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1.

Objective

To determine the socio-demographic and health factors associated with a biomedical phenotype of successful aging (SA) among Mexican community-dwelling elderly.

Design, setting and participants

Cross-sectional study of 935 older adults aged 70 or older participating in the Mexican Study of Nutritional and Psychosocial Markers of Frailty.

Measurements

SA was operationalized in accordance with the phenotype proposed by Rowe and Kahn. Univariate and multivariate logistic regression analyses were carried out in order to identify the correlates of SA.

Results

The phenotype of SA was present in 10% of participants. Age (P < 0.001), illiteracy (P = 0.021), polypharmacy (P < 0.001), and physical pain (P < 0.001) were factors independently and inversely associated with the presence of the SA phenotype. The only variable positively associated with SA was good self-perceived health-status (P < 0.001).

Conclusion

Although age is not modifiable, several other factors associated with SA are. If we are to promote SA, efforts should be made towards improving those modifiable factors negatively associated with its presence, such as pain or polypharmacy. Also, enhancing factors positively associated to it might play a role in improving wellbeing.
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2.

Background

Hepatitis C virus (HCV) is a major health issue worldwide. New generation of direct-active antiviral medications is an epoch-making turning point in the management of HCV infections.

Objective

Conducing a cost-effectiveness analysis comparing the combination of elbasvir/grazoprevir and sofosbuvir?+?pegylated interferon/ribavirin for the management of all HCV patients (even those in the initial stages of fibrosis).

Methods

A Markov model was built on the natural history of the disease to assess the efficacy of the alternatives. The outcomes are expressed in terms of quality adjusted life-years (QALYs) and result in terms of incremental cost-effectiveness ratio).

Results

Elbasvir/grazoprevir implies an expenditure of €21,104,253.74 with a gain of 19,287.90 QALYs and sofosbuvir?+?pegylated interferon/ribavirin implies an expenditure of €31,904,410.11 with a gain of 18,855.96 QALYs. Elbasvir/grazoprevir is thus a dominant strategy.

Conclusion

Consideration should be given to the opportunity cost of not treating patients with a lower degree of fibrosis (F0–F2).
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3.

Objectives

There is increasing attention for dietary patterns as a potential strategy to prevent cognitive decline. We examined the association between adherence to a recently developed Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) diet with cognitive function and cognitive decline, taking into account the interaction between the apolipoprotein E ε4 genotype and the MIND diet.

Design

Population-based prospective cohort study.

Participants

A total of 16,058 older women aged 70 and over from the Nurses’ Health Study.

Measurements

Dietary intake was assessed five times between 1984 and 1998 with a 116-item Food Frequency Questionnaire. The MIND score includes ten brain-healthy foods and five unhealthy foods. Cognition was assessed four times by telephone from 1995 to 2001 (baseline) with the Telephone Interview for Cognitive Status (TICS) and by calculating composite scores of verbal memory and global cognition. Linear regression modelling and linear mixed modelling were used to examine the associations of adherence to the MIND diet with average cognitive function and cognitive change over six years, respectively.

Results

Greater long-term adherence to the MIND diet was associated with a better verbal memory score (multivariable-adjusted mean differences between extreme MIND quintiles=0.04 (95%CI 0.01-0.07), p-trend=0.006), but not with cognitive decline over 6 years in global cognition, verbal memory or TICS.

Conclusion

Long-term adherence to the MIND diet was moderately associated with better verbal memory in later life. Future studies should address this association within populations at greater risk of cognitive decline.
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4.

Objective

The aim of the study was to investigate the outcome of change in body weight associated with use of a structured preventive care process among persons with dementia assessed as at risk of malnutrition or malnourished. The preventive care process is a pedagogical model used in the Senior Alert (SA) quality register, where nutrition is one of the prioritized areas and includes four steps: assessment, analysis of underlying causes, actions performed and outcome.

Design

An analysis of data from SA with a pre-post design was performed.

Setting

The participants were living in ordinary housing or special housing in Sweden.

Participants

1912 persons, 65 years and older, registered in both SA and the dementia quality register Svedem were included.

Intervention

A national preventive care program including individualized actions.

