Sex-specific trends in incidence of first myocardial infarction among people with and without diabetes between 1985 and 2016 in a German region.

BACKGROUND: The reduction of myocardial infarction (MI) and narrowing the gap between the populations with and without diabetes are important goals of diabetes care. We analyzed time trends for sex-specific incidence rates (IR) of first MI (both non-fatal MI and fatal MI) as well as separately for first non-fatal MI and fatal MI in the population with and without diabetes. METHODS: Using data from the KORA myocardial infarction registry (Augsburg, Germany), we estimated age-adjusted IR in people with and without diabetes, corresponding relative risks (RR), and time trends from 1985 to 2016 using Poisson regression. RESULTS: There were 19,683 people with first MI (34% fatal MI, 71% men, 30% with diabetes) between 1985 and 2016. In the entire study population, the IR of first MI decreased from 359 (95% CI: 345-374) to 236 (226-245) per 100,000 person years. In men with diabetes, IR decreased only in 2013-2016. This was due to first non-fatal MI, where IR in men with diabetes increased until 2009-2012, and slightly decreased in 2013-2016. Overall, fatal MI declined stronger than first non-fatal MI corresponding to IRs. The RR of first MI substantially increased among men from 1.40 (1.22-1.61) in 1985-1988 to 2.60 (2.26-2.99) in 1997-2000 and moderately decreased in 2013-2016: RR: 1.75 (1.47-2.09). Among women no consistent time trend for RR was observed. Time trends for RR were similar regarding first non-fatal MI and fatal MI. CONCLUSIONS: Over the study period, we found a decreased incidence of first MI and fatal MI in the entire study population. The initial increase of first non-fatal MI in men with diabetes needs further research. The gap between populations with and without diabetes remained.

Incidence of Stroke in People With Diabetes Compared to Those Without Diabetes: A Systematic Review.

BACKGROUND: One of the goals of the St. Vincent Declaration was to reduce serious complications of diabetes, including strokes. However, it remains uncertain whether this goal has been achieved. STUDY AIM: To evaluate the incidence of stroke in the diabetic population and its differences regarding sex, ethnicity, age, and region, to compare the incidence rate in people with and without diabetes, and to investigate time trends. MATERIALS AND METHODS: A systematic review was conducted according to the guidelines for meta-analysis of observational studies in epidemiology (the MOOSE group) and the PRISMA group guidelines. RESULTS: Nineteen of the 6.470 studies retrieved were included in the analysis. The incidence of stroke in the population with diabetes ranged from 238 per 100,000 person-years in Germany in 2014 to 1191 during the 1990s in the United Kingdom. The relative risk comparing people with diabetes to those without diabetes varied between 1.0 and 2.84 for total stroke, 1.0 and 3.7 for ischemic stroke, and 0.68 and 1.6 for hemorrhagic stroke. Differences between fatal and non-fatal stroke were significant, depending on the time period and the population. We found decreasing time trends in people with diabetes and stable incidence rates of stroke over time in people without diabetes. CONCLUSION: The considerable differences between results can partly be explained by differences in study designs, statistical methods, definitions of stroke, and methods used to identify patients with diabetes. The lack of evidence arising from these differences ought to be rectified by new studies.

PHQ-9, CES-D, health insurance data-who is identified with depression? A Population-based study in persons with diabetes.

AIMS: Several instruments are used to identify depression among patients with diabetes and have been compared for their test criteria, but, not for the overlaps and differences, for example, in the sociodemographic and clinical characteristics of the individuals identified with different instruments. METHODS: We conducted a cross-sectional survey among a random sample of a statutory health insurance (SHI) (n = 1,579) with diabetes and linked it with longitudinal SHI data. Depression symptoms were identified using either the Centre for Epidemiological Studies Depression (CES-D) scale or the Patient Health Questionnaire-9 (PHQ-9), and a depressive disorder was identified with a diagnosis in SHI data, resulting in 8 possible groups. Groups were compared using a multinomial logistic model. RESULTS: In total 33·0% of our analysis sample were identified with depression by at least one method. 5·0% were identified with depression by all methods. Multinomial logistic analysis showed that identification through SHI data only compared to the group with no depression was associated with gender (women). Identification through at least SHI data was associated with taking antidepressants and previous depression. Health related quality of life, especially the mental summary score was associated with depression but not when identified through SHI data only. CONCLUSION: The methods overlapped less than expected. We did not find a clear pattern between methods used and characteristics of individuals identified. However, we found first indications that the choice of method is related to specific underlying characteristics in the identified population. These findings need to be confirmed by further studies with larger study samples.

