John A. Gallis

Effect of Advancing Age on Outcomes of Deep Brain Stimulation for Parkinson Disease

IMPORTANCE Deep brain stimulation (DBS) is a well-established modality for the treatment of advanced Parkinson disease (PD). Recent studies have found DBS plus best medical therapy to be superior to best medical therapy alone for patients with PD and early motor complications. Although no specific age cutoff has been defined, most clinical studies have excluded patients older than 75 years of age. We hypothesize that increasing age would be associated with an increased number of postoperative complications. OBJECTIVE To evaluate the stepwise effect of increasing age (in 5-year epochs) on short-term complications following DBS surgery. DESIGN, SETTING, AND PARTICIPANTS A large, retrospective cohort study was performed using the Thomson Reuters MarketScan national database that examined 1757 patients who underwent DBS for PD during the period from 2000 to 2009. MAIN OUTCOMES AND MEASURES Primary measures examined included hospital length of stay and aggregate and individual complications within 90 days following surgery. Multivariate logistic regression analysis was used to calculate complication-related odds ratios (ORs) for each 5-year age epoch after controlling for covariates. RESULTS Overall, 132 of 1757 patients (7.5%) experienced at least 1 complication within 90 days, including wound infections (3.6%), pneumonia (2.3%), hemorrhage or hematoma (1.4%), or pulmonary embolism (0.6%). After adjusting for covariates, we found that increasing age (ranging from <50 to 90 years of age) did not significantly affect overall 90-day complication rates (OR, 1.10 per 5-year increase [95% CI, 0.96-1.25]; P = .17). The 2 most common procedure-related complications, hemorrhage (OR, 0.82 [95% CI, 0.63-1.07]; P = .14) and infection (OR, 1.04 [95% CI, 0.87-1.24]; P = .69), did not significantly increase with age. CONCLUSIONS AND RELEVANCE Older patients with PD (>75 years) who were selected to undergo DBS surgery showed a similar 90-day complication risk (including postoperative hemorrhage or infection) compared with younger counterparts. Our findings suggest that age alone should not be a primary exclusion factor for determining candidacy for DBS. Instead, a clear focus on patients with medication-refractory and difficult to control on-off fluctuations with preserved cognition, regardless of age, may allow for an expansion of the traditional therapeutic window.

Cell phone Intervention for You (CITY): A randomized, controlled trial of behavioral weight loss intervention for young adults using mobile technology

To determine the effect on weight of two mobile technology‐based (mHealth) behavioral weight loss interventions in young adults.

Review of Recent Methodological Developments in Group-Randomized Trials: Part 2—Analysis

In 2004, Murray et al. reviewed methodological developments in the design and analysis of group-randomized trials (GRTs). We have highlighted the developments of the past 13 years in design with a companion article to focus on developments in analysis. As a pair, these articles update the 2004 review. We have discussed developments in the topics of the earlier review (e.g., clustering, matching, and individually randomized group-treatment trials) and in new topics, including constrained randomization and a range of randomized designs that are alternatives to the standard parallel-arm GRT. These include the stepped-wedge GRT, the pseudocluster randomized trial, and the network-randomized GRT, which, like the parallel-arm GRT, require clustering to be accounted for in both their design and analysis.

Impact of advancing age on post-operative complications of deep brain stimulation surgery for essential tremor

