Effect of electroconvulsive therapy on neural response to affective pictures: A randomized,sham-controlled fMRI study

Electroconvulsive therapy (ECT) is the most effective treatment for severe depression but its neurocognitive mechanisms are unclear. This randomized, sham-controlled functional magnetic resonance imaging (fMRI) study explored the effects of a single ECT on neural response to affective pictures. Twenty-seven patients with major depressive disorder were randomized to a single active ECT (N?=?15) or sham (N?=?12) session in a double-blind, parallel-group design. On the following day, patients underwent fMRI during which they viewed pleasant, unpleasant and neutral pictures and performed a free recall test after the scan. Mood symptoms were assessed before ECT/sham and at the time of fMRI. Subsequently, all patients continued active ECT as usual. Mood symptoms were reassessed after six active ECT sessions. A single ECT vs. sham session reduced neural response to unpleasant vs. pleasant pictures in the medial prefrontal cortex, a region showing greater response in the more depressed patients. This effect occurred in the absence of between-group differences in picture recall, mood symptoms or concomitant medication. In conclusion, modulation of medial prefrontal hyper-activity during encoding of negative affective information may be a common mechanism of distinct biological depression treatments.     

Analysis of observational studies in the presence of treatment selection bias: effects of invasive cardiac management on AMI survival using propensity score and instrumental variable methods

Context  Comparisons of outcomes between patients treated and untreated in observational studies may be biased due to differences in patient prognosis between groups, often because of unobserved treatment selection biases. Objective  To compare 4 analytic methods for removing the effects of selection bias in observational studies: multivariable model risk adjustment, propensity score risk adjustment, propensity-based matching, and instrumental variable analysis. Design, Setting, and Patients  A national cohort of 122 124 patients who were elderly (aged 65-84 years), receiving Medicare, and hospitalized with acute myocardial infarction (AMI) in 1994-1995, and who were eligible for cardiac catheterization. Baseline chart reviews were taken from the Cooperative Cardiovascular Project and linked to Medicare health administrative data to provide a rich set of prognostic variables. Patients were followed up for 7 years through December 31, 2001, to assess the association between long-term survival and cardiac catheterization within 30 days of hospital admission. Main Outcome Measure  Risk-adjusted relative mortality rate using each of the analytic methods. Results  Patients who received cardiac catheterization (n = 73 238) were younger and had lower AMI severity than those who did not. After adjustment for prognostic factors by using standard statistical risk-adjustment methods, cardiac catheterization was associated with a 50% relative decrease in mortality (for multivariable model risk adjustment: adjusted relative risk [RR], 0.51; 95% confidence interval [CI], 0.50-0.52; for propensity score risk adjustment: adjusted RR, 0.54; 95% CI, 0.53-0.55; and for propensity-based matching: adjusted RR, 0.54; 95% CI, 0.52-0.56). Using regional catheterization rate as an instrument, instrumental variable analysis showed a 16% relative decrease in mortality (adjusted RR, 0.84; 95% CI, 0.79-0.90). The survival benefits of routine invasive care from randomized clinical trials are between 8% and 21%. Conclusions  Estimates of the observational association of cardiac catheterization with long-term AMI mortality are highly sensitive to analytic method. All standard risk-adjustment methods have the same limitations regarding removal of unmeasured treatment selection biases. Compared with standard modeling, instrumental variable analysis may produce less biased estimates of treatment effects, but is more suited to answering policy questions than specific clinical questions.      

Taking ACE inhibitors during early pregnancy: Is it safe?

QUESTION I knew that angiotensin-converting enzyme (ACE) inhibitors were risky to use during late pregnancy because they can cause renal shutdown in the fetus. Recently I heard of a study that claimed first-trimester exposure (when many patients still are unaware of their pregnancies) can also cause major malformations. Is this proven?ANSWER A recent study did suggest an increased risk of malformations after first-trimester exposure to ACE inhibitors among women treated for hypertension. We believe this study had serious limitations that preclude drawing any conclusions at present.     

Dopamine D2 Receptor Occupancy as a Predictor of Catalepsy in Rats: A Pharmacokinetic-Pharmacodynamic Modeling Approach

Objectives

Dopamine D₂ receptor occupancy (D₂RO) is the major determinant of efficacy and safety in schizophrenia drug therapy. Excessive D₂RO (>80%) is known to cause catalepsy (CAT) in rats and extrapyramidal side effects (EPS) in human. The objective of this study was to use pharmacokinetic and pharmacodynamic modeling tools to relate CAT with D₂RO in rats and to compare that with the relationship between D₂RO and EPS in humans.

