Understanding the Impact of Adverse Childhood Experiences on Non-suicidal Self-Injury in Youth: A Systematic Review.

Objective: Non-suicidal self-injury (NSSI), defined as a deliberate destruction of one's own body without a suicidal intent, is a global public health issue. Adverse childhood events (ACEs) have been shown to be associated with various mental illnesses; however, to date the impact of such events on NSSI in youth has not been reviewed. Methods: We conducted a systematic review, searched 5 databases for published articles evaluating ACE and NSSI in youth less than or equal to 21 years of age. After screening 247 articles, we included 21 unique articles in this systematic review. Results: Increasing ACE score, physical, sexual or emotional abuse, parental neglect and substance use, parental separation or dysfunctional family, and death of a close family member had statistically significant correlation with NSSI. Conclusion: Non-suicidal self-injury is an impairing diagnosis with far reaching psychiatric manifestations and repercussions. Practitioners having high clinical suspicion for ACEs in youth with NSSI must intervene early by administering the ACEs questionnaire. Effective treatment of NSSI in those with ACEs with psychotherapy significantly improves outcomes and prevents suicide in youth.

Clinical Outcomes of Ustekinumab in Inflammatory Bowel Disease.

Inflammatory bowel diseases including Crohn's disease (CD) and ulcerative colitis (UC) are characterized by abdominal pain, diarrhea, blood in stools, weight loss, and fatigue. It presents in patients with varying severity from mild to severe depending on the inflammation. Detailed analysis and guidelines are required for the safe usage of biological therapies in the treatment of inflammatory bowel diseases as surgery is reserved for more complex cases. There is also geographical variation in inflammatory bowel disease (IBD) incidence and prevalence based on environmental and climate changes, and socio-demographics. Studies also show that there is more hospitalization and reduced health-related quality of life in IBD patients when compared to normal people. We conducted an extensive literature database search for articles with keywords within the last 10 years on adults >18 years of age with IBD and its treatment, especially with ustekinumab. Ustekinumab is a human immunoglobulin G1 (IgG1) kappa monoclonal antibody, that blocks IL-12 and IL-23 and was approved by the FDA for the treatment of moderate to severe IBD, especially in patients who are intolerant to immunomodulators or corticosteroids treatment. There are several retrospective studies that show the effectiveness of ustekinumab dosage escalation every four weeks in IBD patients. This escalation of dose not only improved the clinical outcome but also reduced the worsening of the disease. Previous studies also show the importance of considering dosage escalation before switching biological agents in the IBD treatment. Ustekinumab has also demonstrated both efficacy and safety in the induction and maintenance of the treatment of this disease. There are certain challenges and opportunities associated with ustekinumab usage in IBD patients that require further research. Ustekinumab seems to be more cost-effective in the tumor necrosis factor (TNF)-alpha-inhibitor failure population when compared to previously used biological treatment regimes.

The Prevalence of Anemia in Working Women.