Measurements

The Mini Nutritional Assessment-Short Form was used to assess nutritional status at baseline. Body weight was measured during baseline and follow-up (7-106 days after baseline).

Results

74.3% persons were malnourished or at risk of malnutrition. Those at risk of malnutrition or malnourished who were registered in all four steps of the preventive care process, increased in body weight from baseline (Md 60.0 kg) to follow-up (Md 62.0 kg) (p=0.013). In those with incomplete registration no increase in body weight was found.

Conclusion

Using all steps in the structured preventive care process seems to improve nutritional status of persons with dementia assessed as at risk of malnutrition or malnourished. This study contributes to the development of evidence-based practice regarding malnutrition and persons with dementia.
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5.

Purpose

The question of whether orthotopic neobladder (ONB) reconstruction is superior to ileal conduit diversion (ICD) with respect to health-related quality of life (HRQoL) remains controversial. The goal of this study is to perform a meta-analysis to compare post-ICD and post-ONB HRQoL in patients with bladder cancer.

Methods

A systematic search of Medline, Embase, the Cochrane Central Register of Controlled Trials, and the annual congress abstracts of the European Association of Urology (EAU), the American Urological Association (AUA) and the Société Internationale d’Urologie (SIU) up to June 2017 was conducted to identify all relevant clinical trials using validated questionnaires to assess HRQoL. A systematic review and meta-analysis were then performed.

Results

A total of 2507 patients from 26 eligible studies were included. Meta-analyses showed significant differences favouring ONB patients in global health status (WMD?+?9.13, p?=?0.004), physical functioning (WMD?+?11.57, p?=?0.0001), role functioning (WMD?+?9.64, p?=?0.002), and social functioning (WMD?+?6.81, p?=?0.03) based on the EORTC-QLQ-C30 questionnaire and in the total score of FACT questionnaire (WMD?+?6.80, p?=?0.001). However, ONB patients were more likely to have postoperative urinary symptoms than ICD patients (WMD ??22.19, p?=?0.0001).

Conclusions

ONB patients are more likely to have a better global health status than ICD patients. Regardless of the type of urinary diversion (UD) surgery, a gradual improvement in HRQoL over preoperative status tended to stabilise after 12 months postoperatively.
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6.

Background

The alarming increase in the cost of cancer care is forcing all stakeholders to re-evaluate their approach to treatment. Drugs are the main contributor to the cost. To evaluate the significance of drug substitution on the cost of care we assessed the economic value of panitumumab vs. cetuximab in chemo-refractory metastatic CRC (mCRC) with wild-type KRAS from a US societal perspective.

Methods

We developed a Markov model with three health states: progression-free, progressive, and death. We calculated the transition probabilities between states using the ASPECCT trial report and US life tables. Costs of drug and administration were based on the Medicare reimbursement rates. Published data were used for cost of toxicities and utilities. All costs were converted to 2017 US dollars. The model used quality-adjusted life-years (QALYs) to measure health outcomes for each treatment option.

Results

Panitumumab and cetuximab produced 0.45 QALYs at a per patient cost of $66,006 and $71,956, respectively. The incremental net monetary benefit of panitumumab compared to cetuximab is $5237 under a societal willingness-to-pay threshold of $150,000. The model showed robustness to one-way sensitivity analyses and various alternative scenarios and was found to be most sensitive to the cost of cetuximab.

Conclusions

Panitumumab can lower the cost of care without impacting outcomes in chemo-refractory mCRC settings. This finding provides a strong argument to consider panitumumab in lieu of cetuximab in these patients.
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7.

Background

Inflammatory bowel disease (IBD) might have economic and social impacts in Brazil, where its prevalence has increased recently. This study aimed to assess disability due to IBD in the Brazilian population and demographic factors potentially associated with absence from work.

Methods

Analysis was performed using the computerized Single System of Social Security Benefits Information, with a cross-check for aid pension and disability retirement, for Crohn’s disease (CD) and ulcerative colitis (UC). Additional data were obtained from the platform, including the average values, benefit duration, age, gender and region of the country.

