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Esophageal food bolus and/or foreign body (FB) impaction is a common gastrointestinal emergency. This meta-analysis reports on the pooled outcomes of cap-assisted endoscopic removal of esophageal FB.We conducted a comprehensive search of several databases (inception to February 2022) to identify studies reporting on the use of a cap in the endoscopic treatment of esophageal FB ingestion. A random effects model was used to calculate the pooled odds ratio (OR) and mean difference (MD), and ISix studies were analyzed that included 677 patients treated with cap-assisted and 694 with conventional endoscopy. The cap-assisted method demonstrated statistically significant superiority regarding technical success (pooled OR 7.1, 95% confidence interval [CI] 1.9-26.9; P=0.004), en bloc removal (pooled OR 26.6, 95%CI 17.6-40.2; P0.001), as well as a significantly shorter procedure time (4.6 min, 95%CI -6.5 to -2.8; P0.001), compared to conventional methods. Better technical success was achieved with the cap-assisted method performed under anesthesia (OR 8.7, 95%CI 1.6-47.7; P=0.01); however, a shorter procedure time was noted for the cap-assisted method without anesthesia (MD -1.5, 95%CI -2.7 to -0.4; P=0.01). Pooled adverse events were comparable. Pooled OR for mucosal tear was significantly lower with cap in food bolus impaction (OR 0.07, 95%CI 0.01-0.38; P=0.02).Cap-assisted endoscopic removal of esophageal FB is associated with better technical success and en bloc removal, and a shorter procedure time compared to conventional methods, with comparable adverse events.

BackgroundThe workup for idiopathic normal pressure hydrocephalus (INPH) can be difficult to coordinate, and determining appropriate patients for ventriculoperitoneal shunting can be challenging. Therefore, we hypothesized that implementing a formalized protocol can improve patient selection for a shunt. In conjunction with neurology and neurosurgery, we instituted a standardized means of assessing patients whose presentation is concerning for INPH and compared their workup with similar patients seen without the Protocol (i.e., preprotocol [PP]) regarding baseline characteristics, assessment, and outcomes.MethodsTwenty-six PP patients were compared with 40 Protocol patients on measures, including baseline deficits, workup, neurosurgical evaluation, and response to shunt.ResultsAverage age was similar between groups, and the percentage of patients who had a decline in gait, cognition, and/or incontinence was not statistically different (p > 0.05). Significantly more Protocol patients underwent high-volume lumbar puncture (HVLP; 97.5%; PP, 61.5%; p < 0.001) and received formalized gait assessment with the Gait Scale (90%; PP, 0%, p < 0.001) and standardized cognitive testing (95%; PP, 38.5%; p < 0.001). Significantly more Protocol patients had no improvement after HVLP (33.3%; PP, 6.25%; p < 0.045); subsequently, fewer got shunted (57.5%; PP, 84.6%; p < 0.030). More Protocol patients who were shunted reported gait improvement (100%; PP, 72.7%; p = 0.009), although there was no difference in cognition (59.2%; PP, 82.6%; p = 0.108) or incontinence (18.2%; PP, 39.1%; p = 0.189).ConclusionsImplementing an INPH Protocol leads to standardized and more extensive assessment and better patient selection for and subsequent outcomes from shunting, specifically regarding gait.

Autophagy is a fundamental cellular process that eliminates molecules and subcellular elements, including nucleic acids, proteins, lipids and organelles, via lysosome-mediated degradation to promote homeostasis, differentiation, development and survival. While autophagy is intimately linked to health, the intricate relationship among autophagy, aging and disease remains unclear. This Review examines several emerging features of autophagy and postulates how they may be linked to aging as well as to the development and progression of disease. In addition, we discuss current preclinical evidence arguing for the use of autophagy modulators as suppressors of age-related pathologies such as neurodegenerative diseases. Finally, we highlight key questions and propose novel research avenues that will likely reveal new links between autophagy and the hallmarks of aging. Understanding the precise interplay between autophagy and the risk of age-related pathologies across organisms will eventually facilitate the development of clinical applications that promote long-term health.