INTRODUCTION: Anemia can be defined as a reduction in the amount of hemoglobin (Hb) in red blood cells (RBCs). It is becoming a growing socioeconomic issue. It is important to identify the causes of anemia and educate people about its symptoms. This can aid in the early identification and diagnosis of anemia, thereby preventing the disease's complications. The complications of anemia include the risk of low birth weight, prematurity, prenatal and neonatal mortality, and maternal mortality. OBJECTIVE: The objective of the study is to investigate the factors contributing to anemia among working-class women employed in government or private sectors located in Karachi, Pakistan. By identifying the causes and risk factors of anemia, participants can be counseled to adopt a healthier lifestyle, a well-balanced diet, and activities that may eliminate the causes of anemia, further preventing the incidence of anemia. The objectives of the study are specific, measurable, achievable, realistic, and time-bound (SMART). The study was conducted from November 2019 to August 2021 despite facing COVID-19-related restrictions. The sample size fit the inclusion criteria, and the objectives were accomplished successfully with adequate resources. METHODOLOGY: The cross-sectional study was conducted after receiving clearance from institutions and consent from participants. A total of 180 participants provided consent after receiving a thorough explanation of the study, and they had the right to refuse to participate. In respect of confidentiality, the participants were not required to provide their names, as they were not included in our data analysis. The inclusion criteria included women of the working class, aged 18-45 years, working a minimum of four to five hours per week, and employed in government or private sectors located in Karachi, Pakistan. The exclusion criteria included women with bleeding or hematological disorders, a history of surgery in the last 12 months, pregnancy, or systemic disease. Data collection was divided into two sections: section one (questionnaire) and section two (investigations). The questionnaire was given to each participant via Google Forms and was filled out before section two of data collection, which included blood tests via a finger prick to measure hemoglobin with a Veri-Q Multi Meter hemoglobin monitoring system (manufactured by Q-line BIOTECH, New Delhi, India). RESULTS: The mean Hb was 11.15 ± 1.29 mg/dl (n = 180). The study revealed that 58.3% of the participants had a normal hemoglobin concentration according to the WHO anemia classification, while 41.7% were anemic. Overall, the prevalence of anemia was 41.7%, and the majority (56%) of the participants had mild anemia. CONCLUSION: The majority of the participants had mild anemia. Education on anemia and its symptoms, eating habits, occupational status, and stress-related factors can affect the hemoglobin concentration in RBCs. A diet low in meat, leafy vegetables, and fruit leads to anemia. Despite knowledge of anemia and its symptoms, non-medical professionals, especially young adults, had a higher prevalence of anemia than medical professionals, although the difference was minor.

Cystic Fibrosis Transmembrane Conductance Regulator Protein Modulators in Children and Adolescents with different CF Genotypes - Systematic Review and Meta-Analysis.

OBJECTIVE: To determine the efficacy of the first triple CFTR protein modulators in children and adolescents with cystic fibrosis. METHODS: Systematic review and meta-analysis were conducted, following PRISMA guidelines. The following databases were searched extensively: PubMed/Medline, Clinical trials.gov, Google Scholar, Scopus, Embase, and Europe PMC using the keywords: "Ivacaftor," "Elexacaftor," "Tezacaftor," VX_661", VX_770", "VX_445", "cystic fibrosis". A total of ten randomized clinical trials were included in our analysis. Primary outcomes included: Absolute change in predicted FEV1 from baseline, Absolute change in sweat chloride test from baseline, Absolute change in BMI from baseline, Absolute change in CF-QR from baseline, and Adverse Events. RESULTS: Among primary findings, significant absolute change in predictive FEV1 from baseline through 4 weeks favoured the triple CFTR protein modulators. [MD=11.80,95%CI=8.47_15.12, p value=<0.00001]; as well as CF_QR score [MD=0.00,95%CI=-2.50_2.50, p value=1.00], and BMI kg/m² change [MD=16.90,95%CI=12.73_21.06, p value=<0.00001]. No significant change was noted for CFTR channels activity in the treatment group when compared to placebo or VX_770/VX_661 [MD= -12.57,95%CI=-94.46_69.32, p value=0.76]. CONCLUSION: In children aged ≥ 6 y old and adolescents with F508del_CFTR mutation, Elexacaftor-Tezacaftor-Ivacaftor tend to be more effective than first-generation therapy, demonstrating promising results by exhibiting significant improvement in lung function, body weight, and respiratory-related quality of life.

The Role of the US Trauma Centers in Older Adult Fall Prevention: A National Survey.

INTRODUCTION: Approximately 27.5% of adults 65 and older fall each year, over 3 million are treated in an emergency department, and 32 000 die. The American College of Surgeons and its Committee on Trauma (ACSCOT) have urged trauma centers (TCs) to screen for fall risk, but information on the role of TC in this opportunity for prevention is largely unknown. METHODS: A 29-item survey was developed by an ACSCOT Injury Prevention and Control Committee, Older Adult Falls workgroup, and emailed to 1000 trauma directors of the National Trauma Data Bank using Qualtrics. US TCs were surveyed regarding fall prevention, screening, intervention, and hospital discharge practices. Data collected and analyzed included respondent's role, location, population density, state designation or American College of Surgeons (ACS) level, if teaching facility, and patient population. RESULTS: Of the 266 (27%) respondents, 71% of TCs include fall prevention as part of their mission, but only 16% of TCs use fall risk screening tools. There was no significant difference between geographic location or ACS level. The number of prevention resources (F = 31.58, P < .0001) followed by the presence of a formal screening tool (F = 21.47, P < .0001) best predicted the presence of a fall prevention program. CONCLUSION: Older adult falls remain a major injury risk and injury prevention opportunity. The majority of TCs surveyed include prevention of older adult falls as part of their mission, but few incorporate the components of a fall prevention program. Development of best practices and requiring TCs to screen and offer interventions may prevent falls.

