Effectiveness and Safety of Ketamine for Unipolar Depression: a Systematic Review

Major Depressive Disorder (MDD) is a common psychiatric disorder with major implications for healthcare system and socioeconomic burden. For chronic and treatment-resistant depression, Ketamine has emerged as a possible treatment option. This systematic review explores the evidence for the effectiveness and tolerability of Ketamine in patients with MDD. This systematic review was conducted following the guidelines of Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) checklist. Eight electronic databases were searched by using search terms: (ketamine) AND (trial OR RCT OR clinical-trial) AND (depressive OR depression OR “depressive-disorder”). After a rigorous screening process against the predetermined eligibility criteria, 35 randomized controlled trials (RCTs) were included. Quality assessment of included studies was done by using the Cochrane risk-of-bias tool for RCTs. Thirty-five RCTs are included in this review article with majority of studies from United States, Iran, and China. Intravenous (IV) Ketamine was effective in 70% (21/30) of the included studies whereas oral and Intranasal (IN) Ketamine were effective in two and three studies, respectively. The majority of studies (6/8) using Ketamine as anesthetic agent during electroconvulsive therapy (ECT) failed to show an improvement compared to the participants receiving ECT and placebo. The most common reported side effects were nausea, vomiting, dizziness, diplopia, drowsiness, dysphoria, hallucinations, and confusion. Ketamine is an effective treatment option for patients with MDD with undesirable effects when administered via oral, IV and IN routes. Ketamine agumentation of ECT requires further exploration in well-designed studies with adequate sample size. The short-lived antidepressant effect of Ketamine is a potential limitation, therefore, further studies administering multiple infusions for acute treatment and maintenance are necessary.

     

A 3′ untranslated region polymorphism rs2304277 in the DNA repair pathway gene OGG1 is a novel risk modulator for urothelial bladder carcinoma

Altered DNA repair capacity may affect an individual's susceptibility to cancers due to compromised genomic integrity. This study was designed to elucidate the association of selected polymorphisms in DNA repair genes with urothelial bladder carcinoma (UBC). OGG1 rs1052133 and rs2304277, XRCC1 rs1799782 and rs25487, XRCC3 rs861539, XPC rs2228001, and XPD rs13181 were genotyped using polymerase chain reaction–restriction fragment length polymorphism (PCR‐RFLP) in 200 UBC cases and 200 controls. We found association of OGG1 rs2304277 [odds ratio (OR)_GG = 3.55, 95% confidence interval (CI) = 1.79–7.06] and XPC rs2228001 (OR_AC = 2.38, 95% CI = 1.43–3.94) with UBC. In stratified analysis with respect to smoking status, OGG1 rs2304277 and XPC rs2228001 exhibited increased risk in smokers [(rs2304277 OR_GG = 4.96, 95% CI = 1.51–16.30) (rs2228001 OR_AC = 2.19, 95% CI = 1.02–4.72)] as well as nonsmokers [(rs2304277 OR_GG = 2.95, 95% CI = 1.26–6.90) (rs2228001 OR_AC = 2.57, 95% CI = 1.31–5.04)]. These polymorphisms were also associated with both low‐grade [(rs2304277 OR_GG = 3.73, 95% CI = 1.72–8.09) (rs2228001 OR_AC = 2.18, 95% CI = 1.21–3.92)] and high‐grade tumors [(rs2304277 OR_GG = 3.45, 95% CI = 1.52–7.80) (rs2228001 OR_AC = 2.81, 95% CI = 1.48–5.33)] as well as with non–muscle‐invasive bladder cancer [(rs2304277 OR_GG = 4.03, 95% CI = 1.87–8.67) (rs2228001 OR_AC = 2.14, 95% CI = 1.20–3.81)] and muscle‐invasive bladder cancer [(rs2304277 OR_GG = 3.06, 95%CI = 1.31–7.13) (rs2228001 OR_AC = 2.95, 95%CI = 1.51–5.75)]. This is the first study on DNA repair gene polymorphisms and UBC in the Pakistani population. It identifies OGG1 rs2304277 and replicates XPC rs2228001 as significant modulators of UBC susceptibility.     

