Systematic Review and Meta-Analysis: Medical and Recreational Cannabis Legalization and Cannabis Use Among Youth in the United States.

OBJECTIVE: Dramatic changes in state-level cannabis laws (CL) over the past 25 years have shifted societal beliefs throughout the United States, with unknown implications for youth. In the present study, we conducted an updated systematic review and meta-analysis examining estimated effects of medical cannabis legalization (MCL) and recreational cannabis legalization (RCL) on past-month cannabis use among US youth. METHOD: A systematic review was conducted following Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, followed by a subsequent meta-analysis investigating the associations between state-level cannabis laws (ie, MCL vs non-MCL, and RCL vs non-RCL) and past-month cannabis use prevalence among US adolescents and young adults. Supplemental analyses examined age-group effects and design-related factors. RESULTS: Our search identified 4,604 citations, 34 and 30 of which were included in qualitative and quantitative analyses, respectively. Meta-analysis of MCL studies identified no significant association between MCL and change in past-month youth cannabis use (odds ratio [OR] = 0.981, 95% CI = 0.960, 1.003). Meta-analysis of RCL studies showed significantly increased odds of past-month cannabis use (OR = 1.134, 95% CI = 1.116-1.153). Meta-analysis of more recent studies, however, showed a significantly increased odds of past-month cannabis use among both adolescents and young adults (OR = 1.089, 95% CI = 1.015,1.169, and OR = 1.221, 95% CI = 1.188,1.255, respectively). CONCLUSION: Cannabis legalization has complex and heterogenous effects on youth use that may differ across law types. Our meta-analytic results showed modest positive effects of RCL on past-month cannabis use (more so in young adults than in adolescents) and minimal effects of MCL on these outcomes in US youth. Given the shift toward recreational legalization, additional focus on RCL effects is warranted.

Decisional Regret Surrounding Dialysis Initiation: A Comparative Analysis.

Rationale & Objective: Dialysis comes with a substantial treatment burden, so patients must select care plans that align with their preferences. We aimed to deepen the understanding of decisional regret with dialysis choices. Study Design: This study had a mixed-methods explanatory sequential design. Setting & Participants: All patients from a single academic medical center prescribed maintenance in-center hemodialysis or presenting for home hemodialysis or peritoneal dialysis check-up during 3 weeks were approached for survey. A total of 78 patients agreed to participate. Patients with the highest (15 patients) and lowest decisional regret (20 patients) were invited to semistructured interviews. Predictors: Decisional regret scale and illness intrusiveness scale were used in this study. Analytical Approach: Quantitatively, we examined correlations between the decision regret scale and illness intrusiveness scale and sorted patients into the highest and lowest decision regret scale quartiles for further interviews; then, we compared patient characteristics between those that consented to interview in high and low decisional regret. Qualitatively, we used an adapted grounded theory approach to examine differences between interviewed patients with high and low decisional regret. Results: Of patients invited to participate in the interviews, 21 patients (8 high regret, 13 low regret) agreed. We observed that patients with high decisional regret displayed resignation toward dialysis, disruption of their sense of self and social roles, and self-blame, whereas patients with low decisional regret demonstrated positivity, integration of dialysis into their identity, and self-compassion. Limitations: Patients with the highest levels of decisional regret may have already withdrawn from dialysis. Patients could complete interviews in any location (eg, home, dialysis unit, and clinical office), which may have influenced patient disclosure. Conclusions: Although all patients experienced disruption after dialysis initiation, patients' approach to adversity differs between patients experiencing high versus low regret. This study identifies emotional responses to dialysis that may be modifiable through patient-support interventions.

As part of a quality improvement initiative in our dialysis practice, a patient stated, "I wish I never started dialysis." This quote served as the catalyst for embarking on a research project with the aim to understand why patients living with end-stage kidney disease have regret about starting and continuing dialysis, a lifesaving but time-intensive measure. We surveyed and interviewed patients on the topic and learned that patients experiencing regret had a disrupted sense of self and blamed themselves for their need of dialysis. Patients with little to no regret demonstrated positivity and self-compassion. These findings will help health care professionals as they work with patients considering dialysis or having newly started dialysis.

