Correction to: Treatment patterns in patients with osteoporosis at high risk of fracture in Japan: retrospective chart review.

In this article it was mistakenly stated that Akimitsu Miyauchi is affiliated with both Miyauchi Medical Center, Osaka and Amgen Astellas BioPharma K.K., Tokyo. In fact he is affiliated only with Miyauchi Medical Center; he has no connection with Amgen Astellas.

Treatment patterns in patients with osteoporosis at high risk of fracture in Japan: retrospective chart review.

Osteoporosis (OP) causes reduced bone strength and increases risk of fractures. Medical records from specialist clinics in Japan of postmenopausal women with OP and high risk of fracture were analysed. Majority of patients were treated for OP as recommended and were prescribed OP medications soon after high-risk OP diagnosis. PURPOSE: The incidence of osteoporosis (OP) in Japan is predicted to increase significantly in coming decades. Resultant osteoporotic fractures are a significant contributor of economic and social burden among elderly osteoporosis patients. This retrospective chart review was conducted as a response to the current evidence gap in the treatment patterns for OP patients with high risk of fracture in Japan. METHODS: This was a multi-centre retrospective chart review that analysed data extracted from the medical records of postmenopausal OP patients at high risk for fracture who received care at 11 specialist clinics and medical centers in Japan for at least 18 to 24 months. Main outcome was OP treatment patterns. RESULTS: The study included 709 eligible patients of whom 623 (87.9%) were prescribed OP medication during the study period. The most common reason for not taking OP medication was patient unwillingness to take medication. The most common OP medications prescribed initially were minodronic acid (20.1%), alendronate (19.9%), raloxifene (14.1%), weekly teriparatide acetate (12.4%) and eldecalcitol (11.4%). Majority of patients (62.1%) were still taking their initial medication at the end of the 18-24 month follow-up. CONCLUSIONS: A high percentage of patients (87.9%) in Japan received OP medications soon after their high-risk diagnosis, with bisphosphonates, selective estrogen receptor modulators and teriparatide being the predominant treatment options.

Lifestyle-Related Metabolic Disorders, Osteoporosis, and Fracture Risk in Asia: A Systematic Review.

BACKGROUND: The prevalence of both lifestyle-related metabolic disorders and osteoporosis is increasing in Asia. OBJECTIVES: To conduct a systematic review of the published literature to identify studies examining disorders of glucose and lipid metabolism (type 2 diabetes, hyperglycemia, hypercholesterolemia, hyperlipidemia, dyslipidemia, metabolic syndrome [MetS], and atherosclerosis) as risk factors for osteoporosis and fracture in Asian populations. Studies examining the relationship between metabolic disorders and bone mineral density (BMD) were also included. METHODS: EMBASE (including MEDLINE) and the Cochrane Library were searched. Studies conducted only within Asia, which reported multivariate analysis with a sample size of 200 or more subjects, were included. RESULTS: A total of 32 studies were included. All six studies examining diabetes and fracture found that subjects with diabetes had a significantly higher risk of fracture than did subjects without diabetes (risk estimate range 1.26-4.73). Two studies found that subjects with atherosclerosis had a significantly higher risk of fracture (risk estimate range 1.10-2.52). Studies consistently reported that MetS is likely associated with osteoporosis or decreased BMD in men but not women. No consistent association was found for diabetes and BMD, with studies reporting contrasting results. There was limited evidence investigating lipid metabolism and hyperglycemia and risk of fracture or bone loss in Asian populations. CONCLUSIONS: These findings suggest that diabetes is a risk factor for fracture in Asian populations. MetS may be associated with bone loss in Asian men and atherosclerosis associated with increased fractures; however, caution is needed interpreting these findings given limitations in study design.

Rapid evidence assessment: increasing the transparency of an emerging methodology.

RATIONALE, AIMS AND OBJECTIVES: Within the field of evidence-based practice, policy makers, health care professionals and consumers require timely reviews to inform decisions on efficacious health care and treatments. Rapid evidence assessment (REA), also known as rapid review, has emerged in recent years as a literature review methodology that fulfils this need. It highlights what is known in a clinical area to the target audience in a relatively short time frame. METHODS: This article discusses the lack of transparency and limited critical appraisal that can occur in REA, and goes on to propose general principles for conducting a REA. The approach that we describe is consistent with the principles underlying systematic review methodology, but also makes allowances for the rapid delivery of information as required while utilizing explicit and reproducible methods at each stage. RESULTS: Our method for conducting REA includes: developing an explicit research question in consultation with the end-users; clear definition of the components of the research question; development of a thorough and reproducible search strategy; development of explicit evidence selection criteria; and quality assessments and transparent decisions about the level of information to be obtained from each study. In addition, the REA may also include an assessment of the quality of the total body of evidence. CONCLUSIONS: Transparent reporting of REA methodologies will provide greater clarity to end-users about how the information is obtained and about the trade-offs that are made between speed and rigour.

