Mesenchymal stem cells for chronic knee pain secondary to osteoarthritis: A systematic review and meta-analysis of randomized trials.

OBJECTIVE: To assess the effectiveness of mesenchymal stem cells (MSCs) for chronic knee pain secondary to osteoarthritis (OA). METHODS: We searched MEDLINE, EMBASE, CINAHL, and Cochrane Central to September 2023 for trials that (1) enrolled patients with chronic pain associated with knee OA, and (2) randomized them to MSC therapy vs. placebo or usual care. We performed random-effects meta-analysis and used Grading of Recommendations, Assessment, Development, and Evaluation to assess the certainty of evidence. RESULTS: We included 16 trials (807 participants). At 3-6 months, MSC therapy probably results in little to no difference in pain relief (weighted mean difference [WMD] -0.74 cm on a 10 cm visual analog scale [VAS], 95% confidence interval [95%CI] -1.16 to -0.33; minimally important difference [MID] 1.5 cm) or physical functioning (WMD 2.23 points on 100-point 36-item Short Form Survey (SF-36) physical functioning subscale, 95%CI -0.97 to 5.43; MID 10-points; both moderate certainty). At 12 months, injection of MSCs probably results in little to no difference in pain (WMD -0.73 cm on a 10 cm VAS, 95%CI -1.69 to 0.24; moderate certainty) and may improve physical functioning (WMD 19.36 points on 100-point SF-36 PF subscale, 95%CI -0.19 to 38.9; low certainty). MSC therapy may increase risk of any adverse events (risk ratio [RR] 2.67, 95%CI 1.19 to 5.99; low certainty) and pain and swelling of the knee joint (RR 1.58, 95%CI 1.04 to 2.38; low certainty). CONCLUSIONS: Intra-articular injection of MSCs for chronic knee pain associated with OA probably provides little to no improvement in pain or physical function.

Predictors of fatal and nonfatal overdose after prescription of opioids for chronic pain: a systematic review and meta-analysis of observational studies.

BACKGROUND: Higher doses of opioids, mental health comorbidities, co-prescription of sedatives, lower socioeconomic status and a history of opioid overdose have been reported as risk factors for opioid overdose; however, the magnitude of these associations and their credibility are unclear. We sought to identify predictors of fatal and nonfatal overdose from prescription opioids. METHODS: We systematically searched MEDLINE, Embase, CINAHL, PsycINFO and Web of Science up to Oct. 30, 2022, for observational studies that explored predictors of opioid overdose after their prescription for chronic pain. We performed random-effects meta-analyses for all predictors reported by 2 or more studies using odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Twenty-eight studies (23 963 716 patients) reported the association of 103 predictors with fatal or nonfatal opioid overdose. Moderate- to high-certainty evidence supported large relative associations with history of overdose (OR 5.85, 95% CI 3.78-9.04), higher opioid dose (OR 2.57, 95% CI 2.08-3.18 per 90-mg increment), 3 or more prescribers (OR 4.68, 95% CI 3.57-6.12), 4 or more dispensing pharmacies (OR 4.92, 95% CI 4.35-5.57), prescription of fentanyl (OR 2.80, 95% CI 2.30-3.41), current substance use disorder (OR 2.62, 95% CI 2.09-3.27), any mental health diagnosis (OR 2.12, 95% CI 1.73-2.61), depression (OR 2.22, 95% CI 1.57-3.14), bipolar disorder (OR 2.07, 95% CI 1.77-2.41) or pancreatitis (OR 2.00, 95% CI 1.52-2.64), with absolute risks among patients with the predictor ranging from 2-6 per 1000 for fatal overdose and 4-12 per 1000 for nonfatal overdose. INTERPRETATION: We identified 10 predictors that were strongly associated with opioid overdose. Awareness of these predictors may facilitate shared decision-making regarding prescribing opioids for chronic pain and inform harm-reduction strategies SYSTEMATIC REVIEW REGISTRATION: Open Science Framework (https://osf.io/vznxj/).

Predictors of Persistent Post-Surgical Pain Following Total Knee Arthroplasty: A Systematic Review and Meta-Analysis of Observational Studies.

