, and having above average personal income. Age, prior history of psychotropic medication use, and being prescribed treatment from a psychiatrist rather than from a general medical practitioner, in comparison, were associated with a lower probability of this type of discontinuation. However, these predictors varied substantially depending on patient-reported reasons for discontinuation. CONCLUSION: Dropping out early is not necessarily negative with almost half of individuals noting they felt better. The study underscores the diverse reasons given for dropping out and the need to evaluate how and whether dropping out influences short- or long-term functioning.

Structural Characterization and Rat Aortic Vascular Reactivity of Bradykinin-Potentiating Peptides (BPPs) from the Snake Venom of Bothrops moojeni from Delta do Parnaíba Region, Brazil.

Snake venoms contain various bradykinin-potentiating peptides (BPPs). First studied for their vasorelaxant properties due to angiotensin converting enzyme (ACE) inhibition, these molecules present a range of binding partners, among them the argininosuccinate synthase (AsS) enzyme. This has renewed interest in their characterization from biological sources and the evaluation of their pharmacological activities. In the present work, the low molecular weight fraction of Bothrops moojeni venom was obtained and BPPs were characterized by mass spectrometry. Eleven BPPs or related peptides were sequenced, and one of them, BPP-Bm01, was new. Interestingly, some oxidized BPPs were detected. The three most abundant peptides were BPP-Bm01, BPP-Bax12, and BPP-13a, and their putative interactions with the AsS enzyme were investigated in silico. A binding cavity for these molecules was predicted, and docking studies allowed their ranking. Three peptides were synthesized and submitted to vasorelaxation assays using rat aortic rings. While all BPPs were active, BPP-Bm01 showed the highest potency in this assay. This work adds further diversity to BPPs from snake venoms and suggests, for the first time, a putative binding pocket for these molecules in the AsS enzyme. This can guide the design of new and more potent AsS activators.

Direct oral anticoagulants versus vitamin K antagonists in patients with atrial fibrillation and stage 5 chronic kidney disease under dialysis: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: In patients with atrial fibrillation (AF) and normal or slightly impaired renal function, the use of direct oral anticoagulants (DOACs) is preferable to vitamin K antagonists (VKAs). However, in patients undergoing hemodialysis, the efficacy, and safety of DOACs compared with VKAs are still unknown. PURPOSE: To review current evidence about the safety and efficacy of DOACs compared to VKAs, in patients with AF and chronic kidney disease under hemodialysis. METHODS: We systematically searched PubMed, Scopus, and Cochrane databases for RCTs comparing DOACs with VKAs for anticoagulation in patients with AF on dialysis therapy. Outcomes of interest were: (1) stroke; (2) major bleeding; (3) cardiovascular mortality; and (4) all-cause mortality. Statistical analysis was performed using RevMan 5.1.7 and heterogeneity was assessed by I2 statistics. RESULTS: Three randomized controlled trials were included, comprising a total of 383 patients. Of these, 218 received DOACs (130 received apixaban; 88 received rivaroxaban), and 165 were treated with VKAs (116 received warfarin; 49 received phenprocoumon). The incidence of stroke was significantly lower in patients treated with DOACs (4.7%) compared with those using VKAs (9.5%) (RR 0.42; 95% CI 0.18-0.97; p = 0.04; I2 = 0%). However, the difference was not statistically significant in the case of ischemic stroke specifically (RR 0.42; 95% CI 0.17-1.04; p = 0.06; I2 = 0%). As for the major bleeding outcome, the DOAC group (11%) had fewer events than the VKA group (13.9%) but without statistical significance (RR 0.75; 95% CI 0.45-1.28; p = 0.29; I2 = 0%). There was no significant difference between groups regarding cardiovascular mortality (RR 1.23; 95% CI 0.66-2.29; p = 0.52; I2 = 13%) and all-cause mortality (RR 0.98; 95% CI 0.77-1.24; p = 0.84; I2 = 16%). CONCLUSION: This meta-analysis suggests that in patients with AF on dialysis, the use of DOACs was associated with a significant reduction in stroke, and a numerical trend of less incidence of major bleeding compared with VKAs, but in this case with no statistical significance. Results may be limited by a small sample size or insufficient statistical power.

Prevalence and acceptability of psychological and/or economic intimate partner violence, and utilization of mental health services by its survivors in Lithuania.

