Psychostimulant prescribing trends in a paediatric population in Ireland: a national cohort study.

BACKGROUND: Psychotropic paediatric prescribing trends are increasing internationally. The aim of this study is to examine the prevalence and secular trends in psychotropic prescribing in Irish children and adolescents between 2002 and 2011. METHODS: Data was obtained from the Irish General Medical Services (GMS) scheme pharmacy claims database from the Health Service Executive Primary Care Reimbursement Services (HSE-PCRS). Prescribing rates per 1000 eligible population and associated 95% confidence intervals (CIs) were calculated across years (2002-2011), age groups (0-4, 5-11, 12-15 years) and gender. Rates of concomitant prescriptions for psycholeptics and antidepressants were also examined. The total expenditure costs were calculated and expressed as a percentage of the cost of all prescriptions for this age group (≤ 15 years). RESULTS: In 2002, 3.77/1000 GMS population (95% CI: 3.53-4.01) received at least one psychostimulant prescription and this rate increased to 8.63/1000 GMS population (95% CI: 8.34-8.92) in 2011. Methylphenidate was the most frequently prescribed psychostimulant. For both males and females the prevalence of medication use was highest among the 12-15 year old group. On average, a psycholeptic medication was prescribed to 8% of all psychostimulant users and an antidepressant was concomitantly prescribed on average to 2%. Total expenditure rose from €89,254 in 2002 to €1,532,016 in 2011. CONCLUSIONS: The rate and cost of psychostimulant prescribing among GMS children and adolescents in Ireland increased significantly between 2002 and 2011. Further research is necessary to assess the safety, efficacy and economic impact of concomitant psychotropic prescribing in this population.

Prevalence of potentially inappropriate prescribing and prescribing omissions in older Irish adults: findings from The Irish LongituDinal Study on Ageing study (TILDA).

PURPOSE: We sought to estimate the prevalence of potentially inappropriate prescriptions (PIP) and potential prescribing omissions (PPOs) using a subset of the STOPP/START criteria in a population based sample of Irish adults aged ≥ 65 years using data from The Irish LongituDinal Study on Ageing (TILDA). METHODS: A subset of 26 PIP indicators and 10 PPO indicators from the STOPP/START criteria were applied to the TILDA dataset. PIP/PPO prevalence according to individual STOPP/START criteria and the overall prevalence of PIP/PPO were estimated. The relationship between PIP and PPOs and polypharmacy, age, gender and multimorbidity was examined using logistic regression. RESULTS: The overall prevalence of PIP in the study population (n=3,454) was 14.6 %. The most common examples of PIP identified were NSAID with moderate-severe hypertension (200 participants; 5.8 %) and aspirin with no history of coronary, cerebral, or peripheral vascular symptoms or occlusive event (112 participants; 3.2 %). The overall prevalence of PPOs was 30 % (n=1,035). The most frequent PPO was antihypertensive therapy where systolic blood pressure consistently >160 mmHg (n=341, 9.9 %), There was a significant association between PIP and PPO and polypharmacy when adjusting for age, sex and multimorbidity (adjusted OR 2.62, 95 % CI 2.05-3.33 for PIP and adjusted OR 1.46, 95 % CI 1.23-1.75 for prescribing omissions). CONCLUSION: Our findings indicate prescribing omissions are twice as prevalent as PIP in the elderly using a subset of the STOPP/START criteria as an explicit process measure of potentially inappropriate prescribing and prescribing omissions. Polypharmacy was independently associated with both PPO and PIP. Application of such screening tools to prescribing decisions may reduce unnecessary medication, related adverse events, healthcare utilisation and cost.

Potentially inappropriate prescribing among older people in the United Kingdom.

