Hair regrowth treatment efficacy and resistance in androgenetic alopecia: A systematic review and continuous Bayesian network meta-analysis.

Background: Androgenetic alopecia (AGA) affects almost half the population, and several treatments intending to regenerate a normal scalp hair phenotype are used. This is the first study comparing treatment efficacy response and resistance using standardized continuous outcomes. Objective: To systematically compare the relative efficacy of treatments used for terminal hair (TH) regrowth in women and men with AGA. Methods: A systematic literature review was conducted (from inception to August 11, 2021) to identify randomized, Placebo-controlled trials with ≥ 20 patients and reporting changes in TH density after 24 weeks. Efficacy was analyzed by sex at 12 and 24 weeks using Bayesian network meta-analysis (B-NMA) and compared to frequentist and continuous outcomes profiles. Results: The search identified 2,314 unique articles. Ninety-eight were included for full-text review, and 17 articles met the inclusion criteria for data extraction and analyses. Eligible treatments included ALRV5XR, Dutasteride 0.5 mg/day, Finasteride 1 mg/day, low-level laser comb treatment (LLLT), Minoxidil 2% and 5%, Nutrafol, and Viviscal. At 24 weeks, the B-NMA regrowth efficacy in TH/cm2 and significance (**) in women were ALRV5XR: 30.09**, LLLT: 16.62**, Minoxidil 2%: 12.13**, Minoxidil 5%: 10.82**, and Nutrafol: 7.32**, and in men; ALRV5XR: 21.03**, LLLT: 18.75**, Dutasteride: 18.37**, Viviscal: 13.23, Minoxidil 5%: 13.13**, Finasteride: 12.38, and Minoxidil 2%: 10.54. Two distinct TH regrowth response profiles were found; Continuous: ALRV5XR regrowth rates were linear in men and accelerated in women; Resistant: after 12 weeks, LLLT, Nutrafol, and Viviscal regrowth rates attenuated while Dutasteride and Finasteride plateaued; Minoxidil 2% and 5% lost some regrowth. There were no statistical differences for the same treatment between women and men. B-NMA provided more accurate, statistically relevant, and conservative results than the frequentist-NMA. Conclusion: Some TH regrowth can be expected from most AGA treatments with less variability in women than men. Responses to drug treatments were rapid, showing strong early efficacy followed by the greatest resistance effects from flatlining to loss of regrowth after 12-16 weeks. Finasteride, Minoxidil 2% and Viviscal in men were not statistically different from Placebo. LLLT appeared more efficacious than pharmaceuticals. The natural product formulation ALRV5XR showed better efficacy in all tested parameters without signs of treatment resistance (see Graphical abstract). Systematic review registration: www.crd.york.ac.uk/PROSPERO/display_record.asp?ID=CRD42021268040, identifier CRD42021268040.

Safety and efficacy of ALRV5XR in men with androgenetic alopecia: A randomised, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Androgenetic alopecia (AGA) is the most common hair loss disorder seen in men. It can have an early onset but has also been associated with ageing and senescence. It often induces pronounced psychological impact. ALRV5XR, a new hair loss treatment herein evaluated, was designed to target multiple molecular pathways involved in hair growth and hair follicle stem cell biology. The main objectives of the study were the assessment of safety and efficacy profiles of ALRV5XR in men. METHODS: This 24-week, parallel randomised, placebo-controlled, double-blinded clinical trial was performed in a USA community clinic. Healthy men (age 22-65) with AGA and belonging to the Hamilton-Norwood (HN) classification I-VII and Fitzpatrick skin type (FST) I-VI, were randomly allocated in a 1:1 ratio into ALRV5XR or placebo treatment groups. Dermatologist assessment, phototrichograms, and blood samples were obtained in a blinded fashion at baseline, 12 and 24 weeks. Subjects were given a masked treatment consisting of oral capsules, shampoo, conditioner, and follicle serum, which was intended for daily use. Efficacy was assessed via absolute and per cent changes in terminal hair (TH) density, and response rates. The trial was registered with clinicaltrials.gov (NCT04450589) and is completed. FINDINGS: Forty-six subjects were enroled in the study, 23 allocated to the ALRV5XR treatment and 23 to the placebo group. Enrolment occurred from April 11 to October 23, 2018. Thirty-six subjects completed the trial (17 ALRV5XR, 19 placebo) and 11 subjects in each group were evaluable for TH outcomes. At 24 weeks, the absolute change in TH density improved by 21·0 THs/cm2 (95% CI: 9·2-32·8; p = 0·0014), and the relative density increased by 16·4% (95% CI: 7·4%-25·5%; p = 0·0012). The odds ratio for being a responder (≥ 0 change) was 87·4. TH density increased linearly and was not affected by HN, FST, ethnicity, age, or body mass index. All subjects in the ALRV5XR group responded to treatment while 81·8% of the placebo group decreased TH density. ALRV5XR induced statistically significant changes in both decrease in vellus hair (VH) density as well as in concomitant increase of the TH/VH ratio when compared to placebo. ALRV5XR was well tolerated, and no adverse events were observed. INTERPRETATION: ALRV5XR treatment resulted in clinically significant TH regrowth in men with AGA. Furthermore, it appeared to reverse the characteristic hair miniaturisation seen in this condition. When compared to results of published trials of standard therapy, ALRV5XR showed a multi-fold increase both in efficacy and in response rates. In addition, the continuance of TH regrowth from 12 to 24 weeks suggests that the normal structure and function of non-productive telogen follicles is restored and that a normal hair phenotype may be attained by extended ALRV5XR treatment. FUNDING: Arbor Life Labs.