Hospitalisation rate and mortality among people with and without diabetes during the COVID-19 pandemic year 2020.

Most studies reported reduced health care use among people with diabetes during the COVID-19 pandemic. This may be due to restricted medical services or people avoiding health care services because they fear being infected with COVID-19 in health care facilities. The aim of our study was to analyse hospitalisation and mortality in people with and without diabetes in Germany during the COVID-19 pandemic year 2020 compared to 2017-2019. The data were sourced from a German statutory health insurance company covering 3.2 million people. We estimated age-sex standardised rates of mortality, all-cause hospitalisation, hospitalisation due to coronary heart disease (CHD), acute myocardial infarction (AMI), stroke, diabetic foot syndrome (DFS), and major and minor amputations in people with and without diabetes. We predicted rates for 2020 using Poisson regression based on results from 2017-2019 and compared these with the observed rates.In people with diabetes, the hospitalisation rate for major amputation was significantly increased, while all-cause hospitalisation rate and hospitalisation due to CHD, AMI and DFS were significantly decreased compared to the previous period. Moreover, we found a significantly increased mortality and hospitalisation rate for minor amputation in people without diabetes while all-cause hospitalisation and hospitalisation due to CHD and AMI was significantly lower during the COVID-19 pandemic year 2020.We observed changes in health care utilisation and outcomes during the COVID-19 pandemic compared to previous years in people with and without diabetes. Concerning diabetes care, the increase of hospitalisations due to amputation in people with diabetes with a simultaneous reduction in DFS needs special attention.

Incidence of myocardial infarction in people with diabetes compared to those without diabetes: a systematic review protocol.

BACKGROUND: Diabetes mellitus is an established risk factor for acute myocardial infarction (AMI). Incidence of AMI in people with diabetes remains significantly higher than in those without diabetes. However, published data are conflicting, and previous reviews in this field have some limitations regarding the definitions of AMI and source population (general population or people with diabetes as a population at risk) and concerning the statistical presentation of results. AIMS: To analyse the incidence of AMI in people with diabetes compared to those without diabetes and to investigate time trends. METHODS: We will perform a systematic literature search in MEDLINE, Embase and LILACS designed by an experienced information scientist. Two review authors will independently screen the abstracts and full texts of all references on the basis of inclusion criteria regarding types of study, types of population and the main outcome. Data extraction and assessment of risk of bias will be undertaken by two review authors working independently. We will assess incidence rate or cumulative incidence and relative risk of AMI comparing populations with and without diabetes. DISCUSSION: This review will summarise the available data concerning the incidence of AMI in people with and without diabetes and will thus contribute to the assessment and interpretation of the wide variations of incidence, relative risks and time trends of AMI in these populations. SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42020145562.

Renal Replacement Therapy in People With and Without Diabetes in Germany, 2010-2016: An Analysis of More Than 25 Million Inhabitants.

OBJECTIVE: Epidemiological studies have shown contradictory results regarding the time trend of end-stage renal disease (ESRD) in people with diabetes. This study aims to analyze the incidence of ESRD, defined as chronic renal replacement therapy (RRT), to investigate time trends among people with and without diabetes in Germany and to examine whether these patterns differ by age and sex. RESEARCH DESIGN AND METHODS: The data were sourced from nationwide data pooled from two German branches of statutory health insurances covering ∼25 million inhabitants. We estimated age- and sex-standardized incidence rates (IRs) for chronic RRT among people with and without diabetes in 2010-2016 and the corresponding relative risks. Time trends were analyzed using Poisson regression. RESULTS: We identified 73,638 people with a first chronic RRT (male 60.0%, diabetes 60.6%, mean age 71.3 years). The IR of chronic RRT among people with diabetes (114.1 per 100,000 person-years [95% CI 110.0-117.2]) was almost six times higher than among people without diabetes (19.6 [19.4-19.8]). A consistent decline in IR was observed among people with diabetes (3% annual reduction, P < 0.0001) for both sexes and all age classes. In contrast, no consistent change of IR was identified in people without diabetes. Only among women aged <40 years (P = 0.0003) and people aged ≥80 years (P < 0.0001) did this IR decrease significantly. CONCLUSIONS: Incidence of chronic RRT remained significantly higher among people with diabetes. The IR decreased significantly in people with diabetes independent of age and sex. Time trends were inconsistent in people without diabetes.