BACKGROUND: Potentially inappropriate prescribing (PIP) in older people is associated with increases in morbidity, hospitalisation and mortality. The objective of this study was to estimate the prevalence of and factors associated with PIP, among those aged ≥70 years, in the United Kingdom, using a comprehensive set of prescribing indicators and comparing these to estimates obtained from a truncated set of the same indicators. METHODS: A retrospective cross-sectional study was carried out in the UK Clinical Practice Research Datalink (CPRD), in 2007. Participants included those aged ≥ 70 years, in CPRD. Fifty-two PIP indicators from the Screening Tool of Older Persons Potentially Inappropriate Prescriptions (STOPP) criteria were applied to data on prescribed drugs and clinical diagnoses. Overall prevalence of PIP and prevalence according to individual STOPP criteria were estimated. The relationship between PIP and polypharmacy (≥4 medications), comorbidity, age, and gender was examined. A truncated, subset of 28 STOPP criteria that were used in two previous studies, were further applied to the data to facilitate comparison. RESULTS: Using 52 indicators, the overall prevalence of PIP in the study population (n = 1,019,491) was 29%. The most common examples of PIP were therapeutic duplication (11.9%), followed by use of aspirin with no indication (11.3%) and inappropriate use of proton pump inhibitors (PPIs) (3.7%). PIP was strongly associated with polypharmacy (Odds Ratio 18.2, 95% Confidence Intervals, 18.0-18.4, P < 0.05). PIP was more common in those aged 70-74 years vs. 85 years or more and in males. Application of the smaller subset of the STOPP criteria resulted in a lower PIP prevalence at 14.9% (95% CIs 14.8-14.9%) (n = 151,598). The most common PIP issues identified with this subset were use of PPIs at maximum dose for > 8 weeks, NSAIDs for > 3 months, and use of long-term neuroleptics. CONCLUSIONS: PIP was prevalent in the UK and increased with polypharmacy. Application of the comprehensive set of STOPP criteria allowed more accurate estimation of PIP compared to the subset of criteria used in previous studies. These findings may provide a focus for targeted interventions to reduce PIP.

Potential for alcohol and drug interactions in older adults: evidence from the Irish longitudinal study on ageing.

BACKGROUND: Older adults are susceptible to adverse effects from the concomitant use of prescription medications and alcohol. This study estimates the prevalence of exposure to alcohol interactive (AI) medications and concomitant alcohol use by therapeutic class in a large, nationally representative sample of older adults. METHODS: Cross-sectional analysis of a population based sample of older Irish adults aged ≥60 years using data from The Irish Longitudinal Study on Ageing (TILDA) (N = 3,815). AI medications were identified using Stockley's Drug Interactions, the British National Formulary and the Irish Medicines Formulary. An in-home inventory of medications was used to characterise AI drug exposure by therapeutic class. Self-reported alcohol use was classified as non-drinker, light/moderate and heavy drinking. Comorbidities known to be exacerbated by alcohol were also recorded (diabetes mellitus, hypertension, peptic ulcer disease, liver disease, depression, gout or breast cancer), as well as sociodemographic and health factors. RESULTS: Seventy-two per cent of participants were exposed to AI medications, with greatest exposure to cardiovascular and CNS agents. Overall, 60% of participants exposed to AI medications reported concomitant alcohol use, compared with 69.5% of non-AI exposed people (p < 0.001). Almost 28% of those reporting anti-histamine use were identified as heavy drinkers. Similarly almost one in five, combined heavy drinking with anti-coagulants/anti-platelets and cardiovascular agents, with 16% combining heavy drinking with CNS agents. Multinomial logistic regression showed that being male, younger, urban dwelling, with higher levels of education and a history of smoking, were associated with an increased risk for concomitant exposure to alcohol consumption (both light/moderate and heavier) and AI medications. Current smokers and people with increasing co-morbidities were also at greatest risk for heavy drinking in combination with AI medications. CONCLUSIONS: The concurrent use of alcohol with AI medications, or with conditions known to be exacerbated by alcohol, is common among older Irish adults. Prescribers should be aware of potential interactions, and screen patients for alcohol use and provide warnings to minimize patient risk.

The GFR and GFR decline cannot be accurately estimated in type 2 diabetics.

There are no adequate studies that have formally tested the performance of different estimating formulas in patients with type 2 diabetes both with and without overt nephropathy. Here we evaluated the agreement between baseline GFRs, GFR changes at month 6, and long-term GFR decline measured by iohexol plasma clearance or estimated by 15 creatinine-based formulas in 600 type 2 diabetics followed for a median of 4.0 years. Ninety patients were hyperfiltering. The number of those identified by estimation formulas ranged from 0 to 24:58 were not identified by any formula. Baseline GFR was significantly underestimated and a 6-month GFR reduction was missed in hyperfiltering patients. Long-term GFR decline was also underestimated by all formulas in the whole study group and in hyper-, normo-, and hypofiltering patients considered separately. Five formulas generated positive slopes in hyperfiltering patients. Baseline concordance correlation coefficients and total deviation indexes ranged from 32.1% to 92.6% and from 0.21 to 0.53, respectively. Concordance correlation coefficients between estimated and measured long-term GFR decline ranged from -0.21 to 0.35. The agreement between estimated and measured values was also poor within each subgroup considered separately. Thus, our study questions the use of any estimation formula to identify hyperfiltering patients and monitor renal disease progression and response to treatment in type 2 diabetics without overt nephropathy.

