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Background no studies have examined the impact of residential medication management review (RMMR, a 24-year government subsidised comprehensive medicines review program) in Australian residential aged care facilities (RACFs) on hospitalisation or mortality. Objective to examine associations between RMMR provision in the 6–12 months after RACF entry and the 12-month risk of hospitalisation and mortality among older Australians in RACFs. Design retrospective cohort study. Subjects individuals aged 65–105 years taking at least one medicine, who entered an RACF in three Australian states between 1 January 2012 and 31 December 2015 and spent at least 6 months in the RACF (n  = 57,719). Methods Cox regression models estimated adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) for associations between RMMR provision and mortality. Adjusted subdistribution hazard ratios were estimated for associations between RMMR provision and next (i) emergency department (ED) presentation or unplanned hospitalisation or (ii) fall-related ED presentation or hospitalisation. Results there were 12,603 (21.8%) individuals who received an RMMR within 6–12 months of RACF entry, of whom 22.2% (95%CI 21.4–22.9) died during follow-up, compared with 23.3% (95%CI 22.9–23.7) of unexposed individuals. RMMR provision was associated with a lower risk of death due to any cause over 12-months (aHR 0.96, 95%CI 0.91–0.99), but was not associated with ED presentations or hospitalisations for unplanned events or falls. Conclusions provision of an RMMR in the 6–12 months after RACF entry is associated with a 4.4% lower mortality risk over 12-months but was not associated with changes in hospitalisations for unplanned events or falls. [ABSTRACT FROM AUTHOR]

Co‐prescribing of opioids and sedatives is a known risk factor for opioid‐induced ventilatory impairment (OIVI). Prevalence data for sedative and opioid co‐prescription in inpatients in Australia are unknown. Our objective was to determine the prevalence of inpatient sedative and opioid co‐prescribing and to identify factors associated with co‐prescription. We conducted a retrospective cross‐sectional study from July 2017 to October 2017 across four South Australian hospitals utilizing a centralized electronic health record. Multivariate analysis was used to identify characteristics predictive of co‐prescribing of a strong opioid (fentanyl, hydromorphone, morphine, and oxycodone) and sedative medications (benzodiazepines, antiepileptics, antipsychotics, and tricyclic antidepressants). Of the 6170 inpatients, 2795 (45.3%) were prescribed a strong opioid and of those, 1889 (30.6% of all inpatients) were co‐prescribed a sedative. Of those prescribed a strong opioid, five (0.18%) developed OIVI. Patients prescribed a strong opioid had a 27–77% increased likelihood of being prescribed a sedative. Factors predictive of sedative co‐prescribing included the presence of disease of the central nervous system adjusted OR (aOR) 8.66 [95% CI 5.83–12.9] and respiratory disease aOR 1.42 [95% CI 1.17–1.72]. Nearly, one third of all hospital inpatients were co‐prescribed a strong opioid and a sedative medication. Patients with comorbidities resulting in increased risk of respiratory depression/OIVI were more likely to have sedative co‐prescription. Clinicians should be aware of the effects of high‐risk medications and ensure that systems and monitoring are in place that help mitigate adverse outcomes. [ABSTRACT FROM AUTHOR]

Initial Assessment: Older people are at increased risk of medication-related potentially preventable hospitalizations (MR-PPH) due to the presence of multiple chronic conditions (multimorbidity) and subsequent polypharmacy.Choice Of Solution: A pilot study was conducted, using evidence-based indicators to detect older patients in a chronic disease management program (CDMP) at risk of hospitalization due to sub-optimal medication use.Implementation: Previously validated indicators for MR-PPH were applied to patients with multimorbidity, aged 65 years or older and who were enrolled in a national community-based CDMP. Nurse-led telephone interviews and case note abstraction were used as data sources.Evaluation: Nineteen patients triggered the MR-PPH indicators 85 times with a median of four per patient. Sub-optimal medication management was identified 34 times (40%) with a median of two per patient. The most common reasons for sub-optimal medication management were exposure to medications associated with falls, underuse of angiotensin-converting enzyme inhibitor/angiotensin-2 receptor blocker medications for cardiovascular disease and low rates of hemoglobin A1c and renal monitoring in patients with diabetes.Lessons Learned: This study has shown the utility of MR-PPH indicators within a CDMP to identify and monitor sub-optimal medication-related care. Implementation and ongoing monitoring of these types of indicators can support the development of targeted programs to reduce the ongoing risk of adverse events in the older population and improve the overall quality of life. [ABSTRACT FROM AUTHOR]

