Compassionate use of delamanid in adults and children for drug-resistant tuberculosis: 5-year update.

BACKGROUND: Although delamanid has been approved for the treatment of multidrug-resistant TB (MDR-TB) in numerous regions, in areas where it is not yet registered it can be accessed as part of salvage therapy (in particular for those patients with limited treatment options) via the Otsuka compassionate use programme. Here we present the analysis of interim treatment outcomes by 24 weeks of more than 200 MDR-TB patients globally who received delamanid under this programme. METHODS: We evaluated treatment efficacy with respect to culture negativity at 24 weeks, as well as the safety profile of delamanid, in an MDR-TB patient cohort treated under compassionate use between 2014 and 2019. RESULTS: Among patients who received delamanid as part of a multidrug regimen, 123 (61%) out of 202 had extensively drug-resistant TB (XDR-TB), 66 (33%) out of 202 had HIV co-infection and 34 (17%) out of 202 were children aged between 6 and 17 years. Of those patients who were culture positive at delamanid treatment initiation and who completed 24 weeks of delamanid treatment in combination with other anti-tuberculosis (TB) drugs, culture negativity was achieved in 116 (79%) out of 147 cases. The corresponding rates of culture negativity for patients with XDR-TB and HIV co-infection, as well as the paediatric subgroup were 69 (77%) out of 90, 44 (92%) out of 48 and 20 (80%) out of 25, respectively. QT interval prolongation was the most frequently observed serious adverse event and was reported in 8% of patients receiving delamanid. Overall, treatment safety outcomes did not reveal any new or unidentified risks. CONCLUSIONS: The use of delamanid combined with other active drugs has the potential to achieve high rates of culture negativity in difficult-to-treat drug-resistant TB cases, with a favourable safety profile.

Direct cost and predictive factors for treatment in patients with ocular hypertension or early, moderate and advanced primary open-angle glaucoma: the CoGIS study in Germany.

BACKGROUND: The main objectives of this analysis were to assess the treatment costs and to identify major cost drivers and factors predicting direct costs in German patients with ocular hypertension (OHT) or primary open-angle glaucoma (POAG). METHODS: This non-interventional cross-sectional study was conducted in two university hospitals and 13 ophthalmology practices in Germany regions (Bavaria, Rhineland-Palatinate, North Rhine-Westphalia, Hamburg and Mecklenburg-Western Pomerania) between May 2009 and January 2010 to assess resource utilisation in patients with OHT (ICD-10: 40.0) or POAG (ICD-10: 40.1) at early, moderate or advanced stages, according to the European Glaucoma Society classification Guidelines. Treatment patterns and direct costs were evaluated retrospectively for 5 years. Resource utilisation data (medication, hospitalisation, outpatient surgery, visits to ophthalmologists) were abstracted from the charts, and unit costs were applied to estimate direct costs per year (in Euros, 2009), calculated from the perspective of the statutory health insurance in Germany (Gesetzliche Krankenversicherung). Factors predicting costs were assessed in multivariate regression analysis. RESULTS: One hundred and fifty-four patients (17.5% OHT, 27.9% early, 22.7% moderate, and 31.8% advanced POAG), on average 67 years old (SD 11) were included in the study. Average total annual direct costs per patient for OHT were 226 (SD 117), for early POAG 423 (SD 647), moderate 493 (SD 385) and advanced POAG 809 (SD 877). Glaucoma-related medications and hospitalisation represented the two major components of direct costs, increasing with the progression of glaucoma. In addition to treatment switches (p = 0.0001), factors predictive of an increase in total direct costs included the number of hospital interventions (p < 0.0001), disease-state changes since the start of treatment (p = 0.05), and current disease state (p = 0.05). CONCLUSIONS: Direct costs of treatment are higher in glaucoma compared to OHT and further increase in more severe glaucoma states. Additional treatment changes are major contributing factors to the increased treatment costs of glaucoma. If intraocular pressure can be controlled over the long term, progression to moderate and advanced states avoided, and patients remain on initial treatments, treatment costs could decline due to reduced and less expensive healthcare resource utilisation.

Health- and vision-related quality of life in patients with ocular hypertension or primary open-angle glaucoma.

