Efficacy of Multimodal Analgesia for Postoperative Pain Management in Head and Neck Cancer Patients.

Postoperative opioid use has been linked to the subsequent development of opioid dependency. Multimodal analgesia (MMA) can reduce the use of opioids in the postoperative period, but MMA has not been well-studied after major head and neck surgery. Our goal is to explore the association between MMA and postoperative opioid use and pain control in patients undergoing major head and neck surgery. We performed a retrospective study in adult (age ≥ 18 years) patients undergoing primary head and neck cancer resection with free-flap reconstruction. All patients were treated using an established care pathway. The baseline group was treated between January 2015-December 2015 (n = 41), prior to the implementation of MMA, and were compared to an MMA-treated cohort treated between December 2017-June 2019 (n = 97). The primary outcome was the proportion of opioids prescribed and oral morphine equivalents (OMEs) consumed during the hospitalization. The secondary outcome was pain control. We found that the post-MMA group consumed fewer opioids in the postoperative period compared to the pre-MMA group. Prior to post-operative day (POD) 6, pain control was better in the post-MMA group; however, the pain control lines intersect on POD 6 and the pre-MMA group appeared to have better pain control from PODs 7-10. In conclusion, our data suggest MMA is an effective method of pain control and opioid reduction in patients undergoing surgery for head and neck cancer with free flap reconstruction. MMA use was associated with a significant decrease in the quantity of opioids consumed postoperatively. The MMA protocol was associated with improved pain management early in the postoperative course. Finally, the MMA protocol is a feasible method of pain control and may reduce the adverse side effects associated with opioid use.

Outdoor Air Pollution and Depression in Canada: A Population-Based Cross-Sectional Study from 2011 to 2016.

To assess whether exposure to increased levels of outdoor air pollution is associated with psychological depression, six annual iterations of the Canadian Community Health Survey (n ≈ 127,050) were used to estimate the prevalence of a major depressive episode (2011-2014) or severity of depressive symptoms (2015-2016). Survey data were linked with outdoor air pollution data obtained from the Canadian Urban Environmental Health Research Consortium, with outdoor air pollution represented by fine particulate matter ≤2.5 micrometers (µm) in diameter (PM2.5), ozone (O3), sulfur dioxide (SO2), and nitrogen dioxide (NO2). Log-binomial models were used to estimate the association between outdoor air pollution and depression, and included adjustment for age, sex, marital status, income, education, employment status, urban versus rural households, cigarette smoking, and chronic illness. No evidence of associations for either depression outcomes were found. Given the generally low levels of outdoor air pollution in Canada, these findings should be generalized with caution. It is possible that a meaningful association with major depression may be observed in regions of the world where the levels of outdoor air pollution are greater, or during high pollution events over brief time intervals. Future research is needed to replicate these findings and to further investigate these associations in other regions and populations.

Describing organ dysfunction in the intensive care unit: a cohort study of 20,000 patients.

BACKGROUND: Multiple organ dysfunction is a common cause of morbidity and mortality in intensive care units (ICUs). Original development of the Sequential Organ Failure Assessment (SOFA) score was not to predict outcome, but to describe temporal changes in organ dysfunction in critically ill patients. Organ dysfunction scoring may be a reasonable surrogate outcome in clinical trials but further exploration of the impact of case mix on the temporal sequence of organ dysfunction is required. Our aim was to compare temporal changes in SOFA scores between hospital survivors and non-survivors. METHODS: We performed a population-based observational retrospective cohort study of critically ill patients admitted from January 1, 2004, to December 31, 2013, to 4 multisystem adult intensive care units (ICUs) in Calgary, Canada. The primary outcome was temporal changes in daily SOFA scores during the first 14 days of ICU admission. SOFA scores were modeled between hospital survivors and non-survivors using generalized estimating equations (GEE) and were also stratified by admission SOFA (≤ 11 versus > 11). RESULTS: The cohort consisted of 20,007 patients with at least one SOFA score and was mostly male (58.2%) with a median age of 59 (interquartile range [IQR] 44-72). Median ICU length of stay was 3.5 (IQR 1.7-7.5) days. ICU and hospital mortality were 18.5% and 25.5%, respectively. Temporal change in SOFA scores varied by survival and admission SOFA score in a complicated relationship. Area under the receiver operating characteristic (ROC) curve using admission SOFA as a predictor of hospital mortality was 0.77. The hospital mortality rate was 5.6% for patients with an admission SOFA of 0-2 and 94.4% with an admission SOFA of 20-24. There was an approximately linear increase in hospital mortality for SOFA scores of 3-19 (range 8.7-84.7%). CONCLUSIONS: Examining the clinical course of organ dysfunction in a large non-selective cohort of patients provides insight into the utility of SOFA. We have demonstrated that hospital outcome is associated with both admission SOFA and the temporal rate of change in SOFA after admission. It is necessary to further explore the impact of additional clinical factors on the clinical course of SOFA with large datasets.