Impact of COVID­19 infection in patients with neurodegenerative diseases with particular focus on Alzheimer's and Parkinson's disease.

Neurodegenerative disorders (NDD) are chronic neurological diseases characterized by loss and/or damage to neurons along with the myelin sheath, and patients are at higher risk of severe infection with the SARS­CoV­2. A comprehensive literature search was performed using relevant terms and inclusion­exclusion criteria. Recent articles, subjects older than 50 years, and articles written in the English language were included, whereas letters to the editor and articles related to pregnant women were excluded from the review study. COVID­19 appears to damage angiotensin­II receptors which cause natural killer cells to lose the ability to clear virus­infected cells, owing to worse outcomes in patients with NDD. COVID­19 can worsen the symptoms of Alzheimer's disease. In addition, COVID­19 worsens drug­responsive motor symptoms in Parkinson's disease (PD) and other symptoms like fatigue and urinary complaints. Vitamin D is essential in decreasing pro­inflammatory and increasing anti­inflammatory cytokines in ongoing COVID­19 infections and reducing angiotensin receptors and, hence, decreasing COVID­19 infection severity. Telemedicine shows promise for patients with NDD but is yet to overcome legal issues and personal barriers. COVID­19 has a significant effect on neurodegenerative conditions, which appears partly to the nature of the NDD and the neuro­invasive capabilities of the SARS­CoV­2. The protective role of vitamin D in patients with NDD further supports this hypothesis. Modifications in current health care, like the telemedicine platform, are required to address the increased risk of serious infection in this population. Further studies will be required to clarify conflicting reports in many fields.

Atezolizumab plus bevacizumab versus sorafenib or atezolizumab alone for unresectable hepatocellular carcinoma: A systematic review.

BACKGROUND: Despite the use of current standard therapy, the prognosis of patients with unresectable hepatocellular carcinoma (HCC) is poor, with median survival times of 40 mo for intermediate HCC (Barcelona Clinic Liver Cancer [BCLC] stage B) and 6-8 mo for advanced HCC (BCLC stage C). Although patients with early-stage HCC are usually suitable for therapies with curative intention, up to 70% of patients experience relapse within 5 years. In the past decade, the United States Food and Drug Administration has approved different immunogenic treatment options for advanced HCC, the most common type of liver cancer among adults. Nevertheless, no treatment is useful in the adjuvant setting. Since 2007, the multi-kinase inhibitor sorafenib has been used as a first-line targeted drug to address the increased mortality and incidence rates of HCC. However, in 2020, the IMbrave150 trial demonstrated that combination therapy of atezolizumab (anti-programmed death-ligand 1 [PD-L1]) and bevacizumab (anti-vascular endothelial growth factor [VEGF]) is superior to sorafenib, a single anti-programmed death 1/PD-L1 antibody inhibitor used as an anti-cancer monotherapy for HCC treatment. AIM: To conduct a systematic literature review to evaluate the evidence supporting the efficacy and safety of atezolizumab/bevacizumab as preferred first-line drug therapy over the conventional sorafenib or atezolizumab monotherapies, which are used to improve survival outcomes and reduce disease progression in patients with unresectable HCC and non-decompensated liver disease. METHODS: A comprehensive literature review was conducted using the PubMed, Scopus, ScienceDirect, clinicaltrials.gov, PubMed Central, Embase, EuropePMC, and CINAHL databases to identify studies that met the inclusion criteria using relevant MeSH terms. This systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and risk of bias (RoB) were assessed using the Cochrane RoB 2 tool and Sevis. RESULTS: In the atezolizumab/bevacizumab group, an improvement in overall tumor response, reduction of disease progression, and longer progression-free survival were observed compared to monotherapy with either sorafenib or atezolizumab. Hypertension and proteinuria were the most common adverse events, and the rates of adverse events were comparable to those with the monotherapy. Of the studies, there were two completed trials and two ongoing trials analyzed using high quality and low bias. A more thorough analysis was only performed on the completed trials. CONCLUSION: Treatment of HCC with atezolizumab/bevacizumab combination therapy was confirmed to be an effective first-line treatment to improve survival in patients with unresectable HCC and non-decompensated liver disease compared to monotherapy with either sorafenib or atezolizumab.