BACKGROUND: The main objective of this analysis was to assess the impact of severity of disease on the quality of life (QoL) of patients with ocular hypertension (OHT) and early, moderate, or advanced primary open-angle glaucoma (POAG). METHODS: This multicenter study was conducted at 2 university hospitals and 13 ophthalmology practices in Germany. QoL data were assessed by the Health Utility Index (HUI3) and the 25-item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25). RESULTS: 154 patients (17.5% OHT, 27.9% early, 22.7% moderate, and 31.8% advanced POAG) were included. The HUI3 scores for OHT, early, moderate, and advanced POAG were 0.87 ± 0.09, 0.85 ± 0.15, 0.75 ± 0.23, and 0.58 ± 0.32, respectively. Compared to a normal population matched by age and gender, for moderate and severe POAG a difference of -0.06 ± 0.24 and -0.19 ± 0.28, respectively, was observed. NEI-VFQ-25 scores illustrate different dimensions of the impact on QoL; reduced peripheral vision or difficulties to drive a car were more crucial to glaucoma patients than social factors. CONCLUSIONS: The key difference for QoL impairment in glaucoma lies between OHT/early POAG versus moderate/severe POAG, hence every possible effort needs to be made to prevent disease progression over this threshold.

Validated assessment scales for the mid face.

BACKGROUND: The improvement of aesthetic treatment options for age-related mid face changes, such as volume loss, and the increase in patient expectations necessitates the development of more-complex and globally accepted assessment tools. OBJECTIVE: To develop three grading scales for objective assessment of the infraorbital hollow and upper and lower cheek fullness and to establish the reliability of these scales for clinical research and practice. METHODS AND MATERIALS: Three 5-point rating scales were developed to assess infraorbital hollow and upper and lower cheek fullness objectively. Twelve experts rated identical mid face photographs of 50 subjects in two separate rating cycles using the mid face scales. Test responses of raters were analyzed to assess intra- and interrater reliability. RESULTS: Interrater reliability was substantial for the infraorbital hollow, upper cheek fullness, and lower cheek fullness scales. Intrarater reliability was high for all three scales. Both of the cheek fullness scales yielded higher reliabilities when three rather than two views were used to assess the volume changes of the cheek. CONCLUSION: The mid face scales are reliable tools for valid and reproducible assessment of age-related mid face changes.

Validated assessment scales for the lower face.

BACKGROUND: Aging in the lower face leads to lines, wrinkles, depression of the corners of the mouth, and changes in lip volume and lip shape, with increased sagging of the skin of the jawline. Refined, easy-to-use, validated, objective standards assessing the severity of these changes are required in clinical research and practice. OBJECTIVE: To establish the reliability of eight lower face scales assessing nasolabial folds, marionette lines, upper and lower lip fullness, lip wrinkles (at rest and dynamic), the oral commissure and jawline, aesthetic areas, and the lower face unit. METHODS AND MATERIALS: Four 5-point rating scales were developed to objectively assess upper and lower lip wrinkles, oral commissures, and the jawline. Twelve experts rated identical lower face photographs of 50 subjects in two separate rating cycles using eight 5-point scales. Inter- and intrarater reliability of responses was assessed. RESULTS: Interrater reliability was substantial or almost perfect for all lower face scales, aesthetic areas, and the lower face unit. Intrarater reliability was high for all scales, areas and the lower face unit. CONCLUSION: Our rating scales are reliable tools for valid and reproducible assessment of the aging process in lower face areas.

Validated assessment scale for neck volume.

BACKGROUND: Sagging of the neck aesthetic area is an important indicator of age. The development of complex and globally accepted tools for proper assessment of the change in neck volume is an essential contribution to aesthetic research and the routine clinical setting. OBJECTIVE: To develop a grading scale for the objective assessment of the neck volume and to establish the reliability of this scale for clinical research and practice. MATERIALS AND METHODS: A 5-point rating scale was developed to assess neck volume objectively. Twelve experts rated frontal and lateral neck photographs of 50 subjects in two separate rating cycles using the neck volume scale. Responses of raters were analyzed to assess inter- and intrarater reliability. RESULTS: Interrater reliability for the neck volume scale was almost perfect, with intraclass correlation coefficients for the first and second rating cycles of 0.85 and 0.84, respectively. Intrarater reliability for the neck volume scale was high (0.90) and Pearson correlation coefficients ranged between 0.88 and 0.95 and were statistically significant. CONCLUSION: The neck volume scale demonstrates optimal reliability for clinical research and practice.