OBJECTIVE: Approximately one in four total knee replacement patients develop persistent pain. Identification of those at higher risk could help inform optimal management. METHODS: We searched MEDLINE, EMBASE, CINAHL, AMED, SPORTDiscus, and PsycINFO for observational studies that explored the association between risk factors and persistent pain (≥3 months) after total knee replacement. We pooled estimates of association for all independent variables reported by >1 study. RESULTS: Thirty studies (26,517 patients) reported the association of 151 independent variables with persistent pain after knee replacement. High certainty evidence demonstrated an increased risk of persistent pain with pain catastrophizing (absolute risk increase [ARI] 23%, 95% confidence interval [CI] 12 to 35), younger age (ARI for every 10-year decrement from age 80, 4%, 95% CI 2 to 6), and moderate-to-severe acute post-operative pain (ARI 30%, 95% CI 20 to 39). Moderate certainty evidence suggested an association with female sex (ARI 7%, 95% CI 3 to 11) and higher pre-operative pain (ARI 35%, 95% CI 7 to 58). Studies did not adjust for both peri-operative pain severity and pain catastrophizing, which are unlikely to be independent. High to moderate certainty evidence demonstrated no association with pre-operative range of motion, body mass index, bilateral or unilateral knee replacement, and American Society of Anesthesiologists score. CONCLUSIONS: Rigorously conducted observational studies are required to establish the relative importance of higher levels of peri-operative pain and pain catastrophizing with persistent pain after knee replacement surgery.

Fatty acid based antimicrobials from Streptomyces sp. SORS-24, an endophyte isolated from Sonchus oleraceus.

Due to the rise in bacterial resistance towards various therapeutic agents, interest is now developing towards fatty acid based antimicrobials because of their non-specific mode of action. A strain SORS 24 isolated from Sonchus oleraceus (Sow thistle) showed significant activity against Escherichia coli ATCC 25922 (25 mm), Chlorella vulgaris (20 mm), Bacillus subtilis DSM 10 (ATCC 6051) and Pseudomonas sp. (15 mm). It displayed an LC50 value of 10 µg/ml against Artemia salina (Brine shrimp) nauplii and an EC50 value of 0.8 µg/ml in the (DPPH) diphenylpicrylhydrazyl antioxidant assay. The strain also displayed genotoxicity against a PolA deficient strain, E. coli K-12 AB 3027 (15 mm). Mass spectrometry (HPLC-MS) showed that the strain produced oleamide (9-Octadecenamide) and erucamide (13-Docosenamide). Both of the purified fatty acid amides showed prominent activity against B. subtilis DSM 10 (ATCC 6051) (20 mm) and E. coli ATCC 25922 (15 mm). Significant genotoxicity was observed against E. coli K-12 AB 3027 (15 mm). The 16S gene sequencing revealed that the strain belonged to species, Streptomyces tanashiensis. As far as our understanding, this is the first report of this species producing these fatty acid based antimicrobials.

Potential role of viral metagenomics as a surveillance tool for the early detection of emerging novel pathogens.

Since the early times, human beings have always been faced with deadly microbial infections, both bacterial and viral. Pathogens such as viruses are always evolving owing to the processes of antigenic shift and drift. Such viral evolution results in the emergence of new types and serovars that prove deadly for humans-like influenza pandemics, severe acute respiratory syndrome (SARS) and Middle East respiratory syndrome (MERS). The pandemic of novel coronavirus SARS-CoV-2 is the recent example. It has resulted in a great loss of human lives and a serious burden on economy across the globe. To counter such situations, a system should exist for the early detection of emerging viral pathogens. This will help prevent possible outbreaks and save human lives. Most of such deadly novel viruses and viral outbreaks are known to be originated from animal hosts. Regular monitoring of potential hot spots of such emerging microbes, such as zoos and animal markets, through metagenomics could help assess the presence of new viruses and pathogens. In this review, we focus on the potential of viral metagenomics and propose a surveillance system based on it for the early detection and hence prevention of such emerging viral infections.

Bacillus cereus biofilm formation on central venous catheters of hospitalised cardiac patients.