Measurable urinary albumin predicts cardiovascular risk among normoalbuminuric patients with type 2 diabetes.

Micro- or macroalbuminuria is associated with increased cardiovascular risk factors among patients with type 2 diabetes, but whether albuminuria within the normal range predicts long-term cardiovascular risk is unknown. We evaluated the relationships between albuminuria and cardiovascular events in 1208 hypertensive, normoalbuminuric patients with type 2 diabetes from the BErgamo NEphrologic Diabetes Complication Trial (BENEDICT), all of whom received angiotensin-converting enzyme inhibitor (ACEI) therapy at the end of the trial and were followed for a median of 9.2 years. The main outcome was time to the first of fatal or nonfatal myocardial infarction; stroke; coronary, carotid, or peripheral artery revascularization; or hospitalization for heart failure. Overall, 189 (15.6%) of the patients experienced a main outcome event (2.14 events/100 patient-years); 24 events were fatal. Albuminuria independently predicted events (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.02-1.08). Second-degree polynomial multivariable analysis showed a continuous nonlinear relationship between albuminuria and events without thresholds. Considering the entire study population, even albuminuria at 1-2 µg/min was significantly associated with increased risk compared with albuminuria <1 µg/min (HR, 1.04; 95% CI, 1.02-1.07). This relationship was similar in the subgroup originally randomly assigned to non-ACEI therapy. Among those originally receiving ACEI therapy, however, the event rate was uniformly low and was not significantly associated with albuminuria. Taken together, among normoalbuminuric patients with type 2 diabetes, any degree of measurable albuminuria bears significant cardiovascular risk. The association with risk is continuous but is lost with early ACEI therapy.

Prescribing patterns of glucosamine in an older population: a national cohort study.

BACKGROUND: Glucosamine is commonly prescribed as a disease modulating agent in osteoarthritis. However, the evidence to date suggests that it has a limited impact on the clinical symptoms of the disease including joint pain, radiological progression, function and quality of life. The aim of this study was to examine the prescribing patterns of glucosamine from 2002-2011 in an elderly Irish national population cohort using data from the Health Service Executive Primary Care Reimbursement (HSE-PCRS) General medical services (GMS) Scheme. METHODS: Patients aged ≥ 70 years on the HSE-PCRS pharmacy claims database between January 2002 and December 2011 were included. ATC code M01AX05 (glucosamine) was extracted. Prevalence rates per 1000 eligible population with 95% confidence intervals were calculated for all years and age groups (70-74 years, ≥75 years). A negative binomial regression analysis was used to determine longitudinal usage trends and compare prevalence rates across years, sex and age groups. RESULTS: The annual patient rate of glucosamine prescribing increased significantly from 13.0/1000 eligible population (95% CI 12.6-13.4) in 2002 to 68.7/1000 population (95% CI 67.8-69.5) in 2009 before decreasing to 62.4/1000 population (95% CI 61.6-63.2) in 2011. The rate of prescribing of glucosamine varied with sex, with women receiving significantly more prescriptions than men. The cost of glucosamine also increased from 2002-2008. In 2008 total expenditure reached a high of €4.6 million before decreasing to €2.6 million in 2011. CONCLUSION: The national trend in prescribing of glucosamine increased significantly from 2002 to 2009 before decreasing in 2010 and 2011, in keeping with current international guidelines. There is a need for awareness among healthcare professionals and patients alike of the best available evidence to inform decision making relating to the prescription and consumption of such supplements.

Prognostic value of the ABCD² clinical prediction rule: a systematic review and meta-analysis.