Markedly decreasing incidence of cause-specific blindness in Saxony (Eastern Germany).

PURPOSE: To analyze the recent time trend in Saxony. METHODS: Data were based on administrative files in Saxony (Eastern Germany) to assess recipients of blindness allowance newly registered between January 1, 2009, and December 31, 2017. We estimated age-sex standardized incidence of all-cause and cause-specific blindness and used Poisson regression to examine age- and sex-adjusted time trends. RESULTS: We identified 5114 new cases of blindness (63.3% female, 59.9% ≥ 80 years). We observed a markedly decrease in incidence of blindness: all-causes 2009: 15.7 per 100,000 person years [95% confidence interval: 14.6-17.0]; 2017: 8.9 [8.1-9.8]; age-related macular degeneration 2009: 6.9 [6.1-7.7], 2017: 3.8 [3.3-4.3]; glaucoma 2009: 2.6 [2.2-3.1], 2017: 1.8 [1.4-2.2]; diabetic retinopathy 2009: 1.5 [1.2-1.9], 2017: 0.7 [0.5-1.0]; myopia 2009: 0.7 [0.5-1.1], 2017: 0.4 [0.2-0.5]; optic atrophy 2009: 0.9 [0.6-1.2], 2017: 0.5 [0.3-0.7]; and cataract 2009: 0.5 [0.3-0.8], 2017: 0.1 [0.1-0.3]. The annual reduction was between 5 (glaucoma, relative risk 0.95 [0.92-0.98]) and 16% (cataract, relative risk 0.84 [0.78-0.91]). CONCLUSION: The age- and sex-standardized incidence of blindness decreased among all common causes of blindness in Saxony in the last decade.

Incidence of stroke in the diabetic compared with the non-diabetic population: A systematic review protocol.

People with diabetes have a largely increased risk of stroke compared with people without diabetes. Exact data on incidence of stroke in people with and without diabetes are important for improvements in preventive diabetes care, avoidance of fatal outcomes and as a solid basis for health policy and the economy. However, published data are conflicting, underlining the necessity for this systematic review of population-based studies on incidence, relative risks (RRs) and changes in stroke rates over time. The purpose of our review is to evaluate the incidence of stroke in the diabetic population and its differences with regard to sex, ethnicity, age and regions; to compare the incidence rate (IR) in the diabetic and non-diabetic populations and to investigate time trends. We will perform a systematic literature search in MEDLINE, Embase and LILACS designed by an experienced information scientist. Two review authors will independently screen the abstracts and full texts of all references on the basis of inclusion criteria regarding types of study, types of population and the main outcome. Data extraction and assessment of risk of bias will be undertaken by two review authors working independently. We will assess IR or cumulative incidence (CumI) and RR of stroke comparing the diabetic and non-diabetic populations. The attributable risk (AR = proportion of stroke among persons with diabetes that is attributable to diabetes) and the population attributable risk (PAR = proportion of stroke in the whole population that is attributable to diabetes) will be considered where available. In conclusion, this review will help to summarize the available evidence for incidence of stroke in the diabetic and nondiabetic population. The publication of this protocol will contribute to making the search strategy, methods, and assessment of reviews transparent and accessible for all involved professional groups.

Using statutory health insurance data to evaluate non-response in a cross-sectional study on depression among patients with diabetes in Germany.