Formation of bacterial biofilms is a risk with many in situ medical devices. Biofilm-forming Bacillus species are associated with potentially life-threatening catheter-related blood stream infections in immunocompromised patients. Here, bacteria were isolated from biofilm-like structures within the lumen of central venous catheters (CVCs) from two patients admitted to cardiac hospital wards. Isolates belonged to the Bacillus cereus group, exhibited strong biofilm formation propensity, and mapped phylogenetically close to the B. cereus emetic cluster. Together, whole genome sequencing and quantitative PCR confirmed that the isolates constituted the same strain and possessed a range of genes important for and up-regulated during biofilm formation. Antimicrobial susceptibility testing demonstrated resistance to trimethoprim-sulphamethoxazole, clindamycin, penicillin and ampicillin. Inspection of the genome revealed several chromosomal ß-lactamase genes and a sulphonamide resistant variant of folP. This study clearly shows that B. cereus persisting in hospital ward environments may constitute a risk factor from repeated contamination of CVCs.

Anoxic growth optimization for metal respiration and photobiological hydrogen production by arsenic-resistant Rhodopseudomonas and Rhodobacter species.

The current research focuses on anaerobic respiration of arsenic and other toxic metals by purple nonsulfur bacteria (PNSB). Among the optimization assays performed were carbon utilization, cross metal resistance, and metal respiration, along with a comparison of each assay in photoheterotrophic and chemoheterotrophic growth. The bacteria were identified by the classification of 16S ribosomal RNA gene sequences. Rhodobacter sp. PI3 proved to be more versatile in carbon source utilization (acetate, lactate, citrate, and oxalate), whereas Rhodopseudomonas palustris PI5 proved to be more versatile in metal resistance (arsenate, arsenite, cobalt, lead, selenium, and nickel). Both the strains were found to be positive for photofermentative hydrogen production along with arsenic respiration. This study reveals that anaerobic conditions are more appropriate for better efficiency of PNSB. Our study demonstrates that R. palustris PI5 and Rhodobacter sp. PI3 can be promising candidates for the biohydrogen production along with metal detoxification using heavy metal-polluted effluents as a substrate.

Opioids for Chronic Noncancer Pain: A Systematic Review and Meta-analysis.

Importance: Harms and benefits of opioids for chronic noncancer pain remain unclear. Objective: To systematically review randomized clinical trials (RCTs) of opioids for chronic noncancer pain. Data Sources and Study Selection: The databases of CENTRAL, CINAHL, EMBASE, MEDLINE, AMED, and PsycINFO were searched from inception to April 2018 for RCTs of opioids for chronic noncancer pain vs any nonopioid control. Data Extraction and Synthesis: Paired reviewers independently extracted data. The analyses used random-effects models and the Grading of Recommendations Assessment, Development and Evaluation to rate the quality of the evidence. Main Outcomes and Measures: The primary outcomes were pain intensity (score range, 0-10 cm on a visual analog scale for pain; lower is better and the minimally important difference [MID] is 1 cm), physical functioning (score range, 0-100 points on the 36-item Short Form physical component score [SF-36 PCS]; higher is better and the MID is 5 points), and incidence of vomiting. Results: Ninety-six RCTs including 26 169 participants (61% female; median age, 58 years [interquartile range, 51-61 years]) were included. Of the included studies, there were 25 trials of neuropathic pain, 32 trials of nociceptive pain, 33 trials of central sensitization (pain present in the absence of tissue damage), and 6 trials of mixed types of pain. Compared with placebo, opioid use was associated with reduced pain (weighted mean difference [WMD], -0.69 cm [95% CI, -0.82 to -0.56 cm] on a 10-cm visual analog scale for pain; modeled risk difference for achieving the MID, 11.9% [95% CI, 9.7% to 14.1%]), improved physical functioning (WMD, 2.04 points [95% CI, 1.41 to 2.68 points] on the 100-point SF-36 PCS; modeled risk difference for achieving the MID, 8.5% [95% CI, 5.9% to 11.2%]), and increased vomiting (5.9% with opioids vs 2.3% with placebo for trials that excluded patients with adverse events during a run-in period). Low- to moderate-quality evidence suggested similar associations of opioids with improvements in pain and physical functioning compared with nonsteroidal anti-inflammatory drugs (pain: WMD, -0.60 cm [95% CI, -1.54 to 0.34 cm]; physical functioning: WMD, -0.90 points [95% CI, -2.69 to 0.89 points]), tricyclic antidepressants (pain: WMD, -0.13 cm [95% CI, -0.99 to 0.74 cm]; physical functioning: WMD, -5.31 points [95% CI, -13.77 to 3.14 points]), and anticonvulsants (pain: WMD, -0.90 cm [95% CI, -1.65 to -0.14 cm]; physical functioning: WMD, 0.45 points [95% CI, -5.77 to 6.66 points]). Conclusions and Relevance: In this meta-analysis of RCTs of patients with chronic noncancer pain, evidence from high-quality studies showed that opioid use was associated with statistically significant but small improvements in pain and physical functioning, and increased risk of vomiting compared with placebo. Comparisons of opioids with nonopioid alternatives suggested that the benefit for pain and functioning may be similar, although the evidence was from studies of only low to moderate quality.

