Debating the evidence : oral contraceptives containing drospirenone and risk of blood clots

Skepticism is an essential quality in science. We doubt, re-examine and demand the highest quality of evidence. However, sometimes this puts us in an awkward situation. How much evidence do we need before we act? This dilemma is a constant problem in drug safety. Treatment decisions are always a balance of risks and benefits and there may be a paucity of evidence about rare or very rare adverse events.

Nurses and personal attendants' diabetes knowledge : in regional public residential care

Aim: Identify staff knowledge about diabetes medicines and organisational factors that influence safe medicines use in two large Australian regional public RACs that comply with national accreditation standards.

Background: Diabetes management is complicated in residential aged care facilities (RAC). Managing medicines is complex, especially in older people. Little is known about diabetes-specific medicine knowledge of various care staff (registered nurses (RN), enrolled nurses (EN) and patient care attendants (PCA) working in RAC.

Methods: A triangulation of methods was used to collect the data: anonymous self-complete questionnaire (ADKnowl) staff interviews to clarify practice issues that could affect safe medicine use, and a case file audit to identify medicine-related data. Questionnaires were distributed to all RNs, ENs and PCAs in the two services via nursing management (N=540). The ADKnowl was supplemented with additional questions and vignettes derived from actual case notes in each RAC to assess translation of knowledge into practice. Only medicine related data are reported.

Results: Sixty-eight people returned completed questionnaires (12.5% response rate). Knowledge deficits were identified in administering oral hypoglycaemic agents and insulin, their action and potential adverse events. Most ENs and PCAs did not know why HbA1c was measured. Almost half the RNs and ENs and 80% of PCAs did not know how diabetes comorbidities affect medicine choices. RN achieved higher overall average knowledge scores,74.3%, compared to ENs and PCA, 49%. The interviews suggest lack of time, unclear communication processes, inadequate knowledge about medications and resident behaviour compromises optimal medicine administration. Twenty case files audits were undertaken in each RAC and revealed residents were taking on average nine medicines.

Conclusion: Staff involved in caring for residents with diabetes had suboptimal general and medicine-specific diabetes knowledge to deliver optimal care. System issues and unpredictable resident behaviours made medicine management difficult and compromised safety.

Characteristics and outcomes of patients requiring unplanned transfer from subacute to acute care

The study aims to identify the reasons for, and outcomes from, unplanned transfers from subacute care to acute care. A retrospective patient record review of patients requiring unplanned transfer from subacute to an acute care emergency department (ED) from 1 July 2008 to 30 June 2009 was undertaken. Data collected included patient demographics, clinical characteristics in preceding transfer, and on ED arrival and outcome data. There were 136 patients included in the study with a median age of 81 years. The most common reasons for transfer were respiratory problems and altered conscious state. In the 24 h preceding transfer, 92.6% of patients had ≥ 1 physiological abnormality and 10.3% of patients had no physiological parameters documented. On ED arrival, 75% of patients had physiological abnormalities. Hospital admission occurred in 75% of patients and the inpatient mortality rate was 14.7%. Factors associated with inpatient mortality were tachypnoea and severe hypoxaemia in 24 h preceding transfer and tachypnoea, hypoxaemia, hypoxaemia, severe hypoxaemia and hypothermia on ED arrival. Patients requiring unplanned transfer had higher inpatient mortality than older hospital users. Reasons for unplanned transfer reflect known predictors of in-hospital adverse events so predictive use of physiological data and patient characteristics might optimize patient safety.

The cost-effectiveness of the Dose Adjustment for Normal Eating (DAFNE) structured education programme: an update using the Sheffield Type 1 Diabetes policy model

AIMS: 
To estimate the cost-effectiveness of training in flexible intensive insulin therapy [as provided in the Dose Adjustment for Normal Eating (DAFNE) structured education programme] compared with no training for adults with Type 1 diabetes mellitus in the UK using the Sheffield Type 1 Diabetes Policy Model.