BACKGROUND: Low response rates do not indicate poor representativeness of study populations if non-response occurs completely at random. A non-response analysis can help to investigate whether non-response is a potential source for bias within a study. METHODS: A cross-sectional survey among a random sample of a health insurance population with diabetes (n = 3642, 58.9% male, mean age 65.7 years), assessing depression in diabetes, was conducted in 2013 in Germany. Health insurance data were available for responders and non-responders to assess non-response bias. The response rate was 51.1%. Odds ratios (ORs) for responses to the survey were calculated using logistic regression taking into consideration the depression diagnosis as well as age, sex, antihyperglycaemic medication, medication utilization, hospital admission and other comorbidities (from health insurance data). RESULTS: Responders and non-responders did not differ in the depression diagnosis [OR 0.99, confidence interval (CI) 0.82-1.2]. Regardless of age and sex, treatment with insulin only (OR 1.73, CI 1.36-2.21), treatment with oral antihyperglycaemic drugs (OAD) only (OR 1.77, CI 1.49-2.09), treatment with both insulin and OAD (OR 1.91, CI 1.51-2.43) and higher general medication utilization (1.29, 1.10-1.51) were associated with responding to the survey. CONCLUSION: We found differences in age, sex, diabetes treatment and medication utilization between responders and non-responders, which might bias the results. However, responders and non-responders did not differ in their depression status, which is the focus of the DiaDec study. Our analysis may serve as an example for conducting non-response analyses using health insurance data.

Incidence and relative risk of renal replacement therapy in people with and without diabetes between 2002 and 2016 in a German region.

AIMS/HYPOTHESIS: Data on trends of end-stage renal disease among people with diabetes are lacking. We analysed the incidence of end-stage renal disease, defined as renal replacement therapy, among people with and without diabetes, and the corresponding relative risk. Moreover, we investigated time trends for the period 2002-2016. METHODS: In this retrospective population-based study we analysed data from one dialysis centre of a region in Germany covering a population of about 310,000 inhabitants. We estimated the age- and sex-standardised incidence rates for chronic renal replacement therapy among adults with and without diabetes and the corresponding relative risks. The time trend was analysed using Poisson regression models. RESULTS: Between 2002 and 2016, 1107 people (61.2% male; mean age 71.6 years; 48.7% with diabetes) had a first renal replacement therapy. During the study period, the incidence rate in the population with diabetes varied from 93.6 (95% CI 50.4, 136.7) in 2002 to 140.5 (95% CI 80.6, 200.4) in 2016 per 100,000 person-years. In the population without diabetes the incidence rate was substantially lower and reached 17.3 (95% CI 10.9, 23.6) in 2002 and 24.6 (95% CI 17.5, 31.7) in 2009. The relative risk comparing people with and without diabetes was 3.57 (95% CI 3.09, 4.13). No significant change in the incidence rates was found during the observation period, either in the population with or in the population without diabetes, and thus the relative risk also remained constant. CONCLUSIONS/INTERPRETATION: People with diabetes have a higher risk of needing renal replacement therapy than those without diabetes, a fact that remained constant over a time period of 15 years.

Secondary data in diabetes surveillance - co-operation projects and definition of references on the documented prevalence of diabetes.

In addition to the Robert Koch Institute's health surveys, analyses of secondary data are essential to successfully developing a regular and comprehensive description of the progression of diabetes as part of the Robert Koch Institute's diabetes surveillance. Mainly, this is due to the large sample size and the fact that secondary data are routinely collected, which allows for highly stratified analyses in short time intervals. The fragmented availability of data means that various sources of secondary data are required in order to provide data for the indicators in the four fields of action for diabetes surveillance. Thus, a milestone in the project was to check the suitability of different data sources for their usability and to carry out analyses. Against this backdrop, co-operation projects were specifically funded in the context of diabetes surveillance. This article presents the results that were achieved in co-operation projects between 2016 and 2018 that focused on a range of topics: from evaluating the usability of secondary data to statistically modelling the development of epidemiological indices. Moreover, based on the data of the around 70 million people covered by statutory health insurance, an initial estimate was calculated for the documented prevalence of type 2 diabetes for the years 2010 and 2011. To comparably integrate these prevalences over the years in diabetes surveillance, a reference definition was established with external expertise.