Predicting the Lateral Load Carrying Capacity of Reinforced Concrete Rectangular Columns: Gene Expression Programming

This research presents a novel approach of artificial intelligence (AI) based gene expression programming (GEP) for predicting the lateral load carrying capacity of RC rectangular columns when subjected to earthquake loading. To achieve the desired research objective, an experimental database assembled by the Pacific Earthquake Engineering Research (PEER) center consisting of 250 cyclic tested samples of RC rectangular columns was employed. Seven input variables of these column samples were utilized to develop the coveted analytical models against the established capacity outputs. The selection of these input variables was based on the linear regression and cosine amplitude method. Based on the GEP modelling results, two analytical models were proposed for computing the flexural and shear capacity of RC rectangular columns. The performance of both these models was evaluated based on the four key fitness indicators, i.e., coefficient of determination (R²), root mean squared error (RMSE), mean absolute error (MAE), and root relative squared error (RRSE). From the performance evaluation results of these models, R², RMSE, MAE, and RRSE were found to be 0.96, 53.41, 38.12, and 0.20, respectively, for the flexural capacity model, and 0.95, 39.47, 28.77, and 0.22, respectively, for the shear capacity model. In addition to these fitness criteria, the performance of the proposed models was also assessed by making a comparison with the American design code of concrete structures ACI 318-19. The ACI model reported R², RMSE, MAE, and RRSE to be 0.88, 101.86, 51.74, and 0.39, respectively, for flexural capacity, and 0.87, 238.74, 183.66, and 1.35, respectively, for shear capacity outputs. The comparison depicted a better performance and higher accuracy of the proposed models as compared to that of ACI 318-19.     

A proposal for shoring up Federal Trade Commission protections for electronic health record–connected consumer apps under 21st Century Cures

Under the 21st Century Cures Act and the Office of the National Coordinator for Health Information Technology (ONC) rule implementing its interoperability provisions, a patient’s rights to easily request and obtain digital access to portions of their medical records are now supported by both technology and policy. Data, once directed by a patient to leave a Health Insurance Portability and Accountability Act–covered health entity and enter a consumer app, will usually fall under Federal Trade Commission oversight. Because the statutory authority of the ONC does not extend to health data protection, there is not yet regulation to specifically address privacy protections for consumer apps. A technologically feasible workflow that could be widely adopted and permissible under ONC’s rule, involves using the SMART on FHIR OAuth authorization routine to present standardized information about app behavior. This approach would not bias the patient in a way that triggers penalties under information blocking provisions of the rule.     

Asparaginase-associated pancreatitis in children

l-asparaginase has been an element in the treatment for acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma since the late 1960s and remains an essential component of their combination chemotherapy. Among the major toxicities associated with l-asparaginase therapy are pancreatitis, allergic reactions, thrombotic events, hepatotoxicity and hyperlipidaemia. Acute pancreatitis is one of the most common reasons for stopping treatment with l-asparaginase. Short-term complications of asparaginase-associated pancreatitis include development of pseudocysts and pancreatic necrosis. Long-term complications include chronic pancreatitis and diabetes. The pathophysiology of asparaginase-associated pancreatitis remains to be uncovered. Individual clinical and genetic risk factors have been identified, but they are only weak predictors of pancreatitis. This review explores the definition, possible risk factors, treatment and complications of asparaginase-associated pancreatitis.     

Association of rs10490924 in ARMS2/HTRA1 with age‐related macular degeneration in the Pakistani population

Age‐related macular degeneration (AMD) is a disease of the elderly in which central vision is lost because of degenerative changes of the macula. The current study investigated the association of single‐nucleotide polymorphisms (SNPs) with AMD in the Pakistani population. Four SNPs were analyzed in this study: rs1061170 in the CFH, rs429608 near CFB, rs2230199 in the C3, and rs10490924 in ARMS2/HTRA1. This case‐control association study was conducted on 300 AMD patients (125 wet AMD and 175 dry AMD) and 200 unaffected age‐ and gender‐matched control individuals. The association of the SNP genotypes and allele frequency distributions were compared between patients and healthy controls, keeping age, gender, and smoking status as covariates. A significant genotype and variant allele association was found of rs10490924 in ARMS2/HTRA1 with wet AMD, while the SNPs in CFH, CFB, and C3 were not associated with AMD in the current Pakistani cohort. The lack of association of CFH, CFB, and C3 may be attributed to limited sample size. This study demonstrates that genetic causative factors of AMD differ among populations and supports the need for genetic association studies among cohorts from various populations to increase our global understanding of the disease pathogenesis.     

