Marja Blom

Systematic review and meta-analysis of the efficacy and safety of existing TNF blocking agents in treatment of rheumatoid arthritis

Background and Objectives Five-tumour necrosis factor (TNF)-blockers (infliximab, etanercept, adalimumab, certolizumab pegol and golimumab) are available for treatment of rheumatoid arthritis. Only few clinical trials compare one TNF-blocker to another. Hence, a systematic review is required to indirectly compare the substances. The aim of our study is to estimate the efficacy and the safety of TNF-blockers in the treatment of rheumatoid arthritis (RA) and indirectly compare all five currently available blockers by combining the results from included randomized clinical trials (RCT). Methods A systematic literature review was conducted using databases including: MEDLINE, SCOPUS (including EMBASE), Cochrane library and electronic search alerts. Only articles reporting double-blind RCTs of TNF-blockers vs. placebo, with or without concomitant methotrexate (MTX), in treatment of RA were selected. Data collected were information of patients, interventions, controls, outcomes, study methods and eventual sources of bias. Results Forty-one articles reporting on 26 RCTs were included in the systematic review and meta-analysis. Five RCTs studied infliximab, seven etanercept, eight adalimumab, three golimumab and three certolizumab. TNF-blockers were more efficacious than placebo at all time points but were comparable to MTX. TNF-blocker and MTX combination was superior to either MTX or TNF-blocker alone. Increasing doses did not improve the efficacy. TNF-blockers were relatively safe compared to either MTX or placebo. Conclusions No single substance clearly rose above others in efficacy, but the results of the safety analyses suggest that etanercept might be the safest alternative. Interestingly, MTX performs nearly identically considering both efficacy and safety aspects with a margin of costs.

Automated dose dispensing service for primary healthcare patients: a systematic review

BackgroundAn automated dose dispensing (ADD) service has been implemented in primary healthcare in some European countries. In this service, regularly used medicines are machine-packed into unit-dose bags for each time of administration. The aim of this study is to review the evidence for ADD’s influence on the appropriateness of medication use, medication safety, and costs in primary healthcare.MethodsA literature search was performed in April 2012 in the most relevant databases (n = 10), including the Medline, Embase, and Cochrane Library. The reference lists of the studies selected were manually searched. A study was included in the review if the study was conducted in primary healthcare or nursing home settings and medicines were dispensed in unit-dose bags.ResultsOut of 328 abstracts, seven studies met the inclusion and reporting quality criteria, but none applied a randomized controlled study design. Of the four controlled studies, one was a national register-based study. It showed that the patient group in the ADD scheme more often used three or more psychotropic drugs and anticholinergics than patients using the standard dispensing procedure, while women in the ADD group used less long-acting benzodiazepines and both genders had fewer drug-drug interactions. In another, regional controlled study, the ADD group consisted of patients with higher risk of inappropriate drug use, according to all indicators applied. The third controlled study indicated that ADD user drug treatments were more likely to remain unchanged than in patients using a standard dispensing procedure. A controlled study from Norway showed that ADD reduced discrepancies in the documentation of patient medication records. Costs were not investigated in any of the studies.ConclusionsA very limited number of controlled studies have explored ADD in primary healthcare. Consequently, the evidence for ADD’s influence on appropriateness and safety of medication use is limited and lacking in information on costs. The findings of this review suggest that patients using the ADD have more inappropriate drugs in their regimens, and that ADD may improve medication safety in terms of reducing the discrepancies in medication records. Further evidence is needed to draw sound conclusions on ADD’s outcomes.

Cost-utility of routine cataract surgery.

BackgroundIf decisions on health care spending are to be as rational and objective as possible, knowledge on cost-effectiveness of routine care is essential. Our aim, therefore, was to evaluate the cost-utility of routine cataract surgery in a real-world setting.MethodsProspective assessment of health-related quality of life (HRQoL) of patients undergoing cataract surgery. 219 patients (mean (SD) age 71 (11) years) entering cataract surgery (in 87 only first eye operated, in 73 both eyes operated, in 59 first eye had been operated earlier) filled in the 15D HRQoL questionnaire before and six months after operation. Direct hospital costs were obtained from a clinical patient administration database and cost-utility analysis performed from the perspective of the secondary care provider extrapolating benefits of surgery to the remaining statistical life-expectancy of the patients.ResultsMean (SD) utility score (on a 0–1 scale) increased statistically insignificantly from 0.82 (0.13) to 0.83 (0.14). Of the 15 dimensions of the HRQoL instrument, only seeing improved significantly after operation. Mean utility score improved statistically significantly only in patients reporting significant or major preoperative seeing problems. Of the subgroups, only those whose both eyes were operated during follow-up showed a statistically significant (p < 0.001) improvement. Cost per quality-adjusted life year (QALY) gained was €5128 for patients whose both eyes were operated and €8212 for patients with only one eye operated during the 6-month follow-up. In patients whose first eye had been operated earlier mean HRQoL deteriorated after surgery precluding the establishment of the cost per QALY.ConclusionMean utility gain after routine cataract surgery in a real-world setting was relatively small and confined mostly to patients whose both eyes were operated. The cost of cataract surgery per quality-adjusted life year gained was much higher than previously reported and associated with considerable uncertainty.

