A qualitative study to elicit user requirements for lower limb wearable exoskeletons for gait rehabilitation in spinal cord injury.

OBJECTIVE: We aim to determine a comprehensive set of requirements, perceptions, and expectations that people with spinal cord injury (SCI) and the clinicians in charge of their rehabilitation have regarding the use of wearable robots (WR) for gait rehabilitation. BACKGROUND: There are concerns due to the limited user acceptance of WR for gait rehabilitation. Developers need to emphasize understanding the needs and constraints of all stakeholders involved, including the real-life dynamics of rehabilitation centers. METHODS: 15 people with SCI, 9 without experience with WR and 6 with experience with these technologies, and 10 clinicians from 3 rehabilitation centers in Spain were interviewed. A directed content analysis approach was used. RESULTS: 78 codes grouped into 9 categories (physical results, usability, psychology-related codes, technical characteristics, activities, acquisition issues, context of use, development of the technologies and clinical rehabilitation context) were expressed by at least 20% of the users interviewed, of whom 16 were not found in the literature. The agreement percentage between each group and subgroup included in the study, calculated as the number of codes that more than 20% of both groups expressed, divided over the total amount of codes any of those two groups agreed on (≥ 20%), showed limited agreement between patients and clinicians (50.00%) and between both types of patients (55.77%). The limited accessibility and availability of lower limb exoskeletons for gait rehabilitation arose in most of the interviews. CONCLUSIONS: The limited agreement percentage between patients and clinicians indicates that including both types of users in the design process of these technologies is important, given that their requirements are complementary. Engaging users with prior technology experience is recommended, as they often exhibit strong internal consensus and articulate well-defined requirements. This study adds up the knowledge available in the literature and the new codes found in our data, which enlighten important aspects that ought to be addressed in the field to develop technologies that respond to users' needs, are usable and feasible to implement in their intended contexts. APPLICATION: The set of criteria summarized in our study will be useful to guide the design, development, and evaluation of WR for gait rehabilitation to meet user's needs and allow them to be implemented in their intended context of use.

BRCA testing and outcomes in women with breast cancer.

MAIN PURPOSE: Germline BRCA mutations (BRCAm) strongly influence the risk of developing breast cancer. This study aimed to understand the role of BRCAm testing in affected individuals and to assess its impact on the outcome of BRCAm carriers compared to non-carriers (BRCAwt) with breast cancer. RESEARCH QUESTION: The research question is "Does standard of care testing for BRCAm improve survival outcomes of breast cancer patients?" METHODS: In a single institution observational cohort study, demographic and clinical characteristics were compared between breast cancer patients with and without BRCAm. Frequency of BRCA testing was assessed. Survival outcomes were assessed by initial treatment setting stratified by BRCA status. RESULTS: Of 5712 identified women with breast cancer, 14.6% (n = 835) were tested for a BRCA mutation and had a documented result. The total number and proportion of women tested for a BRCAm increased between 2000 and 2014, resulting in an increased number of BRCAm carriers identified. However, the proportion of women who underwent testing and had a BRCAm decreased during the study period from 27.5% in 2000-2004 to 13.3% in 2010-2014. Disease-free survival was similar in the adjuvant and neoadjuvant treatment settings between BRCAm and BRCAwt patients. Progression-free survival on first line treatment and overall survival for patients with metastatic disease was also similar between BRCAm and BRCAwt patients. CONCLUSIONS: The proportion of women tested and the number of BRCAm identified increased during the study period despite a decreasing proportion of positive results among women tested.

Validity of hospital ICD-10-GM codes to identify anaphylaxis.