Innovative approaches to Alzheimer's therapy: Harnessing the power of heterocycles, oxidative stress management, and nanomaterial drug delivery system.

Alzheimer's disease (AD) presents a complex pathology involving amyloidogenic proteolysis, neuroinflammation, mitochondrial dysfunction, and cholinergic deficits. Oxidative stress exacerbates AD progression through pathways like macromolecular peroxidation, mitochondrial dysfunction, and metal ion redox potential alteration linked to amyloid-beta (Aß). Despite limited approved medications, heterocyclic compounds have emerged as promising candidates in AD drug discovery. This review highlights recent advancements in synthetic heterocyclic compounds targeting oxidative stress, mitochondrial dysfunction, and neuroinflammation in AD. Additionally, it explores the potential of nanomaterial-based drug delivery systems to overcome challenges in AD treatment. Nanoparticles with heterocyclic scaffolds, like polysorbate 80-coated PLGA and Resveratrol-loaded nano-selenium, show improved brain transport and efficacy. Micellar CAPE and Melatonin-loaded nano-capsules exhibit enhanced antioxidant properties, while a tetra hydroacridine derivative (CHDA) combined with nano-radiogold particles demonstrates promising acetylcholinesterase inhibition without toxicity. This comprehensive review underscores the potential of nanotechnology-driven drug delivery for optimizing the therapeutic outcomes of novel synthetic heterocyclic compounds in AD management. Furthermore, the inclusion of various promising heterocyclic compounds with detailed ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) data provides valuable insights for planning the development of novel drug delivery treatments for AD.

Microbial biochemical pathways of arsenic biotransformation and their application for bioremediation.

Arsenic is a ubiquitous toxic metalloid, the concentration of which is beyond WHO safe drinking water standards in many areas of the world, owing to many natural and anthropogenic activities. Long-term exposure to arsenic proves lethal for plants, humans, animals, and even microbial communities in the environment. Various sustainable strategies have been developed to mitigate the harmful effects of arsenic which include several chemical and physical methods, however, bioremediation has proved to be an eco-friendly and inexpensive technique with promising results. Many microbes and plant species are known for arsenic biotransformation and detoxification. Arsenic bioremediation involves different pathways such as uptake, accumulation, reduction, oxidation, methylation, and demethylation. Each of these pathways has a certain set of genes and proteins to carry out the mechanism of arsenic biotransformation. Based on these mechanisms, various studies have been conducted for arsenic detoxification and removal. Genes specific for these pathways have also been cloned in several microorganisms to enhance arsenic bioremediation. This review discusses different biochemical pathways and the associated genes which play important roles in arsenic redox reactions, resistance, methylation/demethylation, and accumulation. Based on these mechanisms, new methods can be developed for effective arsenic bioremediation.

Impact of osteopathic manipulative techniques on the management of dizziness caused by neuro-otologic disorders: systematic review and meta-analysis.