OBJECTIVE: The purpose of this systematic review with meta-analysis is to determine the predictive value of the ABCD ²at 7 and 90 days across three strata of risk. Background. The risk of stroke after transient ischaemic attack (TIA) is significant. The ABCD ²clinical prediction rule is designed to predict early risk of stroke after TIA. A number of independent validation studies have been conducted since the rule was derived. METHODS: A systematic literature search was conducted to identify studies that validated the ABCD². The derived rule was used as a predictive model and applied to subsequent validation studies. Comparisons were made between observed and predicted number of strokes stratified by risk group: low (0-3 points), moderate (4-5 points) and high (6-7 points). Pooled results are presented as risk ratios (RRs) with 95% confidence intervals (CIs), in terms of over-prediction (RR > 1) or under-prediction (RR < 1) of stroke at 7 and 90 days. RESULTS: We include 16 validation studies. Fourteen studies report 7-day stroke risk (n = 6282, 388 strokes). The ABCD² rule correctly predicts occurrence of stroke at 7 days across all three risk strata: low [RR 0.86, 95% CI (0.47-1.58), I² = 16%], moderate [RR 0.99, 95% CI (0.67-1.47), I² = 68%] and high [RR 0.84, 95% CI (0.6-1.19), I² = 46%]. Eleven studies report 90-day stroke risk (n = 6304). There is a non-significant trend towards over-prediction of stroke in all risk categories at 90 days. There are 426 strokes observed in contrast to a predicted 626 strokes. As the trichotomized ABCD² score increases, the risk of stroke increases (P < 0.01). There is no evidence of publication bias in these studies (P > 0.05). CONCLUSION: The ABCD² is a useful CPR, particularly in relation to 7-day risk of stroke.

Sirolimus therapy to halt the progression of ADPKD.

Activation of mammalian target of rapamycin (mTOR) pathways may contribute to uncontrolled cell proliferation and secondary cyst growth in patients with autosomal dominant polycystic kidney disease (ADPKD). To assess the effects of mTOR inhibition on disease progression, we performed a randomized, crossover study (The SIRENA Study) comparing a 6-month treatment with sirolimus or conventional therapy alone on the growth of kidney volume and its compartments in 21 patients with ADPKD and GFR>or=40 ml/min per 1.73 m2. In 10 of the 15 patients who completed the study, aphthous stomatitis complicated sirolimus treatment but was effectively controlled by topical therapy. Compared with pretreatment, posttreatment mean total kidney volume increased less on sirolimus (46+/-81 ml; P=0.047) than on conventional therapy (70+/-72 ml; P=0.002), but we did not detect a difference between the two treatments (P=0.45). Cyst volume was stable on sirolimus and increased by 55+/-75 ml (P=0.013) on conventional therapy, whereas parenchymal volume increased by 26+/-30 ml (P=0.005) on sirolimus and was stable on conventional therapy. Percentage changes in cyst and parenchyma volumes were significantly different between the two treatment periods. Sirolimus had no appreciable effects on intermediate volume and GFR. Albuminuria and proteinuria marginally but significantly increased during sirolimus treatment. In summary, sirolimus halted cyst growth and increased parenchymal volume in patients with ADPKD. Whether these effects translate into improved long-term outcomes requires further investigation.

ABCB1 genotypes predict cyclosporine-related adverse events and kidney allograft outcome.

Cyclosporine A (CsA) is a substrate of P-glycoprotein, an efflux transporter encoded by the ABCB1 gene. Compared with carriers of the wild-type gene, carriers of T allelic variants in exons 21 or 26 have reduced P-glycoprotein activity and, secondarily, increased intracellular concentration of CsA; therefore, carriers of T variants might be at increased risk for CsA-related adverse events. We evaluated the associations between ABCB1 genotypes (in exons 12, 21, and 26) and CsA-related outcomes in 147 renal transplant recipients who were receiving CsA-based immunosuppression and were included in the Mycophenolate Steroids Sparing study. During a median of 65.5 mo follow-up, carriers of T allelic variants in exons 21 or 26 had a three-fold risk for delayed graft function (DGF), a trend to slower recovery of renal function and lower GFR at study end, and significantly higher incidences of new-onset diabetes and cytomegalovirus reactivation compared with carriers of the wild-type genotype. T variants in both exons 21 and 26 were independently associated with 3.8- and 3.5-fold higher risk for DGF, respectively (P = 0.022 and P = 0.034). The incidence of acute rejection and the mean CsA dose and blood levels were comparable in genotype groups. In conclusion, renal transplant recipients with T allelic variants in ABCB1 exons 21 or 26 are at increased risk for CsA-related adverse events. Genetic evaluation may help to identify patients at risk and to modulate CsA therapy to optimize graft and patient outcomes.