BACKGROUND: Lithuania has one of the highest averages in the European Union when it comes to psychological and/or economic intimate partner violence (PE-IPV). IPV survivors are several times more likely to have mental health conditions than those without IPV experiences. The aim of this article is to study the prevalence, characteristics and attitudes of PE-IPV survivors in Lithuania, and the predictors of them accessing mental health services. METHODS: A cross-sectional study based on a national survey representative of the adult population. The survey was implemented by a third-party independent market research company employing an online survey panel. Logistic regression models were used in the analysis. RESULTS: Almost 50% of women in Lithuania experience PE-IPV. Females are significantly more likely to experience it than males. The vast majority of women find PE-IPV unacceptable; however, only one-third of survivors seek any type of help. Only one-tenth approach mental health services, with divorcees being at higher odds of doing so. CONCLUSIONS: Further research is needed to explore predictors and contextual factors of why IPV survivors seek mental healthcare, or not. Policy implications include the need to eliminate IPV and mental health stigma; develop accessible mental health services and effective treatment approaches.

Optical pH Sensor Based on a Long-Period Fiber Grating Coated with a Polymeric Layer-by-Layer Electrostatic Self-Assembled Nanofilm.

An optical fiber pH sensor based on a long-period fiber grating (LPFG) is reported. Two oppositely charged polymers, polyethylenimine (PEI) and polyacrylic acid (PAA), were alternately deposited on the sensing structure through a layer-by-layer (LbL) electrostatic self-assembly technique. Since the polymers are pH sensitive, their refractive index (RI) varies when the pH of the solution changes due to swelling/deswelling phenomena. The fabricated multilayer coating retained a similar property, enabling its use in pH-sensing applications. The pH of the PAA dipping solution was tuned so that a coated LPFG achieved a pH sensitivity of (6.3 ± 0.2) nm/pH in the 5.92-9.23 pH range. Only two bilayers of PEI/PAA were used as an overlay, which reduces the fabrication time and increases the reproducibility of the sensor, and its reversibility and repeatability were demonstrated by tracking the resonance band position throughout multiple cycles between different pH solutions. With simulation work and experimental results from a low-finesse Fabry-Perot (FP) cavity on a fiber tip, the coating properties were estimated. When saturated at low pH, it has a thickness of 200 nm and 1.53 ± 0.01 RI, expanding up to 310 nm with a 1.35 ± 0.01 RI at higher pH values, mostly due to the structural changes in the PAA.

Epidemiological profile of luxations injuries with or without dental fractures in permanent teeth: A 10-years retrospective study.

BACKGROUND/AIM: This study assessed the epidemiology of luxation injuries with or without dental fractures in patients attending the outpatient clinic of a Brazilian dental school over the past decade. MATERIAL AND METHODS: We reviewed clinical records from a specialized center for dental trauma care in Brazil, focusing on patients who experienced at least one traumatic dental injury (TDI) in a permanent tooth between 2012 and 2022. The extracted data included sex, age, etiology, time between trauma occurrence and the search for initial care, TDI classification, and the need for endodontic treatment. The statistical analysis involved Pearson's chi-squared and Fisher's exact tests at a 5% significance level. RESULTS: The 366 analyzed clinical records included 166 patients (350 teeth) with luxation injuries. Men (n = 102) showed a higher prevalence of luxation injuries than women (n = 64). Extrusive luxation prevailed (n = 99 patients and 208 teeth). Patients with luxation injuries sought care promptly after dental trauma incidents (p = .02) and demonstrated a higher incidence of endodontic treatment (p < .0001) than those without luxation injuries. Lateral luxation was notably associated with traffic accidents (p < .0001). The combination of luxation injuries and tooth fractures did not correlate with a higher need for endodontic treatment (p > .05). CONCLUSIONS: Age and trauma etiology seemed to have influenced the epidemiological profile of luxation injuries. Additionally, these injuries affected the time to seek initial care and the need for endodontic treatment.

Photodynamic therapy in the root canal treatment of primary teeth: A systematic review of clinical trials.

BACKGROUND: Dental caries is the most common oral disease worldwide, and it is estimated to affect 2.3 billion people, with at least 530 million of them being schoolchildren with decayed primary teeth. This condition can rapidly evolve into irreversible pulp inflammation and pulp necrosis and thus requiring endodontic intervention. Photodynamic therapy (PDT) is a supplementary method to conventional pulpectomy and is used to improve the protocol used for disinfection. AIM: The main objective of this study was to evaluate through a systematic review the efficacy of supplementary PDT on the pulpectomy of primary teeth. This review was registered a priori on the PROSPERO database (CRD42022310581). DESIGN: Two independent and blinded reviewers carried out a comprehensive search in five databases: PubMed, Cochrane, Scopus, Embase, and Web of Science. Eligible studies were randomized and nonrandomized clinical trials that evaluated in vivo microbiological load or clinical outcomes after using supplementary PDT in infected primary teeth. RESULTS: After the selection process, four studies met the inclusion criteria and were included in this study. Data regarding the sample characteristics and PDT protocols were retrieved. All included trials used phenothiazinium salts as photosensitizer agents. Only one study observed a significant difference in the in vivo microbiological load reduction outcome when performing PDT on primary teeth. The remaining studies all discussed the possible benefits of this intervention; however, none observed a significant difference in this outcome. CONCLUSION: In this systematic review, moderate-to-low certainty of the available evidence was observed, and thus, no significant conclusions can be drawn from the findings.

