Citations

Objective The objective of this study was to provide recommendations for provision of training for sponsor and investigators at Academic Health Centers. Background A subgroup of the Investigational New Drug/Investigational Device Exemption (IND/IDE) Task Force of the Clinical and Translational Science Award (CTSA) program Regulatory Knowledge Key Function Committee was assembled to specifically address how clinical investigators who hold an IND/IDE and thus assume the role of sponsor-investigators are adequately trained to meet the additional regulatory requirements of this role. Methods The participants who developed the recommendations were representatives of institutions with IND/IDE support programs. Through an informal survey, the task force determined that a variety and mix of models are used to provide support for IND/IDE holders within CTSA institutions. In addition, a CTSA consortium-wide resources survey was used. The participants worked from the models and survey results to develop consensus recommendations to address institutional support, training content, and implementation. Recommendations The CTSA IND/IDE Task Force recommendations are as follows: (1) Institutions should assess the scope of Food and Drug Administration–regulated research, perform a needs analysis, and provide resources to implement a suitable training program; (2) The model of training program should be tailored to each institution; (3) The training should specifically address the unique role of sponsor-investigators, and the effectiveness of training should be evaluated regularly by methods that fit the model adopted by the institution; and (4) Institutional leadership should mandate sponsor-investigator training and effectively communicate the necessity and availability of training.

Abstract Background: Despite a large body of literature evaluating the association between recreational physical activity and epithelial ovarian cancer (EOC) risk, the extant evidence is inconclusive, and little is known about the independent association between recreational physical inactivity and EOC risk. We conducted a pooled analysis of nine studies from the Ovarian Cancer Association Consortium to investigate the association between chronic recreational physical inactivity and EOC risk. Methods: In accordance with the 2008 Physical Activity Guidelines for Americans, women reporting no regular, weekly recreational physical activity were classified as inactive. Multivariable logistic regression was utilized to estimate the ORs and 95% confidence intervals (CI) for the association between inactivity and EOC risk overall and by subgroups based upon histotype, menopausal status, race, and body mass index. Results: The current analysis included data from 8,309 EOC patients and 12,612 controls. We observed a significant positive association between inactivity and EOC risk (OR = 1.34; 95% CI, 1.14–1.57), and similar associations were observed for each histotype. Conclusions: In this large pooled analysis examining the association between recreational physical inactivity and EOC risk, we observed consistent evidence of an association between chronic inactivity and all EOC histotypes. Impact: These data add to the growing body of evidence suggesting that inactivity is an independent risk factor for cancer. If the apparent association between inactivity and EOC risk is substantiated, additional work via targeted interventions should be pursued to characterize the dose of activity required to mitigate the risk of this highly fatal disease. Cancer Epidemiol Biomarkers Prev; 25(7); 1114–24. ©2016 AACR.

OBJECTIVE Vagus nerve and sympathetic chain cervical schwannomas (VNCSs and SCCSs) are benign nerve sheath tumors that arise in the head and neck. Despite similar presentations that make accurate preoperative diagnosis more difficult, the potential for morbidity following resection is significantly higher for patients with VNCS. Therefore, the authors analyzed a retrospective case series and performed a comparative analysis of the literature to establish diagnostic criteria to facilitate more accurate preoperative diagnoses. METHODS The authors conducted a blinded review of imaging studies from retrospectively collected, operatively confirmed cases of VNCS and SCCS. They also performed a systematic review of published series that reported patient-specific preoperative imaging findings in VNCS or SCCS. RESULTS Nine patients with VNCS and 11 with SCCS were identified. In the study cohort, splaying of the internal carotid artery (ICA) and internal jugular vein (IJV) did not significantly predict the nerve of origin (p = 0.06); however, medial and lateral ICA displacement were significantly associated with VNCS and SCCS, respectively (p = 0.01 and p = 0.003, respectively). Multivariate analysis demonstrated that ICA and IJV splaying with medial ICA displacement carried an 86% probability of VNCS (p = 0.001), while the absence of splaying with lateral ICA displacement carried a 91% probability of SCCS (p = 0.006). The presence of vocal cord symptoms or peripheral enhancement significantly augmented the predictive probability of VNCS, as did Horner's syndrome or homogeneous enhancement for SCCS. A review of the literature produced 25 publications that incorporated a total of 106 patients, including the present series. Splaying of the ICA and IJV was significantly, but not uniquely, associated with VNCS (p < 0.0001); multivariate analysis demonstrated that ICA and IJV splaying with medial ICA displacement carries a 75% probability of VNCS (p < 0.0001), while the absence of such splaying with lateral ICA displacement carries an 87% probability of SCCS (p = 0.0003). CONCLUSIONS ICA and IJV splaying frequently predicts VNCS; however, this finding is also commonly observed in SCCS and, among the 9 cases in the present study, was observed more often than previously reported. When congruent with splaying, medial or lateral ICA displacement significantly enhances the reliability of preoperative predictions, empowering more accurate prognostication.