PURPOSE: Anaphylaxis (ANA) is an important adverse drug reaction. We examined positive predictive values (PPV) and other test characteristics of ICD-10-GM code algorithms for detecting ANA as used in a multinational safety study (PASS). METHODS: We performed a cross-sectional study on routine data from a German academic hospital (2004-2019, age ≥ 18). Chart review was used for case verification. Potential cases were identified from the hospital administration system. The main outcome required at least one of the following: any type of specific in-hospital code (T78.2, T88.6, and T80.5) OR specific outpatient code in combination with a symptom code OR in-hospital non-specific code (T78.4, T88.7, and Y57.9) in combination with two symptom codes. PPV were calculated with 95% confidence interval. Sensitivity analyses modified type of codes, unit of analysis, verification criteria and time period. The most specific algorithm used only primary codes for ANA (numbers added in brackets). RESULTS: Four hundred and sixteen eligible cases were evaluated, and 78 (37) potential ANA cases were identified. PPV were 62.8% (95% CI 51.1-73.5) (main) and 77.4% (58.9-90.4) (most specific). PPV from all modifications ranged from 12.9% to 80.6%. The sensitivity of the main algorithm was 66.2%, specificity 91.5%, and negative predictive value 92.6%. Corresponding figures for the most specific algorithm were 32.4%, 98.0%, and 87.0%. CONCLUSIONS: The PPV of the main algorithm seems of acceptable validity for use in comparative safety research but will underestimate absolute risks by about a third. Restriction to primary discharge codes markedly improves PPV to the expense of reducing sensitivity.

Use of intravenous iron and risk of anaphylaxis: A multinational observational post-authorisation safety study in Europe.

PURPOSE: This post-authorisation safety study estimated the risk of anaphylaxis in patients receiving intravenous (IV) iron in Europe, with interest in iron dextran and iron non-dextrans. Studies conducted in the United States have reported risk of anaphylaxis to IV iron ranging from 2.0 to 6.8 per 10 000 first treatments. METHODS: Cohort study of IV iron new users, captured mostly through pharmacy ambulatory dispensing, from populations covered by health and administrative data sources in five European countries from 1999 to 2017. Anaphylaxis events were identified through an algorithm that used parenteral penicillin as a positive control. RESULTS: A total of 304 210 patients with a first IV iron treatment (6367 iron dextran), among whom 13-16 anaphylaxis cases were identified and reported as a range to comply with data protection regulations. The pooled unadjusted incidence proportion (IP) ranged from 0.4 (95% confidence interval [CI], 0.2-0.9) to 0.5 (95% CI, 0.3-1.0) per 10 000 first treatments. No events were identified at first dextran treatments. There were 231 294 first penicillin treatments with 30 potential cases of anaphylaxis (IP = 1.2; 95% CI, 0.8-1.7 per 10 000 treatments). CONCLUSION: We found an IP of anaphylaxis from 0.4 to 0.5 per 10 000 first IV iron treatments. The study captured only a fraction of IV iron treatments administered in hospitals, where most first treatments are likely to happen. Due to this limitation, the study could not exclude a differential risk of anaphylaxis between iron dextran and iron non-dextrans. The IP of anaphylaxis in users of penicillin was consistent with incidences reported in the literature.

Utilization and safety of onabotulinumtoxinA for the prophylactic treatment of chronic migraine from an observational study in Europe.

Objective To examine treatment utilization patterns and safety of onabotulinumtoxinA for the prophylactic treatment of chronic migraine in routine clinical practice. Background Clinical trials support onabotulinumtoxinA for the prophylaxis of headache in patients with chronic migraine, but real-world data are limited. Design/methods A prospective, observational, post-authorization study in adult patients with chronic migraine treated with onabotulinumtoxinA. Data were collected at the first study injection and approximately every three months for ≤52 weeks for utilization and ≤64 weeks for safety data, and summarized using descriptive statistics. Results Eighty-five physicians (81% neurologists) at 58 practices in the United Kingdom, Germany, Spain, and Sweden participated and recruited 1160 patients (84.2% female, median age 46.6 years). At baseline, 85.8% of patients had physician diagnoses of chronic migraine/transformed migraine and reported an average of 11.3 (SD = 6.9) severe headache days per 28 days; 50.6% had previously used onabotulinumtoxinA for chronic migraine. A total of 4017 study treatments were observed. The median number of injection sites (n = 31) and total dose (155 U) were consistent across all treatment sessions, with a median 13.7 weeks observed between sessions. At least one treatment-related adverse event was reported by 291 patients (25.1%); the most frequently reported treatment-related adverse event was neck pain (4.4%). Most patients (74.4%) were satisfied/extremely satisfied with onabotulinumtoxinA treatment. Conclusions Patient demographics/characteristics are consistent with published data on the chronic migraine population. Utilization of onabotulinumtoxinA treatment for chronic migraine appears to be consistent with the Summary of Product Characteristics and published PREEMPT injection paradigm. No new safety signals were identified.