Frailty and Kidney Transplant Waitlisting: A Single-Center Experience.

BACKGROUND: Frailty is widely prevalent among kidney transplant (KT) candidates and is associated with poor peri and post-transplant outcomes. Whether frailty is a modifiable risk factor in KT candidates is unknown. Efforts to intervene in frailty have been hindered by a lack of a standardized approach to testing and treating frailty in clinical practice. METHODS: Patients undergoing evaluation for kidney transplantation underwent frailty testing during their clinical visits using a combination of the Short Physical Performance Battery (SPPB) and Groningen Frailty Indicator (GFI) instruments. Scores from the SPPB and GFI were combined to stratify patients into 4 risk groups. Patients in the highest-risk groups were referred to physical therapy (PT) and returned for repeat frailty testing. Pre- and post-PT scores were compared with assessment for improvement. RESULTS: Forty patients met the criteria for PT, of which 16 (40%) completed PT and returned for repeat frailty testing. The mean SPPB score improved from 5.88 to 8.94 after PT (P < .01). The mean GFI score improved from 5.25 to 4.06 after PT but was not statistically significant (P = .081). CONCLUSIONS: Our unique approach of using 2 validated scores, SPPB and GFI, together addressed many components of frailty evaluation, including physical, cognitive, and psychosocial components. We used PT as a targeted intervention for addressing both the physical and non-physical impairments among frail KT candidates. Physical therapy was noted to have a positive impact on each of these components.

Altered immune cell phenotypes within chronically ischemic human kidneys distal to occlusive renal artery disease.

Renal artery stenosis (RAS) is a major cause of ischemic kidney disease, which is largely mediated by inflammation. Mapping the immune cell composition in ischemic kidneys might provide useful insight into the disease pathogenesis and uncover therapeutic targets. We used mass cytometry (CyTOF) to explore the single-cell composition in a unique data set of human kidneys nephrectomized due to chronic occlusive vascular disease (RAS, n = 3), relatively healthy donor kidneys (n = 6), and unaffected sections of kidneys with renal cell carcinoma (RCC, n = 3). Renal fibrosis and certain macrophage populations were also evaluated in renal sections. Cytobank analysis showed in RAS kidneys decreased cell populations expressing epithelial markers (CD45-/CD13+) and increased CD45+ inflammatory cells, whereas scattered tubular-progenitor-like cells (CD45-/CD133+/CD24+) increased compared with kidney donors. Macrophages switched to proinflammatory phenotypes in RAS, and the numbers of IL-10-producing dendritic cells (DC) were also lower. Compared with kidney donors, RAS kidneys had decreased overall DC populations but increased plasmacytoid DC. Furthermore, senescent active T cells (CD45+/CD28+/CD57+), aged neutrophils (CD45+/CD15+/CD24+/CD11c+), and regulatory B cells (CD45+/CD14-/CD24+/CD44+) were increased in RAS. RCC kidneys showed a distribution of cell phenotypes comparable with RAS but less pronounced, accompanied by an increase in CD34+, CD370+, CD103+, and CD11c+/CD103+ cells. Histologically, RAS kidneys showed significantly increased fibrosis and decreased CD163+/CD141+ cells. The single-cell platform CyTOF enables the detection of significant changes in renal cells, especially in subsets of immune cells in ischemic human kidneys. Endogenous pro-repair cell types in RAS warrant future study for potential immune therapy.NEW & NOTEWORTHY The single-cell platform mass cytometry (CyTOF) enables detection of significant changes in one million of renal cells, especially in subsets of immune cells in ischemic human kidneys distal to renal artery stenosis (RAS). We found that pro-repair cell types such as scattered tubular-progenitor-like cells, aged neutrophils, and regulatory B cells show a compensatory increase in RAS. Immune cell phenotype changes may reflect ongoing inflammation and impaired immune defense capability in the kidneys.

Smartphone-based diagnostics for biosensing infectious human pathogens.