Primary treatment for oropharyngeal squamous cell carcinoma in Alberta, Canada: A population-based study.

BACKGROUND: The incidence of human papillomavirus (HPV)-related oropharyngeal squamous cell carcinoma (SCC) is increasing and has better survival than non-HPV related oropharyngeal SCC. This study compared surgical to nonsurgical treatments and demographic, clinical, and survival differences in patients with oropharyngeal SCC, stratified by p16 status. METHODS: We assembled a cohort of adult patients with oropharyngeal SCC diagnosed between 2000 and 2008 in Alberta. The tumor p16 biomarker was measured using fluorescent immunohistochemistry. RESULTS: In this cohort, p16 data were available for 115 of 357 patients; and 66% (n = 76) were p16-positive. Patients with p16 data had comparable outcomes to those without. Surgically treated p16-negative patients had improved 5-year disease-specific survival (DSS) and overall survival (OS) compared with nonsurgical patients. There were no differences in survival outcomes between surgical and nonsurgical treatment for patients with p16-positive disease. CONCLUSION: Patients with p16-positive oropharyngeal SCC had similar outcomes regardless of treatment. Patients with p16-negative tumors may benefit from primary surgery with postoperative adjuvant therapy.

Validation of the Model of End-Stage Liver Disease for Liver Transplant Allocation in Alberta: Implications for Future Directions in Canada.

Background. Since 2002, the Model of End-Stage Liver Disease (MELD) has been used for allocation of liver transplants (LT) in the USA. In Canada, livers were allocated by the CanWAIT algorithm. The aim of this study was to compare the abilities of MELD, Child-Pugh (CP), and CanWAIT status to predict 3-month and 1-year mortality before LT in Canadian patients and to describe the use of MELD in Canada. Methods. Validation of MELD was performed in 320 patients listed for LT in Alberta (1998-2002). In October 2014, a survey of MELD use by Canadian LT centers was conducted. Results. Within 1 year of listing, 47 patients were removed from the waiting list (29 deaths, 18 too ill for LT). Using logistic regression, the MELD and CP were better than the CanWAIT at predicting 3-month (AUROC: 0.79, 0.78, and 0.59; p = 0.0002) and 1-year waitlist mortality (AUROC: 0.70, 0.70, and 0.55; p = 0.0023). Beginning in 2004, MELD began to be adopted by Canadian LT programs but its use was not standardized. Conclusions. Compared with the CanWAIT system, the MELD score was significantly better at predicting LT waitlist mortality. MELD-sodium (MELD-Na) has now been adopted for LT allocation in Canada.

Understanding the impact of a clinical care pathway for major head and neck cancer resection on postdischarge healthcare utilization.