Multimorbidity is associated with use of multiple medicines, increased risk of adverse events and treatment conflicts. This study aimed to examine how older patients with multimorbidity and clinicians balance the benefits and harms associated with a medication and in the presence of competing health outcomes. Interviews were conducted with 15 participants aged $65 years with 2 or more chronic conditions. Three clinical scenarios were presented to understand patient preference to take a medicine according to i) degree of benefit, ii) type of adverse event and impact on daily living and iii) influence of comorbid conditions as competing health outcomes. Semi-structured interviews were also conducted with participants (n=15) and clinicians (n=5) to understand patient preferences and treatment decisions, in the setting of multimorbidity. The median age of participants was 79 years, 55% had 5 or more conditions and 47% took 8 or more medicines daily. When the level of benefit of the medicine ranged from 14% to 70%, 80% of participants chose to take the medicine, but when adverse effects were present, this was reduced to 0-33% depending upon impact on daily activities. In the presence of competing health outcomes, 13%-26% of patients chose to take the medicine. Two-thirds of patients reported that their doctor respects and considers their preferences and discussed medication benefits and harms. Interviews with clinicians showed that their overall approach to treatment decision-making for older individuals with multimorbidity was based upon 2 main factors, the patients' prognosis and their preferences. The degree of benefit gained was not the driver of patients' preference to take a medicine; rather, this decision was influenced by type and severity of adverse effects. Inclusion of patient preferences in the setting of risks and benefits of medicines with consideration and prioritization of competing health outcomes may result in improved health outcomes for people with multimorbidity. [ABSTRACT FROM AUTHOR]

Objective: To assess the impact of individualised, reconciled evidence-based recommendations (IRERs) and multidisciplinary care in patients with chronic heart failure (CHF) on clinical guideline compliance for CHF and common comorbid conditions. Design and setting: A retrospective hospital clinical audit conducted between 1st July 2006 and February 2011. Participants: A total of 255 patients with a diagnosis of CHF who attended the Multidisciplinary Ambulatory Consulting Services (MACS) clinics, at the Royal Adelaide Hospital, were included. Main outcome measures: Compliance with Australian clinical guideline recommendations for CHF, atrial fibrillation, diabetes mellitus and ischaemic heart disease. Results: Study participants had a median of eight medical conditions (IQR 6–10) and were on an average of 10 (±4) unique medications. Compliance with clinical guideline recommendations for pharmacological therapy for CHF, comorbid atrial fibrillation, diabetes or ischaemic heart disease was high, ranging from 86% for lipid lowering therapy to 98% anti-platelet agents. For all conditions, compliance with lifestyle recommendations was lower than pharmacological therapy, ranging from no podiatry reviews for CHF patients with comorbid diabetes to 75% for heart failure education. Concordance with many guideline recommendations was significantly associated if the patient had IRERs determined, a greater number of recommendations, more clinic visits or if patients participated in a heart failure program. Conclusions: Despite the high number of comorbid conditions and resulting complexity of the management, high compliance to clinical guideline recommendations was associated with IRER determination in older patients with CHF. Importantly these recommendations need to be communicated to the patient’s general practitioner, regularly monitored and adjusted at clinic visits. [ABSTRACT FROM AUTHOR]

Objective: To identify if there is a dose-dependent risk of diabetes complications in patients treated with corticosteroids who have both diabetes and chronic obstructive pulmonary disorder (COPD).Research Design and Methods: A retrospective study of administrative claims data from the Australian Government Department of Veterans' Affairs, from 1 July 2001 to 30 June 2008, of diabetes patients newly initiated on metformin or sulfonylurea. COPD was identified by dispensings of tiotropium or ipratropium in the 6 months preceding study entry. Total corticosteroid use (inhaled and systemic) in the 12 months after study entry was determined. The outcome was time to hospitalization for a diabetes-related complication. Competing risks and Cox proportional hazard regression analyses were conducted with adjustment for a number of covariates.Results: A total of 18,226 subjects with diabetes were identified, of which 5.9% had COPD. Of those with COPD, 67.2% were dispensed corticosteroids in the 12 months from study entry. Stratification by dose of corticosteroids demonstrated a 94% increased likelihood of hospitalization for a diabetes complication for those who received a total defined daily dose (DDD) of corticosteroids≥0.83/day (subhazard ratio 1.94 [95% CI 1.14-3.28], P=0.014), by comparison with those who did not receive a corticosteroid. Lower doses of corticosteroid (<0.83 DDD/day) were not associated with an increased risk of diabetes-related hospitalization.Conclusions: In patients with diabetes and COPD, an increased risk of diabetes-related hospitalizations was only evident with use of high doses of corticosteroids. This highlights the need for constant revision of corticosteroid dose in those with diabetes and COPD, to ensure that the minimally effective dose is used, together with review of appropriate response to therapy. [ABSTRACT FROM AUTHOR]