Essential tremor (ET) was the original indication for deep brain stimulation (DBS), with USA Food and Drug Administration approval since 1997. Despite the efficacy of DBS, it is associated with surgical complications that cause sub-optimal clinical outcomes. Given that ET is a progressive disease with increase in symptom severity with increasing age, this study evaluated the impact of increasing age on short-term complications following DBS surgery for ET. The Thomson-Reuters MarketScan database was utilized (New York, NY, USA). Patients selected were over age 18 and underwent DBS for ET between the years 2000 and 2009. Multivariable logistic regression analysis was used to calculate complication odds ratios (OR) for a 5 year increase in age, after controlling for other covariates. Six hundred sixty-one patients were included in the analysis. The mean (standard deviation) age was 61.9 (14.3) years, with 17% of individuals aged ⩾75 years. Overall 56.9% of patients were male, and 44.6% had a Charlson Comorbidity Score of ⩾1. Additionally, 7.1% of patients experienced at least one complication within 90 days, including wound infections (3.0%), pneumonia (2.4%), hemorrhage or hematoma (1.5%), or pulmonary embolism (0.6%). Increasing age was not significantly associated with the overall 90 day complication rates (OR 0.89; 95% confidence interval [CI] 0.77-1.02; p=0.102). The risk of the two most common procedure-related complications, hemorrhage and infection, did not significantly increase with age (hemorrhage: OR 1.02; 95%CI 0.77-1.37; p=0.873; and infection: OR 0.88; 95%CI 0.72-1.07; p=0.203). Our findings suggest that age should not be a primary exclusion factor for determining candidacy for DBS and also suggest a possible expansion of the traditional therapeutic window since post-operative complications remained relatively stable.

Comparison of Bilateral vs. Staged Unilateral Deep Brain Stimulation (DBS) in Parkinson's Disease in Patients Under 70 Years of Age

The most popular surgical method for deep brain stimulation (DBS) in Parkinsons disease (PD) is simultaneous bilateral DBS. However, some centers conduct a staged unilateral approach advocating that reduced continuous intraoperative time reduces postoperative complications, thus justifying the cost of a second operative session. To test these assumptions, we performed a retrospective analysis of the Truven Health MarketScan® Database.

The effectiveness of the peer delivered Thinking Healthy Plus (THPP+) Programme for maternal depression and child socio-emotional development in Pakistan: study protocol for a three-year cluster randomized controlled trial

BackgroundThe negative effects of perinatal depression on the mother and child start early and persist throughout the lifecourse (Lancet 369(9556):145–57, 2007; Am J Psychiatry 159(1):43-7, 2002; Arch Dis Child 77(2):99–101, 1997; J Pak Med Assoc 60(4):329; J Psychosoma Res 49(3):207–16, 2000; Clin Child Fam Psychol Rev 14(1):1–27, 2011). Given that 10–35% of children worldwide are exposed to perinatal depression in their first year of life (Int Rev Psychiatry 8(1):37–54, 1996), mitigating this intergenerational risk is a global public health priority (Perspect Public Health 129(5):221–7, 2009; Trop Med Int Health 13(4):579–83, 2008; Br Med Bull 101(1):57–79, 2012). However, it is not clear whether intervention with depressed women can have long-term benefits for the mother and/or her child. We describe a study of the effectiveness of a peer-delivered depression intervention delivered through 36 postnatal months, the Thinking Healthy Program Peer-delivered PLUS (THPP+) for women and their children in rural Pakistan.Methods/designThe THPP+ study aims are: (1) to evaluate the effects of an extended 36-month perinatal depression intervention on maternal and index child outcomes using a cluster randomized controlled trial (c-RCT) and (2) to determine whether outcomes among index children of perinatally depressed women in the intervention arm converge with those of index children born to perinatally nondepressed women. The trial is designed to recruit 560 pregnant women who screened positive for perinatal depression (PHQ-9 score ≥10) from 40 village clusters, of which 20 receive the THPP+ intervention. An additional reference group consists of 560 perinatally nondepressed women from the same 40 clusters as the THPP+ trial. The women in the nondepressed group are not targeted to receive the THPP+ intervention; but, by recruiting pregnant women from both intervention and control clusters, we are able to evaluate any carryover effects of the THPP+ intervention on the women and their children. Perinatally depressed women in the THPP+ intervention arm receive bimonthly group-based sessions. Primary outcomes are 3-year maternal depression and 3-year child development indicators. Analyses are intention-to-treat and account for the clustered design.DiscussionThis trial, together with the reference group, has the potential to further our understanding of the early developmental lifecourse of children of both perinatally depressed and perinatally nondepressed women in rural Pakistan and to determine whether intervening with women’s depression in the perinatal period can mitigate the negative effects of maternal depression on 36-month child development.Trial registrationTHPP-P ClinicalTrials.gov Identifier: NCT02111915 (registered on 9 April 2014).THPP+ ClinicalTrials.gov Identifier: NCT02658994 (registered on 21 January 2016).Sponsor: Human Development Research Foundation (HDRF).