METHODS: 
The Sheffield Type 1 Diabetes Policy Model was used to simulate the development of long-term microvascular and macrovascular diabetes-related complications and the occurrence of diabetes-related adverse events in 5000 adults with Type 1 diabetes. Total costs and quality-adjusted life years were estimated from a National Health Service perspective over a lifetime horizon, discounted at a rate of 3.5%. The treatment effectiveness of DAFNE was modelled as a reduction in HbA1c that affected the risk of developing long-term diabetes-related complications. Probabilistic and structural sensitivity analyses were conducted.

RESULTS:
DAFNE resulted in greater life expectancy and reduced incidence of some diabetes-related complications compared with no DAFNE. DAFNE was found to generate an average of 0.0294 additional quality-adjusted life years for an additional cost of £426 per patient, leading to an incremental cost-effectiveness ratio of £14 400 compared with no DAFNE. There was a 54% probability that DAFNE would be cost-effective at a willingness-to-pay threshold of £20 000 per quality-adjusted life year.

CONCLUSIONS: 
The results of this study suggest that DAFNE is a cost-effective structured education programme for people with Type 1 diabetes and support its provision by the National Health Service in the UK.

Additional Saturday rehabilitation improves functional independence and quality of life and reduces length of stay: a randomised controlled trial

Background

Many inpatients receive little or no rehabilitation on weekends. Our aim was to determine what effect providing additional Saturday rehabilitation during inpatient rehabilitation had on functional independence, quality of life and length of stay compared to 5 days per week of rehabilitation.

This was a multicenter, single-blind (assessors) randomized controlled trial with concealed allocation and 12-month follow-up conducted in two publically funded metropolitan inpatient rehabilitation facilities in Melbourne, Australia. Patients were eligible if they were adults (aged ≥18 years) admitted for rehabilitation for any orthopedic, neurological or other disabling conditions excluding those admitted for slow stream rehabilitation/geriatric evaluation and management. Participants were randomly allocated to usual care Monday to Friday rehabilitation (control) or to Monday to Saturday rehabilitation (intervention). The additional Saturday rehabilitation comprised physiotherapy and occupational therapy. The primary outcomes were functional independence (functional independence measure (FIM); measured on an 18 to 126 point scale), health-related quality of life (EQ-5D utility index; measured on a 0 to 1 scale, and EQ-5D visual analog scale; measured on a 0 to 100 scale), and patient length of stay. Outcome measures were assessed on admission, discharge (primary endpoint), and at 6 and 12 months post discharge.

We randomly assigned 996 adults (mean (SD) age 74 (13) years) to Monday to Saturday rehabilitation (n = 496) or usual care Monday to Friday rehabilitation (n = 500). Relative to admission scores, intervention group participants had higher functional independence (mean difference (MD) 2.3, 95% confidence interval (CI) 0.5 to 4.1, P = 0.01) and health-related quality of life (MD 0.04, 95% CI 0.01 to 0.07, P = 0.009) on discharge and may have had a shorter length of stay by 2 days (95% CI 0 to 4, P = 0.1) when compared to control group participants. Intervention group participants were 17% more likely to have achieved a clinically significant change in functional independence of 22 FIM points or more (risk ratio (RR) 1.17, 95% CI 1.03 to 1.34) and 18% more likely to have achieved a clinically significant change in health-related quality of life (RR 1.18, 95% CI 1.04 to 1.34) on discharge compared to the control group. There was some maintenance of effect for functional independence and health-related quality of life at 6-month follow-up but not at 12-month follow-up. There was no difference in the number of adverse events between the groups (incidence rate ratio = 0.81, 95% CI 0.61 to 1.08).

Providing an additional day of rehabilitation improved functional independence and health-related quality of life at discharge and may have reduced length of stay for patients receiving inpatient rehabilitation. 