Population-scale genetic studies can identify drug targets and allow disease risk to be predicted with resulting benefit for management of individual health risks and system-wide allocation of health care delivery resources. Although population-scale projects are underway in many parts of the world, genetic variation between population groups means that additional projects are warranted. South Asia has a population whose genetics is the least characterized of any of the world’s major populations. Here we describe GenomeAsia studies that characterize population structure in South Asia and that create tools for economical and accurate genotyping at population-scale. Prior work on population structure characterized isolated population groups, the relevance of which to large-scale studies of disease genetics is unclear. For our studies we used whole genome sequence information from 4,807 individuals recruited in the health care delivery systems of Pakistan, India and Bangladesh to ensure relevance to population-scale studies of disease genetics. We combined this with WGS data from 927 individuals from isolated South Asian population groups, and developed a custom SNP array (called SARGAM) that is optimized for future human genetic studies in South Asia. We find evidence for high rates of reproductive isolation, endogamy and consanguinity that vary across the subcontinent and that lead to levels of homozygosity that approach 100 times that seen in outbred populations. We describe founder effects that increase the power to associate functional variants with disease processes and that make South Asia a uniquely powerful place for population-scale genetic studies.

This article provides an overview of FDA's regulatory processes for drug development and approval, and the estimated costs associated with the development of a drug, and also examines the issues and challenges facing the FDA in the near future.A literature search was performed using MEDLINE to summarize the current FDA drug approval processes and future directions. MEDLINE was further utilized to search for all cost analysis studies performed to evaluate the pharmaceutical industry RD productivity and drug development cost estimates.While the drug approval process remains at high risk and spans over multiple years, the FDA drug review and approval process has improved, with the median approval time for new molecular drugs been reduced from 19 months to 10 months. The overall cost to development of a drug remains quite high and has been estimated to range from $868M to $1,241M USD. Several new laws have been enacted, including the FDA Safety and Innovation Act (FDASIA) of 2013, which is designed to improve the drug approval process and enhance access to new medicines.The FDA's improved processes for drug approval and post-market surveillance have achieved the goal of providing patients with timely access to effective drugs while minimizing the risk of drug-related harm. The FDA drug approval process is not without controversy, as a number of well-known gastroenterology drugs have been withdrawn from the US market over the past few years. With the approval of the new FDASIA law, the FDA will continue to improve their processes and, working together with the ACG through the FDA-Related Matters Committee, continue to develop safe and effective drugs for our patients.

Background: Deep brain stimulation (DBS) of the globus pallidus internus is established as efficacious for dystonia, yet the optimal target within this structure is not well defined. Published evidence suggests that spatial normalization provides a better estimate of DBS lead location than traditional methods based on standard stereotactic coordinates. Methods: We retrospectively reviewed our pallidal implanted dystonia population. Patient imaging scans were morphed into an MRI atlas using a nonlinear image registration algorithm. Active contact locations were projected onto the atlas and clusters analyzed for the degree of variance in two groups: (1) good and poor responders and (2) cervical (CD) and generalized dystonia (GD). Results: The average active contact location between CD and GD good responders was distinct but not significantly different. The mean active contact for CD poor responders was significantly different from CD responders and GD poor responders in the dorsoventral direction. Conclusions: A normalized imaging space is arguably more accurate in visualizing postoperative leads. Despite some separation between groups, this data suggests there was not an optimal pallidal target for common dystonia patients. Degrees of variance overlapped due to a large degree of individual target variation. Patient selection may ultimately be the key to maximizing patient outcomes. © 2014 S. Karger AG, Basel

PURPOSE: To assess the pattern of recovery of the visual field of patients with optic neuritis and to determine whether all affected portions of the visual field recover similarly or certain portions of the visual field have greater recovery. METHODS: We reviewed the Humphrey Visual Field (Allergan-Humphrey Inc, San Leandro, California) data from the initial and 6-month examination for the involved and fellow eyes of patients enrolled in the Optic Neuritis Treatment Trial (ONTT). The average threshold for each patient was calculated for the entire tested field and for locations within concentric rings having a radius 3, 9, 15, 21, and 27 degrees from fixation. The absolute amount of improvement and percentage improvement in average threshold between entry and the 6-month follow-up examination were determined for each patient. These measurements were compared within the concentric rings to assess patterns of recovery. RESULTS: Patients with localized defects recovered 86% ± 20% of their initial defect in average threshold, whereas those having diffuse defects recovered an average of 85% ± 23%. The area about fixation had the greatest relative recovery of threshold (87% ± 21% at 3 degrees); the relative recovery decreased with increasing eccentricity from fixation ( P CONCLUSIONS: Patients with optic neuritis have a marked return of visual field function that does not appear to differ between patients with diffuse or localized field defects. The reduced redundancy of axons in the periphery of the field compared with near fixation may be responsible for the greater relative recovery of threshold near fixation.