Diseases Transmitted by the Black-Legged Ticks in the United States: A Comprehensive Review of the Literature.

The black-legged tick is endemic to the midwestern, northeastern, western, south-eastern, and southern regions of the United States. There has been an increased burden of black-legged ticks in humans in recent years. COVID-19 pandemic has further heightened this burden. We thereby reviewed the literature to discuss the seasonality, infections, and clinical spectrum of diseases transmitted by the black-legged ticks. We also discuss the reported delay in the diagnosis of these diseases during the pandemic situation, the alpha-gal syndrome, the importance of prompt diagnosis, and early medical intervention with an aim to increase awareness of the black-legged tick-borne diseases.

The Influence of Coronavirus Disease-2019 (COVID-19) On Parkinson's Disease: An Updated Systematic Review.

BACKGROUND: COVID-19 has affected global communities with multiple neurological complications in addition to other critical medical issues. COVID-19 binds to the host's angiotensin-converting enzyme 2 (ACE2) receptors, which are expressed in the neurons and glial cells, acting as an entry port to the central nervous system (CNS). ACE2 receptors are abundantly expressed on dopamine neurons, which may worsen the prognosis of motor symptoms in Parkinson's disease (PD). SARS-CoV-2 may lead to an indirect response via immune-mediated cytokine storms and propagate through the CNS leading to damage. In this systematic review, we aim to provide thorough analyses of associations between COVID-19 and neurological outcomes for patients with PD. METHODS: Using PRISMA statement 2020, a systematic review was conducted to isolate confirmed COVID-19 patients and analyze the PD-associated neurological outcomes using the following databases: PubMed, Science Direct, Google Scholar, and Cochrane databases. The following keywords were used "COVID19, SARS-CoV-2, Parkinson's disease, Pandemic, Mortality." A modified Delphi process was employed. RESULTS: Of the 355 studies located during the initial round of screening, 16 were included in the final synthesis. Of PD patients who tested positive for SARS-CoV-2, worsening motor symptoms and other viral-associated symptoms were reported. These symptoms included bradykinesia, tremors, gait disturbances, delirium and dementia, and severe spasms of arms and legs. Encephalopathy was presented in 2 of the included studies. Increased mortality rates were identified for hospitalized patients due to COVID-19 and PD as compared to other patient groups. CONCLUSION: Patients with PD may experience substantial worsening of symptoms due to COVID 19. Given the novelty of neurological-viral associations, clinical studies in the future ought to explore the disease severity and neurological outcomes in COVID-19 positive patients with PD as compared to non-PD patients, in addition to understanding the role of ACE2 in increased vulnerability to contracting the infection and as a treatment modality.

The Safety and Efficacy of Anakinra, an Interleukin-1 Antagonist in Severe Cases of COVID-19: A Systematic Review and Meta-Analysis.