BACKGROUND: The purposes of this study were to explore the association of a postoperative clinical care pathway for patients undergoing major head and neck surgery with microvascular reconstruction on postdischarge health care utilization and cost and to compares a nonpathway group (n = 60) to a prospective, pathway-managed group (n = 54). Our primary purpose was to understand whether pathway-managed patients used postdischarge health care resources differently than patients managed without a care pathway. METHODS: Health care utilization data (counts and costs) were collected for the 3 months after discharge. Differences in utilization were compared using Poisson regression. The null hypothesis was that there were no differences in utilization between the pathway and nonpathway groups. RESULTS: Pathway patients had fewer postdischarge encounters in 2 of 4 sectors. Readmission costs were significantly less in the pathway group only. CONCLUSION: A postoperative inpatient clinical care pathway in patients with head and neck cancer is associated with decreased health care utilization and inpatient costs in the 3 months after discharge. © 2015 Wiley Periodicals, Inc. Head Neck 38: E1216-E1220, 2016.

MRI texture heterogeneity in the optic nerve predicts visual recovery after acute optic neuritis.

PURPOSE: To test the feasibility of using multi-scale MRI texture analysis to assess optic nerve pathology and to investigate how visual recovery relates to the severity of acute tissue damage in the optic nerve in patients after optic neuritis (ON). MATERIALS AND METHODS: We recruited 25 patients with acute ON. Retinal nerve fiber layer (RNFL) thickness; MRI lesion length and enhancement; optic nerve area ratio; and multi-scale MRI texture analysis, a measure of structural integrity, were used to assess tissue damage at baseline, and at 6 and 12 months. The recovery in vision was defined as the functional outcome. Eight healthy subjects were imaged for control. RESULTS: We identified 25 lesions in the affected eyes (9 enhanced) and 5 in the clinically non-affected eyes (none enhanced). At baseline, we found that RNFL values were 20% thicker and lesion texture 14% more heterogeneous in the affected eyes than in the non-affected eyes, and lesion texture ratio of affected to non-affected eyes was greater in patients than in controls. In the affected eyes, visual acuity recovered significantly over 6 (18/23 patients) and 12 months (18/21 patients) when RNFL thickness and optic nerve area ratio decreased over time. Texture heterogeneity in the standard MRI of acute optic nerve lesions was the only measure that predicted functional recovery after ON. CONCLUSIONS: Tissue heterogeneity may be a potential measure of functional outcome in ON patients and advanced analysis of the texture in standard MRI could provide insights into mechanisms of injury and recovery in patients with similar disorders.

Electrothermal arthroscopic capsulorrhaphy: old technology, new evidence. A multicenter randomized clinical trial.

BACKGROUND: Radiofrequency technology for shoulder instability was rapidly adopted despite limited clinical evidence and a poor understanding of its indications. Reports of serious adverse events followed, leading to its abandonment. This paper presents findings from a multicenter randomized clinical trial evaluating the safety and efficacy of electrothermal arthroscopic capsulorrhaphy (ETAC) compared with open inferior capsular shift (ICS) and reviews the role of randomized trials in adopting new technology. METHODS: Patients (>14 years) diagnosed with multidirectional instability or multidirectional laxity with anteroinferior instability and failed nonoperative treatment were enrolled. Patients with bone lesions or labral, biceps anchor, or full-thickness rotator cuff tears were excluded intraoperatively. Outcomes included Western Ontario Shoulder Instability Index, function and recurrent instability at 2 years postoperatively, and surgical times. RESULTS: Fifty-four subjects (mean age, 23 years; 37 women) were randomized to ETAC (n = 28) or open ICS (n = 26). The groups were comparable at baseline, except for external rotation at the side. At 2 years postoperatively, there were no statistically or clinically significant differences between groups for the Western Ontario Shoulder Instability Index (P = .71), American Shoulder and Elbow Surgeons score (P = .43), Constant score (P = .43), and active range of motion. Recurrent instability was not statistically different (ETAC, 2; open, 4; P = .41). ETAC (23 minutes) was significantly shorter than open ICS (59 minutes) (P < .01) surgery. Three subjects (1 ETAC, 2 open) had stiff shoulders. CONCLUSIONS: At 2 years postoperatively, quality of life and functional outcomes between groups were not clinically different. ETAC had fewer complications and episodes of recurrence compared with open surgery. This evidence reinforces the need to critically evaluate new technology before widespread clinical use.

