Persistence and Adherence to Cardiovascular Medicines in Australia

BACKGROUND: The burden of cardiovascular disease is increasing, with many people treated for multiple cardiovascular conditions. We examined persistence and adherence to medicines for cardiovascular disease treatment or prevention in Australia. METHODS AND RESULTS: Using national dispensing claims for a 10% random sample of people, we identified adults (≥18 years) initiating antihypertensives, statins, oral anticoagulants, or antiplatelets in 2018. We measured persistence to therapy using a 60-day permissible gap, and adherence using the proportion of days covered up to 3 years from initiation, and from first to last dispensing. We reported outcomes by age, sex, and cardiovascular multimedicine use. We identified 83 687 people initiating antihypertensives (n=37 941), statins (n=34 582), oral anticoagulants (n=15 435), or antiplatelets (n=7726). Around one-fifth of people discontinued therapy within 90 days, with 50% discontinuing within the first year. Although many people achieved high adherence (proportion of days covered ≥80%) within the first year, these rates were higher when measured from first to last dispensing (40.5% and 53.2% for statins; 55.6% and 80.5% for antiplatelets, respectively). Persistence was low at 3 years (17.5% antiplatelets to 37.3% anticoagulants). Persistence and adherence increased with age, with minor differences by sex. Over one-third of people had cardiovascular multimedicine use (reaching 92% among antiplatelet users): they had higher persistence and adherence than people using medicines from only 1 cardiovascular group. CONCLUSIONS: Persistence to cardiovascular medicines decreases substantially following initiation, but adherence remains high while people are using therapy. Cardiovascular multimedicine use is common, and people using multiple cardiovascular medicines have higher rates of persistence and adherence

Pralidoxime in Acute Organophosphorus Insecticide Poisoning-A Randomised Controlled Trial

Background: Poisoning with organophosphorus (OP) insecticides is a major global public health problem, causing an estimated 200,000 deaths each year. Although the World Health Organization recommends use of pralidoxime, this antidote's effectiveness remains unclear. We aimed to determine whether the addition of pralidoxime chloride to atropine and supportive care offers benefit. Methods and Findings: We performed a double-blind randomised placebo-controlled trial of pralidoxime chloride (2 g loading dose over 20 min, followed by a constant infusion of 0.5 g/h for up to 7 d) versus saline in patients with organophosphorus insecticide self-poisoning. Mortality was the primary outcome; secondary outcomes included intubation, duration of intubation, and time to death. We measured baseline markers of exposure and pharmacodynamic markers of response to aid interpretation of clinical outcomes. Two hundred thirty-five patients were randomised to receive pralidoxime (121) or saline placebo (114). Pralidoxime produced substantial and moderate red cell acetylcholinesterase reactivation in patients poisoned by diethyl and dimethyl compounds, respectively. Mortality was nonsignificantly higher in patients receiving pralidoxime: 30/121 (24.8%) receiving pralidoxime died, compared with 18/114 (15.8%) receiving placebo (adjusted hazard ratio HR] 1.69, 95% confidence interval CI] 0.88-3.26, p = 0.12). Incorporating the baseline amount of acetylcholinesterase already aged and plasma OP concentration into the analysis increased the HR for patients receiving pralidoxime compared to placebo, further decreasing the likelihood that pralidoxime is beneficial. The need for intubation was similar in both groups (pralidoxime 26/121 21.5%], placebo 24/114 21.1%], adjusted HR 1.27 95% CI 0.71-2.29]). To reduce confounding due to ingestion of different insecticides, we further analysed patients with confirmed chlorpyrifos or dimethoate poisoning alone, finding no evidence of benefit. Conclusions: Despite clear reactivation of red cell acetylcholinesterase in diethyl organophosphorus pesticide poisoned patients, we found no evidence that this regimen improves survival or reduces need for intubation in patients with organophosphorus insecticide poisoning. The reason for this failure to benefit patients was not apparent. Further studies of different dose regimens or different oximes are required

Salbutamol in acute organophosphorus insecticide poisoning - a pilotdose-response phase II study