Safety and efficacy of ALRV5XR in women with androgenetic alopecia or telogen effluvium: A randomised, double-blinded, placebo-controlled clinical trial.

BACKGROUND: Scalp hair loss (alopecia) in women is a common ageing and senescing condition. It usually presents as androgenetic alopecia (AGA) or telogen effluvium (TE) and often has pronounced psychological consequences. ALRV5XR is a novel treatment aiming to regenerate a normal hair phenotype by targeting multiple molecular pathways linked to hair growth promotion and hair follicle stem cell activation. The primary objectives of this 24-week trial were to evaluate the safety and efficacy of ALRV5XR in terminal hair (TH) regrowth in women with AGA or TE. METHODS: This randomised, double-blind, placebo-controlled trial was performed in a USA community clinic. Healthy women 18-65 years of age with AGA or TE of Ludwig classification I-II and Fitzpatrick skin type I-VI were enrolled. They were allocated in a 1:1 ratio into ALRV5XR or placebo treatment groups using a random number table. Masked dermatologist assessments, phototrichograms and blood samples were obtained at baseline, 12 and 24 weeks. Subjects were given a masked treatment regimen of oral capsules, shampoo, conditioner and follicle serum for daily administration. Main outcomes were absolute and per cent changes in TH density and response rates. The trial was registered with clinicaltrials.gov (NCT04450602) and is completed. FINDINGS: 46 subjects (23 ALRV5XR, 23 placebo) were enrolled between April 3 and October 20, 2018. Five subjects dropped out and two were non-compliant. Thirty-nine subjects completed the trial (18 ALRV5XR, 21 placebo). At 24 weeks, the absolute change in TH density improved by 30·1THs/cm2 (95% CI: 15·1-45·1; p=0·0002), and the relative density increased by 19·7% (95% CI: 8·0%-31·4%; p=0·0016). The odds ratio for being a responder (≥0 change) was 2·7. Efficacy increased 133% from week 12 to 24. Efficacy outcomes were similar in AGA and TE subjects. 66·7% of the ALRV5XR group responded by regrowing 40THs/cm2 or more hair. No adverse events were reported. INTERPRETATION: In women with AGA or TE, ALRV5XR treatment significantly increased hair regrowth without adverse events. ALRV5XR displayed a multi-fold improved efficacy and response rate when compared to published trials of standard therapy. Progressive acceleration of TH regrowth suggests regeneration of the structure and function of non-productive telogen follicles and prolonged treatment may restore a normal hair phenotype.

Safety Profile and Costs of Related Adverse Events of Trastuzumab Emtansine for the Treatment of HER2-Positive Locally Advanced or Metastatic Breast Cancer Compared to Capecitabine Plus Lapatinib from the Perspective of the Canadian Health-Care System.

