Minority Enrollment in Parkinson's Disease Clinical Trials: Meta-Analysis and Systematic Review of Studies Evaluating Treatment of Neuropsychiatric Symptoms.

BACKGROUND: Randomized clinical trials (RCTs) in Parkinson's disease (PD) have historically enrolled a low number of underrepresented minorities, lessening the generalizability of therapeutic developments. Although there are racial disparities in PD, little is known regarding neuropsychiatric symptoms and other nonmotor manifestations across all races/ethnicities. OBJECTIVE: To assess minority participation in PD trials evaluating the treatment of neuropsychiatric symptoms and explore underlying reasons. METHODS: We systematically searched PubMed and Embase for RCTs with a primary goal of treating neuropsychiatric symptoms in PD patients from 2000-2019. The pooled prevalence and 95% confidence interval (CI) of being white and enrolled in a clinical trial was calculated using the inverse variance method. I-square was calculated as a measure of heterogeneity and meta-regression was used to evaluate temporal trends. RESULTS: We included 63 RCTs with a total of 7,973 patients. In pooled analysis, 11 (17.5%) RCTs reported race/ethnicity. Of studies reporting this data, 5 African American (0.2%), 16 Hispanics (0.64%), and 539 Asians (21.44%) were enrolled. The pooled prevalence of being white in clinical trials was 98% (CI 0.97-0.98, p < 0.001), with 1,908 patients (75.8%). NIH-funded studies were most likely to report racial data when compared to non-NIH trials (p = 0.032). CONCLUSION: This large pooled analysis found a small percentage of RCTs reporting race/ethnicity when evaluating treatment of neuropsychiatric symptoms in PD. There was a disproportionally high number of white patients when compared to African Americans and Hispanics. More studies are needed to investigate this discrepancy and improve rates of & minority enrollment in PD trials.

Acute Cerebral Ischemia Temporally Associated with Marijuana Use.

The cerebrovascular effects of marijuana use are not well described. With increasing legalization of cannabis for medical and recreational use in North America, identification of potential risks of the drug is necessary. We present the case of a 31-year-old man who had two ischemic infarctions in different vascular distributions, without other identifiable etiology, which were temporally associated with marijuana use. We additionally identified the level of metabolites in his system and discussed the need for a systematic description of these cases to determine whether a dose-dependent effect exists.

Percutaneous Transluminal Angioplasty with Stent Placement versus Best Medical Therapy Alone in Symptomatic Intracranial Arterial Stenosis: A Best Evidence Review.

Intracranial arterial stenosis (ICAS) is a common cause of stroke, and the risk of ischemic stroke from a stenotic intracranial artery remains high despite best medical therapy (BMT). As a result, clinicians have increasingly turned to percutaneous transluminal angioplasty and stenting (PTAS) over the last decade as an alternative therapy in high-risk patients with symptomatic ICAS. In this review, we will critically analyze multiple clinical trials to assess the safety and efficacy of PTAS with BMT versus BMT alone. The Stenting and Aggressive Medical Management for Preventing Recurrent Stroke in Intracranial Stenosis (SAMMPRIS) trial reported a higher rate of stroke or death within 30 days in the PTAS plus BMT group (14.7%) than the BMT only group (5.8%, p = 0.002). The rate of any stroke during the follow-up period (mean = 32 months) was higher in the PTAS plus BMT group (22.3%) than the BMT only group (14.1%, p = 0.03). The Vitesse Intracranial Stent Study for Ischemic Stroke Therapy (VISSIT) trial reported a higher rate of stroke or death within 30 days in the PTAS plus BMT cohort (24.1%) than the BMT only cohort (9.4%, p = 0.05). There was also a higher rate of hard transient ischemic attack (TIA) or stroke within one year in the PTAS plus BMT group (36.2%) than the BMT only group (15.1%, p = 0.02). The Vertebral Artery Ischaemia Stenting (VIST) trial reported the rate of any stroke during the follow-up period to be two events in 50 person-years in the PTAS plus BMT cohort versus four events in 45 person-years in the BMT only cohort, with a calculated hazard ratio of 0.47 (p = 0.39). Vertebral Artery Stenting Trial (VAST) reported a higher incidence of stroke, MI, or vascular death in the PTAS with BMT cohort (22%) than the BMT only cohort (0%). Tang et al. reported no significant difference in the incidence of vascular events at one year and three years between the PTAS plus BMT and BMT only cohorts. However, the distribution of vascular events was more concentrated in the first postoperative week in the PTAS plus BMT cohort (75% of all vascular events) versus the BMT only cohort (17%). Feng et al. reported a lower periprocedural complication rate (9.1%) with the Enterprise stent in comparison to the Wingspan and balloon-expandable stents used in the SAMMPRIS and VISSIT trials. We conclude that PTAS should not be employed as first-line treatment in patients with symptomatic ICAS. However, PTAS should be considered in symptomatic ICAS patients that are hemodynamically unstable or have repeatedly failed BMT, especially at sites with lower rates of perioperative complications than those reported here.

