Evaluation of a pilot, community-led mental illness de-stigmatization theater intervention in rural uganda.

BACKGROUND: In rural areas of low- and middle- income countries, mental health care is often unavailable and inaccessible, and stigma is a major barrier to treatment. Destigmatization can increase treatment-seeking attitudes, community support, and acceptance of individuals suffering from mental illness. This study's primary objective was to evaluate the impact of a community-led, theater-based destigmatization campaign for mental illness conducted in the Busoga region of Eastern Uganda. METHODS: One hundred residents of the Busoga region were randomly selected via cluster sampling to complete a structured questionnaire assessing mental health stigma. Four focus groups were conducted for qualitative data on mental health stigma. Common misconceptions and specific points of stigma were identified from these responses, and local village health team personnel developed and performed a culturally-adapted theatrical performance addressing these points. Changes in perceptions of mental illness were measured among 57 attendees using two measures, the Broad Acceptance Scale (designed to reflect factors that contribute to structural stigma) and Personal Acceptance Scale (designed to reflect factors that contribute to interpersonal, or public stigma), before and after the performance. RESULTS: There was a significant increase in acceptance according to the Broad Acceptance Scale (p < .001) and Personal Acceptance Scale (p < .001). Qualitative responses from play attendees also indicated a decrease in stigma and an increased sense of the importance of seeking treatment for mentally ill patients. CONCLUSION: This study shows community-led, theater intervention may be an effective tool for the destigmatization of mental illness in rural areas of Uganda. Larger studies are needed to further test the efficacy of this approach and potential for longer-term scalabilityand sustainability.

Intraoperative Endotracheal Cuff Pressure Study: How Education and Availability of Manometers Help Guide Safer Pressures.

INTRODUCTION: Endotracheal intubation is a medical procedure that is often indicated in both the perioperative and critical care environments. Cuffed endotracheal tubes (ETT) allow for safer and more efficient delivery of positive pressure ventilation, as well as create a barrier to reduce the risk of micro-aspiration and anesthetic pollution in the operating room environment. Over-inflation of the endotracheal cuff can lead to serious and harmful sequelae. This study aimed to assess if departmental education paired with ready access to a manometer to assess cuff pressure would result in an improvement in the proportion of ETT cuff pressures in the goal range. MATERIALS AND METHODS: A quality improvement study was conducted at the San Antonio Military Medical Center (SAMMC; Department of Defense hospital in San Antonio, TX). The initiative was divided into three key periods: pre-implementation, implementation, and post-implementation. During the pre-implementation period, ETT cuff pressures were obtained to assess the baseline state of ETT cuff pressures for patients in the operating room; the proportion of in-range (20-30 cmH2O) pressures was calculated. During the implementation phase, operating rooms were equipped with manometers and anesthesia departmental education was performed regarding the use of the manometers. Three months later, post-implementation cuff pressures were measured in the OR, and the proportion of in-range pressures was again calculated. RESULTS: The pre-implementation data showed an average cuff pressure of 48.92 cmH2O and a median of 38.5 cmH2O. Of the 100 pre-implementation pressures, 20 were in the goal range. Post-implementation data had an average cuff pressure of 41.96 cmH2O and a median of 30 cmH2O. A chi-squared test of pressures in the safe range from the pre-implementation versus post-implementation values yielded a highly significant p-value of 0.0003. CONCLUSION: The data from this study clearly demonstrated a statistically significant improvement in the proportion of in-range cuff pressures following the quality improvement initiative. This study supports the use of department-wide education and the availability of manometers in each OR to yield safer cuff pressures for intubated patients. This study did not aim to determine an optimal ETT cuff pressure, but utilized data already available to determine a safe cuff pressure. Further research needs to be performed to assess whether routine monitoring of cuff pressure results in improved patient outcomes.

Dexmedetomidine as a Rescue Therapy for Emergence Delirium in Adults: A Case Series.