Results

Temporary disability occurred more frequently with UC, whereas permanent disability was more frequent with CD. Temporary disability affected more younger patients with CD than patients with UC. Temporary work absences due to UC and CD were greater in the South, and the lowest absence rates due to CD were noted in the North and Northeast. Absence from work was longer (extending for nearly a year) in patients with CD compared to those with UC. The rates of temporary and permanent disability were greater among women. Permanent disability rates were higher in the South (UC) and Southeast (CD). The value of benefits paid for IBD represented approximately 1% of all social security benefits. The benefits paid for CD were higher than for UC, whereas both tended to decrease from 2010 to 2014.

Conclusions

In Brazil, IBD frequently causes disability for prolonged periods and contributes to early retirement. Reduction trends may reflect improvements in access to health care and medication. Vocational rehabilitation programs may positively impact social security and the patients’ quality of life.
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8.

Background

Among persons with opioid use disorder (OUD), neuropsychological dysfunction is associated with depression, and better neuropsychological function is associated with opioid abstinence. However, it is unknown whether depressive symptomatology or adherence to opiate agonist treatment are associated with neuropsychological change over time.

Methods

We recruited 20 buprenorphine/naloxone-treated adults with OUD (M Age?=?45.2 years [SD?=?8.1]; 25% female) to complete baseline and 6 month visits containing a neuropsychological test battery and self-reported measures of depressive symptomatology and medication adherence.

Results

Depressive symptomatology was not significantly related to neuropsychological change (p’s?>?.05). Greater adherence to buprenorphine/naloxone was associated with improvements in learning, memory, and global functioning (r’s?=?.52–60; p’s?<?.05).

Conclusions

Among OUD patients, greater adherence to buprenorphine/naloxone is associated with improved neuropsychological functioning over time. In contrast, depressive symptomatology is not associated with neuropsychological functioning over time. Supporting adherence to buprenorphine/naloxone may improve and/or preserve learning and memory functioning in individuals treated for OUD.

Trial registration

NCT01108679. Registered 21 April 2010.
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9.

Background

Plasma is used to treat acquired coagulopathy or thrombotic thrombocytopenic purpura, or to reverse warfarin effect. Scant data are available, however, about its costs.

Objective

To estimate total costs of plasma from production through administration, from the perspective of a US hospital blood donor center (BDC).

Study Design and Methods

Six sequential decision analytic models were constructed and informed by primary and secondary data on time, tasks, personnel, and supplies for donation, processing, and administration. Expected values of the models were summed to yield the BDC’s total cost of producing, preparing, and transfusing plasma. Costs ($US 2015) are reported for a typical patient using three units of plasma. Models assume plasma was obtained from whole blood donation and transfused in an inpatient setting. Univariate sensitivity analyses were performed to test the impact of changing inputs for personnel costs and adverse event (AE) rates and costs.

Results

BDC production cost of plasma was $91.24/patient ($30.41/unit), a $30.16/patient savings versus purchased plasma. Administration and monitoring costs totaled $194.64/patient. Sensitivity analyses indicated that modifying BDC personnel costs during donation and processing has little impact on total plasma costs. However, the probability and cost of transfusion-associated circulatory overload (TACO) have a significant impact on costs.

Conclusion

Plasma produced by our BDC may be less costly than purchased plasma. Though plasma processes have multiple tasks involving staff time, these are not the largest cost driver. Major plasma-related AEs are uncommon, but are the biggest driver of total plasma costs.
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10.

Background

This study evaluates the cost-effectiveness of the DAZT program for scaling up treatment of acute child diarrhea in Gujarat India using a net-benefit regression framework.

Methods

Costs were calculated from societal and caregivers’ perspectives and effectiveness was assessed in terms of coverage of zinc and both zinc and Oral Rehydration Salt. Regression models were tested in simple linear regression, with a specified set of covariates, and with a specified set of covariates and interaction terms using linear regression with endogenous treatment effects was used as the reference case.

Results

The DAZT program was cost-effective with over 95% certainty above $5.50 and $7.50 per appropriately treated child in the unadjusted and adjusted models respectively, with specifications including interaction terms being cost-effective with 85–97% certainty.

Discussion

Findings from this study should be combined with other evidence when considering decisions to scale up programs such as the DAZT program to promote the use of ORS and zinc to treat child diarrhea.
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11.