The widespread usage of smartphones has made accessing vast troves of data easier for everyone. Smartphones are powerful, handy, and easy to operate, making them a valuable tool for improving public health through diagnostics. When combined with other devices and sensors, smartphones have shown potential for detecting, visualizing, collecting, and transferring data, enabling rapid disease diagnosis. In resource-limited settings, the user-friendly operating system of smartphones allows them to function as a point-of-care platform for healthcare and disease diagnosis. Herein, we critically reviewed the smartphone-based biosensors for the diagnosis and detection of diseases caused by infectious human pathogens, such as deadly viruses, bacteria, and fungi. These biosensors use several analytical sensing methods, including microscopic imaging, instrumental interface, colorimetric, fluorescence, and electrochemical biosensors. We have discussed the diverse diagnosis strategies and analytical performances of smartphone-based detection systems in identifying infectious human pathogens, along with future perspectives.

Insights From the Eye for Patients With Kidney Transplant.

The eye and the kidney share structural and developmental similarities on a cellular and clinical level, and they are often affected by the same disease processes. Performing an eye exam to look for signs of conditions such as hypertension and diabetes can provide a helpful window into the health of the kidney. Patients with kidney transplants (KT) are a unique population that require close monitoring. These patients are maintained on a number of immunosuppressive medications and may face complications such as medication side effects, infections, and graft rejection. Patients with KT are at higher risk of both infectious and noninfectious eye conditions related to underlying systemic disease or use of immunosuppressive medications. Screening for eye conditions is important because preserving visual function is integral to quality of life, and also because the eye exam can help with early detection and treatment of systemic conditions. Here we describe some of the common eye findings and conditions in patients with KT. We recommend that patients with KT receive annual eye exams, and we hope that the information provided here can help nephrologists become more familiar with eye findings and identify situations where a referral to ophthalmology is warranted.

Microvascular remodeling and altered angiogenic signaling in human kidneys distal to occlusive atherosclerotic renal artery stenosis.

BACKGROUND: Renal artery stenosis (RAS) is an important cause of chronic kidney disease and secondary hypertension. In animal models, renal ischemia leads to downregulation of growth factor expression and loss of intrarenal microcirculation. However, little is known about the sequelae of large-vessel occlusive disease on the microcirculation within human kidneys. METHOD: This study included five patients who underwent nephrectomy due to renovascular occlusion and seven nonstenotic discarded donor kidneys (four deceased donors). Micro-computed tomography was performed to assess microvascular spatial densities and tortuosity, an index of microvascular immaturity. Renal protein expression, gene expression and histology were studied in vitro using immunoblotting, polymerase chain reaction and staining. RESULTS: RAS demonstrated a loss of medium-sized vessels (0.2-0.3 mm) compared with donor kidneys (P = 0.037) and increased microvascular tortuosity. RAS kidneys had greater protein expression of angiopoietin-1, hypoxia-inducible factor-1α and thrombospondin-1 but lower protein expression of vascular endothelial growth factor (VEGF) than donor kidneys. Renal fibrosis, loss of peritubular capillaries (PTCs) and pericyte detachment were greater in RAS, yet they had more newly formed PTCs than donor kidneys. Therefore, our study quantified significant microvascular remodeling in the poststenotic human kidney. RAS induced renal microvascular loss, vascular remodeling and fibrosis. Despite downregulated VEGF, stenotic kidneys upregulated compensatory angiogenic pathways related to angiopoietin-1. CONCLUSIONS: These observations underscore the nature of human RAS as a microvascular disease distal to main vessel stenosis and support therapeutic strategies directly targeting the poststenotic kidney microcirculation in patients with RAS.

Do patients with high versus low treatment and illness burden have different needs? A mixed-methods study of patients living on dialysis.

