Cost-effectiveness of psychological intervention within services for depression delivered by primary care workers in Nepal: economic evaluation of a randomized control trial.

Background: Integrating services for depression into primary care is key to reducing the treatment gap in low- and middle-income countries. We examined the value of providing the Healthy Activity Programme (HAP), a behavioral activation psychological intervention, within services for depression delivered by primary care workers in Chitwan, Nepal using data from the Programme for Improving Mental Health Care. Methods: People diagnosed with depression were randomized to receive either standard treatment (ST), comprised of psychoeducation, antidepressant medication, and home-based follow up, or standard treatment plus psychological intervention (T + P). We estimated incremental costs and health effects of T + P compared to ST, with quality adjusted life years (QALYs) and depression symptom scores over 12 months as health effects. Nonparametric uncertainty analysis provided confidence intervals around each incremental effectiveness ratio (ICER); results are presented in 2020 international dollars. Results: Sixty participants received ST and 60 received T + P. Implementation costs (ST = $329, T + P = $617) were substantially higher than service delivery costs (ST = $18.7, T + P = $22.4) per participant. ST and T + P participants accrued 46.5 and 49.4 QALYs, respectively. The ICERs for T + P relative to ST were $4422 per QALY gained (95% confidence interval: $2484 to $9550) - slightly above the highly cost-effective threshold - and -$53.21 (95% confidence interval: -$105.8 to -$30.2) per unit change on the Patient Health Questionnaire. Conclusion: Providing HAP within integrated depression services in Chitwan was cost-effective, if not highly cost-effective. Efforts to scale up integrated services in Nepal and similar contexts should consider including evidence-based psychological interventions as a part of cost-effective mental healthcare for depression.

Responses of the Human Brain to Mild Dehydration and Rehydration Explored In Vivo by 1H-MR Imaging and Spectroscopy.

BACKGROUND AND PURPOSE: As yet, there are no in vivo data on tissue water changes and associated morphometric changes involved in the osmo-adaptation of normal brains. Our aim was to evaluate osmoadaptive responses of the healthy human brain to osmotic challenges of de- and rehydration by serial measurements of brain volume, tissue fluid, and metabolites. MATERIALS AND METHODS: Serial T1-weighted and (1)H-MR spectroscopy data were acquired in 15 healthy individuals at normohydration, on 12 hours of dehydration, and during 1 hour of oral rehydration. Osmotic challenges were monitored by serum measures, including osmolality and hematocrit. MR imaging data were analyzed by using FreeSurfer and LCModel. RESULTS: On dehydration, serum osmolality increased by 0.67% and brain tissue fluid decreased by 1.63%, on average. MR imaging morphometry demonstrated corresponding decreases of cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus. These changes reversed during rehydration. Continuous fluid ingestion of 1 L of water for 1 hour within the scanner lowered serum osmolality by 0.96% and increased brain tissue fluid by 0.43%, on average. Concomitantly, cortical thickness and volumes of the whole brain, cortex, white matter, and hypothalamus/thalamus increased. Changes in brain tissue fluid were related to volume changes of the whole brain, the white matter, and hypothalamus/thalamus. Only volume changes of the hypothalamus/thalamus significantly correlated with serum osmolality. CONCLUSIONS: This is the first study simultaneously evaluating changes in brain tissue fluid, metabolites, volume, and cortical thickness. Our results reflect cellular volume regulatory mechanisms at a macroscopic level and emphasize that it is essential to control for hydration levels in studies on brain morphometry and metabolism in order to avoid confounding the findings.

Subcortical volumetric reductions in adult Niemann-Pick disease type C: a cross-sectional study.

BACKGROUND AND PURPOSE: Voxel-based analysis has suggested that deep gray matter rather than cortical regions is initially affected in adult Niemann-Pick type C. We sought to examine a range of deep gray matter structures in adults with NPC and relate these to clinical variables. MATERIALS AND METHODS: Ten adult patients with NPC (18-49 years of age) were compared with 27 age- and sex-matched controls, and subcortical structures were automatically segmented from normalized T1-weighted MR images. Absolute volumes (in cubic millimeters) were generated for a range of deep gray matter structures and were compared between groups and correlated with illness variables. RESULTS: Most structures were smaller in patients with NPC compared with controls. The thalamus, hippocampus, and striatum showed the greatest and most significant reductions, and left hippocampal volume correlated with symptom score and cognition. Vertex analysis of the thalamus, hippocampus, and caudate implicated regions involved in memory, executive function, and motor control. CONCLUSIONS: Thalamic and hippocampal reductions may underpin the memory and executive deficits seen in adult NPC. Volume losses in other subcortical regions may also be involved in the characteristic range of motor, psychiatric, and cognitive deficits seen in the disease.

Comparison and evaluation of segmentation techniques for subcortical structures in brain MRI.

The automation of segmentation of medical images is an active research area. However, there has been criticism of the standard of evaluation of methods. We have comprehensively evaluated four novel methods of automatically segmenting subcortical structures using volumetric, spatial overlap and distance-based measures. Two of the methods are atlas-based - classifier fusion and labelling (CFL) and expectation-maximisation segmentation using a dynamic brain atlas (EMS), and two model-based - profile active appearance models (PAM) and Bayesian appearance models (BAM). Each method was applied to the segmentation of 18 subcortical structures in 270 subjects from a diverse pool varying in age, disease, sex and image acquisition parameters. Our results showed that all four methods perform on par with recently published methods. CFL performed significantly better than the other three methods according to all three classes of metrics.

Comparing the similarity of statistical shape models using the Bhattacharya metric.

A variety of different methods of finding correspondences across sets of images to build statistical shape models have been proposed, each of which is likely to result in a different model. When dealing with large datasets (particularly in 3D), it is difficult to evaluate the quality of the resulting models. However, if the different methods are successfully modelling the true underlying shape variation, the resulting models should be similar. If two different techniques lead to similar models, it suggests that they are indeed approximating the true shape change. In this paper we explore a method of comparing statistical shape models by evaluating the Bhattacharya overlap between their implied shape distributions. We apply the technique to investigate the similarity of three models of the same 3D dataset constructed using different methods.

Carbon dioxide narcosis-induced apnea in a rat model of cardiac arrest and resuscitation.

In the clinical literature there are reports of patients failing to breathe and becoming comatose when supplied with 100% oxygen for respiratory distress. This effect has been attributed to a loss of respiratory drive. Recent studies have established that this explanation is incorrect, but have left the phenomenon unexplained. We propose that the apnea and coma reported is due to carbon dioxide narcosis. We have reproduced this effect in an animal model and have documented PCO2 values in excess of 250 mmHg during the apneic period. Our results suggest that this level of PCO2 suppresses both brainstem auditory evoked potentials and spontaneous respiration. The high PCO2 is due to inadequate gas exchange, and is easily remedied by provision of adequate ventilation.

The value of pancuronium in prolonged intraocular operations.

We wished to determine the effectiveness of Pancuronium, a non-depolarizing muscle relaxant, in prolonged intraocular operations. We compared the variations in intraocular pressure when using four different methods of induction of general anesthesia. With Pancuronium the intraocular pressure fell initially and then rose to just below pre-induction levels and remained there. Our study suggests that pancuronium stabilizes intraocular pressure at a level which is highly desirable for intraocular surgery.