Lifetime cost effectiveness of a through-school nutrition and physical programme: Project Energize.

Project Energize, a multicomponent through-school physical activity and nutrition programme, is delivered to all primary school children in the Waikato region. The programme aim is to improve the overall health and reduce the rate of weight gain of all Waikato primary school children. An existing economic model was used to extrapolate the programme effects, initial costs, lifetime health treatment cost structures, quality-adjusted-life-years gained and increased life expectancy to the general and Maori child population of New Zealand. In March 2011, a sample of 2474 younger (7.58 ± 0.57 years, mean ± SD) and 2330 older (10.30 ± 0.51 years) children (36% Maori) attending Energize schools had body mass index measured and compared using mixed effect modelling with unEnergized comparison children from 2004 and 2006 from the same region. In 2011 the median body mass index reduction compared with the comparison younger children was -0.504 (90% CI -0.435 to -0.663) kg/m(2) and in the older children -0.551 (-0.456 to -0.789) kg/m(2). In 2010 there were 42,067 children attending Energize schools and in the same year NZ$1,891,175 was spent to deliver the programme; a cost of $44.96/child/year. Compared to the comparison children the increment in cost/quality-adjusted-life-year gained was $30,438 for the younger and $24,690 for the older children, and lower for Maori (younger $28,241, older $22,151) and for the middle socioeconomic status schools ($23,211, $17,891). Project Energize would improve quality and length of life and when compared with other obesity prevention programmes previously assessed with this model, it would be relatively cost-effective from the health treatment payer's perspective.

Disease status, patient quality of life and healthcare resource use for ulcerative colitis in the UK: an observational study.

BACKGROUND: Ulcerative colitis is a lifelong, chronic, relapsing-remitting disease. OBJECTIVE: To assess the relationship between ulcerative colitis disease status and patient quality of life, and to determine the impact of ulcerative colitis on healthcare costs and work productivity, in the UK. METHODS: Clinicians assessed 173 adult patients' current disease status at a single study visit using the partial Mayo (pMayo) instrument. Patients completed the Euro Quality of Life 5-dimension, 5-level (EQ-5D-5L) questionnaire, the Work Productivity and Activity Impairment (WPAI) questionnaire. Healthcare resource use was determined from questionnaires and from patients' medical charts. RESULTS: Patients in remission had a significantly higher EQ-5D-5L scores (mean (SD) 0.86 (0.15)) than patients with active disease (0.71 (0.20); p<0.001). Patients with mild disease had significantly higher mean (SD) EQ-5D-5L scores than patients with moderate/severe disease: 0.77 (0.11) and 0.66 (0.24), respectively (p<0.001). The mean percent productivity impairment was greater for patients with active disease than for patients in remission on all items of the WPAI questionnaire: 24.6% vs 1.8% for work time missed, 34.1% vs 12.9% for impairment while working, 40.8% vs 14.4% for overall work impairment and 42.7% vs 13.0% for activity impairment (p<0.001 for all comparisons). The mean (SD) total cost of healthcare for ulcerative colitis in the prior 3 months was £1211 (1588). CONCLUSIONS: When compared with patients in remission, patients with active ulcerative colitis have significantly worse quality of life and significantly more work impairment. The healthcare costs of ulcerative colitis are considerable.

Relationship between disease severity and quality of life and assessment of health care utilization and cost for ulcerative colitis in Australia: a cross-sectional, observational study.