BACKGROUND: Approximately 750,000 people in the U.S. live with end-stage kidney disease (ESKD); the majority receive dialysis. Despite the importance of adherence to dialysis, it remains suboptimal, and one contributor may be patients' insufficient capacity to cope with their treatment and illness burden. However, it is unclear what, if any, differences exist between patients reporting high versus low treatment and illness burden. METHODS: We sought to understand these differences using a mixed methods, explanatory sequential design. We enrolled adult patients receiving dialysis, including in-center hemodialysis, home hemodialysis, and peritoneal dialysis. Descriptive patient characteristics were collected. Participants' treatment and illness burden was measured using the Illness Intrusiveness Scale (IIS). Participants scoring in the highest quartile were defined as having high burden, and participants scoring in the lowest quartile as having low burden. Participants in both quartiles were invited to participate in interviews and observations. RESULTS: Quantitatively, participants in the high burden group were significantly younger (mean = 48.4 years vs. 68.6 years respectively, p = <0.001). No other quantitative differences were observed. Qualitatively, we found differences in patient self-management practices, such as the high burden group having difficulty establishing a new rhythm of life to cope with dialysis, greater disruption in social roles and self-perception, fewer appraisal focused coping strategies, more difficulty maintaining social networks, and more negatively portrayed experiences early in their dialysis journey. CONCLUSIONS AND RELEVANCE: Patients on dialysis reporting the greatest illness and treatment burden have difficulties that their low-burden counterparts do not report, which may be amenable to intervention.

Global epigenetic alterations of mesenchymal stem cells in obesity: the role of vitamin C reprogramming.

Obesity promotes dysfunction and impairs the reparative capacity of mesenchymal stem/stromal cells (MSCs), and alters their transcription, protein content, and paracrine function. Whether these adverse effects are mediated by chromatin-modifying epigenetic changes remains unclear. We tested the hypothesis that obesity imposes global DNA hydroxymethylation and histone tri-methylation alterations in obese swine abdominal adipose tissue-derived MSCs compared to lean pig MSCs. MSCs from female lean (n = 7) and high-fat-diet fed obese (n = 7) domestic pigs were assessed using global epigenetic assays, before and after in-vitro co-incubation with the epigenetic modulator vitamin-C (VIT-C) (50 µg/ml). Dot blotting was used to measure across the whole genome 5-hydroxyemthycytosine (5hmC) residues, and Western blotting to quantify in genomic histone-3 protein tri-methylated lysine-4 (H3K4me3), lysine-9 (H3K9me3), and lysine-27 (H3K27me3) residues. MSC migration and proliferation were studied in-vitro. Obese MSCs displayed reduced global 5hmC and H3K4m3 levels, but comparable H3K9me3 and H3K27me3, compared to lean MSCs. Global 5hmC, H3K4me3, and HK9me3 marks correlated with MSC migration and reduced proliferation, as well as clinical and metabolic characteristics of obesity. Co-incubation of obese MSCs with VIT-C enhanced 5hmC marks, and reduced their global levels of H3K9me3 and H3K27me3. Contrarily, VIT-C did not affect 5hmC, and decreased H3K4me3 in lean MSCs. Obesity induces global genomic epigenetic alterations in swine MSCs, involving primarily genomic transcriptional repression, which are associated with MSC function and clinical features of obesity. Some of these alterations might be reversible using the epigenetic modulator VIT-C, suggesting epigenetic modifications as therapeutic targets in obesity.

General Public's Information-Seeking Patterns of Topics Related to Obesity: Google Trends Analysis.

BACKGROUND: Obesity is a major public health challenge, and recent literature sheds light on the concept of "normalization" of obesity. OBJECTIVE: We aimed to study the worldwide pattern of web-based information seeking by public on obesity and on its related terms and topics using Google Trends. METHODS: We compared the relative frequency of obesity-related search terms and topics between 2004 and 2019 on Google Trends. The mean relative interest scores for these terms over the 4-year quartiles were compared. RESULTS: The mean relative interest score of the search term "obesity" consistently decreased with time in all four quartiles (2004-2019), whereas the relative interest scores of the search topics "weight loss" and "abdominal obesity" increased. The topic "weight loss" was popular during the month of January, and its median relative interest score for January was higher than that for other months for the entire study period (P<.001). The relative interest score for the search term "obese" decreased over time, whereas those scores for the terms "body positivity" and "self-love" increased after 2013. CONCLUSIONS: Despite a worldwide increase in the prevalence of obesity, its popularity as an internet search term diminished over time. The reason for peaks in months should be explored and applied to the awareness campaigns for better effectiveness. These patterns suggest normalization of obesity in society and a rise of public curiosity about image-related obesity rather than its medical implications and harm.