Prices and distribution margins of in-patent drugs in pharmacy: a comparison in seven European countries.

OBJECTIVES: To compare prices of in-patent active ingredients (AIs) in Europe at three levels (ex-factory prices, net distribution margins and third party payers' prices). METHODS: We compared the prices in seven EU countries (Belgium, France, Germany, Italy, the Netherlands, Spain and the UK) of the 20 in-patent AIs most sold on the Italian retail market in 2004, based on "sell in" sales data. We calculated the average ex-factory price per unit of each compound in each of the seven countries, weighted by the volumes of all reimbursable package sizes and strengths. We estimated net distribution margins according to the 2004 domestic regulations by deducting any type of mandatory discount. Finally, we added VAT to calculate "third party payer's prices". All prices were expressed in index numbers (Italy=100). RESULTS: Italy had the lowest average ex-factory prices, the Netherlands and particularly the UK had by far the lowest distribution margins, while Germany had by far the highest third party payers' prices. The Netherlands and particularly UK showed a steep decrease from ex-factory to third party payers' prices, while Belgium, Italy and Spain gave the opposite pattern. CONCLUSIONS: Our study suggests that public authorities can deal with drug prices both by strictly controlling ex-factory prices and by establishing appropriate distribution margins. The latter might be facilitated by liberalizing the distribution sector.

Healthcare costs of COPD in Italian referral centres: a prospective study.

BACKGROUND: This study estimated the healthcare resource utilisation and costs of chronic obstructive pulmonary disease (COPD) patients, staged by severity, in the Italian pneumology departments (PDs). METHODS: The project was a multi-centre observational study conducted in 11 Italian PDs throughout the country. A total of 268 patients were recruited and followed prospectively for 1 year. For the purpose of analysis, patients were divided into four groups according to the severity at onset: mild COPD (stage I)-postbronchodilator FEV1/FVC <70% and FEV1 >or=80% of predicted; moderate COPD (stage II)-postbronchodilator FEV1/FVC <70% and 50%

Medical costs of glaucoma and ocular hypertension in Italian referral centres: a prospective study.

AIM: This study analyzes the resource utilization and costs of ocular hypertension and glaucoma (staged by severity) in Italian ophthalmology departments. METHODS: The project was a multi-centre observational study conducted in 17 Italian ophthalmology departments throughout the country. A total of 659 patients were recruited and followed prospectively for 1 year. For the purpose of analysis, the patients were divided into 3 groups according to the severity at onset: ocular hypertension, glaucoma and advanced glaucoma. RESULTS: The subgroups differed significantly in the main demographic and clinical variables. As expected, greater severity was associated with older mean age and worse visual acuity, and with higher resource consumption and costs. The annual average cost per patient was EUR 788.7 and rose significantly with disease severity (EUR 572.0 for ocular hypertension, EUR 734.3 for glaucoma and EUR 1,054.9 for advanced glaucoma). Drugs and specialist consultations were by far the largest cost components. CONCLUSIONS: This study offers some information on the medical costs of glaucoma in Italy potentially useful for decision-making in the health care services. Health care resources and costs increased with disease severity.

Medical costs of chronic musculoskeletal pain in Italy.

BACKGROUND AND OBJECTIVES: Musculoskeletal system problems are responsible for more than two-thirds of painful conditions in primary care. However, only one published study, conducted in Finland, has analysed the costs of managing musculoskeletal pain as a whole in primary care. This study analysed the costs of diagnosing and treating chronic musculoskeletal pain in primary care in Italy. A secondary aim of the study was to assess the impact of different drug treatment patterns on medical costs associated with musculoskeletal pain. METHODS: Chronic pain of musculoskeletal origin was defined as continuous or recurrent pain persisting over 3 months with involvement of the musculoskeletal system, i.e. arising from primary musculoskeletal disorders or from the late consequences of external events (injuries, medical care or surgery). A total of 52 general practitioners (GPs) recruited 581 patients. We focussed on the differences between patients treated (410) and not treated (171) with drugs. Within the treated group, we also analysed subgroups given non-selective NSAID-based therapy (subgroup A, 169 patients) or cyclo-oxygenase-2 (COX-2) inhibitor-based therapy (subgroup B, 52 patients). RESULTS: The annual average cost of treating a patient with chronic musculoskeletal pain was euro 212.60. Hospital admissions and GP consultations were the largest cost components, both accounting for around a quarter of the total cost. Not surprisingly, the treated group included older patients, who had more co-morbidities and more severe pain. This was associated with annual costs more than four times those of untreated patients (euro 274.50 vs euro 63.90, respectively). Subgroups A and B did not differ with respect to major demographic and clinical variables except in relation to mean age (63 vs 70 years, respectively; p=0.037). They had similar per-patient costs (euro 186.20 vs euro 172.90), although these totals comprised a different mix of components. CONCLUSION: The analysis showed that the annual average cost of treatment of chronic musculoskeletal pain in Italy varied considerably depending on whether drug treatment was used. COX-2 inhibitors and traditional NSAIDs had similar per-patient costs, although this similarity stemmed from a different mix of components.