BACKGROUND & AIMS: The burden of ulcerative colitis (UC) in relation to disease severity is not well documented. This study quantitatively evaluated the relationship between disease activity and quality of life (QoL), as well as health care utilization, cost, and work-related impairment associated with UC in an Australian population. METHODS: A cross-sectional, noninterventional, observational study was performed in patients with a wide range of disease severity recruited during routine specialist consultations. Evaluations included the Assessment of Quality of Life-8-dimension (AQoL-8D), EuroQol 5-dimension, 5-level (EQ-5D-5L), the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ), and the Work Productivity and Activity Impairment (WPAI) instrument. The 3-item Partial Mayo Score was used to assess disease severity. Health care resource utilization was assessed by chart review and patient questionnaires. RESULTS: In 175 patients, mean (SD) AQoL-8D and EQ-5D-5L scores were greater for patients in remission (0.80 [0.19] and 0.81 [0.18], respectively) than for patients with active disease (0.70 [0.20] and 0.72 [0.19], respectively, both Ps<0.001). IBDQ correlated with both AQoL-8D (r=0.73; P<0.0001) and EQ-5D-5L (0.69; P<0.0001). Mean 3-month UC-related health care cost per patient was AUD $2914 (SD=$3447 [mean for patients in remission=$1970; mild disease=$3736; moderate/severe disease=$4162]). Patients in remission had the least work and activity impairment. CONCLUSIONS: More severe UC disease was associated with poorer QoL. Substantial health care utilization, costs, and work productivity impairments were found in this sample of patients with UC. Moreover, greater disease activity was associated with greater health care costs and impairment in work productivity and daily activities.

Histology as a treatment effect modifier in advanced non-small cell lung cancer: a systematic review of the evidence.

BACKGROUND AND OBJECTIVE: We conducted a systematic review of prospective, randomized, controlled trials (RCT) to examine whether histology had a treatment modifying effect (TME) on the efficacy outcomes of chemotherapeutic agents in patients with advanced (stage IIIB-IV) non-small cell lung cancer (NSCLC). METHODS: Potentially pertinent publications were reviewed in full to determine if there was any TME by histology for overall survival (OS), progression-free survival (PFS) or treatment response rate (TRR). RESULTS: Data from three pemetrexed RCT, comparing (i) pemetrexed versus docetaxel, (ii) pemetrexed and cisplatin versus gemcitabine and cisplatin, and (iii) pemetrexed versus placebo, showed a statistically significant TME by histology for OS and PFS. One trial comparing pemetrexed and carboplatin versus gemcitabine and carboplatin found no significant associations between histology and OS. The results of this systematic review indicate that pemetrexed appears to have the most consistent treatment-by-histology interaction effect on the efficacy outcomes of chemotherapeutic agents in patients with advanced or metastatic NSCLC. Patients with non-squamous histology gain the greatest benefit from treatment with pemetrexed. Conversely, patients with squamous cell disease appeared to experience poorer OS when pemetrexed was compared with other active treatments, and similar OS when compared with placebo. Reproducible patterns of TME effect by histology with other chemotherapeutic agents are less clear. CONCLUSIONS: We consider that the historical approach to treating all NSCLC patients with the same chemotherapy regimen is now no longer acceptable.

A systematic review of the clinical effectiveness of 64-slice or higher computed tomography angiography as an alternative to invasive coronary angiography in the investigation of suspected coronary artery disease.

BACKGROUND: This systematic review summarized recent evidence pertaining to the clinical effectiveness of 64-slice or higher computed tomography angiography (CTA) in patients with suspected coronary artery disease (CAD). If CTA proves to be a successful diagnostic performance measure, it could prevent the use of invasive diagnostic procedures in some patients. This would provide multiple health and cost benefits, particularly for under resourced areas where invasive coronary angiography is not always available. METHODS: A systematic method of literature searching and selection was employed with searches limited to December 2006 to March 2009. Included studies were quality assessed using National Health and Medical Research Council (NHMRC) diagnostic levels of evidence and a modified Quality Assessment of Diagnostic Accuracy Studies (QUADAS) tool. Individual and pooled diagnostic performance measures were calculated using standard meta-analytic techniques at the patient, vessel and segment level. A positive result was defined as greater than or equal to 50% stenosis. RESULTS: Twenty-eight studies were included in the systematic review examining 3,674 patients. The primary meta-analysis at the patient-level indicated a sensitivity of 98.2% and specificity of 81.6%. The median (range) positive predictive value (PPV) was 90.5% (76%-100%) and negative predictive value (NPV) 99.0% (83%-100%). In all vessels, the pooled sensitivity was 94.9%, specificity 89.5%, and median (range) PPV 75.0% (53%-95%) and NPV 99.0% (93%-100%). At the individual artery level, overall diagnostic accuracy appeared to be slightly higher in the left main coronary artery and slightly lower in the left anterior descending and circumflex artery. In all segments, the sensitivity was 91.3%, specificity 94.0% and median (range) PPV 69.0% (44%-86%) and NPV 99.0% (98%-100%). CONCLUSIONS: The high sensitivity indicates that CTA can effectively identify the majority of patients with significant coronary artery stenosis. The high NPV at the patient, vessel and segment level establishes CTA as an effective non-invasive alternative to invasive coronary angiography (ICA) for the exclusion of stenosis.