BACKGROUND AND OBJECTIVES: Trastuzumab emtansine (T-DM1, KADCYLA(®)) is an antibody-drug conjugate comprised of the cytotoxic agent DM1 and trastuzumab (HERCEPTIN(®)). The safety profile of T-DM1 in human epidermal growth factor receptor 2 (HER2)-positive locally advanced or metastatic breast cancer previously treated with trastuzumab and a taxane was investigated in the phase III EMILIA trial. The trial demonstrated clinically and statistically meaningful differences in the safety profile between T-DM1 and capecitabine plus lapatinib (CAP + LAP). The objective of this study was to estimate the costs of managing treatment-related grade ≥ 3 adverse events (AEs) that occurred in ≥ 2% of patients and grade 2 AEs that occurred in ≥ 5% of patients taking T-DM1 compared with patients taking CAP + LAP based on the EMILIA trial, from the perspective of Canadian public payers. METHODS: An Excel-based model was utilized to estimate the relevant costs. Clinical data were obtained from the EMILIA trial. Cost information was obtained from the literature, clinical experts, and standard cost sources. The analysis was conducted from the Canadian public-payer perspective and reported in 2014 Canadian dollars (CAD). RESULTS: The management of included treatment-related AEs resulted in higher estimated per-patient costs of CAD6901 for CAP + LAP versus CAD3380 for T-DM1, resulting in savings of CAD3521. CONCLUSIONS: From a Canadian perspective, this analysis demonstrated that utilizing T-DM1 for the management of HER2-positive metastatic breast cancer results in substantial savings to the public health-care system when considering the costs of treatment-related AEs, due to fewer amount of toxicities compared with CAP + LAP. Results of various sensitivity analyses investigating changes in number and costs of AEs confirmed the findings; however, the magnitude of cost savings varied. Further analyses are necessary to determine whether these cost savings would occur in other countries and health-care systems.

Pharmacoeconomics of depot antipsychotics for treating chronic schizophrenia in Sweden.

AIMS: To determine the cost-effectiveness of long-acting injectable (LAI) antipsychotics for chronic schizophrenia in Sweden. METHODS: A 1-year decision tree was developed for Sweden using published data and expert opinion. Five treatment strategies lasting 1 year were compared: paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), risperidone (RIS-LAI), haloperidol decanoate (HAL-LAI) and olanzapine tablets (oral-OLZ). Patients intolerant/failing drugs switched to another depot; subsequent failures received clozapine. Resources and employment time lost (indirect costs) were costed in 2011 Swedish kroner (SEK), from standard government lists. The model calculated the average cost/patient and quality-adjusted life-years (QALYs), which were combined into incremental cost-effectiveness ratios. Multivariate and 1-way sensitivity analyses tested model stability. RESULTS: PP-LAI followed by OLZ-LAI had the lowest cost/patient (189,696 SEK) and highest QALYs (0.817), dominating in the base case. OLZ-LAI followed by PP-LAI cost 229,775 SEK (0.812 QALY), RIS-LAI followed by HAL-LAI cost 221,062 SEK (0.804 QALY), HAL-LAI followed by oral-OLZ cost 243,411 SEK (0.776 QALY), and oral-OLZ followed by HAL-LAI cost 249,422 SEK (0.773 QALY). The greatest proportions of costs (52.5-83.8%) were for institutional care; indirect costs were minor (2.4-3.8%). RESULTS were sensitive to adherence and hospitalization rates, but not drug cost. PP-LAI followed by OLZ-LAI dominated OLZ-LAI followed by PP-LAI in 59.4% of simulations, RIS-LAI followed by HAL-LAI in 65.8%, HAL-LAI followed by oral-OLZ in 94.0% and oral-OLZ followed by HAL-LAI in 95.9%; PP-LAI followed by OLZ-LAI was dominated in 1.1% of the 40,000 iterations. CONCLUSION: PP-LAI followed by OLZ-LAI was cost-effective in Sweden for chronic schizophrenia and cost-saving overall to the healthcare system.