Objectives

Little is known about the severity and long-term health and economic consequences of sarcopenia. We developed a sarcopenia index to measure severity in older Americans and estimated the long-term societal benefits generated by effective interventions to mitigate severity.

Design

Using a micro-simulation model, we quantified the potential societal value generated in the US in 2010–2040 by reductions in sarcopenia severity in older adults. All analyses were performed in Stata and SAS. Setting & Participants: Secondary data from the National Health and Nutrition Examination Survey (NHANES) (N = 1634) and Health and Retirement Study (HRS) (N = 952) were used to develop a sarcopenia severity index in older adults.

Measurements

Multitrait multi-method and factor analyses were used to validate and calibrate the sarcopenia severity index, which was modeled as a function of gait speed, walking without an assistive device, and moderate physical activity.

Results

In representative elderly populations, reducing sarcopenia severity by improving gait speed by 0.1 m/s in those with gait speed under 0.8 m/s generated a cumulative benefit of $65B by 2040 (2015 dollars). Improving walking ability in those with walking difficulty generated cumulative social benefit of $787B by 2040.

Conclusions

Reducing sarcopenia severity would generate significant health and economic benefits to society— almost $800B in the most optimistic scenarios.
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12.

Background

Glaucoma is the leading cause of irreversible blindness in the USA. Glaucomatous vision loss is preventable with proper eye care, including appointment adherence. Therefore, interventions that improve appointment adherence can reduce the number of patients with more severe glaucoma.

Objectives

The primary study aim was to determine the efficacy and cost-effectiveness of a multifaceted personal reminder intervention, which included a customized letter and personal telephone outreach, in improving appointment adherence of patients with glaucoma. A secondary study aim was to identify patient characteristics that were associated with non-adherence.

Methods

This prospective, randomized, controlled study included a cost-effectiveness analysis completed using a decision analytic model. The subjects included 256 patients with glaucoma. Study measures included appointment adherence and incremental cost effectiveness ratios.

Results

Patients in the intervention group were more likely to adhere to appointments (82.31 vs. 69.05 %; RR 1.23; 95 % CI 1.04–1.37, p < 0.012) than patients in the usual care group. Patients in the intervention group were 23 % more likely to adhere to appointments (RR 1.23; 95 % CI 1.08–1.41, p < 0.0021) than patients in the usual care group, when adjusting for age, secondary insurance, primary open angle glaucoma diagnosis, number of previous visits at Wills Eye Hospital, and follow-up recommendation using Poisson regression. Per-patient cost of the program was US$11.32, and cost per follow-up attended within the adherence window was US$73.56.

Conclusions

A low cost reminder intervention consisting of a personalized letter and telephone outreach significantly improved appointment adherence of patients with glaucoma.
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13.

Purpose

Industrial trans fatty acid (TFA) intake leads to impaired glucose metabolism. However, the overall effects reported are inconsistent and vary with the dietary FA composition and TFA isomer type and levels. We investigated TFA effects on glucose uptake, incorporation and oxidation, and glycogen synthesis in incubated soleus muscle under basal conditions or after treatment with insulin and/or palmitate.

Methods

Male Wistar rats were fed either linoleic acid (LA)-enriched (+LA) or LA-deprived (?LA) diet, supplemented (+LA?+?TFA or ?LA?+?TFA) or not with TFA, for 60 days. Soleus muscle glucose metabolism was assessed in the absence or presence of insulin and/or palmitic acid.

Results

Under basal conditions, TFA enhanced glucose uptake and oxidation regardless of the LA status. Both TFA-supplemented groups had lower insulin response to glucose metabolism. Under insulin-stimulated conditions, TFA prevented the palmitate inhibition of muscle glucose uptake and metabolism in the +LA?+?TFA group.

Conclusion

Dietary TFA enhanced glucose utilization in incubated soleus muscle under basal conditions and prevented the palmitate-induced inhibition in insulin-stimulated conditions. However, TFA reduced the insulin response to glucose uptake and metabolism. The effects mentioned above were influenced by the FA profile modifications induced by the dietary LA levels, suggesting that lipid metabolization and incorporation into plasma membrane are important determining factors of glucose metabolism and insulin sensitivity.
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14.