OBJECTIVE--To identify if there is a dose-dependent risk of diabetes complications in patients treated with corticosteroids who have both diabetes and chronic obstructive pulmonary disorder (COPD). RESEARCH DESIGN AND METHODS--A retrospective study of administrative claims data from the Australian Government Department of Veterans' Affairs, from 1 July 2001 to 30 June 2008, of diabetes patients newly initiated on metformin or sulfonylurea. COPD was identified by dispensings of tiotropium or ipratropium in the 6 months preceding study entry. Total corticosteroid use (inhaled and systemic) in the 12 months after study entry was determined. The outcome was time to hospitalization for a diabetes-related complication. Competing risks and Cox proportional hazard regression analyses were conducted with adjustment for a number of covariates. RESULTS--A total of 18,226 subjects with diabetes were identified, of which 5.9% had COPD. Of those with COPD, 67.2% were dispensed corticosteroids in the 12 months from study entry. Stratification by dose of corticosteroids demonstrated a 94% increased likelihood of hospitalization for a diabetes complication for those who received a total defined daily dose (DDD) of corticosteroids ≥0.83/day (subhazard ratio 1.94 [95% CI 1.14-3.28], P = 0.014), by comparison with those who did not receive a corticosteroid. Lower doses of corticosteroid (<0.83 DDD/day) were not associated with an increased risk of diabetes-related hospitalization. CONCLUSIONS--In patients with diabetes and COPD, an increased risk of diabetes-related hospitalizations was only evident with use of high doses of corticosteroids. This highlights the need for constant revision of corticosteroid dose in those with diabetes and COPD, to ensure that the minimally effective dose is used, together with review of appropriate response to therapy. [ABSTRACT FROM AUTHOR]

Background: Stroke patients may have multiple hospital separations relating to the same stroke. Understanding the pattern of hospitalisations for these patients enables first and recurrent events to be distinguished to better understand care. The aim of this study was to investigate reasons for hospital separations after transient ischaemic attack (TIA) or ischaemic stroke and construct episode of care criteria. Methods: A retrospective observational study was conducted using the Australian Government Department of Veterans' Affairs administrative claims database. All patients hospitalised for TIA or ischaemic stroke in 2008-2009 were included. Reasons for hospital separations in the 60 days after TIA or ischaemic stroke were classified by a clinical panel as 'probably', 'possibly' or 'unlikely' to be related to the index separation. Based on panel assessment and time between separations, episode of care criteria for TIA and ischaemic stroke were constructed. Results: Of the 4520 veterans alive after the index separation, 32% of TIA patients (n=782) and 63% of ischaemic stroke patients (n=1323) had another separation within 60 days. The clinical panel reviewed 460 unique reasons for readmission. Of the 3263 separations, 55% and 85% were classified as related to the index TIA and ischaemic stroke separation, respectively. Conclusions: Patients hospitalised for ischaemic stroke are likely to have multiple hospital separations for treatment of the same event. Multiple separations for treatment of TIA were less frequent. Consideration of these related separations is recommended when assessing health service utilisation from claims databases. [ABSTRACT FROM AUTHOR]