FORM: an Australian method for formulating and grading recommendations in evidence-based clinical guidelines.

BACKGROUND: Clinical practice guidelines are an important element of evidence-based practice. Considering an often complicated body of evidence can be problematic for guideline developers, who in the past may have resorted to using levels of evidence of individual studies as a quasi-indicator for the strength of a recommendation. This paper reports on the production and trial of a methodology and associated processes to assist Australian guideline developers in considering a body of evidence and grading the resulting guideline recommendations. METHODS: In recognition of the complexities of clinical guidelines and the multiple factors that influence choice in health care, a working group of experienced guideline consultants was formed under the auspices of the Australian National Health and Medical Research Council (NHMRC) to produce and pilot a framework to formulate and grade guideline recommendations. Consultation with national and international experts and extensive piloting informed the process. RESULTS: The FORM framework consists of five components (evidence base, consistency, clinical impact, generalisability and applicability) which are used by guideline developers to structure their decisions on how to convey the strength of a recommendation through wording and grading via a considered judgement form. In parallel (but separate from the grading process) guideline developers are asked to consider implementation implications for each recommendation. CONCLUSIONS: The framework has now been widely adopted by Australian guideline developers who find it to be a logical and intuitive way to formulate and grade recommendations in clinical practice guidelines.

A systematic review of the interobserver variability for histology in the differentiation between squamous and nonsquamous non-small cell lung cancer.

INTRODUCTION: The importance of identifying non-small cell lung cancer (NSCLC) histologic subtype has increased recently because of the development of target-specific chemotherapeutic agents. This systematic review was undertaken to examine the interobserver variability for histology in differentiating between subtypes of NSCLC, specifically the ability to differentiate squamous from nonsquamous histology. METHODS: A systematic literature search was undertaken to identify studies that evaluated the reproducibility of histologic diagnosis by pathologists in their reporting of NSCLC subtypes. Studies were screened using a priori defined eligibility criteria. The National Health and Medical Research Council diagnostic levels of evidence were applied and quality assessed using the Quality Assessment of Diagnostic Accuracy Studies tool. Data were extracted and reanalyzed to permit comparison of agreement in nonsquamous and squamous cell carcinoma by 2 × 2 tables. Percentage agreement and kappa statistics were calculated for each included study. RESULTS: Out of 1480 articles identified through the literature search, six were eligible for inclusion. The percentage agreement for all subtypes of NSCLC in the included studies ranged from 67.1 to 89.6% (κ, 0.42-0.84). Based on the primary reanalysis of data (reanalysis 1), agreement between pathologists in differentiating nonsquamous and squamous histology ranged from 77.0 to 94.2% (κ = 0.48-0.88) indicating a moderate to high level of agreement. CONCLUSION: The reasonably high agreement and kappa statistics for the included studies suggest that pathologists can reproducibly differentiate between nonsquamous and squamous NSCLC. This is clinically important in guiding oncologist decision making in choosing the most appropriate therapy for their patients.

Cost-effectiveness of using recombinant human thyroid-stimulating hormone before radioiodine ablation for thyroid cancer: the Canadian perspective.