Objective

This study evaluated the potential cost-effectiveness of cervical cancer screening in HIV treatment clinics in Nairobi, Kenya.

Methods

A Markov model was used to project health outcomes and costs of cervical cancer screening and cryotherapy at an HIV clinic in Kenya using cryotherapy without screening, visual inspection with acetic acid (VIA), Papanicolaou smear (Pap), and testing for human papillomavirus (HPV). Direct and indirect medical and non-medical costs were examined from societal and clinic perspectives.

Results

Costs of cryotherapy, VIA, Pap, and HPV for women with CD4 200–500 cells/mL were $99, $196, $219, and $223 from a societal perspective and $19, $94, $124, and $113 from a clinic perspective, with 17.3, 17.1, 17.1, and 17.1 years of life expectancy, respectively. Women at higher CD4 counts (>500 cells/mL) given cryotherapy VIA, Pap, and HPV resulted in better life expectancies (19.9+ years) and lower cost (societal: $49, $99, $115, and $102; clinic: $13, $51, $71, and $56). VIA was less expensive than HPV unless HPV screening could be reduced to a single visit.

Conclusions

Preventative cryotherapy was the least expensive strategy and resulted in highest projected life expectancy, while VIA was most cost-effective unless HPV could be reduced to a single visit.
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15.
16.

Background

Hyperlipidemia is a well-established risk factor for cardiac damage, which can lead to cardiovascular diseases. Many studies have shown that Coenzyme Q10(CoQ10) protects against cardiac damage in vivo. The aim of this study was to investigate the possible protective effects of CoQ10 against cardiac damage in apolipoprotein E-deficient (ApoE?/?) mice.

Methods

Eight-week-old male C57BL/6 and ApoE?/? mice were randomly divided into four groups: C57BL/6 mice fed a normal diet (C57BL/6 group); C57BL/6 mice fed a normal diet + CoQ10 (C57BL/6?+?CoQ10 group); ApoE?/? mice fed a high-fat diet (ApoE?/? HD group), and ApoE?/? mice fed a high-fat diet + CoQ10 (ApoE?/? HD?+?CoQ10 group). All groups were fed the different diets for 16?weeks. Blood samples were obtained from the inferior vena cava and collected in serum tubes. The samples were then stored at ??80?°C until used. Coronal sections of heart tissues were fixed in 10% formalin and then embedded in paraffin for histological evaluation. The remainder of the heart tissues was snap-frozen in liquid nitrogen for mRNA or immunohistochemical analysis.

Results

The metabolic parameters such as total cholesterol (TC), low-density lipoprotein-cholesterol (LDL-c), and triglycerides (TG) levels were lower in ApoE?/?HD?+?CoQ10 mice than in ApoE?/? HD mice. There were significant pathophysiological changes (H&E, PAS, Masson and CD68 staining) in ApoE?/? mice in the HD group compared with those in the HD?+?CoQ10 group. CoQ10 reduced HD-induced cardiac tissue damage via autophagy (p62 and LC3), as evidenced by immunoblotting, immunohistochemistry, and RT-qPCR. CoQ10 also inhibited inflammation (IL-6 and TNF-α) gene expression in ApoE?/? mice.

Conclusions

These results indicate that CoQ10 is a potential therapeutic target for cardiac damage caused by hyperlipidemia.
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17.

Objectives

To investigate the effect of a long-term fatty fish intervention on a pure cognitive mechanism important for self-regulation and mental health, i.e. working memory (WM), controlling for age and IQ.

Design

A randomized controlled trial.

Setting

A forensic facility.

Participants

Eighty-four young to middle aged male forensic inpatients with psychiatric disorders.

Intervention

Consumption of farmed salmon or control meal (meat) three times a week during 23 weeks.

Measurement

Performance on WM tasks, both accuracy and mean reaction time, were recorded pre and post intervention.

Results

Performance on a cognitive functioning tasks taxing WM seemed to be explained by age and IQ.

Conclusion

Fatty fish consumption did not improve WM performance in a group of young to middle aged adults with mental health problems, as less impressionable factors such as aging and intelligence seemed to be the key components. The present study improves the knowledge concerning the interaction among nutrition, health and the aging process.
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18.