Treatment of acute organophosphorus (OP) insecticide poisoning is difficult, with many patients dying despite best care. Pre-clinical studies have shown benefit from salbutamol, possibly due speeding alveolar fluid clearance or reducing bronchoconstriction. In this small pilot dose-response study, we aimed to explore whether addition of nebulized salbutamol to standard care might improve resuscitation.We performed a single-blind phase II study comparing the effect of two different doses of nebulized salbutamol versus saline placebo, in addition to standard treatment. Primary outcome was oxygen saturations over the first 60 min of resuscitation; secondary outcomes included heart rate, incidence of dysrhythmias, time to 'atropinization', atropine dose required, and mortality.Seventy-five patients were randomized to receive 5 mg (Salb5, n = 25) or 2.5mg (Salb2.5, n = 25) of salbutamol, or saline placebo (NoSalb, n = 25), by nebulizer. Oxygen saturations did not differ between groups over the first 60 min of resuscitation (median AUC NoSalb: 1376 [95% CI 1282 to 1470], Salb2.5: 1395 [1305 to 1486], Salb5: 1233 [1100 to 1367]; p = .9898). Heart rate was also similar across the three arms. Median time to full atropinization, and atropine dose required, were the same for all three arms (NoSalb 15.0 [10-16] min and 12.6 [8.0-13.4] mg, Salb2.5 15.0 [10-16] min and 12.6 [9.3-16.8] mg, and Salb5 15.0 [10-20] min and 12.6 [10.7-20.6] mg; p = .4805 and p = .1871, respectively). Three (12%) patients died in the Salb2.5 and Salb5 groups and two (8%) in the NoSalb group.This pilot study, within the limitations of its small size and variation between patients, found no apparent evidence that administration of nebulized salbutamol improved resuscitation of patients with acute OP insecticide self-poisoning. The data obtained provides a basis to design further studies to ultimately test the role of salbutamol in OP insecticide poisoning

A cost effectiveness analysis of the preferred antidotes for acute paracetamol poisoning patients in Sri Lanka

Background: Acute paracetamol poisoning is a rapidly increasing problem in Sri Lanka. The antidotes are expensive and yet no health economic evaluation has been done on the therapy for acute paracetamol poisoning in the developing world. The aim of this study is to determine the cost effectiveness of using N-acetylcysteine over methionine in the management of acute paracetamol poisoning in Sri Lanka. Methods:Economic analysis was applied using public healthcare system payer perspective. Costs were obtained from a series of patients admitted to the National Hospital of Sri Lanka with a history of acute paracetamol overdose. Evidence on effectiveness was obtained from a systematic review of the literature. Death due to hepatotoxicity was used as the primary outcome of interest. Analysis and development of decision tree models was done using Tree Age Pro 2008. Results: An affordable treatment threshold of Sri Lankan rupees 1,537,120/death prevented was set from the expected years of productive life gained and the average contribution to GDP. A cost-minimisation analysis was appropriate for patients presenting within 10 hours and methionine was the least costly antidote. For patients presenting 10-24 hours after poisoning, n-acetylcysteine was more effective and the incremental cost effectiveness ratio of Sri Lankan rupees 316,182/life saved was well under the threshold. One-way and multi-way sensitivity analysis also supported methionine for patients treated within 10 hours and n-acetylcysteine for patients treated within 10-24 hours as preferred antidotes.Conclusions: Post ingestion time is an important determinant of preferred antidotal therapy for acute paracetamol poisoning patients in Sri Lanka. Using n-acetylcysteine in all patients is not cost effective. On economic grounds, methionine should become the preferred antidote for Sri Lankan patients treated within 10 hours of the acute ingestion and n-acetylcysteine should continue to be given to patients treated within 10-24 hours

The sinus tarsi approach in displaced intra-articular calcaneal fractures: a systematic review

Purpose: Although open reduction and internal fixation is currently considered the gold standard in surgical treatment of displaced intra-articular calcaneal fractures, various different approaches exist including the limited lateral approach. The aim of this systematic review was to combine the results of studies using the sinus tarsi approach, which is the most frequently applied limited lateral approach. Method: A literature search in the electronic databases of the Cochrane Library and Pubmed Medline, between January 1st 2000 to December 1st 2010, was conducted to identify studies in which the sinus tarsi approach or a modified sinus tarsi approach was utilized for the treatment of displaced intra-articular calcaneal fractures. The methodological quality of the included studies was assessed using the Coleman methodology score. Results: A total of eight case series reporting on 256 patients with 271 calcaneal fractures was identified. Overall good to excellent outcome was reached in three-quarters of all patients. An average complication rate of minor wound complications of 4.1% was reported and major wound complications in 0.7%. The need for a secondary subtalar arthrodesis occurred at an average rate of 4.3%. The average Coleman methodology score was 56.8 (range 39-72) points. Conclusion: The results, i.e. functional outcome and complication rates, of the sinus tarsi approach compare similarly or favourably to the extended lateral approach. Therefore, in the process of tailoring the best treatment modality to the right patient and the right fracture type, the sinus tarsi approach might be a valuable asset

Walks4work: Rationale and study design to investigate walking at lunchtime in the workplace setting