CONTEXT: Osteopathic manipulative treatment (OMT) has been utilized by osteopathic clinicians as primary or adjunctive management for dizziness caused by neuro-otologic disorders. To our knowledge, no current systematic reviews provide pooled estimates that evaluate the impact of OMT on dizziness. OBJECTIVES: We aimed to systematically evaluate the effectiveness and safety of OMT and analogous techniques in the treatment of dizziness. METHODS: We performed a literature search in CINAHL, Embase, MEDLINE, Allied and Complementary Medicine Database (AMED), EMCare, Physiotherapy Evidence Database (PEDro), PubMed, PsycINFO, Osteopathic Medicine Digital Library (OSTMED.DR), and Cochrane Central Register of Controlled Trials (CENTRAL) from inception to March 2021 for randomized controlled trials (RCTs) and prospective or retrospective observational studies of adult patients experiencing dizziness from neuro-otological disorders. Eligible studies compared the effectiveness of OMT or OMT analogous techniques with a comparator intervention, such as a sham manipulation, a different manual technique, standard of care, or a nonpharmacological intervention like exercise or behavioral therapy. Assessed outcomes included disability associated with dizziness, dizziness severity, dizziness frequency, risk of fall, improvement in quality of life (QOL), and return to work (RTW). Assessed harm outcomes included all-cause dropout (ACD) rates, dropouts due to inefficacy, and adverse events. The meta-analysis was based on the similarities between the OMT or OMT analogous technique and the comparator interventions. The risk of bias (ROB) was assessed utilizing a modified version of the Cochrane Risk of Bias Tool for RCTs and the Cochrane Risk of Bias in Non-randomized Studies - of Interventions (ROBINS-I) for observational studies. The quality of evidence was determined utilizing the Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) approach. RESULTS: There were 3,375 studies identified and screened, and the full text of 47 of them were reviewed. Among those, 12 (11 RCTs, 1 observational study, n=367 participants) met the inclusion criteria for data extraction. Moderate-quality evidence showed that articular OMT techniques were associated with decreases (all p<0.01) in disability associated with dizziness (n=141, mean difference [MD]=-11, 95% confidence interval [CI]=-16.2 to -5.9), dizziness severity (n=158, MD=-1.6, 95% CI=-2.4 to -0.7), and dizziness frequency (n=136, MD=-0.6, 95% CI=-1.1 to -0.2). Low-quality evidence showed that articular OMT was not associated with ACD rates (odds ratio [OR]=2.2, 95% CI=0.5 to 10.2, p=0.31). When data were pooled for any type of OMT technique, findings were similar; however, disability associated with dizziness and ACD rates had high heterogeneity (I2=59 and 46%). No studies met all of the criteria for ROB. CONCLUSIONS: The current review found moderate-quality evidence that treatment with articular OMT techniques was significantly associated with decreased disability associated with dizziness, dizziness severity, and dizziness frequency. However, our findings should be interpreted cautiously because of the high ROB and small sample sizes in the eligible studies.

Frequency of Congenital Cardiac Disease in Various Divisions of Khyber Pakhtunkhwa (KPK) Based on a Six-Month Analysis of Inpatients at a Tertiary Care Hospital's Pediatric Cardiology Unit.

OBJECTIVE: To identify the frequency of congenital heart disease (CHD) in various Khyber Pakhtunkhwa (KPK) divisions. MATERIALS AND METHODS: To perform this research, we reviewed the medical records of pediatric cardiology patients hospitalized between January 2022 and July 2022. Data was taken from the cardiology department's computerized data system between January 1 and July 31, 2022. To prevent any errors in diagnosis and address them during input by the ward clerk, patients' addresses, diagnoses, and gender were verified with the computerized medical record. Data were analyzed, and frequency and percentages were calculated. Per the digital mapping of KPK districts, we stratified and examined the data among various KPK divisions. RESULTS: Out Of the 371 patients with CHD who were admitted, 36.98% (137) were from the Peshawar division, 28.84% (107) from the Malakand division, 16.71% (62) from the Mardan division, 6.1% (23) from the Kohat division, 4.3% (16) from the Bannu division, 3.5% (13) from the Dera Ismail Khan division, and 3.5% (13) from the Hazara division. A total of 371 had CHD, of which 234 (63.07%) were cyanotic and 137 (36.92%) were cyanotic. The most prevalent acynotic congenital heart defect was patent ductus arteriosus (PDA) at 36.32% (85), followed by a ventricular septal defect (VSD) at 35.04 (82). The most frequent acyanotic congenital cardiac abnormality was tetralogy of Fallot (TOF) at 49.63% (68), which was followed by transposition of the great arteries (TGA) at 33.57% (46). CONCLUSION: In KPK, congenital heart disease is most prevalent in the divisions of Peshawar and Malakand, while it is least prevalent in Hazara.

Predictors of Recovery Following Lumbar Microdiscectomy for Sciatica: A Systematic Review and Meta-Analysis of Observational Studies.