Objective To identify the prevalence of potentially preventable medication-related hospitalizations amongst elderly Australian veterans by applying clinical indicators to administrative claims data. Design and Setting Retrospective cohort study in the Australian veteran population from 1 January 2004 to 31 December 2008. Participants A total of 109 044 veterans with one or more hospitalizations defined by the medication-related clinical indicator set, during the 5-year study period. Main Outcome Measure The prevalence of potentially preventable medication-related hospitalizations as a proportion of all hospitalizations defined by the clinical indicator set. Results During the 5-year study period, there were a total of 1 630 008 hospital admissions of which 216 527 (13.3%) were for conditions defined by the medication-related clinical indicator set for 109 044 veterans. The overall proportion of potentially preventable medication-related hospitalizations was 20.3% (n= 43 963). Of the 109 044 veterans included in the study, 28 044 (25.7%) had at least one potentially preventable medication-related hospitalization and 7245 (6.6%) veterans had two or more potentially preventable admissions. Conditions with both a high prevalence of hospitalization and preventability included asthma/chronic obstructive pulmonary disorder, depression and thromboembolic cerebrovascular event (23.3, 18.5 and 18.3%, respectively, were potentially preventable). Other hospitalizations that were less common but had a high level of preventability (at least 20%) included hip fracture, impaction, renal failure, acute confusion, bipolar disorder and hyperkalaemia. Conclusions The results of this study highlight those conditions where hospitalizations could potentially be avoided through improved medication management. Strategies to increase the awareness, identification and resolution of these medication-related problems contributing to these hospitalizations are required in Australia. [ABSTRACT FROM AUTHOR]

A prescribing cascade occurs when a new medicine is prescribed to 'treat' an adverse reaction to another drug in the mistaken belief that a new medical condition requiring treatment has developed. Adverse outcomes associated with prescribing cascades can result when the second drug increases the severity of the adverse reaction to the first drug or when the second drug places the patient at risk of additional adverse drug reactions. The factors that are associated with an increased likelihood of an adverse drug reaction may also lead to prescribing cascades. The elderly, those using multiple medicines, women, and people using high risk medicines are more likely to get adverse drug reactions. The key to preventing prescribing cascades lies in the avoidance and early detection of adverse drug reactions and an increased awareness and recognition of the potential for adverse reactions. [ABSTRACT FROM AUTHOR]

Objectives: the study aimed to examine the prevalence of comorbidity, the prescribing of potentially inappropriate medications and treatment conflicts in a large sample of older people who have been dispensed an antidepressant medicine. [ABSTRACT FROM PUBLISHER]

Background: The prevalence of comorbidity is high, with 80% of the elderly population having three or more chronic conditions. Comorbidity is associated with a decline in many health outcomes and increases in mortality and use of health care resources. The aim of this study was to identify, review and summarise studies reporting the prevalence of comorbidity of chronic diseases in Australia. Methods: A systematic review of Australian studies (1996 - May 2007) was conducted. The review focused specifically on the chronic diseases included as national health priorities; arthritis, asthma, cancer, cardiovascular disease (CVD), diabetes mellitus and mental health problems. Results: A total of twenty five studies met our inclusion criteria. Over half of the elderly patients with arthritis also had hypertension, 20% had CVD, 14% diabetes and 12% mental health problem. Over 60% of patients with asthma reported arthritis as a comorbidity, 20% also had CVD and 16% diabetes. Of those with CVD, 60% also had arthritis, 20% diabetes and 10% had asthma or mental health problems. Conclusion: There are comparatively few Australian studies that focused on comorbidity associated with chronic disease. However, they do show high prevalence of comorbidity across national health priority areas. This suggests integration and co-ordination of the national health priority areas is critical. A greater awareness of the importance of managing a patients' overall health status within the context of comorbidity is needed together with, increased research on comorbidity to provide an appropriate scientific basis on which to build evidence based care guidelines for these multimorbid patients. [ABSTRACT FROM AUTHOR]

Background: The correct classification of an adverse drug reaction (ADR) as allergy (immunological) or intolerance (non-immunological) has important clinical implications. The aim of this study was to examine the ability of health professionals to discriminate between allergy and intolerance, classify the severity of the ADR and degree of contraindication. Methods: Health professionals were presented ten 'real-life' ADR scenarios using an online questionnaire and asked to: categorise the reaction as allergy or intolerance, rate the severity of the reaction and judge the level of contraindication of the causative drug. The number and proportion of responses were calculated for each of the cases presented and associations between classification of reaction type, severity and level of contraindication were examined. Results: A total of 394 responses were received. Overall 59.0% (SD 28.9) correctly categorised the cases, 60.8% (SD 16.8) classified the severity correct, and less than half (44.7%, SD 28.6) correctly identified the level of contraindication. The proportion of health professionals correctly answering the type, severity and level of contraindication for the allergy case was significantly higher (p < 0.0001) by comparison to the intolerance cases (type: 56.6% ± 33.1; severity: 57.3 ± 11.9; level of contraindication: 38.5 ± 19.9). Conclusions: Health professionals have suboptimal understanding of classification of ADRs. Strategies are required to strictly avoid re-exposure of patients to drugs which carry an increased risk of inducing a dangerous reaction, whilst minimising the avoidance of drugs which are of minimal risk or allowing the use of low-risk drugs where the benefits may be significant. [ABSTRACT FROM AUTHOR]