OBJECTIVES: Radioiodine ablation for the treatment of thyroid cancer is traditionally performed after preparing patients by inducing hypothyroidism. Exogenous stimulation of thyroid-stimulating hormone (TSH) using recombinant human TSH (rhTSH) avoids hypothyroidism and hastens the clearance of radioiodine from the patient. These advantages are achieved without jeopardizing the success rate of remnant ablation. An economic analysis was performed to place the increased acquisition cost of rhTSH in the context of the health benefits achieved and the earlier discharge from radioprotection. METHODS: Markov modeling, using 17 individual weekly cycles, was used to assess the incremental cost per quality-adjusted life-year (QALY) associated with exogenous stimulation. Clinical inputs were largely sourced from a multicenter, randomized, controlled trial comparing remnant ablation success after either rhTSH or hypothyroid preparation. The model applied Canadian unit costs, taking a societal perspective. Additional costs associated with rhTSH were considered in the context of the clinical benefits and cost offsets. These included avoidance of hypothyroidism, increased work productivity, earlier administration of ablation after surgery, and earlier discharge from the radio-protective ward because of faster radioiodine clearance following rhTSH preparation. The model duration avoided the need for discounting. RESULTS: The additional benefits of rhTSH (0.0576 QALY) are obtained with an incremental cost of CDN$87, generating an incremental cost per QALY of CDN$1520. Deterministic one-way and two-way sensitivity analyses demonstrated the result to be robust. CONCLUSIONS: The use of rhTSH before radioiodine ablation represents a reasonable allocation of costs, with the benefits to patients, hospitals, and society as a whole, obtained at modest cost.

Extending an evidence hierarchy to include topics other than treatment: revising the Australian 'levels of evidence'.

BACKGROUND: In 1999 a four-level hierarchy of evidence was promoted by the National Health and Medical Research Council in Australia. The primary purpose of this hierarchy was to assist with clinical practice guideline development, although it was co-opted for use in systematic literature reviews and health technology assessments. In this hierarchy interventional study designs were ranked according to the likelihood that bias had been eliminated and thus it was not ideal to assess studies that addressed other types of clinical questions. This paper reports on the revision and extension of this evidence hierarchy to enable broader use within existing evidence assessment systems. METHODS: A working party identified and assessed empirical evidence, and used a commissioned review of existing evidence assessment schema, to support decision-making regarding revision of the hierarchy. The aim was to retain the existing evidence levels I-IV but increase their relevance for assessing the quality of individual diagnostic accuracy, prognostic, aetiologic and screening studies. Comprehensive public consultation was undertaken and the revised hierarchy was piloted by individual health technology assessment agencies and clinical practice guideline developers. After two and a half years, the hierarchy was again revised and commenced a further 18 month pilot period. RESULTS: A suitable framework was identified upon which to model the revision. Consistency was maintained in the hierarchy of "levels of evidence" across all types of clinical questions; empirical evidence was used to support the relationship between study design and ranking in the hierarchy wherever possible; and systematic reviews of lower level studies were themselves ascribed a ranking. The impact of ethics on the hierarchy of study designs was acknowledged in the framework, along with a consideration of how harms should be assessed. CONCLUSION: The revised evidence hierarchy is now widely used and provides a common standard against which to initially judge the likelihood of bias in individual studies evaluating interventional, diagnostic accuracy, prognostic, aetiologic or screening topics. Detailed quality appraisal of these individual studies, as well as grading of the body of evidence to answer each clinical, research or policy question, can then be undertaken as required.

Relationship between disease severity, quality of life and health-care resource use in a cross-section of Australian patients with Crohn's disease.

BACKGROUND AND AIM: New treatments for Crohn's disease are expensive and place economic strain upon health-care systems, and 'value-for-money' needs to be confirmed. This study aimed to correlate disease severity with health-related quality of life and with health-care resource use, to allow evaluation of the cost effectiveness of these treatments. METHODS: A cross-sectional, non-interventional, pharmacoeconomics study was performed with patients completing questionnaires comprising demographic, disease and health-care utilization questions, together with the disease-specific Inflammatory Bowel Disease Questionnaire (IBDQ) and the Assessment of Quality of Life (AQoL) multi-attribute utility instrument. The Crohn's Disease Activity Index (CDAI) was used to assess disease severity. RESULTS: 143 patients with a broad range of disease severity (CDAI 36-446, fistulae 23%) were recruited from referral centers. Stepwise regression analyses demonstrated a negative correlation between disease severity and both IBDQ and AQoL (both P < 0.0001). Age, gender and years since diagnosis did not impact upon either of the quality-of-life outcomes. Mean utility score for non-fistulizing patients with moderate-severe active disease (CDAI >/= 220) was 0.45, mild disease (CDAI 150-219) was 0.68 and for remission (CDAI < 150) was 0.77. Health-care resource utilization increased with increasing CDAI (P < 0.001), with hospital admissions being the largest component cost. Twenty-seven percent of patients (mean age 38 year) received a government benefit, 51% primarily due to their Crohn's disease. CONCLUSION: Crohn's disease severity correlates with poor quality of life. Utility scores determined will permit cost-utility analyses to be made in order to best allocate limited health resources.