Serum Potassium Levels and Risk of Sudden Cardiac Death Among Patients With Chronic Kidney Disease and Significant Coronary Artery Disease

Introduction Chronic kidney disease (CKD) patients have increased risks of sudden cardiac arrest and sudden cardiac death (SCA/SCD) that are not explained by traditional risk factors. We examined associations between serum potassium and SCA/SCD in a large cohort of patients with coronary artery disease (CAD) and moderate CKD. Methods Among 22,009 patients who underwent cardiac catheterization at our institution between 1999 and 2011, 6181 patients had an estimated glomerular filtration rate of ≤60 ml/min per 1.73 m2 and were not receiving renal replacement therapy. The risk of SCA/SCD and all-cause mortality associated with potassium concentration was evaluated at the time of cardiac catheterization (baseline) and most proximate to SCA/SCD events. Covariate-adjusted Cox models were used to examine relationships between baseline potassium measurements and outcomes. A propensity score-matched, case−control design was used to assess risk associations of potassium measurements obtained proximate to SCA events. Results In the baseline potassium analysis, compared with levels in the normal range, there was no significant risk association between hyperkalemia (>5 mEq/l) or hypokalemia (<3.5 mEq/l) and SCA/SCD or all-cause death after covariate adjustment. In the proximate potassium analysis, hyperkalemia occurred more frequently than hypokalemia (16.7% vs. 3%), and was associated with a doubling in SCA/SCD risk (adjusted odd ratio: 2.37; 95% confidence interval: 1.33–4.23) whereas there was no significant relationship between hypokalemia and outcome. Discussion Among CKD patients with significant CAD, elevated serum potassium levels >5.0 mEq/l are common and are associated with an increased short-term risk of SCA/SCD. Early detection and treatment of hyperkalemia may reduce the high risk of SCD among CKD patients.

Socioeconomic status indicators and common mental disorders: Evidence from a study of prenatal depression in Pakistan

There is growing interest in the relationship between socioeconomic status (SES), poverty, and mental health in low and middle-income countries (LMIC). However, it is not clear whether a gradient approach focused on a wider SES distribution or a binary poverty approach is more salient for mental health in LMIC. Yet this distinction has implications for interventions aimed at improving population health. We contribute to the literature by examining how multiple indicators of socioeconomic status, including gradient SES and binary poverty indicators, contribute to prenatal depression symptoms in a LMIC context. Prenatal depression is an important public health concern with negative sequela for the mother and her children. We use data on assets, education, food insecurity, debt, and depression symptoms from a sample of 1154 pregnant women residing in rural Pakistan. Women who screened positive for depression participated in a cluster randomized controlled trial of a perinatal depression intervention; all women were interviewed October 2015-February 2016, prior to the start of the intervention. Cluster-specific sampling weights were used to approximate a random sample of pregnant women in the area. Findings indicate that fewer assets, experiencing food insecurity, and having household debt are independently associated with worse depression symptoms. The association with assets is linear with no evidence of a threshold effect, supporting the idea of a gradient in the association between levels of SES and depression symptoms. A gradient was also initially observed with woman’s educational attainment, but this association was attenuated once other SES variables were included in the model. Together, the asset, food insecurity, and debt indicators explain 14% of the variance in depression symptoms, more than has been reported in high income country studies. These findings support the use of multiple SES indicators to better elucidate the complex relationship between socioeconomic status and mental health in LMIC.