Upregulated tumor necrosis factor-α transcriptome and proteome in adipose tissue-derived mesenchymal stem cells from pigs with metabolic syndrome.

INTRODUCTION: Mesenchymal stem cells (MSCs) have endogenous reparative properties, and may constitute an exogenous therapeutic intervention in patients with chronic kidney disease. The microenvironment of metabolic syndrome (MetS) induces fat inflammation, with abundant expression of tumor necrosis factor (TNF)-α. MetS may also alter the content of adipose tissue-derived MSCs, and we hypothesized that the inflammatory profile of MetS manifests via upregulating MSC mRNAs and proteins of the TNF-α pathway. METHODS: Domestic pigs were fed a 16-week Lean or MetS diet (n = 4 each). MSCs were harvested from abdominal subcutaneous fat, and their extracellular vesicles (EVs) isolated. Expression profiles of mRNAs and proteins in MSCs and EVs were obtained by high-throughput sequencing and proteomics. Nuclear translocation of the pro-inflammatory transcription factor (NF)-kB was evaluated in MSC and in pig renal tubular cells (TEC) co-incubated with EVs. RESULTS: We found 13 mRNAs and 4 proteins in the TNF-α pathway upregulated in MetS- vs. Lean-MSCs (fold-change > 1.4, p < 0.05), mostly via TNF-α receptor-1 (TNF-R1) signaling. Three mRNAs were upregulated in MetS-EVs. MetS-MSCs, as well as TECs co-incubated with MetS-EVs, showed increased nuclear translocation of NF-kB. Using qPCR, JUNB, MAP2K7 and TRAF2 genes followed the same direction of RNA-sequencing findings. CONCLUSIONS: MetS upregulates the TNF-α transcriptome and proteome in swine adipose tissue-derived MSCs, which are partly transmitted to their EV progeny, and are associated with activation of NF-kB in target cells. Hence, the MetS milieu may affect the profile of endogenous MSCs and their paracrine vectors and limit their use as an exogenous regenerative therapy. Anti-inflammatory strategies targeting the TNF-α pathway might be a novel strategy to restore MSC phenotype, and in turn function.

Minimally Invasive Esophagectomy in Semi-Prone Position (Pawar Technique): Technical Aspects and Outcome in 224 Patients.

Background and Objectives There are two patient positions described for minimally invasive esophagectomy (MIE) for esophageal cancer, viz., left lateral and prone positions. To retain the benefits and overcome the disadvantages of these positions, a semi-prone position was developed by us. Our objective was to analyze the feasibility of performing MIE in this position. Materials and Methods A retrospective review of patients who underwent MIE at our center from January 2007 to December 2017 was done. A semi-prone position is a left lateral position with an anterior inclination of 45 degrees. Intraoperative parameters including conversion rate, immediate postoperative outcomes, and long-term oncological outcomes were analyzed. Statistical Analysis Statistical Package for the Social Sciences version 19 (IBM SPSS, IBM Corp., Armonk, New York, United States) was utilized for analysis. Survival analysis was done using Kaplan-Meier graph. Quantitative data were described as mean or median with standard deviation, and qualitative data were described as frequency distribution tables. Results Consecutive 224 patients with good performance status were included. After excluding those who required conversion (14 [6.6%]), 210 patients were further analyzed. Median age was 60 years (range: 27-80 years). Neoadjuvant treatment recipients were 160 (76%) patients. Most common presentation was squamous cell carcinoma (146 [70%]) of lower third esophagus (140 [67%]) of stage III (126 [60%]). Median blood loss for thoracoscopic dissection and for total operation was 101.5 mL (range: 30-180 mL) and 286 mL (range: 93-480 mL), respectively. Median operative time for thoracoscopic dissection alone was 67 minutes (range: 34-98 minutes) and for entire procedure was 215 minutes (range: 162-268 minutes). There was no intraoperative mortality. Median 16 lymph nodes were dissected (range: 5-32). Postoperative complication rate and mortality was 50% and 3.3%, respectively. Disease-free interval was 18 months (range: 3-108 months) and overall survival was 22 months (range: 6-108 months). Conclusion MIE with mediastinal lymphadenectomy in a semi-prone position is feasible, convenient, oncologically safe, which can combine the benefits of the two conventional approaches. Further prospective and comparative studies are required to support our findings.