Decreasing rates of major lower-extremity amputation in people with diabetes but not in those without: a nationwide study in Belgium.

AIMS/HYPOTHESIS: The reduction of major lower-extremity amputations (LEAs) is one of the main goals in diabetes care. Our aim was to estimate annual LEA rates in individuals with and without diabetes in Belgium, and corresponding time trends. METHODS: Data for 2009-2013 were provided by the Belgian national health insurance funds, covering more than 99% of the Belgian population (about 11 million people). We estimated the age-sex standardised annual amputation rate (first per year) in the populations with and without diabetes for major and minor LEAs, and the corresponding relative risks. To test for time trends, Poisson regression models were fitted. RESULTS: A total of 5438 individuals (52.1% with diabetes) underwent a major LEA, 2884 people with above- and 3070 with below-the-knee major amputations. A significant decline in the major amputation rate was observed in people with diabetes (2009: 42.3; 2013: 29.9 per 100,000 person-years, 8% annual reduction, p < 0.001), which was particularly evident for major amputations above the knee. The annual major amputation rate remained stable in individuals without diabetes (2009: 6.1 per 100,000 person-years; 2013: 6.0 per 100,000 person-years, p = 0.324) and thus the relative risk reduced from 6.9 to 5.0 (p < 0.001). A significant but weaker decrease was observed for minor amputation in individuals with and without diabetes (5% and 3% annual reduction, respectively, p < 0.001). CONCLUSIONS/INTERPRETATION: In this nationwide study, the risk of undergoing a major LEA in Belgium gradually declined for individuals with diabetes between 2009 and 2013. However, continued efforts should be made to further reduce the number of unnecessary amputations.

Lower-extremity amputations in people with and without diabetes in Germany, 2008-2012 - an analysis of more than 30 million inhabitants.

BACKGROUND AND PURPOSE: Lower-extremity amputations (LEAs) in people with diabetes are associated with reduced quality of life and increased health care costs. Detailed knowledge on amputation rates (ARs) is of utmost importance for future health care and economics strategies. We conducted the present cohort study in order to estimate the incidences of LEA as well as relative and attributable risk due to diabetes and to investigate time trends for the period 2008-2012. METHODS: On the basis of the administrative data from three large branches of German statutory health insurers, covering ~34 million insured people nationwide (about 40% of the German population), we estimated age-sex-standardized AR (first amputation per year) in the populations with and without diabetes for any, major, and minor LEAs. Time trends were analyzed using Poisson regression. RESULTS: A total of 108,208 individuals (diabetes: 67.3%; mean age 72.6 years) had at least one amputation. Among people with diabetes, we observed a significant reduction in major and minor ARs during 2008-2012 from 81.2 (95% CI 77.5-84.9) to 58.4 (55.0-61.7), and from 206.1 (197.3-214.8) to 177.0 (169.7-184.4) per 100,000 person-years, respectively. Among people without diabetes, the major AR decreased significantly from 14.3 (13.9-14.8) to 11.6 ([11.2-12.0], 12.0), whereas the minor AR increased from 15.8 (15.3-16.3) to 17.0 (16.5-17.5) per 100,000 person-years. The relative risk (RR) comparing the diabetic with the nondiabetic populations decreased significantly for both major and minor LEAs (4% and 5% annual reduction, respectively). CONCLUSION: In this large nationwide population, we still found higher major and minor ARs among people with diabetes compared with those without diabetes. However, AR and RR of major and minor LEAs in the diabetic compared with the nondiabetic population decreased significantly during the study period, confirming a positive trend that has been observed in smaller and regional studies in recent years.

Markedly Decreasing Incidence of Blindness in People With and Without Diabetes in Southern Germany.