Long-Term Risk of Skin Cancer and Lymphoma in Users of Topical Tacrolimus and Pimecrolimus: Final Results from the Extension of the Cohort Study Protopic Joint European Longitudinal Lymphoma and Skin Cancer Evaluation (JOELLE).

PURPOSE: Evidence is insufficient to infer whether topical calcineurin inhibitors (TCIs; tacrolimus and pimecrolimus) cause malignancy. The study objective was to estimate the long-term risk of skin cancer and lymphoma associated with topical TCI use in adults and children, separately. PATIENTS AND METHODS: A cohort study in Denmark, Sweden, UK, and the Netherlands was conducted. Adjusted incidence rate ratios (IRRs) and 95% confidence intervals (CIs) were calculated for nonmelanoma skin cancer (NMSC), melanoma, cutaneous T-cell lymphoma (CTCL), non-Hodgkin lymphoma (NHL) excluding CTCL, and Hodgkin lymphoma (HL) in new users of TCIs versus users of moderate/high-potency topical corticosteroids. RESULTS: The study included 126,908/61,841 adults and 32,605/27,961 children initiating treatment with tacrolimus/pimecrolimus, respectively. Follow-up was ≥10 years for 19% of adults and 32% of children. Incidence rate ratios and (95% confidence intervals) for tacrolimus versus corticosteroid users in adults were <1 for melanoma, non-Hodgkin lymphoma, and Hodgkin lymphoma; and 1.80 (1.25-2.58) for cutaneous T-cell lymphoma. For pimecrolimus, IRRs in adults were <1 for non-Hodgkin lymphoma, cutaneous T-cell lymphoma, and Hodgkin's lymphoma; and 1.21 (1.03-1.41) for melanoma; and 1.28 (1.20-1.35) for nonmelanoma skin cancer. In children, results were inconclusive due to few events. In adults, incidence rate ratios ≥5 years after first topical calcineurin inhibitor exposure were not higher than in overall analyses. CONCLUSION: Overall, we found little evidence associating use of topical calcineurin inhibitors with skin cancer and lymphoma; confounding by indication, surveillance bias, and reverse causation may have influenced these results. Even if causal, the public health impact of these excess risks would be low and confined to the first years of exposure.

Agomelatine Drug Utilisation Study in Selected European Countries: A Multinational, Observational Study to Assess Effectiveness of Risk-Minimisation Measures.

BACKGROUND: Hepatotoxic reactions are an important identified risk listed in the agomelatine risk management plan. This post-authorisation safety study evaluated the effectiveness of additional risk-minimisation measures (aRMMs) for agomelatine. OBJECTIVE: The objective of this study was to evaluate, among physicians prescribing agomelatine and their patients, liver function monitoring adherence, compliance with contraindications and patients' reasons for non-compliance with liver monitoring. METHODS: A non-interventional cohort study was conducted among adults initiating agomelatine in routine clinical practice in Denmark, France, Germany and Spain through a retrospective medical record abstraction (MRA) before and after implementation of aRMMs and a cross-sectional patient survey. RESULTS: Fifty-four sites contributed data on 437 and 404 patients in the before- and after-RMM periods, and 237 patients completed the survey. No patient had cirrhosis in either study period; 98.2% of patients in the before- and 98.0% in the after-RMM period had no active liver disease reported at initiation or during treatment. Compliance to contraindicated medications was > 99% in both periods. The adherence to the liver-monitoring regimen was similar in both periods (15.1% before RMM and 16.3% after RMM). In the after-RMM period, 25.2% of patients had a liver test before or at treatment initiation; 61.5% had a liver test during treatment. Among patients surveyed who did not have a blood test before treatment initiation or during treatment, the most frequently cited reason was a test ordered but not yet performed. CONCLUSIONS: The overall adherence to liver-monitoring recommendations remained weakly influenced by aRMMs. However, patients treated with agomelatine are in compliance with relevant contraindications.

A cohort study on the risk of lymphoma and skin cancer in users of topical tacrolimus, pimecrolimus, and corticosteroids (Joint European Longitudinal Lymphoma and Skin Cancer Evaluation - JOELLE study).