Child and adolescent psychiatry training curriculum: a global trainee's perspective.

This article is a summary of perspectives on training curricula from child and adolescent psychiatry trainees globally. We aimed to identify the relative strengths, weaknesses and gaps in learning needs from a trainee's perspective. The 20 early-career child psychiatrists who contributed are from 16 countries and represent all the five continents. We could identify some global challenges as well as local/regional challenges that need to be addressed to develop competent child psychiatrists.

Alterations in genetic and protein content of swine adipose tissue-derived mesenchymal stem cells in the metabolic syndrome.

INTRODUCTION: Mesenchymal stem cells (MSCs) possess endogenous reparative properties and may serve as an exogenous therapeutic intervention in patients with chronic kidney disease. Cardiovascular risk factors clustering in the metabolic syndrome (MetS) might adversely affect cellular properties. To test the hypothesis that Mets interferes with MSC characteristics, we performed comprehensive comparison of the mRNA, microRNA, and protein content of MSCs isolated from Lean and MetS pigs. METHODS: Domestic pigs were fed a 16-week Lean or MetS diet (n = 4 each). Expression profiles of co-existing microRNAs, mRNAs, and proteins were obtained by high-throughput sequencing and liquid chromatography-mass spectrometry. TargetScan and ComiR were used to predict target genes of differentially expressed microRNAs, and DAVID 6.7 for functional annotation analysis to rank primary gene ontology categories for the microRNA target genes, mRNAs, and proteins. RESULTS: Differential expression analysis revealed 12 microRNAs upregulated in MetS-MSCs compared to Lean-MSCs (fold change>1.4, p < .05), which target 7728 genes, whereas 33 mRNAs and 78 proteins were downregulated (fold change<0.7, p < .05). Integrated analysis showed that targets of those microRNAs upregulated in MetS-MSCs overlap with at least half of mRNAs and proteins dysregulated in those cells. Functional analysis of overlapping mRNAs and proteins suggest that they are primarily involved in mitochondria, inflammation and transcription. MetS-MSCs also exhibited increased nuclear translocation of nuclear factor kappa-B, associated with increased SA-ß-Galactosidase and decreased cytochrome-c oxidase-IV activity. CONCLUSION: MetS alters the transcriptome and proteome of swine adipose tissue-derived MSCs particularly genes involved in mitochondria, inflammation and transcription regulation. These alterations might limit the reparative function of endogenous MSC and their use as an exogenous regenerative therapy.

Noninvasive diagnosis of primary membranous nephropathy using phospholipase A2 receptor antibodies.

Kidney biopsy is the gold standard to diagnose membranous nephropathy (MN). Approximately 70%-80% of patients with primary MN have anti-phospholipase A2 receptor (PLA2R) antibodies. We hypothesized that PLA2R antibody testing without kidney biopsy may be a valid strategy to make a non-invasive diagnosis of MN in patients with a negative work-up for secondary causes. The medical records of all Mayo Clinic patients in Minnesota, Florida, and Arizona with serum PLA2R antibody tests between January 2015 and June 2018 were reviewed. PLA2R antibody testing was performed in 838 unique patients, with 143 testing positive. In 132 of these patients, a native kidney biopsy was performed. The primary diagnosis in all biopsies was MN. Potential secondary causes were identified in 35 cases, with the most common being malignancy and autoimmunity. Ninety-seven patients had a negative work-up for secondary causes of MN. Sixty of those 97 patients had an estimated glomerular filtration rate (eGFR) >60 ml/min/1.73m2. In these patients, the kidney biopsy did not provide significant information that altered management; one patient had a superimposed diabetic nephropathy and a second patient had a superimposed focal segmental glomerulosclerosis (FSGS) lesion. Among the 37 patients with primary MN and eGFR <60 ml/min/1.73m2, additional findings included acute interstitial nephritis, diabetic nephropathy, and cellular crescents in one case each. Thus, among patients with preserved kidney function and no evidence of secondary causes, a positive PLA2R antibody test highly predicts a tissue diagnosis of PLA2R-associated MN. Further validation in a prospective study is warranted to determine whether PLA2R antibody testing be used as a non-invasive diagnostic test to guide therapy.

