Variability in interval production is due to timing‐dependent deficits in Huntington's disease

In Huntington's disease (HD), increased variability is seen in performance of motor tasks that require implicit control of timing. We examined whether timing variability was also evident in an explicit interval‐timing task. Sixty subjects (21 controls, 19 manifest HD, and 20 pre‐manifest HD) performed a single‐interval production task with three target intervals (1.1 s, 2.2 s, 3.3 s). We analyzed accuracy (proportional error) and precision (standard deviation) across groups and intervals. No differences were seen in accuracy across groups or intervals. Precision was significantly lower in manifest (P = 0.0001) and pre‐manifest HD (P = 0.04) compared with controls. This was particularly true for pre‐manifest subjects close to diagnosis (based on probability of diagnosis in 5 years). Precision was correlated with proximity to diagnosis (r² = 0.3, P < 0.01). To examine the source of reduced precision, we conducted linear regression of standard deviation with interval duration. Slope of the regression was significantly higher in manifest HD (P = 0.02) and in pre‐manifest HD close to diagnosis (P = 0.04) compared with controls and pre‐manifest participants far from diagnosis. Timing precision is impaired before clinical diagnosis in Huntington's disease. Slope analysis suggests that timing variability (decreased precision) was attributable to deficits in timing‐dependent processes. Our results provide additional support for the proposal that the basal ganglia are implicated in central timekeeping functions. Because the single interval production task was sensitive to deficits in pre‐manifest HD, temporal precision may be a useful outcome measure in future clinical trials. © 2014 International Parkinson and Movement Disorder Society     

Meta-analysis and trial sequential analysis of randomized evidence comparing general anesthesia vs regional anesthesia for laparoscopic cholecystectomy

BACKGROUND In an effort to further reduce the morbidity and mortality profile of laparoscopic cholecystectomy, the outcomes of such procedure under regional anesthesia(RA) have been evaluated. In the context of cholecystectomy, combining a minimally invasive surgical procedure with a minimally invasive anesthetic technique can potentially be associated with less postoperative pain and earlier ambulation.AIM To evaluate comparative outcomes of RA and general anesthesia(GA) in patients undergoing laparoscopic cholecystectomy.METHODS A comprehensive systematic review of randomized controlled trials with subsequent meta-analysis and trial sequential analysis of outcomes were conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement standards.RESULTS Thirteen randomized controlled trials enrolling 1111 patients were included. The study populations in the RA and GA groups were of comparable age(P = 0.41),gender(P = 0.98) and body mass index(P = 0.24). The conversion rate from RA to GA was 2.3%. RA was associated with significantly less postoperative pain at 4 h [mean difference(MD):-2.22, P 0.00001], 8 h(MD:-1.53, P = 0.0006), 12 h(MD:-2.08, P 0.00001), and 24 h(MD:-0.90, P 0.00001) compared to GA. Moreover, it was associated with significantly lower rate of nausea and vomiting [risk ratio(RR): 0.40, P 0.0001]. However, RA significantly increased postoperative headaches(RR: 4.69, P = 0.03), and urinary retention(RR: 2.73, P = 0.03). The trial sequential analysis demonstrated that the meta-analysis was conclusive for most outcomes, with the exception of a risk of type 1 error for headache and urinary retention and a risk of type 2 error for total procedure time.CONCLUSION Our findings indicate that RA may be an attractive anesthetic modality for daycase laparoscopic cholecystectomy considering its associated lower postoperative pain and nausea and vomiting compared to GA. However, its associated risk of urinary retention and headache and lack of knowledge on its impact on procedure-related outcomes do not justify using RA as the first line anesthetic choice for laparoscopic cholecystectomy.     

Cost and sustainability of a successful package of interventions to improve vaccination coverage for children in urban slums of Bangladesh

Objective

To estimate the incremental economic costs and explore satisfaction with a highly effective intervention for improving immunization coverage among slum populations in Dhaka, Bangladesh. A package of interventions based on extended clinic hours, vaccinator training, active surveillance, and community participation was piloted in two slum areas of Dhaka, and resulted in an increase in valid fully immunized children (FIC) from 43% pre-intervention to 99% post-intervention.

Methods

Cost data and stakeholder perspectives were collected January–February 2010 via document review and 10 key stakeholders interviews to estimate the financial and opportunity costs of the intervention, including uncompensated time, training and supervision costs.

Results

The total economic cost of the 1-year intervention was $18,300, comprised of external management and supervision (73%), training (11%), coordination costs (1%), uncompensated staff time and clinic costs (2%), and communications, supplies and other costs (13%). An estimated 874 additional children were correctly and fully immunized due to the intervention, at an average cost of $20.95 per valid FIC. Key stakeholders ranked extended clinic hours and vaccinator training as the most important components of the intervention. External supervision was viewed as the most important factor for the intervention's success but also the costliest. All stakeholders would like to reinstate the intervention because it was effective, but additional funding would be needed to make the intervention sustainable.

Conclusion

Targeting slum populations with an intensive immunization intervention was highly effective but would nearly triple the amount spent on immunization per FIC in slum areas. Those committed to increasing vaccination coverage for hard-to-reach children need to be prepared for substantially higher costs to achieve results.