OBJECTIVE: Studies comparing the incidence of blindness in persons with and without diabetes are scarce worldwide. In Germany, a decline in the incidence of blindness was found during the 1990s. The aim of this study was to analyze the recent time trend. RESEARCH DESIGN AND METHODS: Data were based on administrative files in southern Germany to assess recipients of blindness allowance newly registered between 1 January 2008 and 31 December 2012. We estimated age- and sex-standardized incidence of blindness in people with and people without diabetes and the corresponding relative risk. Poisson regression was used to examine age- and sex-adjusted time trends. RESULTS: We identified 1,897 new cases of blindness (23.7% of which were associated with diabetes). We observed a strong decrease in incidence in both the population with diabetes (2008, 17.3 per 100,000 person-years [95% CI 13.6-21.1], and 2012, 8.9 per 100,000 person-years [6.3-11.6]: 16% decrease [10-22] per year) and that without diabetes (2008, 9.3 per 100,000 person-years [8.3-10.3], and 2012, 6.6 [5.8-7.4]: 9% decrease [5-13] per year). The relative risk comparing those incidences was 1.70 (95% CI 1.32-2.16) and remained constant in the observation period. Regarding time trend, we found similar results for both sexes. CONCLUSIONS: We found a significant reduction in incidence of blindness in the populations with and without diabetes, which was more prominent among individuals with diabetes compared with the 1990s. Our findings may be explained by effective secondary prevention therapies and improved ophthalmologic care beyond diabetic retinopathy, particularly regarding macular degeneration, which means earlier detection and earlier and better treatment.

Incidence and relative risk of stroke in the diabetic and the non-diabetic population between 1998 and 2014: A community-based stroke register.

One major objective of the St. Vincent Declaration was to reduce excess risk of stroke in people with diabetes mellitus. The aim of this study is to estimate the trend of incidence and relative risk of stroke in the diabetic and the non-diabetic populations in Germany over a 17-year period. We estimated age-sex standardised incidence rates of all stroke and ischaemic stroke in people with and without diabetes based on an ongoing prospective community-based stroke register covering 105,000 inhabitants. Time trends were analysed using Poisson regression. In total, 3,111 individuals (diabetes: 28.4%, men 46.9%, mean age 73.1 years (SD 13.2)) had a first stroke, 84.9% of which were ischaemic stroke. Among people with diabetes we observed a significant reduction in all stroke incidence by 1.5% per year (relative risk: 0.985; 95% confidence interval 0.972-0.9995) Likewise, this incidence tended to decrease for ischaemic stroke by 1% per year (0.993; 0.979-1.008). In contrast, the incidence rate for all stroke remained nearly stable among people without diabetes (1.003; 0.993-1.013) and for ischaemic stroke (1.002; 0.991-1.013). The relative risk comparing diabetic and non-diabetic population decreased for all stroke (two percent annual reduction) but not for ischaemic stroke. Time trends were similar for both sexes regarding all and ischaemic strokes. We found a reduction in risk of stroke in the diabetic population while this rate did not materially change in the non-diabetic population.

Incidence of lower extremity amputations in the diabetic compared with the non-diabetic population: A systematic review.

SYSTEMATIC REVIEW REGISTRATION NUMBER: PROSPERO CRD4201501780.

The Incidence of End-Stage Renal Disease in the Diabetic (Compared to the Non-Diabetic) Population: A Systematic Review.

End-stage renal disease (ESRD) in diabetes is a life threatening complication resulting in a poor prognosis for patients as well as high medical costs. The aims of this systematic review were (1) to evaluate the incidence of ESRD due to all causes and due to diabetic nephropathy in the diabetic population and differences between incidences of ESRD with respect to sex, ethnicity, age and regions, (2) to compare incidence rates in the diabetic and non-diabetic population, and (3) to investigate time trends. The systematic review was conducted according to the PRISMA group guidelines by performing systematic literature searches in the biomedical databases until January 3rd 2015; thirty-two studies were included. Among patients with incident type 1 diabetes the 30-year cumulative incidence ranged from 3.3% to 7.8%. Among patients with prevalent diabetes, incidence rates of ESRD due to all causes ranged from 132.0 to 167.0 per 100,000 person-years, whereas incidence rates of ESRD due to diabetic nephropathy varied from 38.4 to 804.0 per 100,000 person-years. The incidence of ESRD in the diabetic population was higher compared to the non-diabetic population, and relative risks varied from 6.2 in the white population to 62.0 among Native Americans. The results regarding time trends were inconsistent. The review conducted demonstrates the considerable variation of incidences of ESRD among the diabetic population. Consistent findings included an excess risk when comparing the diabetic to the non-diabetic population and ethnic differences. We recommend that newly designed studies should use standardized methods for the determination of ESRD and population at risk.