Objective

Zoledronic acid and denosumab were funded by the Australian government for the management of osteoporosis at an equivalent price to alendronate. The price of alendronate has declined by around 65 %, but the price of the other two therapies has remained stable. Using data published since the listing, this paper reports current estimates of the value of denosumab compared to alendronate from an Australian health system perspective.

Methods

A cohort-based state transition model was developed that predicted changes in bone mineral density (BMD), and calibrated fracture probabilities as a function of BMD, age and previous fracture to estimate differences in costs and QALYs gained over a 10-year time horizon.

Results

The base-case incremental cost per QALY gained for denosumab versus alendronate was $246,749. There is a near zero probability that denosumab is cost-effective at a threshold value of $100,000 per QALY gained. If the price of denosumab was reduced by 50 %, the incremental cost per QALY gained falls to $50,068.

Discussion

Current Australian legislation precludes price reviews when comparator therapies come off patent. The presented analysis illustrates a review process, incorporating clinical data collected since the original submission to inform a price at which denosumab would provide value for money.
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19.

Objective

To examine the clinical and economic impact of vedolizumab compared with infliximab, adalimumab, and golimumab in the treatment of moderately to severely active ulcerative colitis (UC) in the United Kingdom (UK).

Methods

A decision analytic model in Microsoft Excel was used to compare vedolizumab with other biologic treatments (infliximab, adalimumab, and golimumab) for the treatment of biologic-naïve patients with UC in the UK. Efficacy data were obtained from a network meta-analysis using placebo as the common comparator. Other inputs (e.g., unit costs, adverse-event disutilities, probability of surgery, mortality) were obtained from published literature. Costs were presented in 2012/2013 British pounds. Outcomes included quality-adjusted life-years (QALYs). Costs and outcomes were discounted by 3.5% per year. Incremental cost-effectiveness ratios were presented for vedolizumab compared with other biologics. Univariate and multivariate probabilistic sensitivity analyses were conducted to assess model robustness to parameter uncertainty.

Results

The model predicted that anti-tumour necrosis factor-naïve patients on vedolizumab would accrue more QALY than patients on other biologics. The incremental results suggest that vedolizumab is a cost-effective treatment compared with adalimumab (incremental cost-effectiveness ratio of £22,735/QALY) and dominant compared with infliximab and golimumab. Sensitivity analyses suggest that results are most sensitive to treatment response and transition probabilities. However, vedolizumab is cost-effective irrespective of variation in any of the input parameters.

Conclusions

Our model predicted that treatment with vedolizumab improves QALY, increases time in remission and response, and is a cost-effective treatment option compared with all other biologics for biologic-naïve patients with moderately to severely active UC.
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20.

Introduction

Diabetic retinopathy (DR), diabetic kidney disease (DKD) and diabetic foot ulcer (DFU) represent a public health and economic concern that may be assessed with cost-of-illness (COI) studies.

Objectives

(1) To review COI studies published between 2000 and 2015, about DR, DKD and DFU; (2) to analyse methods used.

Methods

Disease definition, epidemiological approach, perspective, type of costs, activity data sources, cost valuation, sensitivity analysis, cost discounting and presentation of costs may be described in COI studies. Each reviewed study was assessed with a methodological grid including these nine items.

Results

The five following items have been detailed in the reviewed studies: epidemiological approach (59 % of studies described it), perspective (75 %), type of costs (98 %), activity data sources (91 %) and cost valuation (59 %). The disease definition and the presentation of results were detailed in fewer studies (respectively 50 and 46 %). In contrast, sensitivity analysis was only performed in 14 % of studies and cost discounting in 7 %. Considering the studies showing an average cost per patient and per year with a societal perspective, DR cost estimates were US $2297 (range 5–67,486), DKD cost ranged from US $1095 to US $16,384, and DFU cost was US $10,604 (range 1444–85,718).

Discussion

This review reinforces the need to adequately describe the method to facilitate literature comparisons and projections. It also recalls that COI studies represent complementary tools to cost-effectiveness studies to help decision makers in the allocation of economic resources for the management of DR, DKD and DFU.
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