Semi-automatic detection of myocardial trabeculation using cardiovascular magnetic resonance: correlation with histology and reproducibility in a mouse model of non-compaction

Background

The definition of left ventricular (LV) non-compaction is controversial, and discriminating between normal and excessive LV trabeculation remains challenging. Our goal was to quantify LV trabeculation on cardiovascular magnetic resonance (CMR) images in a genetic mouse model of non-compaction using a dedicated semi-automatic software package and to compare our results to the histology used as a gold standard.

Methods

Adult mice with ventricular non-compaction were generated by conditional trabecular deletion of Nkx2–5. Thirteen mice (5 controls, 8 Nkx2–5 mutants) were included in the study. Cine CMR series were acquired in the mid LV short axis plane (resolution 0.086?×?0.086x1mm³) (11.75 T). In a sub set of 6 mice, 5 to 7 cine CMR were acquired in LV short axis to cover the whole LV with a lower resolution (0.172?×?0.172x1mm3). We used semi-automatic software to quantify the compacted mass (M_c), the trabeculated mass (M_t) and the percentage of trabeculation (M_t/M_c) on all cine acquisitions_. After CMR all hearts were sliced along the short axis and stained with eosin, and histological LV contouring was performed manually, blinded from the CMR results, and M_t, M_c and M_t/M_c were quantified. Intra and interobserver reproducibility was evaluated by computing the intra class correlation coefficient (ICC).

Results

Whole heart acquisition showed no statistical significant difference between trabeculation measured at the basal, midventricular and apical parts of the LV. On the mid-LV cine CMR slice, the median M_t was 0.92 mg (range 0.07–2.56 mg), M_c was 12.24 mg (9.58–17.51 mg), M_t/M_c was 6.74% (0.66–17.33%). There was a strong correlation between CMR and the histology for M_t, M_c and M_t/ M_c with respectively: r²?=?0.94 (p?<?0.001), r²?=?0.91 (p?<?0.001), r²?=?0.83 (p?<?0.001). Intra- and interobserver reproducibility was 0.97 and 0.8 for M_t; 0.98 and 0.97 for M_c; 0.96 and 0.72 for M_t/M_c, respectively and significantly more trabeculation was observed in the M_c Mutant mice than the controls.

Conclusion

The proposed semi-automatic quantification software is accurate in comparison to the histology and reproducible in evaluating M_c, M_t and M_t/ M_c on cine CMR.

     

Global Supply and Demand of Opioids for Pain Management

Purpose of Review

The goal of this review is to evaluate the global supply and demand of opioids used for pain management and discuss how it relates to the utilization of opioids around the world. The purpose of the review is also to determine the factors that contribute to inappropriate pain management.

Recent Findings

The total global production of opium for opioid manufacturing is enough to supply the growing global demands. However, licit opioids are only consumed by 20% of the world population. Most people throughout the world had no access to opioid analgesics for pain relief in case of need. Opioid misuse and abuse is not only a phenomena plague by the USA but globally across many countries.

Summary

Many countries have a lack of availability of opioids, contributing factors being strict government regulations limiting access, lack of knowledge of the efficacy of opioid analgesics in treating acute and chronic pain and palliative care, and the stigma that opioids are highly addictive. For the countries in which opioids are readily available and prescribed heavily, diversion, misuse, abuse, and the resurgence of heroin have become problems leading to morbidity and mortality. It is pertinent to find a balance between having opioids accessible to patients in need, with ensuring that opioids are regulated along with other illicit drugs to decrease abuse potential.