Diagnosis of appendicitis in adults by ultrasonography or computed tomography: a systematic review and meta-analysis.

OBJECTIVES: The use of ultrasonography and computed tomography (CT) in the diagnosis of appendicitis in adult patients was compared. METHODS: Systematic review and meta-analysis of current evidence in two clinical situations: unselected nonpregnant, adult patients with symptoms of appendicitis, and more selective use in only those patients who still have an equivocal diagnosis subsequent to routine clinical investigations. RESULTS: Meta-analysis of eligible studies shows CT to have better sensitivity and specificity than ultrasound in both clinical situations. CONCLUSIONS: Application of these findings in clinical practice and/or policy would need to evaluate the better diagnostic performance of CT against its cost and availability. In addition, it is imperative that future studies be conducted in patient populations that are well-defined with respect to prior investigations. Sequelae of false-negative and false-positive diagnoses should also be evaluated.

Using recombinant human thyroid-stimulating hormone for the diagnosis of recurrent thyroid cancer.

BACKGROUND: Recombinant human thyroid-stimulating hormone (rhTSH) has been suggested as a diagnostic agent in the diagnosis of recurrent thyroid cancer, instead of the current practice of thyroid hormone (THT) withdrawal. METHODS: An evidenced-based literature review was used as the basis for a cost-utility, decision-analytic model. Outcome measures were safety, efficacy (diagnostic performance and quality of life) and cost effectiveness of rhTSH. RESULTS: The literature search identified six comparative studies of rhTSH versus THT withdrawal. The most common adverse events associated with the use of rhTSH were headache (3.5-11.1%) and nausea (7.7-17%). When used as a diagnostic agent, the unadjusted sensitivity and specificity for rhTSH were 87% and 95%, respectively. Thus the use of rhTSH instead of THT withdrawal would result in a reduction in diagnostic accuracy, with 11% of patients' disease status being misclassified. Use of rhTSH resulted in a higher quality of life in the period prior to diagnostic testing than THT withdrawal (P < 0.001). When the impact of diagnostic performance, patient compliance to follow-up and modified quality of life were modelled over a 5 year time-frame, the incremental cost per QALY of rhTSH relative to THT withdrawal was $51 344.42. CONCLUSIONS: The use of rhTSH as a diagnostic agent appears to be safe but less diagnostically accurate and less cost-effective (on whole of healthcare cost basis) when used in the follow-up of patients with thyroid cancer who have had a previous negative radioiodine scan after thyroid hormone withdrawal.

Discrete choice experiment to derive willingness to pay for methyl aminolevulinate photodynamic therapy versus simple excision surgery in basal cell carcinoma.

OBJECTIVES: This study aimed to determine willingness to pay (WTP) and preference for methyl aminolevulinate (MAL) photodynamic therapy compared with simple surgical excision for basal cell carcinoma (BCC). The relative preferences for individual features of the therapy were also determined. DESIGN: A discrete-choice experiment was conducted to ascertain WTP and relative preferences for treatment of BCC among the general population. SUBJECTS AND METHODS: Sixty members of the general public (34 men, 26 women; mean age 50 +/- 13 years) completed a written questionnaire. Participants indicated their preference between 12 pairs of scenarios representing BCC treatment. The paired scenarios comprised a fixed scenario representing current standard treatment (simple surgical excision) and an alternative scenario. Scenarios comprised five attributes: lesion response rate, risk of scarring, treatment description, possibility of infection and cost. Clinical attributes and levels were derived from clinical trial data. WTP values were in Australian dollars (A dollars, year 2001 values) and the study was conducted from the societal perspective. RESULTS: The probability that MAL photodynamic therapy with topical anaesthesia would be accepted in preference to current treatment was 0.879, if there was no cost differential. Total incremental WTP was 940 A dollars for MAL photodynamic therapy. The primary driver of total WTP was reduced risk of scarring, which contributed 554 A dollars, but treatment description and infection rate also made significant positive contributions. By contrast, the marginally higher lesion response rate with simple surgical excision (93%) compared with MAL photodynamic therapy (84%) did not significantly reduce WTP. Demographic factors had negligible influence upon the results. Sensitivity analyses indicated that incremental WTP for MAL photodynamic therapy was strongly influenced by the presence of anaesthetic. CONCLUSION: There appears to be a sizeable incremental WTP for MAL photodynamic therapy with anaesthetic for the treatment of BCC relative to simple surgical excision, and this is largely driven by better cosmetic outcomes.