Emergence delirium (ED) in adult patients encountered in the postanesthesia care unit (PACU) is not well studied; nor are ED treatment strategies. Similar to delirium in the intensive care unit, ED in the PACU can result in serious complications. We describe 3 cases of ED in the PACU in patients with a history of posttraumatic stress disorder who were successfully treated with dexmedetomidine. Although likely utilized more frequently in recent years, the use of dexmedetomidine in the PACU for treatment of ED is not established in the literature. Further research regarding treatment of ED in adults is necessary, allowing for optimization of patient care and improvement in patient outcomes.

Assessment of asymmetrical dimethylarginine metabolism in patients with critical illness.

BACKGROUND: Critically ill patients experience metabolic disorders including hypercatabolic state and hyperglycaemia, and these are associated with poor outcome. Hyperglycaemia and asymmetrical dimethylarginine (ADMA) are reported to have significant influences on endothelial dysfunction. The aim of this study was to examine the relationship between plasma ADMA and related arginine metabolism in patients with critical illness. MATERIALS AND METHOSDS: Two venous blood samples (EDTA) (104 patients), on admission and follow-up sample in the last day in intensive care unit (ICU) (died or discharge sample median 7, interquartile range (IQR) 6-8, range 5-15). Plasma ADMA, arginine, homoarginine and SDMA were measured by high-performance liquid chromatography (HPLC). RESULT: ADMA (P < 0·01) and SDMA (P < 0·05) were elevated, and homoarginine was decreased (P < 0·05) in nonsurvivors and was directly associated with predicted mortality rate (P < 0·05 and P < 0·001), Sequential Organ Failure Assessment (SOFA) (P < 0·05, P < 0·001), ICU stay (P < 0·05, P < 0·001) and mortality (P < 0·01, P < 0·05). ADMA was directly associated with SDMA (P < 0·001), albumin (P < 0·05), ICU stay and mortality (P < 0·01). SDMA was directly associated with creatinine (P < 0·001) and Acute physiology and Chronic Health Evaluation II score (P < 0·001). In the follow-up measurements, there was a significant decrease in SOFA score (P < 0·01), homoarginine (P < 0·01), aminotransferase (P < 0·01), Laboratory Glucose (P < 0·01) and albumin (P < 0·01). In contrast, there was an increase in arginine (P < 0·01), ADMA (P < 0·01), ADMA:SDMA ratio (P < 0·01) and the norepinephrine administration (P < 0·01). CONCLUSION: In the present longitudinal study, ADMA metabolism was altered in patients with critical illness and was associated with disease severity and mortality.

Nurse led care coordination: trial protocol and development of a best practice resource guide for a cluster controlled clinical trial in Australian aged care facilities.

In this paper we describe (i) the protocol for a cluster controlled clinical trial of nurse led care coordination in residential aged care facilities (RACF); and (ii) the development and content of a best practice resource guide to be implemented as part of this trial. We used published systematic reviews of quantitative studies, existing resources and multidisciplinary expert opinion to develop an intervention for testing in a cluster controlled trial (Australian and New Zealand Clinical Trials Registry Number 12611000933954). The trial will determine whether care coordination of multiple evidenced based strategies can improve quality of life and reduce hospitalization rates amongst people living in RACF. Central to the intervention arm of the trial are two components: (i) experienced nurse practitioners responsible for resident care and (ii) a best practice guide for the care processes being delivered and coordinated by those nurses. In this paper we outline how this practice guide, which is published herein, was refined through consultative processes and practitioner testing.

Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man.

