A brain network for deep brain stimulation induced cognitive decline in Parkinson's disease

Reich et al. show that DBS-induced cognitive decline is associated with connectivity between the stimulation site and a specific brain network implicated in lesion-induced memory impairment. Transforming this network into a heat map can help identify DBS patients at risk of delayed-onset side-effects and guide reprogramming efforts.Deep brain stimulation is an effective treatment for Parkinson's disease but can be complicated by side-effects such as cognitive decline. There is often a delay before this side-effect is apparent and the mechanism is unknown, making it difficult to identify patients at risk or select appropriate deep brain stimulation settings. Here, we test whether connectivity between the stimulation site and other brain regions is associated with cognitive decline following deep brain stimulation. First, we studied a unique patient cohort with cognitive decline following subthalamic deep brain stimulation for Parkinson's disease (n = 10) where reprogramming relieved the side-effect without loss of motor benefit. Using resting state functional connectivity data from a large normative cohort (n = 1000), we computed connectivity between each stimulation site and the subiculum, an a priori brain region functionally connected to brain lesions causing memory impairment. Connectivity between deep brain stimulation sites and this same subiculum region was significantly associated with deep brain stimulation induced cognitive decline (P < 0.02). We next performed a data-driven analysis to identify connections most associated with deep brain stimulation induced cognitive decline. Deep brain stimulation sites causing cognitive decline (versus those that did not) were more connected to the anterior cingulate, caudate nucleus, hippocampus, and cognitive regions of the cerebellum (P-FWE < 0.05). The spatial topography of this deep brain stimulation-based circuit for cognitive decline aligned with an a priori lesion-based circuit for memory impairment (P = 0.017). To begin translating these results into a clinical tool that might be used for deep brain stimulation programming, we generated a 'heatmap' in which the intensity of each voxel reflects the connectivity to our cognitive decline circuit. We then validated this heat map using an independent dataset of Parkinson's disease patients in which cognitive performance was measured following subthalamic deep brain stimulation (n = 33). Intersection of deep brain stimulation sites with our heat map was correlated with changes in the Mattis dementia rating scale 1 year after lead implantation (r = 0.39; P = 0.028). Finally, to illustrate how this heat map might be used in clinical practice, we present a case that was flagged as 'high risk' for cognitive decline based on intersection of the patient's deep brain stimulation site with our heat map. This patient had indeed experienced cognitive decline and our heat map was used to select alternative deep brain stimulation parameters. At 14 days follow-up the patient's cognition improved without loss of motor benefit. These results lend insight into the mechanism of deep brain stimulation induced cognitive decline and suggest that connectivity-based heat maps may help identify patients at risk and who might benefit from deep brain stimulation reprogramming

Implementation and evaluation of a harm-reduction model for clinical care of substance using pregnant women

<p>Abstract</p> <p>Background</p> <p>Methamphetamine (MA) use during pregnancy is associated with many pregnancy complications, including preterm birth, small for gestational age, preeclampsia, and abruption. Hawaii has lead the nation in MA use for many years, yet prior to 2007, did not have a comprehensive plan to care for pregnant substance-using women. In 2006, the Hawaii State Legislature funded a pilot perinatal addiction clinic. The Perinatal Addiction Treatment Clinic of Hawaii was built on a harm-reduction model, encompassing perinatal care, transportation, child-care, social services, family planning, motivational incentives, and addiction medicine. We present the implementation model and results from our first one hundred three infants (103) seen over 3 years of operation of the program.</p> <p>Methods</p> <p>Referrals came from community health centers, hospitals, addiction treatment facilities, private physician offices, homeless outreach services and self-referral through word-of-mouth and bus ads. Data to describe sample characteristics and outcome was obtained prospectively and retrospectively from chart abstraction and delivery data. Drug use data was obtained from the women's self-report and random urine toxicology during the pregnancy, as well as urine toxicology at the time of birth on mothers, and urine and meconium toxicology on the infants. Post-partum depression was measured in mothers with the Edinburgh Post-Partum depression scale. Data from Path clinic patients were compared with a representative cohort of women delivering at Kapiolani Medical Center for Women and Children during the same time frame, who were enrolled in another study of pregnancy outcomes. Ethical approval for this study was obtained through the University of Hawaii Committee for Human Studies.</p> <p>Results</p> <p>Between April 2007 and August 2010, 213 women with a past or present history of addiction were seen, 132 were pregnant and 97 delivered during that time. 103 live-born infants were delivered. There were 3 first-trimester Spontaneous Abortions, two 28-week intrauterine fetal deaths, and two sets of twins and 4 repeat pregnancies. Over 50% of the women had lost custody of previous children due to substance use. The majority of women who delivered used methamphetamine (86%), either in the year before pregnancy or during pregnancy. Other drugs include marijuana (59.8%), cocaine (33%), opiates (9.6%), and alcohol (15.2%). Of the women served, 85% smoked cigarettes upon enrollment. Of the 97 women delivered during this period, all but 4 (96%) had negative urine toxicology at the time of delivery. Of the 103 infants, 13 (12.6%) were born preterm, equal to the state and national average, despite having many risk factors for prematurity, including poverty, poor diet, smoking and polysubstance use. Overwhelmingly, the women are parenting their children, > 90% retained custody at 8 weeks. Long-term follow-up showed that women who maintained custody chose long-acting contraceptive methods; while those who lost custody had a very high (> 50%) repeat pregnancy rate at 9 months post delivery.</p> <p>Conclusion</p> <p>Methamphetamine use during pregnancy doesn't exist is isolation. It is often combined with a multitude of other adverse circumstances, including poverty, interpersonal violence, psychiatric comorbidity, polysubstance use, nutritional deficiencies, inadequate health care and stressful life experiences. A comprehensive harm reduction model of perinatal care, which aims to ameliorate some of these difficulties for substance-using women without mandating abstinence, provides exceptional birth outcomes and can be implemented with limited resources.</p