Economic burden of nausea and vomiting of pregnancy in the USA.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) is the most common medical condition during gestation, affecting 50%-90% of women during their first trimester, and many in the second and third trimester. NVP affects women's quality of life and exerts a large economic impact on patients, caregivers and society. OBJECTIVES: To estimate the overall economic burden of illness of NVP in the USA. METHODS: A spreadsheet model was utilized to estimate this burden including direct and indirect costs. Costs are reported in 2012 US dollars and were estimated from the perspective of society. Cost centers included drug treatments for mild to severe NVP and hospitalizations for hyperemesis gravidarum (HG), as well as time lost from work and caregiver time. Clinical, epidemiologic, and economic data were obtained from the literature to populate the model. Rates of drug use were multiplied by unit costs and summed. RESULTS: The estimated total economic burden in 2012 in the USA was $1,778,473,782 which included $1,062,847,276 (60%) in direct costs and $715,626,506 (40%) in indirect costs. Overall, the average cost to manage one woman for NVP was $1827. Costs increased with increasing severity of NVP. The estimates were conservative, as not all applicable costs could be included. CONCLUSIONS: NVP results in a significant economic impact, and hence effective therapy should be sought. Future prospective research should determine in more detail what resources are utilized in the USA to manage women with NVP.

Prevalence of nausea and vomiting of pregnancy in the USA: a meta analysis.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) is the most common medical condition during gestation, carrying tremendous health burden, especially for the severe form, hyperemesis gravidarum (HG). The rates of NVP in the USA have not been systematically calculated. OBJECTIVES: To estimate the rates of NVP and HG in the USA. METHODS: A meta-analysis was conducted of all peer-reviewed articles from the USA that provided rates of NVP in early or late pregnancy or HG. Medline, Embase and Cochrane databases were searched from inception through November 2012; reviews and articles were hand searched. Rates were combined across studies using a random effects model. RESULTS: Forty-eight articles were identified; 15 were rejected and 33 were included for analysis. Twenty-three studies of 67,602 women provided rates of NVP which had a meta-analytic rate of 68.6% (CI95%:64.4%-72.8%). Three of them (N=5034) reported nausea without vomiting in 28.6% and two studies (N=136) produced a rate for NVP during late pregnancy of 24.0%. HG occurred in 1.2% of the 2.1 million women in 12 studies. CONCLUSIONS: We have summarized rates of NVP and HG, which are similar to those found in other parts of the world. Almost 70% of women suffer some form of the syndrome; 1.2% have the severe form, most of whom were hospitalized because of the HG. Future research should address issues of cost and resource utilization.

Quantifying the global rates of nausea and vomiting of pregnancy: a meta analysis.

BACKGROUND: Nausea and vomiting of pregnancy (NVP) is the most common medical condition in pregnancy, affecting women worldwide. It is unclear whether its prevalence and severity NVP are variable across different nations and races. PURPOSE: To summarize global rates of NVP as reported in the literature using meta-analysis. METHODS: We searched Medline, Embase and Cochrane databases for all peer-reviewed articles reporting rates of NVP and/or hyperemesis gravidarum (HG). No restrictions were imposed on publication year or language. Numbers of women, studies and NVP rates were extracted and aggregated using a random effects model. Outcomes included: overall rates (i.e., women suffering any nausea or vomiting or both) in early and in late pregnancy, rates of nausea only, symptom severity, and HG rates. RESULTS: We identified 116 studies, rejecting 37 and accepting 79, of which 59 provided data for NVP (N=93,753 in 13 countries) and 26 for HG (N= 6,155,578). All developed regions of the world were represented (2 studies from Africa, 1 India; none from Latin America). Reported NVP rates varied from 35%-91% (median 69%); the meta-analytic average rate was 69.4% (CI95%:66.5%-72.3%). Among pregnant women, 32.7% had nausea without vomiting and 23.5% overall had NVP continuing into the third trimester. NVP was rated as mild in 40%, moderate in 46% and severe in 14% of cases. The prevalence of HG was 1.1% (CI95%:0.8%-1.3%), with a range of 0.3%-3.6%. CONCLUSIONS: Almost 70% of women worldwide experience NVP, but reported rates vary widely. HG, the most severe form, affects 1.1%.

Cost-effectiveness analysis of atypical long-acting antipsychotics for treating chronic schizophrenia in Finland.