BACKGROUND: Diesel exhaust inhalation causes cardiovascular dysfunction including impaired vascular reactivity, increased blood pressure, and arterial stiffness. We investigated the role of nitric oxide (NO) bioavailability in mediating these effects. METHODS AND RESULTS: In 2 randomized double-blind crossover studies, healthy nonsmokers were exposed to diesel exhaust or filtered air. Study 1: Bilateral forearm blood flow was measured during intrabrachial infusions of acetylcholine (ACh; 5 to 20 µg/min) and sodium nitroprusside (SNP; 2 to 8 µg/min) in the presence of the NO clamp (NO synthase inhibitor N(G)-monomethyl-l-arginine (l-NMMA) 8 µg/min coinfused with the NO donor SNP at 90 to 540 ng/min to restore basal blood flow). Study 2: Blood pressure, arterial stiffness, and cardiac output were measured during systemic NO synthase inhibition with intravenous l-NMMA (3 mg/kg). Following diesel exhaust inhalation, plasma nitrite concentrations were increased (68±48 versus 41±32 nmol/L; P=0.006) despite similar l-NMMA-induced reductions in basal blood flow (-20.6±14.7% versus -21.1±14.6%; P=0.559) compared to air. In the presence of the NO clamp, ACh and SNP caused dose-dependent vasodilatation that was not affected by diesel exhaust inhalation (P>0.05 for both). Following exposure to diesel exhaust, l-NMMA caused a greater increase in blood pressure (P=0.048) and central arterial stiffness (P=0.007), but reductions in cardiac output and increases in systemic vascular resistance (P>0.05 for both) were similar to those seen with filtered air. CONCLUSIONS: Diesel exhaust inhalation disturbs normal vascular homeostasis with enhanced NO generation unable to compensate for excess consumption. We suggest the adverse cardiovascular effects of air pollution are, in part, mediated through reduced NO bioavailability. CLINICAL TRIAL REGISTRATION: URL: http://www.ClinicalTrials.gov. Unique identifiers: NCT00845767 and NCT01060930.

Endothelin-A receptor antagonism modifies cardiovascular risk factors in CKD.

Arterial stiffness and impaired nitric oxide (NO) bioavailability contribute to the high risk for cardiovascular disease in CKD. Both asymmetric dimethylarginine (ADMA), an endogenous inhibitor of NO production, and endothelin-1 (ET-1) oppose the actions of NO, suggesting that ET-1 receptor antagonists may have a role in cardiovascular protection in CKD. We conducted a randomized, double-blind, three-way crossover study in 27 patients with proteinuric CKD to compare the effects of the ET(A) receptor antagonist sitaxentan, nifedipine, and placebo on proteinuria, BP, arterial stiffness, and various cardiovascular biomarkers. After 6 weeks of treatment, placebo and nifedipine did not affect plasma urate, ADMA, or urine ET-1/creatinine, which reflects renal ET-1 production; in contrast, sitaxentan led to statistically significant reductions in all three of these biomarkers. No treatment affected plasma ET-1. Reductions in proteinuria and BP after sitaxentan treatment was associated with increases in urine ET-1/creatinine, whereas reduction in pulse-wave velocity, a measure of arterial stiffness, was associated with a decrease in ADMA. Taken together, these data suggest that ET(A) receptor antagonism may modify risk factors for cardiovascular disease in CKD.

Guidelines for a palliative approach for aged care in the community setting: A suite of resources.

In Australia, many people ageing in their own homes are becoming increasingly frail and unwell, approaching the end of life. A palliative approach, which adheres to palliative care principles, is often appropriate. These principles provide a framework for proactive and holistic care in which quality of life and of dying is prioritised, as is support for families. A palliative approach can be delivered by the general practitioner working with the community aged care team, in collaboration with family carers. Support from specialist palliative care services is available if necessary.The Guidelines for a Palliative Approach for Aged Care in the Community Setting were published by the Australian Government Department of Health and Ageing to inform practice in this area. There are three resource documents. The main document provides practical evidence based guidelines, good practice points, tools, and links to resources. This document is written for general practitioners, nurses, social workers, therapists, pastoral care workers, and other health professionals and responded to needs identified during national consultation. Evidence based guidelines were underpinned by systematic reviews of the research literature. Good practice points were developed from literature reviews and expert opinion. Two 'plain English' booklets were developed in a process involving consumer consultation; one is for older people and their families, the other for care workers.The resources are intended to facilitate home care that acknowledges and plans for the client's deteriorating functional trajectory and inevitable death. At a time when hospitals and residential aged care facilities are under enormous pressure as the population ages, such a planned approach makes sense for the health system as a whole. The approach also makes sense for older people who wish to die in their own homes. Family needs are recognised and addressed. Unnecessary hospitalisations or residential placements and clinically futile interventions are also minimised.