Objectives: To introduce the Registry of Senior Australians (ROSA) Outcome Monitoring System, which can monitor the quality and safety of care provided to individuals accessing residential aged care. Development and examination of 12 quality and safety indicators of care and their 2016 prevalence estimates are presented.Design: Retrospective.Setting: 2690 national and 254 South Australian (SA) aged care facilities.Participants: 208 355 unique residents nationally and 18 956 in SA.Main Outcome Measures: Risk-adjusted prevalence of high sedative load, antipsychotic use, chronic opioid use, antibiotic use, premature mortality, falls, fractures, medication-related adverse events, weight loss/malnutrition, delirium and/or dementia hospitalisations, emergency department presentations, and pressure injuries.Results: Five indicators were estimated nationally; antibiotic use (67.5%, 95% confidence interval (CI): 67.3-67.7%) had the highest prevalence, followed by high sedative load (48.1%, 95% CI: 47.9-48.3%), chronic opioid use (26.8%, 95% CI: 26.6-26.9%), antipsychotic use (23.5%, 95% CI: 23.4-23.7%) and premature mortality (0.6%, 95% CI: 0.6-0.7%). Seven indicators were estimated in SA; emergency department presentations (19.1%, 95% CI: 18.3-20.0%) had the highest prevalence, followed by falls (10.1%, 95% CI: 9.7-10.4%), fractures (4.8%, 95% CI: 4.6-5.1%), pressure injuries (2.9%, 95% CI: 2.7-3.1%), delirium and/or dementia related hospitalisations (2.3%, 95% CI: 2.1-2.6%), weight loss/malnutrition (0.7%, 95% CI: 0.6-0.8%) and medication-related events (0.6%, 95% CI: 0.5-0.7%).Conclusions: Twelve quality and safety indicators were developed to monitor aged care provided to older Australians based on the synthesis of existing literature and expert advisory input. These indicators rely on existing data within the aged care and healthcare sectors, therefore creating a pragmatic tool to examine quality and unwarranted care variation. [ABSTRACT FROM AUTHOR]

The purpose of this study was to evaluate the quality of adverse drug reaction (ADR) documentation in a state‐wide electronic health record (EHR), and to assess the impact of the interface design on documentation accuracy and ability to provide decision support. Data were extracted from 43 011 unique records in a state‐wide electronic health record in South Australia, Australia. Information obtained included ADR coding as allergy or intolerance, allergen name, reaction, and occupation of those entering data. Categorization into drug allergy or intolerance was assessed for accuracy. Reactions were entered predominantly by nurses (60.1%), also by doctors (31.0%) and pharmacists (6.1%). Of 27 314 reactions, 86.5% were coded as allergy and 13.5% as intolerance. The majority (78.2%) described reactions to drugs (as opposed to food, environmental or contact allergens), predominantly chosen from the drug database (96.4%). Many entries used free text for the reaction description (27.4%). Terms found in the predefined list under the allergy heading were more likely to be categorized as allergy, even when the mechanism was pharmacological intolerance. Only 45.1% (n = 1671/3705) of reactions consistent with intolerance (eg, “nausea,” “diarrhea”) were correctly categorized as such, although categorization by pharmacists was more accurate (P < .0001). These data suggest that ADR categorization as allergy or intolerance is influenced by the EHR design. The obligatory classification of ADRs into allergy or intolerance was not well understood and does not appear to have practical benefit. [ABSTRACT FROM AUTHOR]