OBJECTIVE: In Finland, regional rates of schizophrenia exceed those in most countries, impacting the healthcare burden. This study determined the cost-effectiveness of long-acting antipsychotic (LAI) drugs paliperidone palmitate (PP-LAI), olanzapine pamoate (OLZ-LAI), and risperidone (RIS-LAI) for chronic schizophrenia. METHOD: This study adapted a decision tree analysis from Norway for the Finnish National Health Service. Country-specific data were sought from the literature and public documents, guided by clinical experts. Costs of health services and products were retrieved from literature sources and current price lists. This simulation study estimated average 1-year costs for treating patients with each LAI, average remission days, rates of hospitalization and emergency room visits and quality-adjusted life-years (QALY). RESULTS: PP-LAI was dominant. Its estimated annual average cost was €10,380/patient and was associated with 0.817 QALY; OLZ-LAI cost €12,145 with 0.810 QALY; RIS-LAI cost €12,074 with 0.809 QALY. PP-LAI had the lowest rates of hospitalization, emergency room visits, and relapse days. This analysis was robust against most variations in input values except adherence rates. PP-LAI was dominant over OLZ-LAI and RIS-LAI in 77.8% and 85.9% of simulations, respectively. Limitations include the 1-year time horizon (as opposed to lifetime costs), omission of the costs of adverse events, and the assumption of universal accessibility. CONCLUSION: In Finland, PP-LAI dominated the other LAIs as it was associated with a lower cost and better clinical outcomes.

Pharmacoeconomic analysis of paliperidone palmitate versus olanzapine pamoate for chronic schizophrenia in Norway.

OBJECTIVE: Paliperidone palmitate long-acting injection (PP-LAI) has recently been approved for treatment of chronic schizophrenia. Its cost-effectiveness has not been established. The objective was to compare direct costs and outcomes between PP-LAI and olanzapine pamoate (OLZ-LAI) in treating chronic schizophrenia in Norway from the perspective of the government payer. METHODS: We used a decision analytic model over a 1-year time horizon. Clinical inputs were derived from the literature and an expert panel; costs were taken from standard lists, adjusted to 2010 Norwegian kroner (NOK). Discounting was not done. Main outcomes included average cost per patient treated, hospitalisations, emergency room (ER) visits and quality-adjusted life years (QALYs). The pharmacoeconomic outcome was the incremental cost per QALY. Robustness was examined using one-way sensitivity analyses on critical variables and a 5000-iteration probabilistic Monte Carlo sensitivity analysis with all variables included. RESULTS: PP-LAI generated 0.845 QALY at a cost of 151 336 NOK of which 23% was due to drugs; 25% of patients were hospitalised and another 12% required ER visits. OLZ-LAI cost 174 351 NOK (21% due to drugs); patient outcomes included 0.844 QALY, 27% hospitalisations and 14% ER visits. PP-LAI dominated OLZ-LAI in the base case. The analysis was reasonably robust against variations in drug cost but sensitive to small changes in adherence and hospitalisation rates. Overall, PP-LAI was dominant over OLZ-LAI in 54.5% of simulations. Replacing OLZ-LAI with PP-LAI would be cost saving for the Norwegian healthcare system. CONCLUSION: PP-LAI was cost-effective compared with OLZ-LAI in treating patients with chronic schizophrenia in Norway but sensitive to changes in adherence and hospitalisation rates.

Pharmacoeconomic analysis of paliperidone palmitate for treating schizophrenia in Greece.

BACKGROUND: Patients having chronic schizophrenia with frequent relapses and hospitalizations represent a great challenge, both clinically and financially. Risperidone long-acting injection (RIS-LAI) has been the main LAI atypical antipsychotic treatment in Greece. Paliperidone palmitate (PP-LAI) has recently been approved. It is dosed monthly, as opposed to biweekly for RIS-LAI, but such advantages have not yet been analysed in terms of economic evaluation. PURPOSE: To compare costs and outcomes of PP-LAI versus RIS-LAI in Greece. METHODS: A cost-utility analysis was performed using a previously validated decision tree to model clinical pathways and costs over 1 year for stable patients started on either medication. Rates were taken from the literature. A local expert panel provided feedback on treatment patterns. All direct costs incurred by the national healthcare system were obtained from the literature and standard price lists; all were inflated to 2011 costs. Patient outcomes analyzed included average days with stable disease, numbers of hospitalizations, emergency room visits, and quality-adjusted life-years (QALYs). RESULTS: The total annual healthcare cost with PP-LAI was €3529; patients experienced 325 days in remission and 0.840 QALY; 28% were hospitalized and 15% received emergency room treatment. With RIS-LAI, the cost was €3695, patients experienced 318.6 days in remission and 0.815 QALY; 33% were hospitalized and 17% received emergency room treatment. Thus, PP-LAI dominated RIS-LAI. Results were generally robust in sensitivity analyses with PP-LAI dominating in 74.6% of simulations. Results were sensitive to the price of PP-LAI. CONCLUSIONS: PP-LAI appears to be a cost-effective option for treating chronic schizophrenia in Greece compared with RIS-LAI since it results in savings to the health care system along with better patient outcomes.