Neurovascular decoupling is associated with severity of cerebral amyloid angiopathy.

OBJECTIVES: We used functional MRI (fMRI), transcranial Doppler ultrasound, and visual evoked potentials (VEPs) to determine the nature of blood flow responses to functional brain activity and carbon dioxide (CO2) inhalation in patients with cerebral amyloid angiopathy (CAA), and their association with markers of CAA severity. METHODS: In a cross-sectional prospective cohort study, fMRI, transcranial Doppler ultrasound CO2 reactivity, and VEP data were compared between 18 patients with probable CAA (by Boston criteria) and 18 healthy controls, matched by sex and age. Functional MRI consisted of a visual task (viewing an alternating checkerboard pattern) and a motor task (tapping the fingers of the dominant hand). RESULTS: Patients with CAA had lower amplitude of the fMRI response in visual cortex compared with controls (p = 0.01), but not in motor cortex (p = 0.22). In patients with CAA, lower visual cortex fMRI amplitude correlated with higher white matter lesion volume (r = -0.66, p = 0.003) and more microbleeds (r = -0.78, p < 0.001). VEP P100 amplitudes, however, did not differ between CAA and controls (p = 0.45). There were trends toward reduced CO2 reactivity in the middle cerebral artery (p = 0.10) and posterior cerebral artery (p = 0.08). CONCLUSIONS: Impaired blood flow responses in CAA are more evident using a task to activate the occipital lobe than the frontal lobe, consistent with the gradient of increasing vascular amyloid severity from frontal to occipital lobe seen in pathologic studies. Reduced fMRI responses in CAA are caused, at least partly, by impaired vascular reactivity, and are strongly correlated with other neuroimaging markers of CAA severity.

Internet-based interventions for disordered gamblers: study protocol for a randomized controlled trial of online self-directed cognitive-behavioural motivational therapy.

BACKGROUND: Gambling disorders affect about one percent of adults. Effective treatments are available but only a small proportion of affected individuals will choose to attend formal treatment. As a result, self-directed treatments have also been developed and found effective. Self-directed treatments provide individuals with information and support to initiate a recovery program without attending formal treatment. In previous research we developed an telephone-based intervention package that helps people to be motivated to tackle their gambling problem and to use basic behavioral and cognitive change strategies. The present study will investigate the efficacy of this self-directed intervention offered as a free online resource. The Internet is an excellent modality in which to offer self-directed treatment for gambling problems. The Internet is increasingly accessible to members of the public and is frequently used to access health-related information. Online gambling sites are also becoming more popular gambling platforms. METHOD/DESIGN: A randomized clinical trial (N=180) will be conducted in which individuals with gambling problems who are not interested in attending formal treatment are randomly assigned to have access to an online self-directed intervention or to a comparison condition. The comparison condition will be an alternative website that offers a self-assessment of gambling involvement and gambling-related problems. The participant's use of the resources and their gambling involvement (days of gambling, dollars loss) and their gambling problems will be tracked for a twelve month follow-up period. DISCUSSION: The results of this research will be important for informing policy-makers who are developing treatment systems. TRIAL REGISTRATION: ISRCTN06220098.

Telomere length correlates with life span of dog breeds.

Telomeric DNA repeats are lost as normal somatic cells replicate. When telomeres reach a critically short length, a DNA damage signal is initiated, inducing cell senescence. Some studies have indicated that telomere length correlates with mortality, suggesting that telomere length contributes to human life span; however, other studies report no correlation, and thus the issue remains controversial. Domestic dogs show parallels in telomere biology to humans, with similar telomere length, telomere attrition, and absence of somatic cell telomerase activity. Using this model, we find that peripheral blood mononuclear cell (PBMC) telomere length is a strong predictor of average life span among 15 different breeds (p < 0.0001), consistent with telomeres playing a role in life span determination. Dogs lose telomeric DNA ~10-fold faster than humans, which is similar to the ratio of average life spans between these species. Breeds with shorter mean telomere lengths show an increased probability of death from cardiovascular disease, which was previously correlated with short telomere length in humans.