Objective: To describe medication-related quality of care (MRQOC) for Australian aged care residents.Design: Retrospective cohort using an administrative healthcare claims database.Setting: Australian residential aged care.Participants: A total of 17 672 aged care residents who were alive at 1 January 2013 and had been a permanent resident for at least 3 months.Main Outcome Measures: Overall, 23 evidence-based MRQOC indicators which assessed the use of appropriate medications in chronic disease, exposure to high-risk medications and access to collaborative health services.Results: Key findings included underuse of recommended cardiovascular medications, such as the use of statins in cardiovascular disease (56.1%). Overuse of high-risk medications was detected for medications associated with falls (73.5%), medications with moderate to strong anticholinergic properties (46.1%), benzodiazepines (41.4%) and antipsychotics (33.2%). Collaborative health services such as medication reviews were underutilised (42.6%).Conclusion: MRQOC activities in this population should be targeted at monitoring and reducing exposure to antipsychotics and benzodiazepines, improving the use of preventative medications for cardiovascular disease and improving access to collaborative health services. Similarity of suboptimal MRQOC between Australia and other countries (UK, USA, Canada and Belgium) presents an opportunity for an internationally collaborative approach to improving care for aged care residents. [ABSTRACT FROM AUTHOR]

Care quality has important implications for people with dementia. We examined trends and geographical variation of four clinical quality indicators (CQIs) in Australia. This retrospective cohort study included all people with dementia using Australian government-subsidised aged care in 2008–2016 (n = 373,695). Quality indicator data were derived from linked national aged care, health, and pharmaceutical datasets. Negative binomial regression modelling assessed trends in CQI performance over time (2011–2016) and funnel plots examined geographical variation in performance. The incidence rate of antipsychotic medicine dispensing decreased slightly from 1.17/1000 person-days to 1.07/1000 person-days (adjusted incidence rate ratio (aIRR) = 0.98, 95%CI 0.98–0.99). Cholinesterase inhibitors and memantine dispensing did not change (aIRR = 1.02, 95%CI 1.00–1.04), while exposure to high sedative load increased slightly from 1.39/1000 person-days to 1.44/1000 person-days (aIRR = 1.01, 95%CI 1.00–1.01). Dementia and delirium-related hospitalisations increased slightly from 0.17/1000 person-days to 0.18/1000 person-days (aIRR = 1.02, 95%CI 1.01–1.03). There was marked variation in cholinesterase inhibitor and memantine dispensing by geographical area (0–41%). There has been little change in four indicators of dementia care quality in Australian aged care users over time. Cholinesterase inhibitor and memantine dispensing varied substantially by geographical region. Existing strategies to improve national performance on these indicators appear to be insufficient, despite the significant impact of these indicators on outcomes for people with dementia. [ABSTRACT FROM AUTHOR]

Objective: To evaluate a holistic multidisciplinary outpatient model of care on hospital readmission, length of stay and mortality in older patients with multimorbidity following discharge from hospital. Design and Participants: A pilot case-control study between March 2006 and June 2009 of patients referred on discharge to a multidisciplinary, integrated outpatient model of care that includes outpatient follow-up, timely GP communication and dial-in service compared with usual care following discharge, within a metropolitan, tertiary referral, public teaching hospital. Controls were matched in a 4:1 ratio with cases for age, gender, index admission diagnosis and length of stay. Main outcome measures: Non-elective readmission rates, total readmission length of stay and overall survival. Results: A total of 252 cases and 1008 control patients were included in the study. Despite the patients referred to the multidisciplinary model of care had slightly more comorbid conditions, significantly higher total length of hospital stay in the previous 12 months and increased prevalence of diabetes and heart failure by comparison to those who received usual care, they had significantly improved survival (adjusted hazard ratio 0.70 95% CI 0.51–0.96, p = 0.029) and no excess in the number of hospitalisations observed. Conclusion: Following discharge from hospital, holistic multidisciplinary outpatient management is associated with improved survival in older patients with multimorbidity. The findings of this study warrant further examination in randomised and cost-effectiveness trials. [ABSTRACT FROM AUTHOR]