Do biologic drugs affect the need for and outcome of joint replacements in patients with rheumatoid arthritis? A register-based study

OBJECTIVES The aim was to study the incidence of joint replacements among biologic drug and disease-modifying anti-rheumatic drug (DMARD) users as well as to investigate the plausible effect of biologic treatment on survival of prostheses in patients with Rheumatoid arthritis (RA). METHODS The study population comprised 2 cohorts of patients [Register of biologic treatment in Finland (ROB-FIN) and the Central Finland RA database] from 1999 to 2010. Records of joint replacements performed in the study population between 1980 and 2010 were retrieved from the Finnish Arthroplasty Register. Propensity score matching was used to equalize patient characteristics between biologics and DMARD users. The incidence rates of primary and revision operations were compared between the 2 treatment groups. Kaplan-Meier survival analysis was used to analyze prosthesis survival. RESULTS Of the 2102 biologics and 2710 DMARD users identified from the registries, 1587 were included in both groups after the matching. Median follow-up times were 3.1 and 8.0 years, respectively. There were more primary operations per 100 patient years in the biologics (3.89, CI 95% 3.41-4.41) vs. DMARD (2.63, 2.35-2.94) group but slightly fewer revisions (0.65, 0.46-0.88 vs. 0.83, 0.68-1.01). Biologics users were more likely to receive a joint replacement to small joints (p < 0.001). The survival of the prostheses installed during or prior to follow-up was similar in both treatment groups. CONCLUSIONS The use of biologic drugs did not reduce the need for joint replacement surgery in patients with a similar on-medication disease activity. Despite possibly lower rate of revisions among biologic users, the durability of prostheses was not improved.

A Systematic Review of Cost-Sharing Strategies Used within Publicly-Funded Drug Plans in Member Countries of the Organisation for Economic Co-Operation and Development

Background Publicly-funded drug plans vary in strategies used and policies employed to reduce continually increasing pharmaceutical expenditures. We systematically reviewed the utilization of cost-sharing strategies and physician-directed prescribing regulations in publicly-funded formularies within member nations of the Organization of Economic Cooperation and Development (OECD). Methods & Findings Using the OECD nations as the sampling frame, a search for cost-sharing strategies and physician-directed prescribing regulations was done using published and grey literature. Collected data was verified by a system expert within the prescription drug insurance plan in each country, to ensure the accuracy of key data elements across plans. Significant variation in the use of cost-sharing mechanisms was seen. Copayments were the most commonly used cost-containment measure, though their use and amount varied for those with certain conditions, most often chronic diseases (in 17 countries), and by socio-economic status (either income or employment status), or with age (in 15 countries). Caps and deductibles were only used by five systems. Drug cost-containment strategies targeting physicians were also identified in 24 countries, including guideline-based prescribing, prescription monitoring and incentive structures. Conclusions There was variable use of cost-containment strategies to limit pharmaceutical expenditures in publicly funded formularies within OECD countries. Further research is needed to determine the best approach to constrain costs while maintaining access to pharmaceutical drugs.

Is longer waiting time for total knee replacement associated with health outcomes and medication costs? Randomized clinical trial.

BACKGROUND The aim of this prospective randomized study was to evaluate the effect of waiting time (WT) on health-related quality of life (HRQoL), knee pain and physical function, and the use and costs of medication of patients awaiting total knee replacement. METHODS When placed on the waiting list, 438 patients were randomized into a short waiting time (SWT ≤ 3 months) or a nonfixed waiting time (NFWT > 3 months) group. HRQoL was measured by the 15D, and pain and physical function by modified Knee Society Clinical Rating System at baseline, admission, and 3 and 12 months postoperatively. The costs of medication due to osteoarthritis were calculated at the same measurement points. All analyses were performed using the intention-to-treat principle. RESULTS The mean WT was 94 and 239 days in the SWT and NFWT groups, respectively. Apart from higher weekly cost of medication in the SWT group at admission and better HRQoL in the NFWT group 1 year postoperatively, there were no statistically significant differences between the groups in other outcomes during the follow-up. CONCLUSION Those in the SWT group had higher weekly costs of medication at admission, and reached better HRQoL 3 months earlier than those in the NFWT group, but the latter had better HRQoL after operation. Otherwise, the length of WT was not associated with different health and HRQoL outcomes in the groups.