Blood pressure and not uraemia is the major determinant of arterial stiffness and endothelial dysfunction in patients with chronic kidney disease and minimal co-morbidity.

INTRODUCTION: Patients with chronic kidney disease (CKD) have increased risk of cardiovascular disease to which co-morbidity and associated conventional risk factors contribute. We hypothesised that arterial stiffness (AS) and endothelial dysfunction (ED), as surrogates of cardiovascular risk, would worsen as renal function declined even in patients without co-morbidity and that this would relate to emerging cardiovascular risk factors. METHODS: Carotid-femoral pulse wave velocity (PWV), as a measure of AS, and flow-mediated dilatation (FMD) of the brachial artery, as a measure of ED, were assessed in CKD patients without established cardiovascular disease or diabetes mellitus. RESULTS: PWV increased linearly as renal function declined (r(2) = 0.08, p < 0.01) whereas FMD was reduced only in patients with advanced kidney disease. In multivariable analysis, blood pressure was the major determinant of PWV and FMD. High-sensitivity C-reactive protein and asymmetric dimethylarginine, and isoprostanes and endothelin-1, were independent predictors of PWV and FMD, respectively. However, renal function did not independently predict either AS or ED. CONCLUSIONS: These findings suggest that declining renal function, in the absence of significant co-morbidity, is associated with progressive arterial stiffness, but only patients close to dialysis exhibit endothelial dysfunction. Whilst blood pressure remains the major determinant of PWV and FMD, inflammation, oxidative stress and endothelin-nitric oxide balance contribute to cardiovascular risk, in this non-comorbid cohort.

The relation between acute changes in the systemic inflammatory response and plasma 25-hydroxyvitamin D concentrations after elective knee arthroplasty.

BACKGROUND: Studies indicate that low plasma 25-hydroxyvitamin D [25(OH)D] is associated with a range of disease processes, many of which are inflammatory. However, other lipid-soluble vitamins decrease during the systemic inflammatory response, and this response may confound the interpretation of plasma 25(OH)D. OBJECTIVE: The objective was to examine whether plasma 25(OH)D concentrations change during evolution of the systemic inflammatory response. DESIGN: Patients (n = 33) who underwent primary knee arthroplasty had venous blood samples collected preoperatively and postoperatively (beginning 6-12 h after surgery and on each morning for 5 d) for the measurement of 25(OH) D, vitamin D-binding protein, parathyroid hormone (PTH), calcium, C-reactive protein, and albumin. A final sample was collected at 3 mo. RESULTS: Preoperatively, most patients were 25(OH)D deficient (<50 nmol/L) and had secondary hyperparathyroidism (PTH > 5 pmol/L). Age, sex, body mass index, season, medical history, and medication use were not associated with significant differences in preoperative plasma 25(OH)D concentrations. By day 2 there was a large increase in C-reactive protein concentrations (P < 0.001) and a significant decrease in 25(OH)D of ≈40% (P < 0.001). C-reactive protein, 25(OH)D, and calculated free 25(OH)D had not returned to preoperative concentrations by 5 d postoperatively (all P < 0.001). At 3 mo, 25(OH)D and free 25(OH)D remained significantly lower (20% and 30%, respectively; P < 0.01). CONCLUSION: Plasma concentrations of 25(OH)D decrease after an inflammatory insult and therefore are unlikely to be a reliable measure of 25(OH)D status in subjects with evidence of a significant systemic inflammatory response.