BACKGROUND: There is a concern that topical tacrolimus and pimecrolimus, indicated for second-line treatment of atopic dermatitis, may increase the risk of lymphoma and skin cancer, particularly in children. OBJECTIVE: The aim of this study was to compare incidence rates (IRs) of lymphoma and skin cancer between new users of topical tacrolimus or pimecrolimus and users of moderate- to high-potency topical corticosteroids (TCSs) and untreated subjects. METHODS: This is a multicenter cohort study with frequency matching by strata of propensity scores in population databases in the Netherlands, Denmark, Sweden, and the UK. IR ratios (IRRs) were estimated using Mantel-Haenszel methods for stratified analysis. RESULTS: We included 19,948 children and 66,127 adults initiating tacrolimus, 23,840 children and 37,417 adults initiating pimecrolimus, 584,121 users of TCSs, and 257,074 untreated subjects. IRs of lymphoma per 100,000 person-years were 10.4 events in children and 41.0 events in adults using tacrolimus and 3.0 events in children and 27.0 events in adults using pimecrolimus. The IRR (95% confidence interval [CI]) for lymphoma, tacrolimus versus TCSs, was 3.74 (1.00-14.06) in children and 1.27 (0.94-1.71) in adults. By lymphoma type, the highest IRR was 3.17 (0.58-17.23) for Hodgkin lymphoma in children and 1.76 (95% CI, 0.81-3.79) for cutaneous T-cell lymphoma (CTCL) in adults. For pimecrolimus versus TCSs, the highest IRR was 1.31 (95% CI, 0.33-5.14) for CTCL in adults. Compared with untreated subjects, adults using TCSs had a higher incidence of CTCL (IRR, 10.66; 95% CI, 2.60-43.75). Smaller associations were found between tacrolimus and pimecrolimus use and the risk of malignant melanoma or nonmelanoma skin cancer. CONCLUSION: Use of topical tacrolimus and pimecrolimus was associated with an increased risk of lymphoma. The low IRs imply that even if the increased risk is causal, it represents a small excess risk for individual patients. Residual confounding by severity of atopic dermatitis, increased monitoring of severe patients, and reverse causation could have affected the results.

Use of Topical Tacrolimus and Topical Pimecrolimus in Four European Countries: A Multicentre Database Cohort Study.

BACKGROUND: Despite the concerns about a potential increased risk of skin cancer and lymphoma with the use of topical tacrolimus and pimecrolimus, no population-based studies have given an overview of the use of these drugs in Europe. OBJECTIVE: To assess the use of topical tacrolimus and pimecrolimus in children and adults in Europe. METHODS: Multicentre database cohort study comprising data from the Netherlands, Denmark, Sweden and the UK. We analysed users of topical tacrolimus and pimecrolimus starting from the date of first availability (between 2002 and 2003) or start establishment of the prescription database in Sweden (2006) through 2011. Use was assessed separately for children (≤ 18 years) and adults. RESULTS: 32,052 children and 104,902 adults were treated with topical tacrolimus, and 32,125 children and 58,280 adults were treated with topical pimecrolimus. The number of users increased rapidly after first availability, especially for topical tacrolimus. Topical tacrolimus was more frequently used in all countries except Denmark. For both drugs, there was a decrease in users after 2004 in the Netherlands and Denmark and after 2005 in the UK, especially among children. This decrease was largest in Denmark. The decrease in the number of users was temporary for topical tacrolimus, while use remained relatively low for topical pimecrolimus. CONCLUSIONS: The number of topical tacrolimus and pimecrolimus users increased rapidly after regulatory approval. A transient reduction in topical tacrolimus use and a persistent reduction in topical pimecrolimus use was seen after 2004 in the Netherlands and Denmark and after 2005 in the UK.

Clinical outcomes of female breast cancer according to BRCA mutation status.