Chronic post-surgical pain is reported by up to 40% of patients after lumbar microdiscectomy for sciatica, a complaint associated with disability and loss of productivity. We conducted a systematic review of observational studies to explore factors associated with persistent leg pain and impairments after microdiscectomy for sciatica. We searched eligible studies in MEDLINE, Embase, and CINAHL that explored, in an adjusted model, predictors of persistent leg pain, physical impairment, or failure to return to work after microdiscectomy for sciatica. When possible, we pooled estimates of association using random-effects models using the Grading of Recommendations Assessment, Development, and Evaluation approach. Moderate-certainty evidence showed that the female sex probably has a small association with persistent post-surgical leg pain (odds ratio (OR) = 1.15, 95% confidence interval (CI) = 0.63 to 2.08; absolute risk increase (ARI) = 1.8%, 95% CI = -4.7% to 11.3%), large association with failure to return to work (OR = 2.79, 95% CI = 1.27 to 6.17; ARI = 10.6%, 95% CI = 1.8% to 25.2%), and older age is probably associated with greater postoperative disability (ß = 1.47 points on the 100-point Oswestry Disability Index for every 10-year increase from age (>/=18 years), 95% CI = -4.14 to 7.28). Among factors that were not possible to pool, two factors showed promise for future study, namely, legal representation and preoperative opioid use, which showed large associations with worse outcomes after surgery. The moderate-certainty evidence showed female sex is probably associated with persistent leg pain and failure to return to work and that older age is probably associated with greater post-surgical impairment after a microdiscectomy. Future research should explore the association between legal representation and preoperative opioid use with persistent pain and impairment after microdiscectomy for sciatica.

The Outcome of Trans-catheter Closure of Patent Ductus Arteriosus: A Single-Center Experience.

Objective The objective is to share our experience of trans-catheter device closure of patent ductus arteriosus (PDA) and review its efficacy and immediate complications. Methodology This cross-sectional observational study was done in the Department of Pediatric cardiology, Lady Reading Hospital, Peshawar from January 2020 to December 2020. A total of 51 patients with isolated PDA, who underwent PDA device closure, were enlisted in this study through consecutive sampling methods, irrespective of their age and gender. Data of the patients were collected on preformed pro forma. Data was entered in SPSS 20 (SPSS Inc., Chicago, IL, USA). Descriptive statistics like mean ± SD for numerical data (age, weight, and hospital stay), while frequency and percentage for categorical variables (Device type, complication, hospital stay, and type of anesthesia given) were calculated. Results Among total 51 patients (33 [64.7%] females and 18 [35.3%] males) with mean age 8.19 ± 6.96 years underwent attempted trans-catheter PDA device closure. In all cases PDA was successfully occluded with appropriate size devices. General anesthesia was given in 38 (74.5%) patients. Complications occurred in only four (7.8%) patients in the form of hemolysis followed by acute kidney injury in one patient, another had device embolization to descending aorta, which was retrieved in cath lab, one had device embolization to the right pulmonary artery, which was retrieved in cath lab and one had mild left ventricular systolic dysfunction. The mean duration of hospital stay was 22.0 ± 10.2 h. Conclusion Trans-catheter PDA device closure is a safe procedure with a high success rate and little morbidity.

Pattern of Vascular Anomalies Associated With Sinus Venosus Atrial Septal Defect.

Objective To evaluate children with sinus venosus atrial septal defect (SV-ASD) for associated vascular anomalies. Methodology A total of 72 children with sinus venosus atrial septal defect with partial anomalous pulmonary venous return who presented to pediatric cardiology unit, Lady Reading Hospital Peshawar, from January 2019 till June 2021 were included in this cross-sectional study. Diagnosis of sinus venosus atrial septal defect was confirmed through two-dimensional (2D) and Doppler echocardiography performed by a pediatric cardiologist. Cardiac CT angiography was performed and assessed by a pediatric cardiac interventionist and radiologist. Patients were managed according to standard protocols and guidelines. The data were entered and analyzed with Statistical Package for the Social Sciences (SPSS) version 20. Percentages were used to express frequencies. Results Mean age was 8.3 ± 2.7 years (interquartile range (IQR): two months to 18 years). There were 37 (51.4%) male and 35 (48.6%) female patients. Out of 72 patients, 64 (88.8%) patients had superior sinus venosus atrial septal defect, while inferior sinus venosus atrial septal defect was found in eight (11.1%) patients. In six (8.3%) patients, associated secundum atrial septal defect was identified. Bilateral superior vena cava was found in seven (9.7%) patients. Left aortic arch was seen in 70 (97.2%) patients, whereas two (2.7%) patients had right aortic arch. Conclusion Sinus venosus ASD is a rare type of atrial septal defect which is also associated with both pulmonary and systemic vascular anomalies. Diagnosing these vascular anomalies is of paramount importance before any corrective intervention can be done. Recognizing the pattern of these anomalies should be known to every interventional cardiologist, radiologist, and cardiac surgeon. Echocardiography alone is not a good tool to assess these extracardiac structures. Imaging modalities like CT angiography and MRI have refined our preoperative workup which is essential for the ultimate outcome of the corrective intervention.