Testing for Human Papillomavirus Strains 16 and 18 Helps Predict the Presence of Anal High-Grade Squamous Intraepithelial Lesions.

BACKGROUND: More than 90% of anal cancers are caused by human papillomavirus, and human papillomavirus strains 16 and 18 are the most oncogenic. Anal high-grade squamous intraepithelial lesions are cancer precursors. Treating these high-grade intraepithelial lesions likely reduces the risk of cancer, but cytology is an imperfect screening test. OBJECTIVE: The purpose of this study was to determine whether human papillomavirus 16 and/or 18 testing better predicts the presence of high-grade squamous intraepithelial lesions. DESIGN: In this retrospective study, 894 consecutive patients underwent anal dysplasia screening with digital anorectal examination, anal cytology, high-risk human papillomavirus testing, and high-resolution anoscopy with biopsy. We calculated the sensitivity, specificity, positive predictive value, and negative predictive value of each test and for a novel screening protocol. The absolute and relative risk of high-grade squamous intraepithelial lesions for all of the cytology/human papillomavirus combinations were also calculated. SETTINGS: The study was conducted at a single practice specializing in anal dysplasia. PATIENTS: Ninety-two percent of participants were men who have sex with men. Forty-four percent were HIV-positive individuals who were well controlled on antiretroviral therapy. The median age was 50 years. MAIN OUTCOME MEASURES: The presence of high-grade squamous intraepithelial lesions as a function of human papillomavirus and the cytology results were measured. RESULTS: High-risk human papillomavirus testing alone demonstrated better sensitivity (96% vs 89%; p = 0.03) and negative predictive value (99% vs 96%; p = 0.008) over cytology. Human papillomavirus 16/18 testing increased specificity (48% to 71%; p < 0.0001) and positive predictive value (24% to 37%; p = 0.003) over testing for all of the high-risk strains. For each cytology category, high-grade squamous intraepithelial lesions were more prevalent when human papillomavirus 16/18 was detected. Benign cytology with 16/18 had a 31-fold increased risk of high-grade squamous intraepithelial lesions. LIMITATIONS: This study was conducted in a single private practice specializing in anal dysplasia screening with a mostly male population, and results might not be generalizable. CONCLUSIONS: Testing of high-risk human papillomavirus strains 16/18 improves specificity and positive predictive value over cytology for anal dysplasia screening. Patients testing positive for strains 16/18 are at a high risk for high-grade squamous intraepithelial lesions and should undergo high-resolution anoscopy regardless of the cytology result. See Video Abstract at http://links.lww.com/DCR/A654.

Non-surgical Pneumoperitoneum in the Setting of Gram-negative Sepsis.

Pneumoperitoneum is described as the presence of free air in the peritoneal cavity. In the majority of cases, it is the manifestation of abdominal viscus perforation, requiring an emergent surgical exploration. In rare cases, however, no evidence of perforation of the gastrointestinal or genitourinary tracts can be found at exploration, and in such cases, the pneumoperitoneum is referred to as non-surgical pneumoperitoneum. We present a case of an 87-year-old man who developed a non-surgical pneumoperitoneum in the setting of gram-negative sepsis. The patient was admitted for treatment of obstructive uropathy and sepsis secondary to a gram-negative urinary tract infection. Despite the initial resuscitation and antibiotic therapy, his hospital course was complicated by worsening abdominal discomfort, and a chest radiograph revealed free air under the diaphragm. He was taken to the operating room for an emergent surgical exploration that revealed no visceral perforation or other possible surgical causes. He tolerated and recovered from surgery well, and had a complete resolution of pneumoperitoneum in the early post-surgery period, per radiographic imaging. This interesting case highlights a rare case of idiopathic nonsurgical pneumoperitoneum in the setting of gram-negative sepsis. Additionally, we discuss considering non-surgical etiologies for patients without clinical signs or surgical evidence of perforation.