BACKGROUND: To investigate breast cancer prognosis (disease-free (DFS) and overall survival (OS)) among carriers of germline BRCA mutations (BRCAm) in Denmark. METHODS: We identified all women in Central and Northern Denmark diagnosed with breast cancer during 2004-2011. We retrieved information on germline BRCAm testing from Clinical Genetics departments and clinical/treatment characteristics from population-based medical registries. Follow-up for recurrence, new primary cancer, and mortality extended from 180days after diagnosis until 31/12/2012. We estimated median DFS and OS and five-year cumulative incidence and incidence rates (IR/1000 person-years), and 95% confidence intervals (95% CI), for each outcome. RESULTS: Among 9874 patients, 523 (5%) underwent BRCA testing-90 were BRCAm carriers, 433 were BRCA wildtype (BRCAwt). Compared with BRCAwt women, BRCAm carriers were younger, had lower stage, and ER- and HER2- tumors. Median time from diagnosis to BRCA testing was 0.91 years and 1.3 years in BRCAm and BRCAwt women; median follow-up to first event was 3.9 and 3.4 years, respectively. Five-year DFS and OS were higher in BRCAm than BRCAwt women: 88% (95%CI=78.3-93.5) vs. 75.3% (95%CI=70.2-79.6) and 97.8% (95%CI=91.4-99.4) vs 92.2% (95%CI=88.5-94.7), respectively. Five-year IRs of recurrence were 36.7/1000 person-years (95%CI=15.8-72.2) in the BRCAm cohort vs. 58.4 (95%CI=42.9-77.6) in the BRCAwt cohort. CONCLUSIONS: BRCAm carriers may have a better prognosis than BRCAwt women. However, limited testing conducted mainly during follow-up, yielded low numbers for precise estimations, and may be attributable to selection bias.

Hormone therapy and cerebrovascular events: a population-based nested case-control study.

OBJECTIVE: The relationship between postmenopausal hormone therapy (HT) and cerebrovascular disease has been examined in several epidemiological studies and clinical trials with conflicting results. The authors aimed to evaluate the association between the use of HT and the incidence of first cerebrovascular event. DESIGN: The study cohort comprised 158,031 women 50 to 69 years old registered in the U.K. General Practice Research Database between 1991 and 1997. The authors conducted a nested case-control analysis using all 920 confirmed cases of cerebrovascular events identified during the follow-up (536 of transient ischemic attack [TIA]; 259 of ischemic stroke; 125 of hemorrhagic stroke) and 10,000 controls. RESULTS: The odds ratios of TIA, ischemic stroke, and hemorrhagic stroke among women currently using HT were 1.48 (95% CI, 1.17-1.87), 1.12 (95% CI, 0.78-1.59) and 1.21 (95% CI, 0.76-1.93), respectively, compared to never users. The overall risk estimate for having a cerebrovascular event was 1.34 (95% CI, 1.11-1.61). The risk of TIA was greater (1.96) among women using high doses of estrogen (95% CI, 1.34-2.87). CONCLUSION: Overall, a small increased risk of stroke associated with HT use of comparable magnitude to the one observed in recent clinical trials was found. The increased risk was more apparent for TIA than for stroke and was greater at higher doses.

Clinical burden and incremental cost of fractures in postmenopausal women in the United Kingdom.

This cohort study of postmenopausal women in the United Kingdom aged ≥50years determined the incremental cost of health care and clinical outcomes in the 12months following incident, selected fractures (non-vertebral non-hip [NVNHF], vertebral [VF] and multiple [MF]). Incremental costs and outcomes of the fracture cohorts were compared with those of cohorts comprised of women without fractures who were individually matched on age and comorbidity. Cohorts were identified from The Health Improvement Network database, a primary health care database, from 2001 to 2005. We estimated 1-year incremental costs (hospitalizations; general practice, accident/emergency, and referral visits; and prescription medications) associated with each fracture type. Descriptive analyses examined occurrence of subsequent fractures and death. No long-term health care costs or outcomes were assessed. Overall, 14,030 women had NVNHF, 1471 had VF, and 193 had MF. The risk of death was greater for women with fractures than for women in the non-fracture cohorts. Mean incremental cost for fractures compared with no fractures was £1152 for VF; £690 for NVNHF, and £2581 for MF. Of the total incremental cost, hospitalizations represented 54%-90% and medications represented 7%-29%. In all fracture cohorts, most of the total annual costs were concentrated in the 6months after the date of fracture. Fractures among postmenopausal women represent an important burden to the health system due to the increase in health resource utilization and related costs. In this study, hospitalizations were the main driver of the overall incremental cost during the 12months following the fracture. Mortality in women in the selected fracture cohorts was higher than in women in the non-fracture cohorts.

Clinical characteristics and outcomes in familial adenomatous polyposis patients with a long-term treatment of celecoxib: a matched cohort study.