Use of coercion in mental healthcare services in Nigeria: Service providers' perspective.

BACKGROUND: There is increasing advocacy to reduce coercive practices in mental healthcare. Little research has been done on the topic in developing countries. AIMS: To explore what mental health professionals in Nigeria think about coercion, why it is used, and what contextual factors influence its use in mental healthcare services. METHODS: Semi-structured interviews were carried out with 16 doctors and 14 nurses from two psychiatric hospitals in two regions of Nigeria. The audio-recorded interviews were analyzed thematically with the aid of MAXQDA software. RESULTS: Three broad categories relating to the perception of, reasons for, and barriers/facilitators to the use of coercion were derived. Coercion was viewed as being for the best interests of patients, a means to an end, and effective for achieving desired outcomes. Safety was both a reason to use a coercive measure and a deterrent to using specific coercive measures thought to be unsafe. The socio-cultural context, obsolete mental health legislation, staff shortages, and attitudes were factors influencing the use of coercion in mental healthcare. CONCLUSION: Coercion was perceived to be ultimately beneficial in mental health practice. There is need for a new mental health legislation and more resources for mental health care in Nigeria to address the problem of coercion.

Impact of passive ultrasonic irrigation on the outcome of non-surgical root canal treatment: a systematic review and meta-analysis of randomized clinical trials.

OBJECTIVE: This systematic review aimed to assess the impact of Passive Ultrasonic Irrigation on the periapical healing rate of primary root canal treatment compared to conventional syringe irrigation. METHODS: Registered a priori in the PROSPERO database, this review was conducted by two independent reviewers who performed an electronic search up to December 2023. The search included databases such as MEDLINE (PubMed), Scopus, Web of Science, Embase, LILACS, and the Cochrane Library, as well as grey literature. We included randomized clinical trials (RCTs) that focused on patients undergoing primary root canal treatments. The study compared intervention groups using PUI with control groups that did not use activation techniques. Periapical healing was assessed over follow-up periods of at least six months, utilizing either periapical radiographs or cone-beam computed tomography. To synthesize the findings, a meta-analysis and trial sequence analysis were conducted, employing the Relative Risk as the measure of effect, with a 95% confidence interval. The GRADE approach was utilized to assess the certainty of the evidence. RESULTS: The meta-analysis incorporated three RCTs, involving 474 patients (501 teeth). The analysis revealed that PUI led to a higher rate of periapical healing compared to CSI (Relative Risk: 1.10; 95% Confidence Interval: 1.01-1.21, I² = 0%), with moderate certainty of evidence. CONCLUSIONS: Despite the limited number of high-quality RCTs, the findings showed a positive impact of PUI on periapical healing rates in primary root canal treatments, in comparison to CSI. REGISTER: CRD42021290894.

Comparative Effectiveness of COVID-19 Vaccines in Preventing Infections and Disease Progression from SARS-CoV-2 Omicron BA.5 and BA.2, Portugal.

We estimated comparative primary and booster vaccine effectiveness (VE) of SARS-CoV-2 Omicron BA.5 and BA.2 lineages against infection and disease progression. During April-June 2022, we implemented a case-case and cohort study and classified lineages using whole-genome sequencing or spike gene target failure. For the case-case study, we estimated the adjusted odds ratios (aORs) of vaccination using a logistic regression. For the cohort study, we estimated VE against disease progression using a penalized logistic regression. We observed no reduced VE for primary (aOR 1.07 [95% CI 0.93-1.23]) or booster (aOR 0.96 [95% CI 0.84-1.09]) vaccination against BA.5 infection. Among BA.5 case-patients, booster VE against progression to hospitalization was lower than that among BA.2 case-patients (VE 77% [95% CI 49%-90%] vs. VE 93% [95% CI 86%-97%]). Although booster vaccination is less effective against BA.5 than against BA.2, it offers substantial protection against progression from BA.5 infection to severe disease.

Refractometric sensitivity of Bloch surface waves: perturbation theory calculation and experimental validation.