The STARRT trial: a cost comparison of optimal vs sub-optimal initiation of dialysis in Canada.

BACKGROUND: Sub-optimal transitioning of patients from chronic kidney disease (CKD) to end stage renal disease (ESRD) may result in poor clinical outcomes and increased healthcare costs. The objectives of this study were to estimate the average total cost per patient who requires initiation of renal replacement therapy (RRT) stratified by status at initiation; optimal (RRT initiation as an outpatient with an arterio-venous [AV] Fistula, Graft or Peritoneal Dialysis [PD] catheter), and sub-optimal (RRT initiation as an inpatient and/or via central venous catheter [CVC]). METHODS: Data from the Study To Assess Renal Replacement Therapy (STARRT), a Canadian, multi-centre, 6 month retrolective study (n = 339), were used for this analysis. Unit costs for resources were obtained from participating hospitals, the literature, and/or standard costing sources. The analysis was performed from the perspective of healthcare payors and reported in 2011 Canadian Dollars (CAD). A propensity score technique was applied to control for potential confounders between the two groups. RESULTS: Two hundred of the eligible patients for analysis (61.9%) were sub-optimally and 123 (38.1%) were optimally prepared. For this analysis, 106 "matched" pairs were used. The average total cost per patient was estimated to be $63,225 (with a 95% CI ranging from $58,663-$67,958) for the sub-optimally initiated patients, and $39,260 (with a 95% CI ranging from $35,683-$43,007) for the optimally initiated patients (p < 0.001). LIMITATIONS: Costs were calculated utilizing a conservative approach, using the cheapest available prices for medications and other resources. Assumptions had to be made for the costing of dialyses. CONCLUSION: The results of this study indicate, after adjusting for potential confounders, that optimally initiated patients for RRT have significantly lower healthcare-associated costs compared to sub-optimally initiated patients.

Willingness to pay for a treatment for pain in multiple sclerosis.

BACKGROUND: Multiple sclerosis (MS) is a chronic neurological disease that affects 240 per 100 000 Canadians. Of these patients, 10-80% (average 70%) experience pain. Sativex is a cannabis-based drug recently approved for neuropathic pain. OBJECTIVES: In this study, we determine individuals' preferences between two treatment options as well as the willingness to pay (WTP) for Sativex, expressed as the amount they would pay in insurance premiums to have access to that treatment. METHODS: The WTP instrument comprised a decision board as a visual aid, and a questionnaire. A decision board helps clinicians standardize the presentation of treatment information. In this study, the decision board described two treatment options: a three-drug combination (gabapentin, amytriptyline, acetaminophen [paracetamol] {i.e. pills}) and the three-drug combination plus Sativex (i.e. 'pills and oral spray'). Information on efficacy and adverse effects was taken from trial data; wording was guided by a panel of neurologists and tested for clarity on lay people. The instrument was administered to 500 participants from Canada's general population using the bidding game approach. Descriptive statistics were calculated. RESULTS: Mean (SD) age of participants was 39 (13) years, with a female : male distribution of 56 : 44. The decision board was presented in both English (85%) and French (15%). Of 500 interviewees, 253 (50.6%) chose the 'pills and oral spray'. Mean monthly WTP for the insurance premium for those who chose the 'pills and oral spray' was Can dollars 8 (SD +/- 15, median 4, range 0-200). CONCLUSIONS: Assuming that 51% of the general population are willing to pay additional premiums as reported in this study, the premiums collected would cover the cost of Sativex for all Canadian MS patients experiencing pain, with a surplus.

Pain due to multiple sclerosis: analysis of the prevalence and economic burden in Canada.