Diabetic retinopathy and health-related quality of life.

OBJECTIVE: To describe the impact of co-morbidities, visual acuity, diabetic retinopathy (DR) grade, and macular edema (ME) on the health-related quality of life (HRQOL) among patients with diabetic retinopathy. METHODS: Analysis of data of 207 patients with diabetic retinopathy from Germany in 2003. HRQOL assessment was done using the generic (SF-12) questionnaire. It was hypothesized that exogenous variables (co-morbidities, visual acuity impairment, DR, and ME) would have an impact on HRQOL. Using a structural equation modelling procedure, the effects of exogenous variables on endogenous variables physical component summaries (PSC) and mental component summaries (MCS) reflecting HRQOL were tested. RESULTS: The number of co-morbidities had a negative effect on visual acuity (b = -0.26, standardized) and a similar negative effect on PCS (b = -0.27). DR grade had a negative effect on visual acuity (b = -0.19) and a positive effect on the variable ME (b = 0.44). ME displayed a negative effect on visual acuity (b = -0.58) and also on MCS (b = -0.29). Visual acuity had a positive effect (b = 0.48) on PCS. CONCLUSIONS: Presence of DR and ME, visual acuity impairment and patient co-morbidities lead to significant impairment of both the physical and mental components of HRQOL.

Epidemiology and cost of treatment of genital warts in Spain.

BACKGROUND: Genital warts (GW) are common and increasing in young people. Ninety percent of GW are due to Human Papillomavirus (HPV) types 6 and 11. The objective of this study was to assess the epidemiology and management costs associated with GW in Spain. METHODS: A 1-year (2005) retrospective observational study was performed among a sample of gynaecologists, dermatologists and urologists in six autonomous regions in Spain. Men and women with newly diagnosed, recurrent or resistant GW were included. We estimated the incidence (new and recurrent cases) and prevalence (also including resistant cases) of GW. Healthcare resource use were collected and combined with unit costs to assess the mean cost of GW management per patient. These figures were extrapolated to the 14- to 64-year-old Spanish population to estimate the total cost of GW management from the Third Party Payer (TPP) and societal perspectives. RESULTS: The overall annual incidence of GW was estimated at 160.4 cases per 100,000. Overall prevalence was calculated as 182.1 cases per 100,000, corresponding to 56 446 GW cases annually (14- to 64-year-old population). The mean management cost was 833 euros and 1056 euro per patient from the TPP and societal perspective, respectively. The overall annual cost was estimated at 47 million euros and 59.6 million euros, from the TPP and societal perspective, respectively. CONCLUSION: This study provides a first overview of the burden of GW in Spain. A quadrivalent HPV vaccine that prevents HPV 6, 11, 16, 18 related diseases will have the potential to significantly decrease the socio-economic burden associated with GW in Spain.

Using patient-reported outcome assessments in clinical practice and their importance in risk management.

Patient-reported outcome (PRO) instruments are related to risk management programmes in that they are tools to measure the benefits and risks of exposure to pharmaceutical products from the patient's perspective. Clinical measures of improvement of certain conditions may not necessarily correlate with improvements in a patient's ability to perform daily activities. PRO data, when properly administered, collected, analysed and returned to physicians are a very useful source of information. This will ultimately address safety concerns, facilitate the physician-patient relationship and improve patients' compliance to treatment in routine patient care. In this article we stress the importance of PRO in risk management.

The economic burden of diabetic retinopathy in Germany in 2002.

BACKGROUND: The aims of our study were to describe the costs associated with diabetic retinopathy (DR), and to evaluate its economic impact in Germany. METHODS: Forty-one German ophthalmologists, randomly selected from a physicians' database in Germany, provided information on adult Type 1 and Type 2 diabetic patients with DR (n = 207). This information included socio-demographics, clinical characteristics and resource use during the year 2002. National-level cost estimates were calculated, based on these results and the prevalence data on DR in Germany. RESULTS: This study found that costs associated with DR tend to increase as DR progresses, being highest in patients with proliferative DR and lowest in patients with mild, non-proliferative DR. The German statutory health insurance (Gesetzliche Krankenversicherung, GKV) covered two-thirds of the total costs paid by all the payers. The total cost of DR from a societal perspective was calculated at 3.51 euros bn for the year 2002, and from the GKV perspective amounted to 2.23 euros bn. CONCLUSIONS: This study is the first comprehensive study to provide estimates of costs associated with DR in Germany. These costs were estimated to account for approximately 1.5% of the total health-care expenditure in 2002.