PURPOSE: To quantify automated visual field defects seen at entry in the Optic Neuritis Treatment Trial (ONTT) to determine whether particular areas of the field are preferentially affected and to determine the extent of visual field involvement in patients having "localized" field defects. METHODS: Review of Humphrey 30-2 Visual Field (Allergan-Humphrey, Inc, San Leandro, CA) data from the involved and fellow eyes of 440 patients who were enrolled in the ONTT. Field defects were evaluated by comparing the involved eye to the fellow eye. RESULTS: Patients with diffuse visual field defects had a relatively equal diminution of visual threshold throughout the tested 30-2 field. Patients with localized central and cecocentral scotomas had their greatest depression of threshold centrally; however, even those patients with mild defects (mean defect, 20 dB) central and cecocentral defects had even greater peripheral depression. Patients with altitudinal or quadrant defects had involvement of the "unaffected" field that also varied with the mean defect. The overall average depression of visual threshold for all patients averaged 36% ± 4% and was relatively uniform throughout the tested field. CONCLUSIONS: Optic neuritis affects the entire central 30-2 field, even in patients who appear to have localized depression of visual threshold. Optic neuritis does not appear to have a predilection for any particular area of the visual field.

Christopher Tolleson,1 John Fang,1 Pengcheng Lu,2 Huiyun Wu,2 Thomas Davis11Movement Disorders, Department of Neurology, 2Department of Biostatistics, Vanderbilt University, Nashville, TN, USABackground: Treating neuropsychiatric problems in Parkinson's disease (PD) remains challenging. Only rivastigmine has US Food and Drug Administration approval for the treatment of PD dementia. Some studies have shown that atypical neuroleptics adequately improve hallucinations while others suggest that side effects and increased mortality negate benefit. We utilized a chart review to assess the tolerability and efficacy of commonly used agents for neuropsychiatric symptoms in PD.Methods: We reviewed patients with a PD diagnosis in our clinic database who were being treated with antidementia agents (donepezil, galantamine, rivastigmine, memantine) or atypical neuroleptics (quetiapine, olanzapine, clozapine) by two PD specialists over 13 years. We determined tolerability by therapy retention in comparison with the accepted gold standard, ie, rivastigmine for dementia and clozapine for hallucinations. Clinician documentation of patient/caregiver or personally perceived clinical improvement was recorded to define therapeutic response. Secondary outcome measures were death, treatment-limiting side effects, and weight change.Results: A total of 171 PD patients met criteria for study inclusion. All medications were similarly retained in comparison with the standard, with the exception of donepezil which was significantly better (P < 0.02) than rivastigmine. Using the documentation metric, no medication was statistically superior to its standard. Olanzapine approached significance because it was inferior to the clozapine standard (P < 0.08). Secondary outcome measures were similar among medications.Conclusion: We conclude that, as a group, acetylcholinesterase inhibitors, atypical neuroleptics, and memantine are well tolerated in treating either cognitive difficulties or hallucinations in PD. They appear to offer variable levels of clinical benefit, as well per documented therapeutic responses. Side effects, death, and weight change were not significantly different among medications.Keywords: Parkinson's disease, atypical neuroleptics, acetylcholinesterase inhibitors, dementia, hallucinations

The purpose of the study was to estimate the cost-effectiveness of gastric bypass in the treatment of severe obesity (body mass index40). A deterministic decision analysis that compared the lifetime expected costs and outcomes between open gastric bypass and no treatment of severe obesity from the payer perspective was performed. Men and women between the ages of 35 and 55 yr, with body mass index between 40 and 50 kg/m(2), who did not have cardiac disease and who failed conservative treatment, including pharmacotherapy, were included. Cost-effectiveness ratio of the base case conditions was made with parameter estimates from the literature and expert discussion and expressed as cost per quality-adjusted life-years (QALY). One- and two-way sensitivity analyses were performed on selected variables. Gastric bypass was not cost-saving, because the reduction in lifetime medical costs was less than the cost of treatment in any subgroup. The base case cost-effectiveness ratios ranged from 5,400 US dollars to 16,100 US dollars for women and from 10,700 US dollars to 35,600 US dollars per QALY for men. Sensitivity analysis demonstrated that in older, less obese men, the cost effectiveness ratio was responsive to the amount of weight lost, obesity-related quality of life, and complication rates. Parameter variation did not significantly affect cost-effectiveness ratios in the remaining patients. The authors concluded that gastric bypass is a cost-effective alternative to no treatment in the severely obese, at less than 50,000 US dollars per QALY.