N-acetylcysteine versus placebo for treating nail biting, a double blind randomized placebo controlled clinical trial

Nail biting is a common behavioral problem. While there are established behavioral interventions for management, they are of modest efficacy, and there is minimal evidence for effective pharmacotherapy. This study investigated the role of N-acetylcysteine (NAC) a potent glutathione and glutamate modulator for the treatment of pathological nail biting in children and adolescents. This pilot randomized, double-blind, placebo-controlled clinical trial of NAC (800mg/day) or placebo enrolled 42 children and adolescents with chronic nail biting. Nail length was the objective outcome. Evaluations were carried out three times; before treatment, one month after enrollment in the study, and two months after enrollment. The duration (chronicity) of nail biting in the NAC and placebo groups was 3.63(2.45) and 5.09(3.74) years (P=0.14). The mean nail length gradually increased in both the NAC and placebo groups during this trial. There was a statistically significant difference between the two groups regarding increased nail length after the first month of trial [(5.21(5.75) and 1.18(3.02) millimeters], however no difference after two months was observed. Two patients in the NAC group discontinued medication due to adverse events. One patient experienced headache, agitation, and social withdrawal, and another patient expressed severe aggression after taking medication and was withdrawn from the study. This study supports the hypothesis that NAC decreases nail biting behavior in children and adolescents over the short term. NAC is relatively well tolerated and severe adverse effects are rare. However, there was a high rate of dropout. Further studies with longer durations that build on these preliminary data are recommended.

Lateral positioning for critically ill adult patients: a systematic review

A systematic review was undertaken to evaluate the effect of lateral positioning compared to other body positions on morbidity, mortality, and clinical adverse events for critically ill patients. Twenty three studies met the criteria. Hypoxaemia was not consistently reported. No clinical practice recommendations could be drawn from the included studies due to methodological shortcomings.

Public sector residential aged care: identifying novel associations between quality indicators and other demographic and health-related factors

Objective : To explore associations among quality indicators (QI; e.g. pressure ulcers, falls and/or fractures, physical restraint, use of multiple medications, unplanned weight loss) of the Victorian Public Sector Residential Aged Care Services (VPSRACS) with other demographic and health-related factors.

Methods : Data for 380 residents over a 3-month period were extracted retrospectively from client databases at four VPSRAC facilities.

Results : Four significant logistic regression models were developed. The strongest models related to falls and polypharmacy. Significant associations for these models included the following: (1) residents with a higher body mass index were 6% less likely (95% confidence interval (CI) 1%–11%) to fall, whereas high levels of cognitive impairment increased the risk of falling by 8% (95% CI 2%–14%); (2) being ambulant with a gait aid more than doubled the risk of falling compared with non-ambulant residents (95% CI 19%–546%); and (3) higher cognitive impairment was associated with a 6% (95% CI 1%–11%) reduction in the likelihood of polypharmacy.

Conclusions : Identification of significant relationships between the VPSRACS QI and other demographic and health-related factors is a preliminary step towards a more in-depth understanding of the factors that influence the QI and predict adverse events.

Ustekinumab for the treatment of moderate to severe psoriasis

This paper presents a summary of the evidence review group (ERG) report into the clinical effectiveness and cost-effectiveness of ustekinumab for the treatment of moderate to severe psoriasis based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's main evidence came from three randomised controlled trials (RCTs), of reasonable methodological quality and measuring a range of clinically relevant outcomes. Higher proportions of participants treated with ustekinumab (45 mg and 90 mg) than with placebo or etanercept achieved an improvement on the Psoriasis Area and Severity Index (PASI) of at least 75% (PASI 75) after 12 weeks. There were also statistically significant differences in favour of ustekinumab over placebo for PASI 50 and PASI 90 results, and for ustekinumab over etanercept for PASI 90 results. A weight-based subgroup dosing analysis for each trial was presented, but the methodology was poorly described and no statistical analysis to support the chosen weight threshold was presented. The manufacturer carried out a mixed treatment comparison (MTC); however, the appropriateness of some of the methodological aspects of the MTC is uncertain. The incidence of adverse events was similar between groups at 12 weeks and withdrawals due to adverse events were low and less frequent in the ustekinumab than in the placebo or etanercept groups; however, statistical comparisons were not reported. The manufacturer's economic model of treatments for psoriasis compared ustekinumab with other biological therapies. The model used a reasonable approach; however, it is not clear whether the clinical effectiveness estimates from the subgroup analysis, used in the base-case analysis, were methodologically appropriate. The base-case incremental cost-effectiveness ratio for ustekinumab versus supportive care was 29,587 pounds per quality-adjusted life-year (QALY). In one-way sensitivity analysis the model was most sensitive to the number of hospital days associated with supportive care, the cost estimate for intermittent etanercept 25 mg and the utility scores used. In the ERG's scenario analysis the model was most sensitive to the price of ustekinumab 90 mg, the proportion of patients with baseline weight > 100 kg and the relative risk of intermittent versus continuous etanercept 25 mg. In the ERG's probabilistic sensitivity analysis ustekinumab had the highest probability of being cost-effective at conventional NICE thresholds, assuming the same price for the 45-mg and 90-mg doses; however, doubling the price of ustekinumab 90 mg resulted in ustekinumab no longer dominating the comparators. In conclusion, the clinical effectiveness and cost-effectiveness of ustekinumab in relation to other drugs in this class is uncertain. Provisional NICE guidance issued as a result of the STA states that ustekinumab is recommended as a treatment option for adults with plaque psoriasis when a number of criteria are met. Final guidance is anticipated in September 2009.