Cost utility of allogeneic stem cell transplantation with matched unrelated donor versus treatment with imatinib for adult patients with newly diagnosed chronic myeloid leukaemia.

OBJECTIVE: To estimate, from the perspective of the German statutory health insurance, the cost utility of allogeneic stem cell transplantation with matched unrelated donor (MUD-SCT) in newly diagnosed, chronic-phase chronic myeloid leukaemia (CML) patients aged 40 years or younger, relative to the treatment with imatinib. METHODS: The incremental cost-effectiveness ratio (ICER) of the additional cost of imatinib versus MUD-SCT per quality-adjusted life year (QALY) gained was chosen as a target assessment. ICER was quantified using a Markov cohort modelling approach. The evaluation encompassed 5 years of treatment with either approach, and only direct medical costs (in euro, year 2005) were considered. RESULTS: There were incremental costs of euro77,410 for imatinib therapy per QALY gained versus MUD-SCT. No strategy was clearly dominant; on average, during 5 years, cost savings of euro63,433 were obtained and 0.82 QALY lost by SCT compared to treatment with imatinib. QALYs gained in CML patients with either treatment resulted in considerable cost to the third-party payer in Germany. The results were particularly sensitive to the price of imatinib. CONCLUSIONS: The analysis finds that imatinib is more costly but more effective (as measured in QALYs) over a 5-year time horizon. The resulting ICER of euro77,410 per QALY is higher than commonly cited thresholds. The cost utility of MUD-SCT to treat CML in patients with a European Group for Blood and Marrow Transplantation score < or = to 2 compares with that of the imatinib strategy.

Resource utilisation and costs in patients with type 2 diabetes mellitus treated with insulin glargine or conventional basal insulin under real-world conditions in Germany: LIVE-SPP study.

OBJECTIVE: To assess and compare the total costs relevant to diabetes care in patients with type 2 diabetes mellitus (T2D) treated at specialised diabetes practices with either insulin glargine- or conventional basal insulin (neutral protamine Hagedorn [NPH])-based therapies from the German statutory health insurance (SHI) perspective. METHODS: The Long Acting Insulin Glargine Versus NPH Cost Evaluation in Specialised Practices (LIVE-SPP) study is an observational, retrolective, multicentre longitudinal cost comparison in adults with T2D. Costs were evaluated from the German SHI perspective based on official 2005 prices. Average total costs per patient for insulin glargine-versus NPH-based therapies were compared using multivariate general linear modelling. Sensitivity analyses were performed by varying the main cost factors by +/- 25%. RESULTS: Patients (n=1,024, 512 patients per cohort) were on average 62 years of age, with an average 8-year diabetes history at study start. The average unadjusted total annual costs per patient were euro 1,868.41 (95% CI 1,744.27-1,992.56) for insulin glargine-based vs. euro 2,063.72 (95% CI 1,922.91-2,204.54) for NPH-based therapies. Average adjusted total annual costs per patient between insulin glargine- (euro 1,241.13) and NPH-based therapies (euro 1,607.86) were statistically significantly different (p=0.0004). The economic advantage for insulin glargine-based therapies resulted mainly from fewer blood glucose measurements and other diabetes-related materials (e.g. needles). The savings remained stable in one-way sensitivity analyses. CONCLUSIONS: The LIVE-SPP study suggests that insulin glargine-based therapies may offer an economic advantage over NPH-based therapies.

Feeding practices of babies and the development of atopic dermatitis in children after 12 months of age in Armenia: is there a signal?

We investigated the influence of feeding practices on development of atopic dermatitis (AD) in Armenian children (n = 240). In multivariate models early introduction to solids, family history of atopy, and breastfeeding by a mother with atopic condition were associated with the development of AD after 12 months post-term. A prospective study in Armenia is recommended to confirm our findings.