Plasma dimethylarginines during the acute inflammatory response.

INTRODUCTION: Asymmetric dimethylarginine (ADMA) concentrations are increased in critically ill patients and may play a role in multiple organ failure. However, plasma ADMA concentrations during the development of the inflammatory response have not been documented. We measured plasma ADMA, as well as urinary excretion of its major metabolite dimethylamine, and nitrate as a marker of nitric oxide synthase (NOS) activity, in a cohort of patients undergoing elective knee arthroplasty that is known to provoke a significant inflammatory response. METHODS: Thirty-eight patients were recruited. Fasting venous blood samples were obtained pre-operatively and at 12h and daily until the fifth post-operative day. ADMA and symmetric dimethylarginine (SDMA) were measured by high-performance liquid chromatography (HPLC). Urinary dimethylamine and nitrate were measured pre-operatively and on each of the post-operative mornings using HPLC and expressed as a ratio to creatinine. RESULTS: Plasma ADMA fell by a median of 31% during the post-operative period, reaching a nadir on day 2, and recovering to baseline by the end of the study. SDMA showed no significant changes. No increase in urinary dimethylamine excretion was noted until day 5 post-op, whereupon it doubled. Urinary nitrate showed a small, but nonsignificant decrease on day 2, suggesting no major activation of NOS activity. CONCLUSIONS: Plasma ADMA concentration decreases rapidly and transiently during the first 48h of acute inflammation. This appears not be caused by increased catabolism and may reflect increased cellular partitioning. This may serve to regulate NOS activity and prevent harmful increases in inducible NOS in situations where it is not appropriate.

The biochemistry, measurement and current clinical significance of asymmetric dimethylarginine.

Asymmetric dimethylarginine (ADMA) is an endogenous competitive inhibitor of nitric oxide synthase and an important cause of endothelial dysfunction. Its increased plasma concentration is associated with a variety of traditional cardiovascular risk factors, and may mediate their effects on the vascular endothelium. ADMA is also an independent predictor of cardiovascular events and mortality, and predicts outcomes in critically ill patients in the intensive care unit. This work has provided insights into the role of ADMA as an endogenous regulator of nitric oxide synthesis. At present there is no specific therapy to modify ADMA concentration, but increasing interest and work on protein arginine methyltransferases and dimethylarginine dimethylaminohydrolase, which synthesize and metabolize ADMA, respectively, might provide novel therapeutic targets.

Circulating methylarginine levels and the decline in renal function in patients with chronic kidney disease are modulated by DDAH1 polymorphisms.

In patients with chronic kidney disease, high plasma levels of the endogenous nitric oxide synthase inhibitor, asymmetric dimethylarginine, are thought to contribute to decline in renal function. Here we took a candidate gene approach to determine any causal role of asymmetric dimethylarginine in the progression of chronic kidney disease. The impact of single-nucleotide polymorphisms in the genes encoding the two isoforms of the asymmetric dimethylarginine-degrading enzyme, dimethylarginine dimethylaminohydrolase (DDAH1 and DDAH2), on enzyme expression, plasma asymmetric dimethylarginine levels, and longitudinal changes in estimated glomerular filtration rate were determined in various patient groups. There was evidence suggesting that the rs17384213 DDAH1 GG genotype was associated with increased expression of its mRNA in kidney allografts. Healthy subjects carrying the rs17384213 G allele had lower plasma asymmetric dimethylarginine, and a similar borderline association was found in patients with chronic kidney disease. This allele, however, was independently associated with a steeper decline in renal function in two separate cohorts of patients with chronic kidney disease. We conclude that polymorphisms in DDAH1 alter the rate of decline of glomerular filtration rate in subjects with chronic kidney disease. Our findings show that DDAH1 modulates plasma asymmetric dimethylarginine and contributes to the decline in renal function. However, it appears that increases in circulating methylarginine did not mediate progressive kidney injury.