Congenital Heart Disease and Its Association in Children With Down Syndrome.

Objective The objective is to determine the frequency of different congenital heart diseases and their association in children with Down syndrome (DS). Methodology This cross-sectional observational study was conducted in the pediatric department of Peshawar Institute of Cardiology, Peshawar, Pakistan from August 2021 to July 2022. A total of 123 children with DS and congenital heart disease (CHD) were included in this cross-sectional study. Detailed history and examination were performed, and findings were documented on performed pro forma. Diagnosis of CHD was confirmed through two-dimensional (2D) and Doppler echocardiography performed by a pediatric cardiologist. Patients were managed according to standard protocols and guidelines. The data including age, gender, mother's age at the time of birth, type of CHD and growth failure were documented and analyzed. Percentages were used to express frequencies. Results The mean age was 2.2 years ± 3.4 years (interquartile range (IQR): 10 days to 14 years). There were 65 (52.8%) male and 58 (47.1%) female patients. Out of 123 patients, 101 (82.1%) had acyanotic CHD and 22 (17.8%) had cyanotic CHD. Among acyanotic CHD, isolated ventricular septal defect (VSD) was the most common observation in 23 (22.3%) and among cyanotic CHD, tetralogy of Fallot (TOF) in seven (31.8%) patients. The most common associations of CHD were VSD+ patent ductus arteriosus (PDA) in 11 (9%) patients and atrial septal defect (ASD)+PDA in nine (7.3%) patients. The median age of the mother at delivery was 31 years (interquartile range (IQR): 20 years to 45 years). Growth failure was seen in 70 (56.9%) patients. Conclusion Based on our data, VSD is the most common CHD followed by a complete atrio-VSD (CAVSD) in children with DS. The most common association of CHD in DS is VSD with PDA. Growth failure is seen in most of the patients with DS having a CHD.

Emergency Department Presentation and Outcome of Children With Cyanotic Congenital Heart Diseases.

Objective This study aimed to assess the outcome and see the spectrum of presenting symptoms of children with cyanotic congenital heart diseases (CHDs) admitted through the emergency department in Lady Reading Hospital (LRH) in Peshawar, Pakistan. Materials and methods This cross-sectional study included 104 children with cyanotic CHD admitted through the emergency department in the pediatric cardiology unit of LRH from February 2019 to January 2020. Diagnosis of cyanotic CHD was confirmed through two-dimensional echocardiography. Patients were treated according to standard protocols for their presenting symptoms. The data were analyzed using Statistical Package for the Social Sciences (SPSS), version 20.0 (IBM Corp., Armonk, NY) and frequencies were expressed as percentages. Results The study included 65 male cases (62.5%) and 39 female cases (37.5%), and participant ages ranged from 10 days to 15 years (mean, 2.7 ± 3.4 years). Of 104 patients, 70 presented with cyanotic spells (84.5%), 53 with fever (10.7%), 28 with respiratory distress (26.5%), 11 with loose stools (10.5%), 10 with hemiplegia (9.6%), and eight with seizures (7.6%). Pneumonia was a precipitating factor in 13 patients (12.5%), infective endocarditis in 12 patients (11%), gastroenteritis in 11 (11%), brain abscess and cerebrovascular accidents in seven patients each (6% each), meningitis in six patients (6%), and tuberculous pericardial effusion in one patient (<1%). The primary CHD was tetralogy of Fallot (TOF) in 52 patients, tricuspid atresia in 14 patients, pulmonary atresia in 13 patients, double outlet right ventricle in 10 patients, transposition of great arteries (TGA) in seven patients, and total anomalous pulmonary venous return (TAPVR), truncus arteriosus, congenitally corrected TGA, and critical pulmonary stenosis in two patients each. Twenty-six patients received treatment of the acute problem and instructions for follow-up monitoring. Twelve patients died during their hospital stay, and three left against medical advice. Fifteen patients received patent ductus arteriosus stenting, and six received right ventricular outflow tract stenting. One patient received a Blalock-Taussig (BT) shunt stent, and one received a left pulmonary artery stent. Two patients received a balloon pulmonary valvotomy, and one received pericardial effusion drainage. Eleven patients received surgical correction of TOF, 11 received surgical correction for BT shunt, four received surgical correction for brain abscess drainage, and two received TAPVR repair. Conclusion TOF was the most common cyanotic heart disease in our study. Cyanotic spells or increased cyanosis was the most common presenting concern. Cyanotic CHDs present with variable extracardiac signs and symptoms in emergencies. Appropriate assessment, immediate management of the acute problem, and timely intervention or surgical management result in good outcomes.