ABSTRACT Supplemental digital content is available in the text. Purpose To present and discuss a case representing both a new sign and symptom of prostaglandin‐associated periorbitopathy. Case Report An 83‐year‐old female patient presented for a 6‐month glaucoma follow‐up in July 2013 with no specific visual or comfort complaints. The patient had a 14‐year history of bilateral primary open angle glaucoma and a 13‐year history of once daily bimatoprost use in both eyes. Evaluation at previous examinations revealed long eyelashes, tight eyelids, small palpebral fissures, and deepening of the upper eyelid sulcus. During slit‐lamp examination of the anterior segment, it was noted that the patient’s eyelids clicked intermittently when she blinked. The patient had not previously noticed the clicking and it was determined to be present in each eye individually. The eyelid clicking has been noted to be present in every follow‐up examination since it was discovered in July 2013. Conclusions Prostaglandin‐associated periorbitopathy and the resulting cosmetic effects noticed visually by patients are well documented. Our case represents a new audible sign and symptom that may be found with prostaglandin‐associated periorbitopathy but has not to our knowledge been reported in the literature.

Background: Clinical misdiagnosis, particularly at early disease stages, is a roadblock to finding new therapies for Lewy body disorders. Biopsy of a peripheral site might provide improved diagnostic accuracy. Previously, we reported, from both autopsy and needle biopsy, a high prevalence of submandibular gland synucleinopathy in Parkinson’s disease (PD). Here, we report on an extension of these studies to subjects with dementia with Lewy bodies (DLB) and other Lewy body disorders in 228 autopsied subjects from the Arizona Study of Aging and Neurodegenerative Disorders. Objective: To provide an estimate of the prevalence of histological synucleinopathy in the submandibular glands of subjects with PD and other Lewy body disorders. Methods: Submandibular gland sections from autopsied subjects were stained with an immunohistochemical method for α-synuclein phosphorylated at serine 129. Included were 146 cases with CNS Lewy-type synucleinopathy (LTS), composed of 46 PD, 28 DLB, 14 incidental Lewy body disease (ILBD), 33 Alzheimer’s disease with Lewy bodies (ADLB) and 2 with progressive supranuclear palsy and Lewy bodies (PSPLB). Control subjects included 79 normal elderly, 15 AD, 12 PSP, 2 conticobasal degeneration (CBD) and 2 multiple system atrophy (MSA). Results: Submandibular gland LTS was found in 42/47 (89%) of the PD subjects, 20/28 (71%) DLB, 4/33 (12%) ADLB and 1/9 (11%) ILBD subjects but none of the 110 control subjects. Conclusions: These results provide support for further clinical trials of in vivo submandibular gland diagnostic biopsy for PD and DLB. An accurate peripheral biopsy diagnosis would assist subject selection for clinical trials and could also be used to verify other biomarkers.

Caring for the growing elderly population will require specialty and subspecialty physicians who have not completed geriatric medicine fellowship training to participate actively in patient care. To meet this workforce demand, a sustainable approach to integrating geriatrics into specialty and subspecialty graduate medical education training is needed. This article describes the use of a geriatrics education team ( GET ) model to develop, implement, and sustain specialty‐specific geriatrics curricula using a systematic process of team formation and needs assessment through evaluation, with a unique focus on developing curricular interventions that are meaningful to each specialty and satisfy training, scholarship, and regulatory requirements. The GET model and associated results from 15 specialty residency and fellowship training programs over a 4‐year period include 93% curriculum sustainability after initial implementation, more than half of the programs introducing additional geriatrics education, and more than 80% of specialty GET s fulfilling their scholarship requirements through their curriculum dissemination. Win–wins and barriers encountered in using the GET model, along with the model's efficacy in curriculum development, sustainability, and dissemination, are summarized.