Methods

Severity of CAT was assessed in rats at hourly intervals over a period of 8 h after antipsychotic drug treatment. An indirect response model with and without Markov elements was used to explain the relationship of D₂RO and CAT.

Results

Both models explained the CAT data well for olanzapine, paliperidone and risperidone. However, only the model with the Markov elements predicted the CAT severity well for clozapine and haloperidol. The relationship between CAT scores in rat and EPS scores in humans was implemented in a quantitative manner. Risk of EPS not exceeding 10% over placebo correlates with less than 86% D₂RO and less than 30% probability of CAT events in rats.

Conclusion

A quantitative relationship between rat CAT and human EPS was elucidated and may be used in drug discovery to predict the risk of EPS in humans from D₂RO and CAT scores measured in rats.     

Cyanosis when head turned to left in an infant with primary ciliary dyskinesia

A 19‐month‐old boy with primary ciliary dyskinesia (PCD), mirror‐image dextrocardia, situs inversus (SI) totalis suffered from persistent hypoxia. Cyanosis became clinically evident when the child turned the head to the left and resolved after turning the head to the right. Echocardiography demonstrated two superior caval veins; the left sided superior vena cava (SVC) entering the left sided right atrium (RA) and the right sided into the right sided left atrium (LA). Surgical redirection of the right sided caval vein into RA was performed. Pediatr Pulmonol. 2013; 48:88–90. © 2012 Wiley Periodicals, Inc.     

Endodontic bacteria from primary and persistent endodontic lesions in Chinese patients as identified by cloning and 16S ribosomal DNA gene sequencing

Background Few literatures pertain to the 16S ribosomal DNA (16S rDNA) analysis of bacteria contributing to primary and persistent endodontic lesions,with no information available for the Chinese popul...     

Physical activity during hospitalization: Activities and preferences of adults versus older adults

ABSTRACT

Objective: Inactivity during hospitalization leads to a functional decline and an increased risk of complications. To date, studies focused on older adults. This study aims to compare the physical activities performed by older adult and adult hospitalized patients. Methods: Patients hospitalized for >3 days at a university hospital completed a questionnaire regarding their physical activities (% of days on which an activity was performed divided by the length of stay) and physical activity needs during hospitalization. Crude and adjusted comparisons of older adult (>60 years) and adult (≤60 years) patients were performed using parametric testing and regression analyses. Results: Of 524 patients, 336 (64%) completed the questionnaire, including 166 (49%) older adult patients. On average, the patients were physically active on 35% or less of the days during their hospitalization. Linear regression analysis showed no significant associations between being an older adult and performing physical activities after adjusting for gender, length of stay, surgical intervention, and meeting physical activity recommendations prior to hospitalization. Most patients were well informed regarding physical activity during hospitalization; however, the older adult patients reported a need for information regarding physical activities after hospitalization more frequently (odds ratios, 2.47) after adjusting for educational level, gender, and physical therapy during hospitalization. Conclusions: Both older adult and adult patients are physically inactive during hospitalization, and older adult patients express a greater need for additional information regarding physical activity after hospitalization than adult patients. Therefore, personalized strategies that inform and motivate patients to resume physical activities during hospitalization are needed regardless of age.     

Cost effectiveness of laparoscopy versus laparotomy in early stage endometrial cancer: a randomised trial

Objective

To determine the cost effectiveness of total laparoscopic hysterectomy (TLH) versus total abdominal hysterectomy (TAH) in early stage endometrial cancer alongside a multicenter randomised controlled trial (RCT).

Methods

An economic analysis was conducted in 279 patients (TLH n = 185; TAH n = 94) with early stage endometrial cancer from a societal perspective, including all relevant costs over a three month time horizon. Health outcomes were expressed in terms of major complication-free rate and in terms of utility based on women's response to the EQ-5D. Comparisons of costs per major complication-free patient gained and costs with utility gain and costs were made, using incremental cost effectiveness ratios.

Results

The mean major complication-free rate and median utility scores were comparable between TLH and TAH at three months. TLH is more costly intraoperatively (Δ$1.129) and less costly postoperatively in-hospital (Δ$−1.350) compared to TAH. Incremental costs per major complication-free patient were $−52. Higher cost ($249) were generated while no gains in utility (−0.02) were observed for TLH compared to TAH. Analysing utility at six weeks, incremental costs per additional point on the EQ-5D scale were $1.617.

Conclusion

TLH is cost effective compared to TAH, based on major complication-free rate as measure of effect. Along with future cost saving strategies in laparoscopy, TLH is assumed to be cost effective for both effect measures. Therefore and due to comparable safety, TLH should be recommended as a standard-of-care surgical procedure in early endometrial cancer.