Cannabis in the management of PTSD: a systematic review.

INTRODUCTION: Existing reviews exploring cannabis effectiveness have numerous limitations including narrow search strategies. We systematically explored cannabis effects on PTSD symptoms, quality of life (QOL), and return to work (RTW). We also investigated harm outcomes such as adverse effects and dropouts due to adverse effects, inefficacy, and all-cause dropout rates. METHODS: Our search in MEDLINE, EMBASE, PsycInfo, CINAHL, Web of Science, CENTRAL, and PubMed databases, yielded 1 eligible RCT and 10 observational studies (n = 4672). Risk of bias (RoB) was assessed with the Cochrane risk of bias tool and ROBINS-I. RESULTS: Evidence from the included studies was mainly based on non-randomized studies with no comparators. Results from unpooled, high RoB studies showed that cannabis was associated with a reduction in overall PTSD symptoms and improved QOL. Dry mouth, headaches, and psychoactive effects such as agitation and euphoria were the commonly reported adverse effects. In most studies, cannabis was well tolerated, but small proportions of patients experienced a worsening of PTSD symptoms. CONCLUSION: Evidence in the current study primarily stems from low quality and high RoB observational studies. Further RCTs investigating cannabis effects on PTSD treatment should be conducted with larger sample sizes and explore a broader range of patient-important outcomes.

Dropout associated with osteopathic manual treatment for chronic noncancerous pain in randomized controlled trials.

CONTEXT: Reviews exploring harm outcomes such as adverse effects (AE), all cause dropouts (ACD), dropouts due to inefficacy, and dropouts due to AE associated with osteopathic manipulative treatment (OMT) or osteopathic manual therapy (OMTh) are scant. OBJECTIVES: To explore the overall AE, ACD, dropouts due to inefficacy, and AE in chronic noncancerous pain (CNCP) patients receiving OMTh through a systematic review of previous literature. METHODS: For this systematic review and meta-analysis, the authors searched MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Physiotherapy Evidence Database (PEDro), EMCare, and Allied and Complementary Medicine Database (AMED), and Ostmed.Dr, as well as the bibliographical references of previous systematic reviews evaluating OMTh for pain severity, disability, quality of life, and return to work outcomes. Randomized controlled trials with CNCP patients 18 years or older with OMTh as an active or combination intervention and the presence of a control or combination group were eligible for inclusion. In this sub-study of a previous, larger systematic review, 11 studies (n=1,015) reported data that allowed the authors to perform meta-analyses on ACD and dropouts due to AE. The risk of bias (ROB) was assessed with the Cochrane ROB tool and the quality of evidence was determined with the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. RESULTS: The pooled analysis showed that ACD was not significantly different for visceral OMTh (vOMTh) vs. OMTh control (odds ratio [OR]=2.66 [95% confidence interval [[CI]], 0.28, 24.93]) or for OMTh vs. standard care (OR=1.26 [95% CI, 0.84, 1.89]; I2=0%). Single study analysis showed that OMTh results were nonsignificant in comparison with chemonucleolysis, gabapentin, and exercise. OMTh in combination with gabapentin (vs. gabapentin alone) and OMTh in combination with exercise (vs. exercise alone) showed nonsignificant ACD. Dropouts due to AE were not significantly different, but the results could not be pooled due to an insufficient number of studies. CONCLUSIONS: Most articles did not explicitly report AEs, ACD rates, or dropouts due to AEs and inefficacy. The limited data available on dropouts showed that OMTh was well tolerated compared with control interventions, and that the ACD and dropouts due to AEs were not significantly different than comparators. Future trials should focus on explicit reporting of dropouts along with beneficial outcomes to provide a better understanding of OMTh efficacy.