Abstract Background: End-stage renal disease is a life-limiting illness associated with significant morbidity. Half of all individuals with end-stage renal disease are unable to participate in decision making at the end of life, which makes advance care planning critical in this population. Objective: We sought to determine the feasibility of embedding palliative medicine consultations in the hemodialysis unit during treatment runs and the impact of this intervention on advance care planning and symptom management. Design: Single-center, prospective cohort study. Setting/Subjects: Adults receiving in-center hemodialysis at a single outpatient unit were eligible. All consultations occurred during the patients' hemodialysis runs between January 1 and June 30, 2012. Measurement: Medical records were reviewed for documentation of advance directives, resuscitation status, and goals of care discussions before and after palliative medicine intervention. Symptom surveys with the Modified Edmonton Symptom Assessment Scale (validated for end-stage renal disease) were performed preintervention and postintervention. Results: Ninety-two patients were eligible; 91 underwent palliative medicine consultation. Symptoms were well controlled at baseline prior to any intervention. After palliative medicine consultation, the prevalence of unknown code status decreased from 23% to 1% and goals of care documentation improved from 3% to 59%. Conclusion: Palliative medicine consultation during in-center outpatient hemodialysis was well received by patients and clinical staff. Patients' symptoms were well managed at baseline by the primary nephrology team. The frequency of goals of care documentation and clarification of code status improved significantly. Embedded palliative medicine specialists on the dialysis care team may be effective in improving multidisciplinary patient-centered care for patients with end-stage renal disease.

ABSTRACT The health care-associated pneumonia (HCAP) criteria have a limited ability to predict pneumonia caused by drug-resistant bacteria and favor the overutilization of broad-spectrum antibiotics. We aimed to derive and validate a clinical prediction score with an improved ability to predict the risk of pneumonia due to drug-resistant pathogens compared to that of HCAP criteria. A derivation cohort of 200 microbiologically confirmed pneumonia cases in 2011 and 2012 was identified retrospectively. Risk factors for pneumonia due to drug-resistant pathogens were evaluated by logistic regression, and a novel prediction score (the drug resistance in pneumonia [DRIP] score) was derived. The score was then validated in a prospective, observational cohort of 200 microbiologically confirmed cases of pneumonia at four U.S. centers in 2013 and 2014. The DRIP score (area under the receiver operator curve [AUROC], 0.88 [95% confidence interval {CI}, 0.82 to 0.93]) performed significantly better ( P = 0.02) than the HCAP criteria (AUROC, 0.72 [95% CI, 0.64 to 0.79]). At a threshold of ≥4 points, the DRIP score demonstrated a sensitivity of 0.82 (95% CI, 0.67 to 0.88), a specificity of 0.81 (95% CI, 0.73 to 0.87), a positive predictive value (PPV) of 0.68 (95% CI, 0.56 to 0.78), and a negative predictive value (NPV) of 0.90 (95% CI, 0.81 to 0.93). By comparison, the performance of HCAP criteria was less favorable: sensitivity was 0.79 (95% CI, 0.67 to 0.88), specificity was 0.65 (95% CI, 0.56 to 0.73), PPV was 0.53 (95% CI, 0.42 to 0.63), and NPV was 0.86 (95% CI, 0.77 to 0.92). The overall accuracy of the HCAP criteria was 69.5% (95% CI, 62.5 to 75.7%), whereas that of the DRIP score was 81.5% (95% CI, 74.2 to 85.6%) ( P = 0.005). Unnecessary extended-spectrum antibiotics were recommended 46% less frequently by applying the DRIP score (25/200, 12.5%) than by use of HCAP criteria (47/200, 23.5%) ( P = 0.004), without increasing the rate at which inadequate treatment recommendations were made. The DRIP score was more predictive of the risk of pneumonia due to drug-resistant pathogens than HCAP criteria and may have the potential to decrease antibiotic overutilization in patients with pneumonia. Validation in larger cohorts of patients with pneumonia due to all causes is necessary.