Background: Following recruitment of a private sector company, an 8week lunchtime walking intervention was implemented to examine the effect of the intervention on modifiable cardiovascular disease risk factors, and further to see if walking environment had any further effect on the cardiovascular disease risk factors. Methods. For phase 1 of the study participants were divided into three groups, two lunchtime walking intervention groups to walk around either an urban or natural environment twice a week during their lunch break over an 8week period. The third group was a waiting-list control who would be invited to join the walking groups after phase 1. In phase 2 all participants were encouraged to walk during their lunch break on self-selecting routes. Health checks were completed at baseline, end of phase 1 and end of phase 2 in order to measure the impact of the intervention on cardiovascular disease risk. The primary outcome variables of heart rate and heart rate variability were measured to assess autonomic function associated with cardiovascular disease. Secondary outcome variables (Body mass index, blood pressure, fitness, autonomic response to a stressor) related to cardiovascular disease were also measured. The efficacy of the intervention in increasing physical activity was objectively monitored throughout the 8-weeks using an accelerometer device. Discussion. The results of this study will help in developing interventions with low researcher input with high participant output that may be implemented in the workplace. If effective, this study will highlight the contribution that natural environments can make in the reduction of modifiable cardiovascular disease risk factors within the workplace. © 2012 Brown et al.; licensee BioMed Central Ltd

A randomized controlled trial of fresh frozen plasma for coagulopathy in Russell's viper (Daboia russelii) envenoming

Background Russell's viper (Daboia russelii) envenoming is a major health issue in South Asia and causes venom induced consumption coagulopathy (VICC). Objectives We investigated the effect of fresh frozen plasma (FFP) and two antivenom doses in correcting VICC. Methods We undertook an open-label randomized controlled trial in patients with VICC at two Sri Lankan hospitals. Patients with suspected Russell's viper bites and coagulopathy were randomly allocated (1:1) high-dose antivenom (20 vials) or low-dose antivenom (10 vials) plus 4U FFP. The primary outcome was the proportion of patients with an international normalized ratio (INR)<2, 6h post-antivenom. Secondary outcomes included anaphylaxis, major haemorrhage, death and clotting factor recovery. Results From 214 eligible patients, 141 were randomized; 71 to high-dose antivenom, 70 to low-dose antivenom/FFP; five had no post-antivenom bloods. The groups were similar except for a delay of 1h in antivenom administration for FFP patients. 6h post-antivenom 23/69 (33%) patients allocated high-dose antivenom had an INR<2 compared with 28/67 (42%) allocated low-dose antivenom/FFP [absolute difference 8%;95%Confidence Interval:-8% to 25%]. 15 patients allocated FFP did not receive it. Severe anaphylaxis occurred equally frequently in each group. One patient given FFP developed transfusion related acute lung injury. Three deaths occurred in low-dose/FFP patients including one intracranial haemorrhage. There was no difference in recovery rates of INR or fibrinogen, but more rapid initial recovery of factor V and X in FFP patients. Conclusion FFP post-antivenom in Russell's viper bites didn't hasten recovery of coagulopathy. Low-dose antivenom/FFP did not worsen VICC, suggesting low-dose antivenom is sufficient

Genetic Background Can Result in a Marked or Minimal Effect of Gene Knockout (GPR55 and CB2 Receptor) in Experimental Autoimmune Encephalomyelitis Models of Multiple Sclerosis

PMCID: PMC379391

Molecular Epidemiology of Campylobacter Isolates from Poultry Production Units in Southern Ireland

This study aimed to identify the sources and routes of transmission of Campylobacter in intensively reared poultry farms in the Republic of Ireland. Breeder flocks and their corresponding broilers housed in three growing facilities were screened for the presence of Campylobacter species from November 2006 through September 2007. All breeder flocks tested positive for Campylobacter species (with C. jejuni and C. coli being identified). Similarly, all broiler flocks also tested positive for Campylobacter by the end of the rearing period. Faecal and environmental samples were analyzed at regular intervals throughout the rearing period of each broiler flock. Campylobacter was not detected in the disinfected house, or in one-day old broiler chicks. Campylobacter jejuni was isolated from environmental samples including air, water puddles, adjacent broiler flocks and soil. A representative subset of isolates from each farm was selected for further characterization using flaA-SVR sub-typing and multi-locus sequence typing (MLST) to determine if same-species isolates from different sources were indistinguishable or not. Results obtained suggest that no evidence of vertical transmission existed and that adequate cleaning/disinfection of broiler houses contributed to the prevention of carryover and cross-contamination. Nonetheless, the environment appears to be a potential source of Campylobacter. The population structure of Campylobacter isolates from broiler farms in Southern Ireland was diverse and weakly clonal