The Effect of Waiting Time on Health‐Related Quality of Life, Pain, and Physical Function in Patients Awaiting Primary Total Hip Replacement: A Randomized Controlled Trial

OBJECTIVE This prospective randomized study assessed the effect of waiting time (WT) on health outcomes in Finnish patients admitted to hospital for primary total hip replacement (THR). METHODS A total of 395 consecutive patients with a need for a primary THR because of osteoarthritis and who were placed on the waiting list between August 2002 and November 2003. After placement on the waiting list, the patients were randomly assigned to a short WT (<or=3 months) group (n = 174) or a nonfixed WT group (n = 221). The patients completed self-administered questionnaires at the time of placing on the waiting list and at hospital admission. Health-related quality of life was measured by the generic 15D instrument. Hip pain and function were measured by the patient self-report Harris hip score (HHS). RESULTS Of the 395 patients, 312 (79%) completed the follow-up (140 patients with short and 172 with nonfixed WT). At admission, the mean 15D scores for patients with short and nonfixed WT were 0.784 and 0.783, respectively. In the intention-to-treatment analysis, the difference between the groups (Delta 0.001, 95% confidence interval [CI]: -0.019 to 0.021) was not statistically significant or clinically important. The mean self-report HHS in patients with short WT was 43.5, and among those with nonfixed WT was 41.9. The difference (Delta 1.6, 95% CI: -1.77 to 4.87) was not statistically significant. CONCLUSIONS Both generic and disease-specific measures revealed that longer WTs did not result in poorer health status at admission.

The effect of waiting time on health and quality of life outcomes and costs of medication in hip replacement patients: a randomized clinical trial

OBJECTIVE To evaluate the effect of waiting time on health and quality of life outcomes and costs of medication in total hip replacement (THR) patients in a randomized clinical trial. METHODS 395 THR patients were recruited into the study. When placed on the waiting list, patients were randomized into a short (< or =3 months) or a non-fixed waiting time (NFWT) (>3 months) group. In the final analyses 309 patients (179 women) with a mean age of 65 years were included. Health-related quality of life (HRQoL) (generic 15D), and pain and function (modified Harris Hip Score (HHS)) were calculated when placed on the waiting list, at hospital admission, and at 3 and 12 months postoperatively. The costs of disease-specific medication were calculated at the same measurement points. All analyses were performed using the intention-to-treat (ITT) principal. RESULTS Of the recruited patients, 309 (78%) completed the follow-up (short group 140 and non-fixed group 169 patients). The mean waiting time was 74 days in the short and 194 days in the NFWT groups. In the ITT analyses there were no statistically significant differences between the groups in the weekly use and costs of medication, HRQoL or HHS at baseline, at admission, or 3 or 12 months after surgery. The only difference was in total medication costs during the waiting time period, at EUR 83 and 171, respectively. CONCLUSIONS The length of the waiting time did not generate different effects on the studied health and quality of life outcomes of the randomized groups. However, those in short waiting time group reached earlier better HRQoL.

Can the efficacy of reduction mammoplasty be predicted? The applicability and predictive value of breast-related symptoms questionnaire in measuring breast-related symptoms pre- and postoperatively

To measure the impact of reduction mammoplasty, the Breast-Related Symptoms Questionnaire (BRSQ) was translated into Finnish and tested among women seeking reduction mammoplasty. This previously validated questionnaire focuses on 13 breast hypertrophy-related symptoms and their frequency. In this prospective multicentre study, the breast-related symptoms of 98 women were measured preoperatively with BRSQ and the health-related quality of life (HRQoL) with the 15 dimension (15D), a well-established generic tool. A total of 59 participants were followed up at least 6 months postoperatively. The women were middle-aged (mean age 44 years) and most of them overweight (mean Body mass index (BMI) 29). All patients had frequent physical symptoms and disability due to their breasts and reported low breast severity symptom score (BSS mean 27, range 13-38). Mean amount of resected breast tissue was 1310 g per patient. Postoperatively, the breast-related symptoms were significantly relieved, and 55 of 59 operated patients reported less frequent or non-existent symptoms (mean BSS 59, range 22-65). BSS score improved especially in obese women and those with pendulous breasts. A low preoperative BSS was related to considerable benefit from surgery. HRQoL score improved significantly from 0.889 to 0.930 (P < 0.001) and significant improvement was seen especially in dimensions, such as discomfort, usual activities and breathing. In conclusion, BRSQ is an easy tool to use to quantify breast-related symptoms. It visualised effectively the impact of the reduction mammoplasty. Surgical breast reduction significantly improves breast-related symptoms and the HRQoL among women with many breast-related symptoms. The present guidelines for patient selection in breast reduction surgery should be updated to use valid measurement and scientific evidence.

Factors relating to effectiveness data use in healthcare management

Purpose - The aim of this study is to produce information concerning factors which may hamper or promote the use of effectiveness data in secondary health care middle and upper management. Additionally, the study aims to acquire knowledge of the ways in which the managers would generate effectiveness data for use in their own work. Design/methodology/approach - The study was conducted by interviewing department directors, chief medical officers and directors of nursing ( Findings - The use of effectiveness data in management was hampered by factors relating to research, managerial work and the organization. Factors relating to the production of effectiveness data, managerial behaviour and a universal demand for evidence-based operations were considered conducive to the use of such information. Managers would cultivate the use of effectiveness data by improving its accessibility, usability and visibility. Practical implications - The findings may help healthcare organizations in developing the use of effectiveness data in their decision-making. Originality/value - The paper addresses managers’ willingness to apply effectiveness data in decision-making although the present quality, reliability and accessibility of effectiveness data do not meet the managers’ needs. The use of effectiveness data in management can be influenced by enhancing organizational patterns of action and supporting managerial decision-making.