Entecavir for the treatment of chronic hepatitis B infection

This paper presents a summary of the evidence review group (ERG) report into the clinical and cost-effectiveness of entecavir for the treatment of chronic hepatitis B (CHB) in adults based upon a review of the manufacturer's submission to the National Institute for Health and Clinical Excellence (NICE) as part of the single technology appraisal (STA) process. The submission's evidence came from five randomised controlled trials (RCTs), of good methodological quality and measuring a range of clinically relevant outcomes, comparing entecavir with lamivudine. After 1 year of treatment entecavir was statistically superior to lamivudine in terms of the proportion of patients achieving hepatitis B virus (HBV) DNA suppression, alanine aminotransferase (ALT) normalisation and histological improvement, but not in terms of the proportion of patients achieving hepatitis B e antigen (HBeAg) seroconversion. The incidence of adverse or serious adverse events was similar for both treatments. The results of the manufacturer's mixed treatment comparison (MTC) model to compare entecavir with the comparator drugs in nucleoside-naive patients were considered to be uncertain because of concerns over its conduct and reporting. For the economic evaluation the manufacturer constructed two Markov state transition models, one in HBeAg-positive and one in HBeAg-negative patients. The modelling approach was considered reasonable subject to some uncertainties and concerns over some of the structural assumptions. In HBeAg-positive patients the base-case incremental cost-effectiveness ratios (ICER) for entecavir compared with lamivudine and pegylated interferon alpha-2a were 14,329 pounds and 8403 pounds per quality-adjusted life-year (QALY) respectively. Entecavir was dominated by telbivudine. In HBeAg-negative patients the base-case ICERs for entecavir compared with lamivudine, pegylated interferon alpha-2a and telbivudine were 13,208 pounds, 7511 pounds and 6907 pounds per QALY respectively. In HBeAg-positive lamivudine-refractory patients entecavir dominated adefovir added to lamivudine. In one-way deterministic sensitivity analysis on all key input parameters for entecavir compared with lamivudine in nucleoside-naive patients, ICERs generally remained under 30,000 pounds per QALY. In probabilistic sensitivity analysis in nucleoside-naive HBeAg-positive patients the probability of the ICER for entecavir being below 20,000 pounds per QALY was 57%, 82% and 45% compared with lamivudine, pegylated interferon alpha-2a and telbivudine respectively. In nucleoside-naive HBeAg-negative patients the probabilities were 90%, 100% and 96% respectively. The manufacturer's lifetime treatment scenario for HBeAg-negative patients and the ERG's 20-year treatment scenario for HBeAg-positive patients increased the ICERs, particularly in the latter case. Amending the HBeAg-negative model so that patients with compensated cirrhosis would also receive lifetime treatment gave probabilities of entecavir being cost-effective at a willingness to pay of 20,000 pounds and 30,000 pounds of 4% and 40% respectively. The NICE guidance issued in August 2008 as a result of the STA states that entecavir is recommended as an option for the treatment of people with chronic HBeAg-positive or HBeAg-negative hepatitis B in whom antiviral treatment is indicated.