Effectiveness and cost-effectiveness of 'BeweegKuur', a combined lifestyle intervention in the Netherlands: Rationale, design and methods of a randomized controlled trial

<p>Abstract</p> <p>Background</p> <p>Improving the lifestyle of overweight and obese adults is of increasing interest in view of its role in several chronic diseases. Interventions aiming at overweight or weight-related chronic diseases suffer from high drop-out rates. It has been suggested that Motivational Interviewing and more frequent and more patient-specific coaching could decrease the drop-out rate. 'BeweegKuur' is a multidisciplinary lifestyle intervention which offers three programmes for overweight persons. The effectiveness and the cost-effectiveness of intensively guided programmes, such as the 'supervised exercise programme' of 'BeweegKuur', for patients with high weight-related health risk, remain to be assessed. Our randomized controlled trial compares the expenses and effects of the 'supervised exercise programme' with those of the less intensively supervised 'start-up exercise programme'.</p> <p>Methods/Design</p> <p>The one-year intervention period involves coaching by a lifestyle advisor, a physiotherapist and a dietician, coordinated by general practitioners (GPs). The participating GP practices have been allocated to the interventions, which differ only in terms of the amount of coaching offered by the physiotherapist. Whereas the 'start-up exercise programme' includes several consultations with physiotherapists to identify barriers hampering independent exercising, the 'supervised exercise programme' includes more sessions with a physiotherapist, involving exercise under supervision. The main goal is transfer to local exercise facilities. The main outcome of the study will be the participants' physical activity at the end of the one-year intervention period and after one year of follow-up. Secondary outcomes are dietary habits, health risk, physical fitness and functional capacity. The economic evaluation will consist of a cost-effectiveness analysis and a cost-utility analysis. The primary outcome measures for the economic evaluation will be the physical activity and the number of quality-adjusted life years. Costs will be assessed from a societal perspective with a time horizon of two years. Additionally, a process evaluation will be used to evaluate the performance of the intervention and the participants' evaluation of the intervention.</p> <p>Discussion</p> <p>This study is expected to provide information regarding the additional costs and effects of the 'supervised exercise programme' in adults with very high weight-related health risk.</p> <p>Trial registration number</p> <p>ISRCTN: <a href="http://www.controlled-trials.com/ISRCTN46574304">ISRCTN46574304</a></p

Transverse tubule remodelling: a cellular pathology driven by both sides of the plasmalemma?

Transverse (t)-tubules are invaginations of the plasma membrane that form a complex network of ducts, 200–400 nm in diameter depending on the animal species, that penetrates deep within the cardiac myocyte, where they facilitate a fast and synchronous contraction across the entire cell volume. There is now a large body of evidence in animal models and humans demonstrating that pathological distortion of the t-tubule structure has a causative role in the loss of myocyte contractility that underpins many forms of heart failure. Investigations into the molecular mechanisms of pathological t-tubule remodelling to date have focused on proteins residing in the intracellular aspect of t-tubule membrane that form linkages between the membrane and myocyte cytoskeleton. In this review, we shed light on the mechanisms of t-tubule remodelling which are not limited to the intracellular side. Our recent data have demonstrated that collagen is an integral part of the t-tubule network and that it increases within the tubules in heart failure, suggesting that a fibrotic mechanism could drive cardiac junctional remodelling. We examine the evidence that the linkages between the extracellular matrix, t-tubule membrane and cellular cytoskeleton should be considered as a whole when investigating the mechanisms of t-tubule pathology in the failing heart

International Consensus Statement on Rhinology and Allergy: Rhinosinusitis

Background: The 5 years since the publication of the first International Consensus Statement on Allergy and Rhinology: Rhinosinusitis (ICAR‐RS) has witnessed foundational progress in our understanding and treatment of rhinologic disease. These advances are reflected within the more than 40 new topics covered within the ICAR‐RS‐2021 as well as updates to the original 140 topics. This executive summary consolidates the evidence‐based findings of the document. Methods: ICAR‐RS presents over 180 topics in the forms of evidence‐based reviews with recommendations (EBRRs), evidence‐based reviews, and literature reviews. The highest grade structured recommendations of the EBRR sections are summarized in this executive summary. Results: ICAR‐RS‐2021 covers 22 topics regarding the medical management of RS, which are grade A/B and are presented in the executive summary. Additionally, 4 topics regarding the surgical management of RS are grade A/B and are presented in the executive summary. Finally, a comprehensive evidence‐based management algorithm is provided. Conclusion: This ICAR‐RS‐2021 executive summary provides a compilation of the evidence‐based recommendations for medical and surgical treatment of the most common forms of RS