The sensitivity of one-dimensional Bloch surface wave (BSW) sensors to external refractive index variations using Kretschmann's configuration is calculated analytically by employing first-order perturbation theory for both TE and TM modes. This approach is then validated by comparison with both transfer matrix method simulations and experimental results for a chosen photonic crystal structure. Experimental sensitivities of (8.4±0.2)×102 and (8.4±0.4)×102 nm/RIU were obtained for the TE and TM BSW modes, corresponding to errors of 0.02% and 4%, respectively, when comparing with the perturbation theory approach. These results provide interesting insights into photonic crystal design for Bloch surface wave sensing by casting light into the important parameters related with sensor performance.

Future lines of research on phase angle: Strengths and limitations.

Bioelectrical impedance analysis (BIA) is the most widely used technique in body composition analysis. When we focus the use of phase sensitive BIA on its raw parameters Resistance (R), Reactance (Xc) and Phase Angle (PhA), we eliminate the bias of using predictive equations based on reference models. In particular PhA, have demonstrated their prognostic utility in multiple aspects of health and disease. In recent years, as a strong association between prognostic and diagnostic factors has been observed, scientific interest in the utility of PhA has increased. In the different fields of knowledge in biomedical research, there are different ways of assessing the impact of a scientific-technical aspect such as PhA. Single frequency with phase detection bioimpedance analysis (SF-BIA) using a 50 kHz single frequency device and tetrapolar wrist-ankle electrode placement is the most widely used bioimpedance approach for characterization of whole-body composition. However, the incorporation of vector representation of raw bioelectrical parameters and direct mathematical calculations without the need for regression equations for the analysis of body compartments has been one of the most important aspects for the development of research in this area. These results provide new evidence for the validity of phase-sensitive bioelectrical measurements as biomarkers of fluid and nutritional status. To enable the development of clinical research that provides consistent results, it is essential to establish appropriate standardization of PhA measurement techniques. Standardization of test protocols will facilitate the diagnosis and assessment of the risk associated with reduced PhA and the evaluation of changes in response to therapeutic interventions. In this paper, we describe and overview the value of PhA in biomedical research, technical and instrumental aspects of PhA research, analysis of Areas of clinical research (cancer patients, digestive and liver diseases, critical and surgical patients, Respiratory, infectious, and COVID-19, obesity and metabolic diseases, Heart and kidney failure, Malnutrition and sarcopenia), characterisation of the different research outcomes, Morphofunctional assessment in disease-related malnutrition and other metabolic disorders: validation of PhA with reference clinical practice techniques, strengths and limitations. Based on the detailed study of the measurement technique, some of the key issues to be considered in future PhA research. On the other hand, it is important to assess the clinical conditions and the phenotype of the patients, as well as to establish a disease-specific clinical profile. The appropriate selection of the most critical outcomes is another fundamental aspect of research.

Phase angle and COVID-19: A systematic review with meta-analysis.

Phase angle (PhA) has been identified as a poor prognostic factor in patients with COVID-19. This study aimed to achieve a systematic review, where we discussed the potential role of PhA value as a prognostic marker of adverse clinical outcomes such as mortality and complication in hospitalized with SARS-CoV2 infection and established the strength of recommendations for use. A systematic literature review with meta-analysis was done in the main electronic databases from 2020 to January 2023. The selected articles had to investigate adverse consequences of the COVID-19 population and raw bioimpedance parameters such as PhA and published in peer-reviewed journals. GRADE tools regarded the quality of the methodology. The review protocol was registered in PROSPERO. Only eight studies, 483 studies, were eligible for the analysis. In general, differences in PhA were seen between the comparative study groups. Patients with a low PhA experienced poor outcomes. A low PhA was associated with a significantly increased mortality risk [RR: 2.44; 95% CI (1.20-4.99), p = 0.01; I2 = 79% (p = 0.0008)] and higher complications risk [OR: 3.47, 95% CI (1.16 - 10.37), p = 0.03; I2 = 82% (p = 0.004)] in COVID-19 patients. Our analysis showed four evidence-based recommendations on the prognostic value of PhA with two strong recommendations, one of moderate and another of low-moderate quality, for predicting mortality and complications, respectively. We recommend using PhA as a prognostic marker for mortality and complications in this population. Although the results are promising, future studies must identify the PhA cut-off to guide therapeutic decisions more precisely.Registration code in PROSPERO: CRD42023391044.

Phase angle as a marker of outcome in hospitalized pediatric patients. A systematic review of the evidence (GRADE) with meta-analysis.