Health status, resource consumption, and costs of dysthymia. A multi-center two-year longitudinal study.

BACKGROUND: In this study we estimated the health status, resource consumption and costs of a large cohort of patients with early and late-onset dysthymia. METHODS: The DYSCO (DYSthymia COsts) project is a multi-center observational study which prospectively followed for two years a randomly chosen sample of patients with dysthymia in the Italian primary health care system. RESULTS: A total of 501 patients were followed for two years; 81% had early-onset dysthymic disorder. During the study, improvement was seen in most domains of the 36-Item Short Form Health Survey (SF-36) questionnaire. Comparison of the SF-36 scores for the two groups showed that only the physical health index significantly differed during the two years. The use of outpatient consultations, laboratory tests and diagnostic procedures was similar in the two groups, but patients with early-onset dysthymia were admitted significantly more than late-onset cases. Hospital admissions were almost entirely responsible for the higher total cost per patient per year of early-onset dysthymia. LIMITATIONS: A first limitation of this study is that general practitioners were selected on the basis of their willingness to participate, not at random; secondly, no information was collected on concomitant psychiatric comorbidities. CONCLUSIONS: The present study provides the first prospective, long-term data on service use and costs in patients with dysthymia. Differently from patients with early-onset dysthymia, patients with late-onset dysthymia were admitted less and cost less.

A simplified approach to the pooled analysis of calibration of clinical prediction rules for systematic reviews of validation studies.

OBJECTIVE: Estimating calibration performance of clinical prediction rules (CPRs) in systematic reviews of validation studies is not possible when predicted values are neither published nor accessible or sufficient or no individual participant or patient data are available. Our aims were to describe a simplified approach for outcomes prediction and calibration assessment and evaluate its functionality and validity. STUDY DESIGN AND METHODS: Methodological study of systematic reviews of validation studies of CPRs: a) ABCD(2) rule for prediction of 7 day stroke; and b) CRB-65 rule for prediction of 30 day mortality. Predicted outcomes in a sample validation study were computed by CPR distribution patterns ("derivation model"). As confirmation, a logistic regression model (with derivation study coefficients) was applied to CPR-based dummy variables in the validation study. Meta-analysis of validation studies provided pooled estimates of "predicted:observed" risk ratios (RRs), 95% confidence intervals (CIs), and indexes of heterogeneity (I(2) ) on forest plots (fixed and random effects models), with and without adjustment of intercepts. The above approach was also applied to the CRB-65 rule. RESULTS: Our simplified method, applied to ABCD(2) rule in three risk strata (low, 0-3; intermediate, 4-5; high, 6-7 points), indicated that predictions are identical to those computed by univariate, CPR-based logistic regression model. Discrimination was good (c-statistics =0.61-0.82), however, calibration in some studies was low. In such cases with miscalibration, the under-prediction (RRs =0.73-0.91, 95% CIs 0.41-1.48) could be further corrected by intercept adjustment to account for incidence differences. An improvement of both heterogeneities and P-values (Hosmer-Lemeshow goodness-of-fit test) was observed. Better calibration and improved pooled RRs (0.90-1.06), with narrower 95% CIs (0.57-1.41) were achieved. CONCLUSION: Our results have an immediate clinical implication in situations when predicted outcomes in CPR validation studies are lacking or deficient by describing how such predictions can be obtained by everyone using the derivation study alone, without any need for highly specialized knowledge or sophisticated statistics.