Matched case-control studies: a review of reported statistical methodology.

BACKGROUND: Case-control studies are a common and efficient means of studying rare diseases or illnesses with long latency periods. Matching of cases and controls is frequently employed to control the effects of known potential confounding variables. The analysis of matched data requires specific statistical methods. METHODS: The objective of this study was to determine the proportion of published, peer-reviewed matched case-control studies that used statistical methods appropriate for matched data. Using a comprehensive set of search criteria we identified 37 matched case-control studies for detailed analysis. RESULTS: Among these 37 articles, only 16 studies were analyzed with proper statistical techniques (43%). Studies that were properly analyzed were more likely to have included case patients with cancer and cardiovascular disease compared to those that did not use proper statistics (10/16 or 63%, versus 5/21 or 24%, P = 0.02). They were also more likely to have matched multiple controls for each case (14/16 or 88%, versus 13/21 or 62%, P = 0.08). In addition, studies with properly analyzed data were more likely to have been published in a journal with an impact factor listed in the top 100 according to the Journal Citation Reports index (12/16 or 69%, versus 1/21 or 5%, P ≤ 0.0001). CONCLUSION: The findings of this study raise concern that the majority of matched case-control studies report results that are derived from improper statistical analyses. This may lead to errors in estimating the relationship between a disease and exposure, as well as the incorrect adaptation of emerging medical literature.

Incidence and outcome of prone positioning following police use of force in a prospective, consecutive cohort of subjects.

The safety of placing suspects in the prone position following police use of force has been debated extensively, particularly in the context of sudden in-custody death. The proportion of individuals who remain in the prone position following police use of force is not known, nor has the epidemiology of sudden in-custody death in any position after police restraint been documented. Using a consecutive cohort of individuals in whom police used force, we prospectively documented the number of individuals who were placed in a prone versus not-prone position, and the prevalence of sudden in-custody death in either position. Data were collected for three consecutive years, through a single urban police service, in a city of over 1.1 million citizens. Officers prospectively documented the final position of the subject, among other data points, via electronic study forms embedded in standard use of force report forms. Final resting position was available for 1255/1269 subjects. The majority of subjects are male and demonstrated one or more abnormalities at the time of the event. We found that the majority (57.2%) of subjects were left in a not-prone position; the remainder were left in prone position. One subject died in a not-prone position, no subjects died in the prone position. The sudden in-custody death rate following police use of force was low overall (0.08%, 95% confidence interval (CI) = 0.002, 0.44) and the difference in the proportion of subjects who died suddenly in either position was not significant at 0.14%, (95%CI = -0.8, 0.9). Our results indicate that prone positioning was common and was not associated with death in our cohort of consecutive subjects following police use of force.

Emergency medical services response time and mortality in an urban setting.

BACKGROUND: A common tenet in emergency medical services (EMS) is that faster response equates to better patient outcome, translated by some EMS operations into a goal of a response time of 8 minutes or less for advanced life support (ALS) units responding to life-threatening events. OBJECTIVE: To explore whether an 8-minute EMS response time was associated with mortality. METHODS: This was a one-year retrospective cohort study of adults with a life-threatening event as assessed at the time of the 9-1-1 call (Medical Priority Dispatch System Echo- or Delta-level event). The study setting was an urban all-ALS EMS system serving a population of approximately 1 million. Response time was defined as 9-1-1 call receipt to ALS unit arrival on scene, and outcome was defined as all-cause mortality at hospital discharge. Potential covariates included patient acuity, age, gender, and combined scene and transport interval time. Stratified analysis and logistic regression were used to assess the response time-mortality association. RESULTS: There were 7,760 unit responses that met the inclusion criteria; 1,865 (24%) were ≥8 minutes. The average patient age was 56.7 years (standard deviation = 21.5). For patients with a response time ≥8 minutes, 7.1% died, compared with 6.4% for patients with a response time ≤7 minutes 59 seconds (risk difference 0.7%; 95% confidence interval [CI]: -0.5%, 2.0%). The adjusted odds ratio of mortality for ≥8 minutes was 1.19 (95% CI: 0.97, 1.47). An exploratory analysis suggested there may be a small beneficial effect of response ≤7 minutes 59 seconds for those who survived to become an inpatient (adjusted odds ratio = 1.30; 95% CI: 1.00, 1.69). CONCLUSIONS: These results call into question the clinical effectiveness of a dichotomous 8-minute ALS response time on decreasing mortality for the majority of adult patients identified as having a life-threatening event at the time of the 9-1-1 call. However, this study does not suggest that rapid EMS response is undesirable or unimportant for certain patients. This analysis highlights the need for further research on who may benefit from rapid EMS response, whether these individuals can be identified at the time of the 9-1-1 call, and what the optimum response time is.