     

Validating drug repurposing signals using electronic health records: a case study of metformin associated with reduced cancer mortality

Objectives Drug repurposing, which finds new indications for existing drugs, has received great attention recently. The goal of our work is to assess the feasibility of using electronic health records (EHRs) and automated informatics methods to efficiently validate a recent drug repurposing association of metformin with reduced cancer mortality.Methods By linking two large EHRs from Vanderbilt University Medical Center and Mayo Clinic to their tumor registries, we constructed a cohort including 32 415 adults with a cancer diagnosis at Vanderbilt and 79 258 cancer patients at Mayo from 1995 to 2010. Using automated informatics methods, we further identified type 2 diabetes patients within the cancer cohort and determined their drug exposure information, as well as other covariates such as smoking status. We then estimated HRs for all-cause mortality and their associated 95% CIs using stratified Cox proportional hazard models. HRs were estimated according to metformin exposure, adjusted for age at diagnosis, sex, race, body mass index, tobacco use, insulin use, cancer type, and non-cancer Charlson comorbidity index.Results Among all Vanderbilt cancer patients, metformin was associated with a 22% decrease in overall mortality compared to other oral hypoglycemic medications (HR 0.78; 95% CI 0.69 to 0.88) and with a 39% decrease compared to type 2 diabetes patients on insulin only (HR 0.61; 95% CI 0.50 to 0.73). Diabetic patients on metformin also had a 23% improved survival compared with non-diabetic patients (HR 0.77; 95% CI 0.71 to 0.85). These associations were replicated using the Mayo Clinic EHR data. Many site-specific cancers including breast, colorectal, lung, and prostate demonstrated reduced mortality with metformin use in at least one EHR.Conclusions EHR data suggested that the use of metformin was associated with decreased mortality after a cancer diagnosis compared with diabetic and non-diabetic cancer patients not on metformin, indicating its potential as a chemotherapeutic regimen. This study serves as a model for robust and inexpensive validation studies for drug repurposing signals using EHR data.     

Impact of socio-economic status on hospital length of stay following injury: a multicenter cohort study

Background

Injury is second only to cardiovascular disease in terms of acute care costs in North America. One key to improving injury care efficiency is to generate knowledge on the determinants of resource use. Socio-economic status (SES) is a documented risk factor for injury severity and mortality but its impact on length of stay (LOS) for injury admissions is unknown. This study aimed to examine the relationship between SES and LOS following injury.This multicenter retrospective cohort study was based on adults discharged alive from any trauma center (2007–2012; 57 hospitals; 65,486 patients) in a Canadian integrated provincial trauma system. SES was determined using ecological indices of material and social deprivation. Mean differences in LOS adjusted for age, gender, comorbidities, and injury severity were generated using multivariate linear regression.

Results

Mean LOS was 13.5 days. Patients in the highest quintile of material/social deprivation had a mean LOS 0.5 days (95 % CI 0.1-0.9)/1.4 days (1.1-1.8) longer than those in the lowest quintile. Patients in the highest quintiles of both social and material deprivation had a mean LOS 2.6 days (1.8-3.5) longer than those in the lowest quintiles.

Conclusions

Results suggest that patients admitted for traumatic injury who suffer from high social and/or material deprivation have longer acute care LOS in a universal-access health care system. The reasons behind observed differences need to be further explored but may indicate that discharge planning should take patient SES into consideration.

     

Effect of Ranitidine on Healing of Peptic Ulcer: A 2-Month Study

A multicenter trial of oral ranitidine 150 mg bid was conducted in 41 patients with duodenal and 30 with gastric ulcers. Patients were randomly allocated in double-blind fashion to 4 wk treatment with either ranitidine or placebo, after which all unhealed patients were given 4 wk on the active drug without breaking the original allocation code. After 4 wk of treatment the healing rate associated with ranitidine was significantly superior to that of placebo in both duodenal and gastric ulcer patients. Further improvement in cumulative healing rates was observed after the 2nd month of the study. After the allocation code was broken and all patients had had the opportunity of up to 8 wk on the active drug, there remained only a single unhealed pyloric ulcer. No serious adverse effects or biochemical abnormalities were observed. Ranitidine is a potent and well-tolerated H2 antagonist. Therapy for 4 or 8 wk is highly effective in the treatment of uncomplicated gastroduodenal ulcer.