High altitude area - A risk factor for gastric perforation? : A case series.

INTRODUCTION: This is an original case series on soldiers evacuated from HAA(High Altitude Area) over last one year(Sept 2017-Aug 2018), of which 100% cases were found to have gastric antrum perforation. This is a deviation from the usual trend that is being noted in Indian subcontinent where duodenal perforations are commonest. DISCUSSION: High altitude associated dyspepsia is a common phenomenon and some studies done in high altitude population have recorded high incidence of antral gastritis and mucosal atrophy on histo-pathological evaluation. This is also supported by high incidence of H. pylori infection. The presence of atrophic gastric mucosa associated with antral gastritis, when exposed to hypobaric hypoxemic conditions faced by soldiers posted to heights above 15,000 ft, may leads to increased intra-luminal pressure and ischemia which probably predisposes individuals for gastric antrum perforations. CONCLUSION: This is a relatively untouched topic as we have not found studies onhigh altitude related gastric perforations and probably this is the first case series of its kind. The acknowledgement of this phenomenon may pave way for further studies for defining the role of high altitude in gastric perforations.

Comparison of Early Intervention Services vs Treatment as Usual for Early-Phase Psychosis: A Systematic Review, Meta-analysis, and Meta-regression.

Importance: The value of early intervention in psychosis and allocation of public resources has long been debated because outcomes in people with schizophrenia spectrum disorders have remained suboptimal. Objective: To compare early intervention services (EIS) with treatment as usual (TAU) for early-phase psychosis. Data Sources: Systematic literature search of PubMed, PsycINFO, EMBASE, and ClinicalTrials.gov without language restrictions through June 6, 2017. Study Selection: Randomized trials comparing EIS vs TAU in first-episode psychosis or early-phase schizophrenia spectrum disorders. Data Extraction and Synthesis: This systematic review was conducted according to PRISMA guidelines. Three independent investigators extracted data for a random-effects meta-analysis and prespecified subgroup and meta-regression analyses. Main Outcomes and Measures: The coprimary outcomes were all-cause treatment discontinuation and at least 1 psychiatric hospitalization during the treatment period. Results: Across 10 randomized clinical trials (mean [SD] trial duration, 16.2 [7.4] months; range, 9-24 months) among 2176 patients (mean [SD] age, 27.5 [4.6] years; 1355 [62.3%] male), EIS was associated with better outcomes than TAU at the end of treatment for all 13 meta-analyzable outcomes. These outcomes included the following: all-cause treatment discontinuation (risk ratio [RR], 0.70; 95% CI, 0.61-0.80; P < .001), at least 1 psychiatric hospitalization (RR, 0.74; 95% CI, 0.61-0.90; P = .003), involvement in school or work (RR, 1.13; 95% CI, 1.03-1.24; P = .01), total symptom severity (standardized mean difference [SMD], -0.32; 95% CI, -0.47 to -0.17; P < .001), positive symptom severity (SMD, -0.22; 95% CI, -0.32 to -0.11; P < .001), and negative symptom severity (SMD, -0.28; 95% CI, -0.42 to -0.14; P < .001). Superiority of EIS regarding all outcomes was evident at 6, 9 to 12, and 18 to 24 months of treatment (except for general symptom severity and depressive symptom severity at 18-24 months). Conclusions and Relevance: In early-phase psychosis, EIS are superior to TAU across all meta-analyzable outcomes. These results support the need for funding and use of EIS in patients with early-phase psychosis.