The effects of a supplemental, theory-based physical activity counseling intervention for adults with type 2 diabetes.

BACKGROUND: Physical activity (PA) is a cornerstone in the management of type 2 diabetes (T2DM). This pilot investigation explores the effects of a standard diabetes education program compared with a supplemental PA intervention on diabetes-related health outcomes. METHODS: Using a prospective 2-armed design, 96 adults with T2DM were randomly assigned to either standard care (diabetes education program; n = 49) or standard care supplemented with an 8-week, individualized-counseling and community-based PA component (n = 47). Measurements were taken at baseline, 3, 6, and 12 months. Primary outcomes were changes in PA (self-report) and HbA1c. Between group changes were compared using analysis of covariance (ANCOVA) and changes over time using repeated-measures ANOVA. RESULTS: In comparison with standard care, the supplemental group demonstrated an increase in PA (Ps < 0.01) and cardiorespiratory fitness (Ps < 0.05) from baseline to all follow-up time-points. HbA1c levels declined (P < .05) from baseline to all time points in the standard care group. Reduction in cholesterol-ratio (P < .01), increase in HDL (P < .05), and reductions in blood pressure, resting heart rate and BMI (approaching statistical significance Ps < 0.10) were also reported for both groups. CONCLUSIONS: PA counseling in addition to standard care is effective for promoting PA behavior change and positive health-related outcomes among individuals with T2DM.

Palmitate alters the rhythmic expression of molecular clock genes and orexigenic neuropeptide Y mRNA levels within immortalized, hypothalamic neurons.

The control of energy homeostasis within the hypothalamus is under the regulated control of homeostatic hormones, nutrients and the expression of neuropeptides that alter feeding behavior. Elevated levels of palmitate, a predominant saturated fatty acid in diet and fatty acid biosynthesis, alter cellular function. For instance, a key mechanism involved in the development of insulin resistance is lipotoxicity, through increased circulating saturated fatty acids. Although many studies have begun to determine the underlying mechanisms of lipotoxicity in peripheral tissues, little is known about the effects of excess lipids in the brain. To determine these mechanisms we used an immortalized, clonal, hypothalamic cell line, mHypoE-44, to demonstrate that palmitate directly alters the expression of molecular clock components, by increasing Bmal1 and Clock, or by decreasing Per2, and Rev-erbα, their mRNA levels and altering their rhythmic period within individual neurons. We found that these neurons endogenously express the orexigenic neuropeptides NPY and AgRP, thus we determined that palmitate administration alters the mRNA expression of these neuropeptides as well. Palmitate treatment causes a significant increase in NPY mRNA levels and significantly alters the phase of rhythmic expression. We explored the link between AMPK and the expression of neuropeptide Y using the AMPK inhibitor compound C and the AMP analog AICAR. AMPK inhibition decreased NPY mRNA. AICAR also elevated basal NPY, but prevented the palmitate-mediated increase in NPY mRNA levels. We postulate that this palmitate-mediated increase in NPY and AgRP synthesis may initiate a detrimental positive feedback loop leading to increased energy consumption.