Patient preference and willingness-to-pay for Humalog Mix25 relative to Humulin 30/70: a multicountry application of a discrete choice experiment.

OBJECTIVES: To assess preference and willingness-to-pay (WTP) for the insulin mixture Humalog Mix25 relative to Humulin 30/70, from the patients' perspective, the relative importance of individual treatment attributes was also determined. Differences among five European countries were investigated. METHODS: Two hundred and ninety patients with type 2 diabetes were recruited from five European countries. Of these, 235 were suitable for inclusion in the analysis. Their mean age was 51.3 years and, on average, patients had had diabetes for 11 years. A discrete-choice conjoint analysis was conducted using face-to-face interviews. Treatment attributes, such as timing of injections around meals, 2-hour postprandial control, effect of prandial dosing, frequency of nocturnal hypoglycemia, and cost, and levels were derived after a systematic review of all published comparative clinical trial data. Meta-analyses were undertaken where appropriate. RESULTS: Ninety percent (95% CI 86-93%) of patients would choose Humalog Mix25 over Humulin 30/70, at the same cost. On average, European subjects were willing to pay 111 euros per month more for Humalog Mix25 (95% CI 86.71-156.91 euros). The primary driver was the reduced risk of nocturnal hypoglycemic events, contributing 49% of WTP. The convenience of dosing immediately before the meal contributed 37%. Preference results were similar in all five countries, although WTP and sensitivity to increasing cost both varied. CONCLUSIONS: Patients in all countries showed a preference and WTP for Humalog Mix25 over Humulin 30/70. The main drivers of patient WTP may be of interest to pharmaceutical prescribers, manufacturers, and reimbursement agencies.

Community-acquired pneumonia mortality: a potential link to antibiotic prescribing trends in general practice.

BACKGROUND: Community prescribing of antibiotics has decreased substantially in the UK in recent years. We examine the association between pneumonia mortality and recent changes in community-based antibiotic prescribing for lower respiratory tract infections (LRTI). METHODS: Retrospective analysis of aggregated data for pneumonia mortality, influenza incidence, and antibiotic prescribing for LRTI in England and Wales during 12-week winter periods between 1993/94 and 1999/2000. RESULTS: Winter antibiotic prescribing for LRTI showed a 30.0% decline since 1995/96. Over the same period, there was a 50.6% increase in winter excess pneumonia mortality adjusted for influenza incidence. Negative binomial regression analysis showed that the incidence of influenza alone had a significant association with winter pneumonia mortality (P<0.001). The analysis also showed the reduction in antibiotic prescribing had a small but significant association with mortality (P<0.001), when simultaneously modelling for influenza incidence. CONCLUSIONS: Our findings suggest an association between recent reductions in antibiotic prescribing for LRTI in general practice and an increase in pneumonia mortality in England and Wales. This retrospective study of aggregate data represents the first attempt to assess the effect of limiting antibiotic prescribing on patient outcomes, and highlights the need to identify which patients benefit from antibiotic treatment for LRTI.

Effect of load during electrical stimulation training in spinal cord injury.

Electrical stimulation training is known to alter skeletal muscle characteristics after a spinal cord injury, but the effect of load on optimizing the training protocol has not been fully investigated. This study investigated two electrical-stimulation training regimes with different loads on intramuscular parameters of the paralyzed lower limbs. Six paraplegic individuals with a spinal cord injury underwent electrical stimulation training (45 min daily for 3 days per week for 10 weeks). One leg was trained statically with load, and the contralateral leg was trained dynamically with minimal load. Isometric force assessed with 35-HZ stimuli increased significantly in both legs from baseline, with the static-trained leg also being significantly higher than the dynamic-trained leg. The vastus lateralis muscle of the statically trained leg showed a significant increase in type I fibers, fiber cross-sectional area, capillary-to-fiber ratio, and citrate synthase activity when compared to both baseline and the dynamically trained leg. Relative oxygenation of the vastus lateralis muscle as determined by near infrared spectroscopy was also significantly greater after static training. This study indicates that the load that is applied to paralyzed muscle during an electrical stimulation training program is an important factor in determining the amount of muscle adaptation that can be achieved.