BACKGROUND: Multiple sclerosis (MS) is a neurological disease affecting approximately 50,000 Canadians. Although studies have described overall MS costs, none have focused specifically on MS-related pain. OBJECTIVES: To estimate the prevalence of MS-related pain in Canada, the proportion of patients treated and responding to treatment for MS-related pain, and the associated economic burden. METHODS: Results were captured through physician and patient surveys. Patients were recruited through MS clinics and the MS Society. Patient-reported outcomes and resource utilization over the previous six months were collected by telephone interview. Costs were measured in 2004 Canadian dollars. The economic burden was extrapolated to the population using national demographics and prevalence. Spearman's rho assessed the relationship between cost and pain severity. RESULTS: Physicians estimated that 46% of their MS patients experienced MS-related pain, and that 35% received treatment for pain. Pain was reported to be relieved somewhat in 29%+/-10% of their patients, adequately in 26%+/-19% and poorly in 27%+/-13%, while 17%+/-9% received no relief. Two hundred ninety-seven participants completed the patient survey. Seventy-one per cent (211 of 297 patients) experienced MS-related pain. Eighty per cent of patients reported taking some type of medication to manage their pain, and of these, 82% reported some reduction in pain. The mean +/- SD direct cost per patient of MS-related pain was dollars 2,528+/-5,695. The mean +/- SD indirect cost per patient was dollars 669+/-875. Total costs were positively correlated with levels of self-reported pain (rho=0.291, rho<0.0001). The estimated six-month burden of pain of MS patients in Canada was dollars 79,444,888. CONCLUSIONS: The prevalence of pain is high in MS patients. This condition may be underdiagnosed and undertreated, and results in a significant economic burden on society.

The weekly cost of nausea and vomiting of pregnancy for women calling the Toronto Motherisk Program.

BACKGROUND: Nausea with or without vomiting of pregnancy (NVP) is the most common medical condition in pregnancy. NVP, even with mild symptoms, is associated with costs to society, patients, and the health care system. OBJECTIVE: The main objective of this study was to estimate the total direct and indirect costs per woman-week associated with the onset of NVP in Canada from the perspective of society. METHODS: A cost of illness study was performed to estimate the cost per woman-week associated with the onset of NVP in Canada, stratified according to the severity of NVP. Data were collected from 139 pregnant women, who called the Motherisk Program at the Hospital for Sick Children in Toronto. Results are reported in 2005 Canadian dollars. RESULTS: From the perspective of society, the total cost per woman-week was $132 ($114 indirect and $18 direct costs), $355 ($271 indirect and $84 direct costs), and $653 ($494 indirect and $159 direct costs) for women with mild, moderate, and severe NVP, respectively. Costs increased with increasing severity of NVP. CONCLUSIONS: Nausea and vomiting of pregnancy imposes an economic burden, particularly with respect to productivity losses. Limitations of the study could be potential recall bias, the unavailability of household income and follow-up interviews.

Meta-analysis of cannabis based treatments for neuropathic and multiple sclerosis-related pain.

OBJECTIVE: Debilitating pain, occurring in 50-70% of multiple sclerosis (MS) patients, is poorly understood and infrequently studied. We summarized efficacy and safety data of cannabinoid-based drugs for neuropathic pain. DATA SOURCES: Studies were identified from Medline, Embase, and Cochrane databases; Bayer Healthcare provided additional trials. STUDY SELECTION: Accepted were randomized, double-blinded placebo-controlled trials of cannabinoid-based treatments for MS-related/neuropathic pain in adults > or = 18 years of age. DATA EXTRACTION: Two reviewers identified studies and extracted data; a third adjudicated disagreements. Data included baseline and endpoint pain scores on visual analog or 11-point ordinal scales. DATA SYNTHESIS: Of 18 articles and three randomized controlled trial (RCT) reports identified, 12 articles and two reports were rejected (9 = inappropriate disease or outcome, 1 = duplicate, 1 = review, and 1 = abstract); six accepted articles and one RCT-report involved 298 patients (222 treated, 76 placebo); four examined Sativex (a cannabidiol/delta-9-tetrahydrocannabinol (THC) buccal spray) (observations = 196), five cannabidiol (n = 41), and three dronabinol (n = 91). Homogeneity chi(2) values were non-significant, allowing data combination. Analyses focused on baseline-endpoint score differences. The cannabidiol/THC buccal spray decreased pain 1.7 +/- 0.7 points (p = 0.018), cannabidiol 1.5 +/- 0.7 (p = 0.044), dronabinol 1.5 +/- 0.6 (p = 0.013), and all cannabinoids pooled together 1.6 +/- 0.4 (p < 0.001). Placebo baseline-endpoint scores did not differ (0.8 +/- 0.4 points, p = 0.023). At endpoint, cannabinoids were superior to placebo by 0.8 +/- 0.3 points (p = 0.029). Dizziness was the most commonly observed adverse event in the cannabidiol/THC buccal spray arms (39 +/- 16%), across all cannabinoid treatments (32.5 +/- 16%) as well as in the placebo arms (10 +/- 4%). CONCLUSION: Cannabinoids including the cannabidiol/THC buccal spray are effective in treating neuropathic pain in MS. LIMITATIONS: This review was based on a small number of trials and patients. Pain related to MS was assumed to be similar to neuropathic pain.