Association between distance to nearest supermarket and provision of fruits and vegetables in English nurseries

Abstract With 796,500 places available for children in England, pre‐school nurseries could serve as an important setting for population‐wide dietary intervention. It is critical to understand the determinants of healthy food provision in this setting, which may include access to food stores. This study examined the association between objective, GIS‐derived supermarket proximity and fruit and vegetable serving frequency, using data from 623 English nurseries. Overall, 116 (18%) nurseries served fruits and vegetables infrequently (<2–3 times/week), but provision differed by supermarket proximity. In adjusted multivariable regression models, nurseries farthest from their nearest supermarket (Q5, 1.7–19.8 km) had 2.38 (95% CI 1.01–5.63) greater odds of infrequent provision. Our results suggest that supermarket access may be important for nurseries in meeting fruit and vegetable provision guidelines. We advance a growing body of international literature, for the first time linking the food practices of institutions to their neighbourhood food retail context. HighlightsWe examined the relationship between nursery supermarket access and the provision of fruits and vegetables to children.We used data from a representative sample of 623 English nurseries, alongside objectively measured supermarket proximity.18% of nurseries served fruits and vegetables infrequently, but this differed systematically by supermarket proximity.Nurseries farthest from their nearest supermarket were significantly less likely to serve fruits and vegetables frequently.Supermarket access may be important for nurseries in meeting guidelines for the provision of fruits and vegetables.

Criterion-related validity and reliability of the Urdu version of the patient health questionnaire in a sample of community-based pregnant women in Pakistan

Background Depression is one of the most prevalent, yet unrecognized but treatable mental disorders in low and middle income countries (LMICs). In such locations, screening tools that are easy-to-administer, valid, and reliable are needed to assist in detecting symptoms of depression. The Patient Health Questionnaire (PHQ-9) is one of the most widely used depression screeners. However, its applicability to community-based settings of Pakistan is limited by the lack of studies examining its validity and reliability in such settings. The current study aimed to demonstrate the criterion-related validity and internal reliability of the Urdu version of the PHQ-9 in a sample of community-based pregnant women in Pakistan compared to a diagnostic clinical interview, the Structured Clinical Interview for DSM disorders (SCID), using data from a depression treatment cluster randomized trial in rural Pakistan. Methods Pregnant women in a rural, low income sub-district in Pakistan were approached between October 2014 and February 2016 and, after providing informed consent, screened for depression using the Urdu version of the PHQ-9, with a cutoff of ≥10 used to indicate significant depressive symptoms. Following the PHQ-9, the diagnostic module for current major depressive episode of the SCID was administered. We examined the psychometric properties of PHQ-9 compared to SCID as a gold standard, using sensitivity, specificity, and negative and positive predictive value to measure the criterion-related validity of the PHQ-9 as an indicator of symptoms of depression. We computed area under the receiver operating characteristic curve to determine diagnostic accuracy, and used Cronbach’s alpha to assess internal reliability. Results A total of 1,731 women in their third trimester of pregnancy were assessed for major depressive disorder. Of these women, 572 (33%) met the cutoff for significant depressive symptoms on PHQ-9, and 454 (26%) were assessed positive for depression using the SCID. The sensitivity and specificity of PHQ-9 at a cutoff of ≥10 was 94.7% and 88.9%, respectively. The positive and negative predictive values were 75.2% and 97.9%, respectively; and the area under the curve was 0.959. Internal reliability, as measured by Cronbach’s alpha, was 0.844. Discussion Valid and reliable screening tools to assist in detecting symptoms of depressive disorder are needed in low income settings where depressive disorders are highly prevalent. The Urdu version of the PHQ-9 has not been previously validated against a well-known assessment of depression in a community setting among pregnant women in Pakistan. This study demonstrates that the Urdu version of the PHQ-9 has acceptable criterion-related validity and reliability for screening for depressive symptoms in Pakistan among community-based pregnant women; and when the recommended cut-off score of ≥10 is used it can also serve as an accurate screening tool for major depressive disorder.