Incidence of lower extremity amputation in the diabetic compared to the non-diabetic population: a systematic review protocol.

BACKGROUND: Diabetic individuals have a largely increased risk of lower extremity amputation (LEA) compared with non-diabetic patients. Prior systematic reviews of incidence of LEA have some limitations with respect to lack of consensus in the definition of LEA, level of LEA (all, major, minor), and definition of source population (general population or population with diabetes at risk). The purpose of our review is to evaluate the incidence of LEA in the diabetic population and its differences with regard to sex, ethnicity, age, and regions; to compare the incidence rate (IR) in the diabetic and non-diabetic population; and to investigate time trends. METHODS/DESIGN: We will perform a systematic literature search in MEDLINE, Embase, Web of Knowledge, and publisher databases such as Journals@OVID and ScienceDirect. We will develop comprehensive systematic search strategies according to established guidelines for meta-analyses of observational studies in epidemiology (the MOOSE group). Two authors will independently screen abstracts and full text of all references on the basis of inclusion criteria with respect to types of study, types of population, and the main outcome. We will exclude studies if they report solely incidences of LEA among persons with diabetes mellitus when referring to the total population (diabetic and non-diabetic) and not exclusively to the diabetic population. Data extraction and assessment of risk of bias will be undertaken by two review authors working independently. We will assess incidence rate (IR) or cumulative incidence (CumI), relative risk of amputations comparing the diabetic to non-diabetic populations, cause of LEA, and type of diabetes. If we find subsets of studies to be homogeneous enough, we will perform meta-analyses for incidence rates by Poisson generalized linear mixed models (GLMM). SYSTEMATIC REVIEW REGISTRATION: PROSPERO CRD42015017809.

[Patient-relevant outcomes and surrogates in the early benefit assessment of drugs: first experiences]. / Patientenrelevante Endpunkte und Surrogate in der frühen Nutzenbewertung von Arzneimitteln: erste Erfahrungen.

The Act on the Reform of the Market for Medicinal Products (AMNOG) became effective in Germany on January 1, 2011. Since then, the assessment of the added benefit of new drugs versus a therapeutic standard on the basis of dossiers submitted by pharmaceutical companies has been required by law. The Federal Joint Committee (G-BA) generally commissions the Institute for Quality and Efficiency in Health Care (IQWiG) with this task. The added benefit is primarily to be demonstrated on the basis of patient-relevant outcomes. The aim of this paper is to describe the feasibility of the early benefit assessment on the basis of patient-relevant outcomes by systematically characterising the outcomes available in company dossiers and comparing the companies' and IQWiG's evaluations regarding patient relevance and surrogate validity. Dossier assessments published between October 2011 and June 2012 were used for this purpose. The outcomes available and the respective evaluations were extracted and compared. 12 out of 22 submitted dossiers contained sufficient data to assess outcomes; all 12 assessable dossiers provided data on patient-relevant outcomes. Data on mortality and adverse events were available in all dossiers, except that one dossier did not contain adverse event data on the relevant subpopulation. In contrast, data on morbidity and health-related quality of life were available in 8 and 7 dossiers, respectively. Of a total of 214 outcomes extracted by IQWiG, 124 patient-relevant and 3 surrogate outcomes were included in IQWiG's assessment (companies: a total of 183 outcomes included, of which 172 were patient-relevant and 11 were surrogates). The first experiences with AMNOG have shown that in principle an early benefit assessment of drugs based on patient-relevant outcomes is feasible. The companies' and IQWiG's evaluations regarding patient relevance and surrogate validity of outcomes partly deviated from each other. By increasingly considering patient-relevant outcomes in approval studies, pharmaceutical companies can create the necessary data basis for the early benefit assessment.