Background: This study assessed whether the number of comorbid conditions unrelated to diabetes was associated with a delay in therapeutic progression of diabetes treatment in Australian veterans. Methodology/Principal Findings: A retrospective cohort study was undertaken using data from the Australian Department of Veterans' Affairs (DVA) claims database between July 2000 and June 2008. The study included new users of metformin or sulfonylurea medicines. The outcome was the time to addition or switch to another antidiabetic treatment. The total number of comorbid conditions unrelated to diabetes was identified using the pharmaceutical-based comorbidity index, Rx-Risk-V. Competing risk regression analyses were conducted, with adjustments for a number of covariates that included age, gender, residential status, use of endocrinology service, number of hospitalisation episodes and adherence to diabetes medicines. Overall, 20134 veterans were included in the study. At one year, 23.5% of patients with diabetes had a second medicine added or had switched to another medicine, with 41.4% progressing by 4 years. The number of unrelated comorbidities was significantly associated with the time to addition of an antidiabetic medicine or switch to insulin (subhazard ratio [SHR] 0.87 [95% CI 0.84-0.91], P,0.001). Depression, cancer, chronic obstructive pulmonary disease, dementia, and Parkinson's disease were individually associated with a decreased likelihood of therapeutic progression. Age, residential status, number of hospitalisations and adherence to anti-diabetic medicines delayed therapeutic progression. Conclusions/Significance: Increasing numbers of unrelated conditions decreased the likelihood of therapeutic progression in veterans with diabetes. These results have implications for the development of quality measures, clinical guidelines and the construction of models of care for management of diabetes in elderly people with comorbidities. [ABSTRACT FROM AUTHOR]

With regard to anti-inflammatory effects of diet away from the gut, altering the balance of dietary polyunsaturated fatty acids (PUFA) in favour of n-3 PUFA provides the best documented examples of effective dietary intervention. PUFA are essential macronutrients of which there are two non-interchangeable classes, n-6 and n-3. These fatty acids are metabolized to mediators that regulate cardiovascular homeostasis and inflammation. n-6 rich diets tend to be pro-inflammatory and, by comparison diets rich in n-3 PUFA are antiinflammatory. The difference is explained by the action of n-3 PUFA as competitive inhibitors of enzymes that metabolize n-6 fats and by the lesser biological activities of most n-3 mediators, compared with their n-6 counterparts. Fish oils are a particularly rich source of desirable long chain n-3 PUFA. Fish oil has been used with benefit in the treatment of inflammatory diseases of joints and other organs and tissues. Our long-term studies in rheumatoid arthritis (RA) show that this approach, in conjunction with pharmacotherapy, can be sustained in the long term (>5 years). A potential collateral benefit is reduced risk for adverse cardiovascular events, which are increased in RA. Lack of knowledge amongst physicians of relevant biochemistry, evidence of efficacy, dose response relationships, latency in effect, availability of affordable preparations and tactics for discussing issues efficiently with patients appears to be a barrier to broader clinical use. [ABSTRACT FROM AUTHOR]

Blood-derived monocytes are found at sites of inflammation as well as in solid tumors and atherosclerotic arteries. They are an abundant source of inflammatory eicosanoids such as prostaglandin E[sub 2] (PGE[sub 2]) and thromboxane A[sub 2], which are formed via arachidonic acid (AA) metabolism by cyclooxygenase-½ (COX-½). In vitro studies of inflammatory mediator production are conducted invariably in room air, which does not reflect the oxygen tensions found in monocyte-containing lesions, which are frequently hypoxic. In this work we examined the effects of hypoxia at levels reported in these lesions, on monocyte COX-2 expression, the related events that lead to eicosanoid synthesis, and relationships with tumor necrosis factor (TNF)-α synthesis. In fresh human monocytes exposed to hypoxia (1% O[sub 2]), there was an increase in COX-2 protein compared with cells in normoxia, and this was attributable to increased transcription and mRNA stability. However, the synthesis of PGE[sub 2] and thromboxane A[sub 2] was reduced in hypoxia and did not reflect the increased level of COX-2. Monocytes prelabeled with [³H]AA followed by lipopolysaccharide stimulation in the presence of hypoxia showed a reduced release of AA compared with cells in normoxia. In addition, hypoxia resulted in decreased phosphorylation of the p44/42 mitogen-activated protein kinase and of cytosolic phospholipase A[sub 2]. Hypoxia also increased TNF-α synthesis, which appeared to play a role in COX-2 expression, and the observed increase TNF-α synthesis appeared to result from reduced PGE[sub 2] synthesis. Overall, the results suggest the existence of an autocrine loop of regulation between monocyte eicosanoid and TNF-α production, which is dysregulated in hypoxia and establishes hypoxia as being an important environmental determinant of inflammatory mediator production. [ABSTRACT FROM AUTHOR]