HPLC analysis of asymmetric dimethylarginine (ADMA) and related arginine metabolites in human plasma using a novel non-endogenous internal standard.

BACKGROUND: Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthesis which has been implicated in the endothelial dysfunction. Methods for ADMA measurement often yield widely differing results, and few methods simultaneously offer satisfactory accuracy and precision. We describe a fully validated HPLC method for analysis of arginine and its methylated derivatives in human plasma using a novel internal standard. METHODS: Arginine and related metabolites are extracted from plasma by solid phase extraction (SPE), derivatised with ortho-phthaldialdehyde and separated by isocratic reverse phase chromatography. Monoethylarginine (MEA), which is not endogenously present in human plasma was used as internal standard. SPE and chromatographic procedures are optimised and recovery, precision, linearity and sensitivity of the assay established. The suitability and performance of MEA is compared with that of monomethylarginine (MMA), the internal standard most commonly used in HPLC methods. RESULTS: SPE yields high and reproducible recoveries (>90%). The analytes of interest are chromatographically well resolved. The method has high sensitivity (LOD, 0.01 micromol/L for arginine and 0.001 micromol/L for ADMA, SDMA and homoarginine) and good precision (CV, 2.5% for ADMA). The data obtained with the internal standards MEA and MMA is comparable in terms of assay precision and population reference intervals. CONCLUSIONS: We describe an optimised isocratic HPLC method for the simultaneous measurement of arginine and related metabolites in plasma which exhibits satisfactory precision and is suitable for routine use. Its main advantage over other published HPLC methods is the use of the novel internal standard, MEA, which unlike other commonly used internal standards is not inherent in human plasma.

Outcomes of chlorine exposure: a 5-year poison center experience in 598 patients.

BACKGROUND: The outcome after chlorine exposures has been poorly described. METHODS: We conducted a 5-year retrospective poison control center review of chlorine exposure cases. The inclusion criteria were self (or surrogate) reported concentrated 'chlorine' liquid (> or =10% concentration of sodium hypochorite) or tablet (> or =90% concentration) exposure. Two reviewers blinded to the main purpose of the study reviewed charts and a third reviewed 10% of the charts, and a kappa score was calculated. Parameters reviewed included the type of exposure (tablets, liquid or both), symptoms (cough, chest pain, etc.), time to symptom onset, treatment received, hospital referral rate and outcomes. RESULTS: A total of 598 patient records were reviewed, with a mean age of 29.63 years (range 11-82); 41.5% (248) were exposures to tablets and 53.5% (320) were exposed to liquid chlorine, with the remainder exposed to both. Complaints included shortness of breath, eye irritation, nasal complaints, cough, and skin complaints. Sixty-nine patients were evaluated at a healthcare facility (11 referred by a poison control center and 58 were self-referrals). Five patients were admitted and four out of the five had a history of reactive airway disease. The mean time to peak symptoms was 94.4 min, 63.2% reached peak symptoms within 30 min, and 82% within 120 min, with 74% of all patients asymptomatic within 150 min. All five admitted patients were discharged within 48 h, and all others remained clinically well at a 24 h telephone follow-up. CONCLUSION: Exposure to chlorine tablets and liquid rarely requires hospital referral with almost all symptoms resolving within 24 h.

Whose health service is it anyway? Community values in healthcare.

There is growing interest in involving the public in decisions about healthcare provision. Citizens' juries, whose members were randomly selected from the electoral roll (rather than derived from consumer interest groups), have been trialled in Western Australia. When asked to take a community focus, presented with balanced evidence and given time to discuss and deliberate, the juries were able to identify and debate issues of broad principle, such as equity. Such issues seem to be best handled by referring to community values. Any public consultation process should provide sufficient information, opportunity for reflection and deliberation, and recognition of the scarcity of resources.