Long-term risk of stroke after transient ischaemic attack: a hospital-based validation of the ABCD² rule.

BACKGROUND: The ABCD2 clinical prediction rule is a seven point summation of clinical factors independently predictive of stroke risk. The purpose of this cohort study is to validate the ABCD2 rule in a Bulgarian hospital up to three years after TIA. METHODS: All consecutive admissions to an emergency department with symptoms of a first TIA were included. Baseline data and clinical examinations including the ABCD2 scores were documented by neurologists. Discrimination and calibration performance was examined using ABCD2 cut-off scores of ≥3, ≥4 and ≥5 points, consistent with the international guidelines. The Hosmer-Lemeshow test was used to examine calibration between the observed and expected outcomes as predicted by ABCD2 score within the logistic regression analysis. RESULTS: Eighty-nine patients were enrolled to the study with a mean age of 63 years (+/- 12 years). Fifty-nine percent (n = 53) of the study population was male. Seven strokes (7.8%) occurred within the first year and six further strokes within the three-year follow-up period. There was no incident of stroke within the first 90 days after TIA. The rule demonstrated good predictive (OR = 1.58, 95% CI 1.09-2.29) and discriminative performance (AUCROC = 0.72, 95% CI 0.58-0.86), as well as a moderate calibration performance at three years. CONCLUSION: This validation of the ABCD2 rule in a Bulgarian hospital demonstrates that the rule has good predictive and discriminative performance at three years. The ABCD2 is quick to administer and may serve as a useful tool to assist clinicians in the long-term management of individuals with TIA.

Cemented versus uncemented fixation in total hip replacement: a systematic review and meta-analysis of randomized controlled trials.

The optimal method of fixation for primary total hip replacements (THR), particularly fixation with or without the use of cement is still controversial. In a systematic review and metaanalysis of all randomized controlled trials comparing cemented versus uncemented THRS available in the published literature, we found that there is no significant difference between cemented and uncemented THRs in terms of implant survival as measured by the revision rate. Better short-term clinical outcome, particularly an improved pain score can be obtained with cemented fixation. However, the results are unclear for the long-term clinical and functional outcome between the two groups. No difference was evident in the mortality and the post operative complication rate. On the other hand, the radiographic findings were variable and do not seem to correlate with clinical findings as differences in the surgical technique and prosthesis design might be associated with the incidence of osteolysis. We concluded in our review that cemented THR is similar if not superior to uncemented THR, and provides better short term clinical outcomes. Further research, improved methodology and longer follow up are necessary to better define specific subgroups of patients in whom the relative benefits of cemented and uncemented implant fixation can be clearly demonstrated.

Effectiveness of medicines review with web-based pharmaceutical treatment algorithms in reducing potentially inappropriate prescribing in older people in primary care: a cluster randomized trial (OPTI-SCRIPT study protocol).

BACKGROUND: Potentially inappropriate prescribing in older people is common in primary care and can result in increased morbidity, adverse drug events, hospitalizations and mortality. In Ireland, 36% of those aged 70 years or over received at least one potentially inappropriate medication, with an associated expenditure of over €45 million.The main objective of this study is to determine the effectiveness and acceptability of a complex, multifaceted intervention in reducing the level of potentially inappropriate prescribing in primary care. METHODS/DESIGN: This study is a pragmatic cluster randomized controlled trial, conducted in primary care (OPTI-SCRIPT trial), involving 22 practices (clusters) and 220 patients. Practices will be allocated to intervention or control arms using minimization, with intervention participants receiving a complex multifaceted intervention incorporating academic detailing, medicines review with web-based pharmaceutical treatment algorithms that provide recommended alternative treatment options, and tailored patient information leaflets. Control practices will deliver usual care and receive simple patient-level feedback on potentially inappropriate prescribing. Routinely collected national prescribing data will also be analyzed for nonparticipating practices, acting as a contemporary national control. The primary outcomes are the proportion of participant patients with potentially inappropriate prescribing and the mean number of potentially inappropriate prescriptions per patient. In addition, economic and qualitative evaluations will be conducted. DISCUSSION: This study will establish the effectiveness of a multifaceted intervention in reducing potentially inappropriate prescribing in older people in Irish primary care that is generalizable to countries with similar prescribing challenges. TRIAL REGISTRATION: Current controlled trials ISRCTN41694007.