Familial adenomatous polyposis (FAP) is a rare genetic disease. Without treatment, FAP patients have a 100% lifetime risk of developing colorectal cancer. This study was conducted to evaluate the effect of celecoxib treatment in prolonging the time to FAP-related events and to document the safety profile of the long-term use of celecoxib (≥6 months) in FAP patients. FAP patients receiving celecoxib in routine clinical practice were individually matched with historical/concurrent FAP patients not receiving celecoxib. The study population included patients aged 12 years or older registered in national and regional FAP registries in Denmark, the United States, Spain, and Canada. Descriptive statistics were used to summarize dose and duration among celecoxib treated patients. The primary study endpoints, time-to-next-FAP events, were examined with Kaplan-Meier method. Fifty four celecoxib-treated patients were recruited and a matched control was identified for 13 of these patients. The Kaplan-Meier estimated probability of not having a polypectomy 12 and 60 months post- ileorectal anastomosis in the celecoxib-treated patients (n = 33) was 60.6% and 42.2%, respectively. The estimated probability of not having a polypectomy 6-60 months post-ileal pouch-anal anastomosis the celecoxib-treated patients (n = 24) was 100%. The median total daily dose of celecoxib was 698.9 mg with the majority treated more than 24 months. Five celecoxib-treated patients experienced 6 serious adverse events with one of these events (rash) considered related to celecoxib. Long term celecoxib treatment appeared to be well tolerated in FAP patients with or without FAP-related surgeries.

Study of the incremental cost and clinical burden of hip fractures in postmenopausal women in the United Kingdom.

OBJECTIVE: To determine the incremental cost of healthcare and clinical outcomes in the 12 months following incident hip fractures among postmenopausal women in the UK. METHODS: Retrospective cohort study of women aged 50 years or older hospitalized for an incident hip fracture within 1 week of the fracture date who were age- and comorbidity-matched to women without fracture. Cohorts were identified in the Health Improvement Network database, and followed up for 1 year. RESULTS: Among 2,427 women who had a hip fracture and a recorded hospitalization, the mean [SD] age was 81 [9.3] years. About 18% of women without fractures were hospitalized during follow-up and 18% of women with hip fractures and 4% of women without fractures had at least one emergency admission (RR, 4.7; 95% CI, 3.8-5.8). There were no major differences in use of general practitioner visit, referral visits, or in prescription of medications. Mortality was 18% in the hip fracture cohort and 7% in the non-fracture cohort (RR, 2.5; 95% CI, 2.1-3.0). The overall 1-year mean incremental cost of hip fractures was £4,222 (95% CI, £4,105-4,339); most of this cost (97%) was for hospitalizations, with an increment of £4,095. About 98% of the incremental cost occurred in the first 6 months following hip fracture. CONCLUSIONS: The results of this study indicate that the cost and clinical burden associated with hip fractures in postmenopausal women in the UK are considerable. The incremental cost is mostly related to the cost of hospitalization and treatment of the hip fracture. Key limitations were the inclusion of only those women with a recorded hospitalization, and that costs associated with rehabilitation services, social services, and long-term care were not recorded in this study, although these are important contributors to the total cost of fractures.

Registries as a tool in evidence-based medicine: example of KIMS (Pfizer International Metabolic Database).

PURPOSE: To evaluate the value of a registry, set in 'real-life practice', as a contribution to evidence-based medicine and to estimate the impact of information collected in such a registry, on the up to date knowledge in growth hormone (GH)-related disorders. METHODS: Analysis of data collected prospectively for a pharmacoepidemiological registry--KIMS (Pfizer International Metabolic Database)--in assessing long-term clinical and safety outcomes of GH treatment (Genotropin) in patients with GH deficiency. The study was based on 11,374 treated (40,000 patient-years of observation) and 263 untreated adult GH deficient patients from 30 countries, in whom background characteristics, clinical values such as lipids and body composition, quality of life (QoL) and GH dosage as well as safety profile were evaluated. Citation analysis for the published papers was also performed. RESULTS: The study depicts the clinical picture of adult patients with GH deficiency managed in current clinical settings. It confirms the features previously detected such as increased cardiovascular risk, mostly dyslipidemia and abnormal body composition as well as impaired QoL. There was considerable heterogeneity of conditions resulting in GH deficiency. The large database also enabled study of rare causes of the condition. The 31 out of 36 KIMS papers were cited 544 times, in 125 different journals. CONCLUSIONS: These findings and the further insight into the response to GH replacement therapy show that the registry methodology is valuable for filling the gaps of information in evidence-based medicine that cannot be addressed by clinical trials.