Phase angle (PhA) is a valuable tool for evaluating the nutritional and inflammatory status, which can accompany acute and severe disorders. PhA is a cellular health biomarker, whose value is particularly substantial due to the negative consequences of these situations in the pediatric population. Relevant literature was collected with the aim of comprehensively analysing the evidence on the association between an altered PhA can serve as a predictive-marker for mortality and poor-outcomes in at-risk-pediatric patients. Understanding this relationship could have significant implications for identifying high-risk individuals and implementing timely interventions. A systematic review with meta-analysis was conducted in the primary electronic databases from inception until January 2023. Overall, four studies with a total of 740 patients were eligible for our analysis. Evidence demonstrates that PhA is associated with nutritional status, reflecting undernutrition and changes in body composition related to illness. This review suggests that PhA can indeed be used as an indicator of nutritional status and a tool for predicting prognosis, including mortality and poor-outcomes, in hospitalized pediatric patients. A low PhA was associated with a significant mortality risk [RR:1.51;95%CI (1.22-1.88),p = 0.0002;I2 = 0%,(p = 0.99)] and an increased complications risk [OR:8.17;95%CI (2.44-27.4),p = 0.0007;I2 = 44%,(p = 0.18)]. These findings highlight the importance of taking a comprehensive approach to clinical nutrition, integrating multiple evaluation aspects to establish an accurate diagnosis and personalized therapeutic plans. While PhA emerges as a valuable tool for assessing the risk of malnutrition and as a prognostic-indicator for poor-outcomes in pediatric patients. Further future studies are needed to focus on investigating this relationship in larger and diverse population to strengthen the evidence base.

Antidepressant use in low- middle- and high-income countries: a World Mental Health Surveys report.

BACKGROUND: The most common treatment for major depressive disorder (MDD) is antidepressant medication (ADM). Results are reported on frequency of ADM use, reasons for use, and perceived effectiveness of use in general population surveys across 20 countries. METHODS: Face-to-face interviews with community samples totaling n = 49 919 respondents in the World Health Organization (WHO) World Mental Health (WMH) Surveys asked about ADM use anytime in the prior 12 months in conjunction with validated fully structured diagnostic interviews. Treatment questions were administered independently of diagnoses and asked of all respondents. RESULTS: 3.1% of respondents reported ADM use within the past 12 months. In high-income countries (HICs), depression (49.2%) and anxiety (36.4%) were the most common reasons for use. In low- and middle-income countries (LMICs), depression (38.4%) and sleep problems (31.9%) were the most common reasons for use. Prevalence of use was 2-4 times as high in HICs as LMICs across all examined diagnoses. Newer ADMs were proportionally used more often in HICs than LMICs. Across all conditions, ADMs were reported as very effective by 58.8% of users and somewhat effective by an additional 28.3% of users, with both proportions higher in LMICs than HICs. Neither ADM class nor reason for use was a significant predictor of perceived effectiveness. CONCLUSION: ADMs are in widespread use and for a variety of conditions including but going beyond depression and anxiety. In a general population sample from multiple LMICs and HICs, ADMs were widely perceived to be either very or somewhat effective by the people who use them.

Rare copy number variation in posttraumatic stress disorder.

Posttraumatic stress disorder (PTSD) is a heritable (h2 = 24-71%) psychiatric illness. Copy number variation (CNV) is a form of rare genetic variation that has been implicated in the etiology of psychiatric disorders, but no large-scale investigation of CNV in PTSD has been performed. We present an association study of CNV burden and PTSD symptoms in a sample of 114,383 participants (13,036 cases and 101,347 controls) of European ancestry. CNVs were called using two calling algorithms and intersected to a consensus set. Quality control was performed to remove strong outlier samples. CNVs were examined for association with PTSD within each cohort using linear or logistic regression analysis adjusted for population structure and CNV quality metrics, then inverse variance weighted meta-analyzed across cohorts. We examined the genome-wide total span of CNVs, enrichment of CNVs within specified gene-sets, and CNVs overlapping individual genes and implicated neurodevelopmental regions. The total distance covered by deletions crossing over known neurodevelopmental CNV regions was significant (beta = 0.029, SE = 0.005, P = 6.3 × 10-8). The genome-wide neurodevelopmental CNV burden identified explains 0.034% of the variation in PTSD symptoms. The 15q11.2 BP1-BP2 microdeletion region was significantly associated with PTSD (beta = 0.0206, SE = 0.0056, P = 0.0002). No individual significant genes interrupted by CNV were identified. 22 gene pathways related to the function of the nervous system and brain were significant in pathway analysis (FDR q < 0.05), but these associations were not significant once NDD regions were removed. A larger sample size, better detection methods, and annotated resources of CNV are needed to explore this relationship further.