Microfluidics: The future of microdissection TESE?

Non-obstructive azoospermia (NOA) is a severe form of infertility accounting for 10% of infertile men. Microdissection testicular sperm extraction (microTESE) includes a set of clinical protocols from which viable sperm are collected from patients (suffering from NOA), for intracytoplasmic sperm injection (ICSI). Clinical protocols associated with the processing of a microTESE sample are inefficient and significantly reduce the success of obtaining a viable sperm population. In this review we highlight the sources of these inefficiencies and how these sources can possibly be removed by microfluidic technology and single-cell Raman spectroscopy.     

Clinical effects of gynecologic laparoscopy courses in the United Arab Emirates

Objective

To evaluate the impact of gynecologic laparoscopy courses on the participants’ laparoscopy practice.

Methods

We conducted 5 repeated laparoscopy courses between 2008 and 2012 at the United Arab Emirates University in Al Ain, United Arab Emirates, so as to enhance performance in the operating room. An electronic questionnaire was sent to all participants from each of the courses to evaluate the impact of course attendance on clinical practice.

Results

Of 70 participants who were approached to complete the online questionnaire, 38 (54.3%) responded. The majority were female (94.7%) and specialists (65.8%). Half the participants (50.0%) thought they would probably not have started performing laparoscopy without having attended the course. Of the participants, 18.4% thought that their operating skills had greatly improved, 63.2% felt that their operating skills had improved moderately to a lot, and 6/12 participants who had not been performing laparoscopy before attendance of the course began doing so. Overall, the course had no significant impact on the participants’ performance of laparoscopy (P = 0.51, McNemar test), but the proportion of participants who performed level II laparoscopy was significantly increased after course attendance (10.5% versus 47.4%; P = 0.001, McNemar test).

Conclusion

Gynecologic laparoscopy courses encourage gynecologists to use laparoscopy in clinical practice.     

Safety,tolerability, pharmacokinetics,pharmacodynamics, and exploratory efficacy of the novel enzyme replacement therapy avalglucosidase alfa (neoGAA) in treatment-naïve and alglucosidase alfa-treated patients with late-onset Pompe disease: A phase 1, open-label,multicenter, multinational,ascending dose study

This multicenter/multinational, open-label, ascending-dose study (NCT01898364) evaluated safety, tolerability, pharmacokinetics, pharmacodynamics, and exploratory efficacy of repeat-dose avalglucosidase alfa (neoGAA), a second-generation, recombinant acid α-glucosidase replacement therapy, in late-onset Pompe disease (LOPD). Patients ≥18 years, alglucosidase alfa naïve (Naïve) or previously receiving alglucosidase alfa for ≥9 months (Switch), with baseline FVC ≥50% predicted and independently ambulatory, received every-other-week avalglucosidase alfa 5, 10, or 20?mg/kg over 24 weeks. 9/10 Naïve and 12/14 Switch patients completed the study. Avalglucosidase alfa was well-tolerated; no deaths/life-threatening serious adverse events (SAEs). One Naïve patient withdrew for study drug-related SAEs (respiratory distress/chest discomfort). Infusion-associated reactions (IARs) affected 8 patients. Most treatment-emergent AEs/IARs were non-serious with mild-to-moderate intensity. At screening, 5 Switch patients tested positive for anti-avalglucosidase alfa antibodies; on-treatment, 2 Switch and 9 Naïve patients seroconverted. Post-infusion, avalglucosidase alfa plasma concentrations declined monoexponentially (t_1/2z～1.0?h). AUC was 5–6?×?higher in the 20?vs 5?mg/kg group. Pharmacokinetics were similar between Switch and Naïve groups and over time. Baseline quadriceps muscle glycogen was low (～6%) in most patients, generally remaining unchanged thereafter. Exploratory efficacy parameters (pulmonary function/functional capacity) generally remained stable or improved. Avalglucosidase alfa's well-tolerated safety profile and exploratory efficacy results support further avalglucosidase alfa development.