Patient safety and gaps management by registered nurses

Patient safety is a global imperative aimed at reducing the incidence and impact of preventable adverse events in healthcare. This study has demonstrated how effective nursing surveillance and successful everyday nursing performance can bridge ‘gaps’ in the system of care, mitigate errors, and protect patients from suffering otherwise preventable harm.

Lovastatin for the adjunctive treatment of schizophrenia: a preliminary randomized double-blind placebo-controlled trial.

While statins target many of the pathways to neuroprogression in schizophrenia, the safety and efficacy of statins for treating schizophrenia has never been examined. This is an 8-week randomized double blind controlled clinical trial examining the efficacy and safety of adjunctive lovastatin (20 mg/day) treatment or placebo for people with schizophrenia. The baseline characteristics of the two groups were not different. Endpoint changes in Positive and Negative Syndrome Scale (PANSS) total and subscale scores did not differ between the two groups. However there was a significant difference between the doses of risperidone used in the two groups. The mean dose in the lovastatin and placebo groups were 4.8(1.8) and 3.4(1.4) mg/day, respectively (P<.03). No serious adverse events were reported. Slowness of movements, muscle rigidity, increased appetite, and decreased energy were the most common adverse effects, and these rates did not differ between the two groups. This study failed to demonstrate a benefit of lovastatin on symptoms of schizophrenia. This combination was well tolerated. However, a higher dosage of risperidone was used for treating the disorder in those taking concomitant lovastatin compared to placebo.

A head-to-head comparison of aripiprazole and risperidone for safety and treating autistic disorders, a randomized double blind clinical trial

Aripiprazole and risperidone are the only FDA approved medications for treating irritability in autistic disorder, however there are no head-to-head data comparing these agents. This is the first prospective randomized clinical trial comparing the safety and efficacy of these two medications in patients with autism spectrum disorders. Fifty nine children and adolescents with autism spectrum disorders were randomized to receive either aripiprazole or risperidone for 2 months. The primary outcome measure was change in Aberrant Behavior Checklist (ABC) scores. Adverse events were assessed. Aripiprazole as well as risperidone lowered ABC scores during 2 months. The rates of adverse effects were not significantly different between the two groups. The safety and efficacy of aripiprazole (mean dose 5.5 mg/day) and risperidone (mean dose 1.12 mg/day) were comparable. The choice between these two medications should be on the basis of clinical equipoise considering the patient's preference and clinical profile.

Barriers and enablers affecting patient engagement in managing medications within specialty hospital settings

Background : Communication problems contribute enormously to medication errors and adverse events. Encouraging patient engagement can help to facilitate effective medication management.

Objectives : To examine barriers and enablers affecting how patients engage with managing their medications in specialty hospital settings.

Design : An exploratory qualitative design was used involving in-depth interviews with doctors, nurses, pharmacists, patients and family members.

Setting : An Australian public, metropolitan teaching hospital was the study site and five specialty hospital settings were used, including cardiac care, emergency care, intensive care, oncology care and perioperative care.

Results : In all, 21 health professionals, 11 patients and 12 family members participated in the study (n = 44). Barriers and enablers involved intrapersonal, interpersonal and environmental aspects, and differences in perceptions and experiences were found between the various settings. Health professionals had preconceived notions of what was appropriate behaviour in conveying information about medications. Many health professionals stated that they deliberately chose not to provide medication-related knowledge. Different barriers for patient engagement existed in various settings – in emergency care, patients could only stay for 4 h; in intensive care, medication changes regularly happened; in cardiac care, patients were discharged prematurely due to urgent need of beds; in oncology, there was lack of availability of oncology consultants; while in perioperative care, surgeons and anaesthetists were available just before surgery.

Conclusions : Complex barriers and enablers are associated with patient engagement in specialty clinical settings. By developing an understanding of these barriers and enablers, health professionals can help patients to understand and participate in their medication management.