Estimates of total analytical error in consumer and hospital glucose meters contributed by hematocrit, maltose, and ascorbate.

BACKGROUND: Patients and physicians expect accurate whole blood glucose monitoring even when patients are anemic, are undergoing peritoneal dialysis, or have slightly elevated ascorbate levels. The objective of this study was to estimate analytical error in two consumer and two hospital glucose meters contributed by variations in hematocrit, maltose, ascorbate, and imprecision. METHODS: The influence of hematocrit (20-60%), maltose, and ascorbate were tested alone and in combination with each glucose meter and with a reference plasma glucose method at three concentrations of glucose. Precision was determined by consecutive analysis (n=20) at three levels of glucose. Multivariate regression analysis was used to estimate the bias associated with the interferences, alone and in combination. Total analytical error was estimated as |% bias|+1.96 (% imprecision). RESULTS: Three meters demonstrated hematocrit bias that was dependent upon glucose concentration. Maltose had profound concentration-dependent positive bias on the consumer meters, and the extent of maltose bias was dependent on hematocrit. Ascorbate produced small but statistically significant biases on three meters. Coincident low hematocrit, presence of maltose, and presence of ascorbate increased the observed bias and was summarized by estimation of total analytical error. Among the four glucose meter devices assessed, estimates of total analytical error in glucose measurement ranged from 6 to 68% under the conditions tested. CONCLUSIONS: The susceptibility of glucose meters to clinically significant analytical biases is highly device-dependent, and low hematocrit exacerbated the observed analytical error.

The prevalence of mental disorders in the working population over the period of global economic crisis.

OBJECTIVES: The ongoing global economic crisis may have affected people's mental health. This study aimed to, among a sample of the working population, estimate and compare the prevalence of depressive and anxiety disorders in different time intervals from January 2008 to October 2009 and to examine the demographic and socioeconomic correlates of mental disorders. METHODS: From January 2008 to October 2009, 3579 employees in Alberta were recruited using the random digit dialing method. Mental disorders were assessed using the World Health Organization's Composite International Diagnostic Interview-Auto 2.1. The lifetime and 12-month prevalence of depressive and anxiety disorders in different time intervals were estimated and compared. RESULTS: The 12-month prevalence of major depressive disorder (MDD) before September 1, 2008; between September 1, 2008, and March 1, 2009; and between March 1, 2009, and October 30, 2009, was 5.1%, 6.8%, and 7.6% (P = 0.03), respectively. The lifetime prevalence of dysthymia reported during the 3 periods was 0.4%, 0.7%, and 1.5% (P = 0.006), respectively. No changes in the 12-month prevalence of social phobia, panic disorder, and generalized anxiety disorder were found over time. CONCLUSIONS: The ongoing global economic crisis may have contributed to the increased prevalence of MDD. Future studies are needed to monitor the changes in the prevalence and to describe how the event may affect people's employment status, income, and health.

Rhythmic clock and neuropeptide gene expression in hypothalamic mHypoE-44 neurons.

The rhythmic expression of specific clock genes: Bmal1, Per2, Clock and Rev-Erbalpha; and specific hypothalamic neuropeptides: NPY, Crh, AgRP, neurotensin and preproghrelin, expressed in clonal hypothalamic neuronal cell lines, was assayed and analyzed using a novel non-linear least squares statistical analysis to determine rhythmicity in an in vitro milieu. In silico analysis of the neuropeptide promoter regions identified putative E-box motifs and a motif in the NPY promoter is bound to in an oscillatory fashion. Within the mHypoE-44 neurons, we demonstrate that mRNA of four core circadian components: Bmal1, Clock, Per2 and Rev-Erbalpha, oscillate with approximate 24h rhythms. NPY and NT demonstrated significant 24h gene expression. However, CRH and preproghrelin mRNA cycled significantly in an ultradian fashion, oscillating approximately every 18h. AgRP mRNA did not show a significant rhythm. We speculate that endogenous rhythmic neuropeptide expression contributes to neuroendocrine homeostasis, which may include energy balance.