This study aims to assess anakinra's safety and efficacy for treating severe coronavirus disease 2019 (COVID-19). Numerous electronic databases were searched and finally 15 studies with a total of 3,530 patients, 757 in the anakinra arm, 1,685 in the control arm were included. The pooled adjusted odds ratio (OR) for mortality in the treatment arm was 0.34 (95% confidence interval [CI], 0.21 - 0.54, I² = 48%), indicating a significant association between anakinra and mortality. A significant association was found regarding mechanical ventilation requirements in anakinra group compared to the control group OR, 0.68 (95% CI, 0.49 - 0.95, I² = 50%). For the safety of anakinra, we evaluated thromboembolism risk and liver transaminases elevation. Thromboembolism risk was OR, 1.59 (95% CI, 0.65 - 3.91, I² = 0%) and elevation in liver transaminases with OR was 1.35 (95% CI, 0.61 - 3.03, I² = 76%). Both were not statistically significant over the control group. Anakinra is beneficial in lowering mortality in COVID-19 patients. However, these non-significant differences in the safety profile between the anakinra and control groups may have been the result of baseline characteristics of the intervention group, and further studies are essential in evaluating anakinra's safety profile.

Upper gastrointestinal bleeding caused by severe esophagitis: a unique clinical syndrome.

BACKGROUND: We have recognized a unique clinical syndrome in patients with upper gastrointestinal bleeding who are found to have severe esophagitis. AIM: We aimed to more clearly describe the clinical entity of upper gastrointestinal bleeding in patients with severe esophagitis. METHODS: We conducted a retrospective matched case-control study designed to investigate clinical features in patients with carefully defined upper gastrointestinal bleeding and severe esophagitis. Patient data were captured prospectively via a Gastrointestinal Bleeding Healthcare Registry, which collects data on all patients admitted with gastrointestinal bleeding. Patients with endoscopically documented esophagitis (cases) were matched with randomly selected controls that had upper gastrointestinal bleeding caused by other lesions. RESULTS: Epidemiologic features in patients with esophagitis were similar to those with other causes of upper gastrointestinal bleeding. However, hematemesis was more common in patients with esophagitis 86% (102/119) than in controls 55% (196/357) (p < 0.0001), while melena was less common in patients with esophagitis 38% (45/119) than in controls 68% (244/357) (p < 0.0001). Additionally, the more severe the esophagitis, the more frequent was melena. Patients with esophagitis had less abnormal vital signs, lesser decreases in hematocrit, and lesser increases in BUN. Both pre- and postRockall scores were lower in patients with esophagitis compared with controls (p = 0.01, and p < 0.0001, respectively). Length of hospital stay (p = 0.002), rebleeding rate at 42 days (p = 0.0007), and mortality were less in patients with esophagitis than controls. Finally, analysis of patients with esophagitis and cirrhosis suggested that this group of patients had more severe bleeding than those without cirrhosis. CONCLUSIONS: We have described a unique clinical syndrome in patients with upper gastrointestinal bleeding who have erosive esophagitis. This syndrome is manifest by typical clinical features and is associated with favorable outcomes.

Worldwide practices for pharmacologic therapy in esophageal variceal hemorrhage.

OBJECTIVE: Pharmacologic therapy (PT) for patients with esophageal variceal hemorrhage (EVH) may improve outcomes. The aim of this article is to assess the current and potential future use of PT in cirrhotic patients with EVH. MATERIAL AND METHODS: We validated a 13-question survey about PT and physician preferences for specific therapies in cirrhotics with EVH; 2349 randomly selected Gastroenterology and Hepatology physicians worldwide were surveyed. The survey addressed institutional location, octreotide or terlipressin use and preference, PT prior to endoscopy, and future plans for terlipressin use, if not already instituted. RESULTS: Of those surveyed, 337 (14%) email addresses were nonfunctioning. Of the remaining 2012 surveyed, 371 (18%) responses were collected. Nearly two-thirds of physicians preferred to use PT prior to endoscopic intervention (p < 0.001). Nearly 70% of respondents only had octreotide available, while 6% had only terlipressin. Of the 24% having both octreotide and terlipressin available, 55% preferred terlipressin compared to 38% who preferred octreotide (p < 0.001). Of those physicians currently not using terlipressin because of its unavailability, 93% would be willing to use it if it were readily available. CONCLUSIONS: Of physicians with both terlipressin and octreotide available for treatment of EVH in cirrhotics, most prefer terlipressin, even if currently unavailable.