Economic evaluation of ondansetron vs dimenhydrinate for prevention of postoperative vomiting in children undergoing strabismus surgery.

BACKGROUND: Although rarely life-threatening, postoperative vomiting (POV) is a distressing complication. The incidence of POV ranges from 34 to 90% in children undergoing strabismus surgery when antiemetics are not administered prophylactically. METHODS: In this study, a cost-consequence analysis (CCA) is used to estimate the economic benefit of ondansetron and dimenhydrinate as antiemetics administered prophylactically in children undergoing strabismus surgery. This retrospective study was conducted at The Hospital for Sick Children based on a review of 70 charts. RESULTS: Ondansetron was more effective with 45.3 POV-free patients (PFP) in an adjusted cohort of 100, while dimenhydrinate resulted in 38.2 PFP in an adjusted cohort of 100. The costs were significantly different between the two groups, CAD dollars 185.90 (+/-26.37, 95% CI, CAD dollars 173,89; CAD dollars 197.90) and CAD dollars 232.90 (+/-CAD dollars 66.84, 95% CI, CAD dollars 198.53; CAD dollars 267.27) per patient for ondansetron and dimenhydrinate, respectively. The length of stay in the postanesthetic care unit (PACU) represented over 97% of total costs, and the mean lengths of stay in the PACU for ondansetron and dimenhydrinate were significantly different, 3.43 and 4.41 h, respectively. CONCLUSION: This study should serve as a pilot for a large-scale investigation on the correlation between the length of stay in the PACU and the antiemetic agent used.

Topical calcineurin inhibitors in the treatment of atopic dermatitis: a meta-analysis of current evidence.

PURPOSE: To summarize success rates of the topical calcineurin inhibitors tacrolimus and pimecrolimus in treating atopic dermatitis. METHODS: Randomized controlled trials (RCTs) comparing either drug to themselves (i.e. dose-ranging studies), each other, the vehicle (or placebo), or corticosteroids were obtained from Medline, EMBASE, and Cochrane databases. Two reviewers identified studies and extracted data, a third reviewer adjudicated disagreements. Outcomes included success, as defined by 90%, 75%, or 50% reductions from baseline in Eczema Area and Severity Index (EASI) scores or equivalent at 1, 3, 6, and 12 months, and also the difference between drug and vehicle (placebo). Rates were combined using a random effects meta-analytic model. RESULTS: Of 180 articles identified, 165 were rejected (142 not RCTs/inappropriate outcome, 23 inappropriate/unextractable data). We included 15 articles reporting on 16 trials (nine tacrolimus and seven pimecrolimus trials) involving a total of 5301 patients, of whom 2107 received tacrolimus, 1225 received pimecrolimus and 1969 patients were controls. Tacrolimus reduced EASI scores by 65.6% at 1 month and 73.0% at 3 months; pimecrolimus reduced scores by 61.5% at 1 month, 60.3% at 6 months, and 61.9% at 12 months. When the difference in EASI score reductions were compared between active drug and placebo, tacrolimus success was 51.5% above placebo at 1 month and pimecrolimus was 45.9% higher at 1 month, 24.9% at 6 months, and 16.1% at 12 months. CONCLUSIONS: Success rates for tacrolimus and pimecrolimus were statistically similar. However, tacrolimus rates were consistently higher numerically than those for pimecrolimus, and tacrolimus was used in patients with more severe disease. A head-to-head RCT is required to determine if true differences exist between these drugs.