Gionfriddo, Michael R.

SummaryBackgroundThe presence of germline mutations in sporadic pheochromocytomas and paragangliomas (SPPs) may change the clinical management of both index patients and their family members. However, the frequency of germline mutations in SPPs is unknown.ObjectiveTo describe the frequency of germline mutations in SPPs and to determine the value of testing index patients and their family members for these mutations.MethodsWe searched databases through June 2012 for observational studies of patients with SPPs who underwent germline genetic testing. The criteria used to define sporadic tumours were (i) the absence of a family history of PCC/PG, (ii) the absence of syndromic features, (iii) the absence of bilateral disease and (iv) the absence of metastatic disease.ResultsWe included 31 studies including 5031 patients (mean age 44). These patients received tests for any of these ten mutations: SDHAF2, RET, SDHD, SDHB, SDHC, VHL, TMEM127, MAX, Isocitrate Dehydrogenase Mutation (IDH) and NF1. The overall frequency of germline mutation in SPP was 551 of 5031 or 11%; when studies with patients fulfilling four criteria for sporadic tumours were used, the frequency was 171 of 1332 or 13%. The most common germline mutation was SDHB 167 of 3611 (4·6%). Little outcome data were available to assess the benefits of genetic testing in index cases and family members.ConclusionsThe frequency of germline mutations in SPPs is approximately 11–13% and the most common mutations affect less than 1 in 20 patients. The value of testing for germline mutations in patients with SPPs and their family members is unknown, as the balance of potential benefits and harms remains unclear.

Chronic conditions are the most important cause of morbidity, mortality and health expense in the USA. Comparative effectiveness research (CER) seeks to provide evidence supporting the relative value of alternative courses of action. This research often concludes with estimates of the likelihood of desirable and undesirable outcomes associated with each option. Patients with chronic conditions should engage with their clinicians in deciding which of these options best fits their goals and context. In practicing shared decision-making (SDM), clinicians and patients should make use of CER to inform their deliberations. In these ways, SDM and CER are interrelated. SDM translates CER into patient-centered practice, while CER provides the backbone evidence about options and outcomes in SDM interventions. In this review, we explore the potential for a SDM–CER synergy in improving healthcare for patients with chronic conditions.

AbstractElectrical stimulation of the brain has a 2000 year history. Deep brain stimulation (DBS), one form of neurostimulation, is a functional neurosurgical approach in which a high‐frequency electrical current stimulates targeted brain structures for therapeutic benefit. It is an effective treatment for certain neuropathologic movement disorders and an emerging therapy for psychiatric conditions and epilepsy. Its translational journey did not follow the typical bench‐to‐bedside path, but rather reversed the process. The shift from ancient and medieval folkloric remedy to accepted medical practice began with independent discoveries about electricity during the 19th century and was fostered by technological advances of the 20th. In this paper, we review that journey and discuss how the quest to expand its applications and improve outcomes is taking DBS from the bedside back to the bench.