Smoking and Second Hand Smoking in Adolescents with Chronic Kidney Disease: A Report from the Chronic Kidney Disease in Children (CKiD) Cohort Study

The goal of this study was to determine the prevalence of smoking and second hand smoking [SHS] in adolescents with CKD and their relationship to baseline parameters at enrollment in the CKiD, observational cohort study of 600 children (aged 1-16 yrs) with Schwartz estimated GFR of 30-90 ml/min/1.73m2. 239 adolescents had self-report survey data on smoking and SHS exposure: 21 [9%] subjects had “ever” smoked a cigarette. Among them, 4 were current and 17 were former smokers. Hypertension was more prevalent in those that had “ever” smoked a cigarette (42%) compared to non-smokers (9%), p\u3c0.01. Among 218 non-smokers, 130 (59%) were male, 142 (65%) were Caucasian; 60 (28%) reported SHS exposure compared to 158 (72%) with no exposure. Non-smoker adolescents with SHS exposure were compared to those without SHS exposure. There was no racial, age, or gender differences between both groups. Baseline creatinine, diastolic hypertension, C reactive protein, lipid profile, GFR and hemoglobin were not statistically different. Significantly higher protein to creatinine ratio (0.90 vs. 0.53, p\u3c0.01) was observed in those exposed to SHS compared to those not exposed. Exposed adolescents were heavier than non-exposed adolescents (85th percentile vs. 55th percentile for BMI, p\u3c 0.01). Uncontrolled casual systolic hypertension was twice as prevalent among those exposed to SHS (16%) compared to those not exposed to SHS (7%), though the difference was not statistically significant (p= 0.07). Adjusted multivariate regression analysis [OR (95% CI)] showed that increased protein to creatinine ratio [1.34 (1.03, 1.75)] and higher BMI [1.14 (1.02, 1.29)] were independently associated with exposure to SHS among non-smoker adolescents. These results reveal that among adolescents with CKD, cigarette use is low and SHS is highly prevalent. The association of smoking with hypertension and SHS with increased proteinuria suggests a possible role of these factors in CKD progression and cardiovascular outcomes

A Systematic Review and Meta-Analysis of the Incidence of Injury in Professional Female Soccer

The epidemiology of injury in male professional football is well documented and has been used as a basis to monitor injury trends and implement injury prevention strategies. There are no systematic reviews that have investigated injury incidence in women’s professional football. Therefore, the extent of injury burden in women’s professional football remains unknown. PURPOSE: The primary aim of this study was to calculate an overall incidence rate of injury in senior female professional soccer. The secondary aims were to provide an incidence rate for training and match play. METHODS: PubMed, Discover, EBSCO, Embase and ScienceDirect electronic databases were searched from inception to September 2018. Two reviewers independently assessed study quality using the Strengthening the Reporting of Observational Studies in Epidemiology statement using a 22-item STROBE checklist. Seven prospective studies (n=1137 professional players) were combined in a pooled analysis of injury incidence using a mixed effects model. Heterogeneity was evaluated using the Cochrane Q statistic and I2. RESULTS: The epidemiological incidence proportion over one season was 0.62 (95% CI 0.59 - 0.64). Mean total incidence of injury was 3.15 (95% CI 1.54 - 4.75) injuries per 1000 hours. The mean incidence of injury during match play was 10.72 (95% CI 9.11 - 12.33) and during training was 2.21 (95% CI 0.96 - 3.45). Data analysis found a significant level of heterogeneity (total Incidence, X2 = 16.57 P < 0.05; I2 = 63.8%) and during subsequent sub group analyses in those studies reviewed (match incidence, X2 = 76.4 (d.f. = 7), P <0.05; I2 = 90.8%, training incidence, X2 = 16.97 (d.f. = 7), P < 0.05; I2 = 58.8%). Appraisal of the study methodologies revealed inconsistency in the use of injury terminology, data collection procedures and calculation of exposure by researchers. Such inconsistencies likely contribute to the large variance in the incidence and prevalence of injury reported. CONCLUSIONS: The estimated risk of sustaining at least one injury over one football season is 62%. Continued reporting of heterogeneous results in population samples limits meaningful comparison of studies. Standardising the criteria used to attribute injury and activity coupled with more accurate methods of calculating exposure will overcome such limitations

Trial efficacy vs real world effectiveness in first line treatment of multiple myeloma

Background: Large randomized clinical trials (RCT) are the foundation of the registration of newly developed drugs. A potential problem with RCTs is that the inclusion/exclusion criteria will make the population different from the actual population treated in real life. Hence, it is important to understand how the results from the RCT can be generalized to a general population. Aims: The primary aim of the present study was to assess the generalizability of the large 1st line RCTs in Multiple Myeloma (MM) to the Nordic setting and to understand potential difference and magnitude in outcomes between RCTs and patients treated in standard care in the Nordics. Methods: A retrospective analysis was performed on an incident cohort of 2960 MM-patients from 24 hospitals in Denmark, Finland, Norway and Sweden. The database contained information on patient baseline characteristics, treatments and outcomes. Data from relevant 1st line MM RCTs was selected from the treatment MP (Waage, A., et al., Blood. 2010], MPT (Waage, A., et al., Blood. 2010) and VMP (San Miguel, J.F., et al., N Engl J Med, 2008) and baseline characteristics were compared to newly diagnosed Nordic MM treated patients. Potential difference in response and overall survival (OS) was estimated by adjusting the RWE population to the RCT population using matching adjusted indirect comparisons. Patients were matched on age (median approximated to mean), gender, calcium, beta2-microglobulin and ISS score 3. These variables were selected because they were reported in all trials and have previously been identified as having prognostic value. Results: Patients in the Nordic database treated with MP (n=880) had a response rate of (PD, NR, PR, VGPR, ≥nCR) of (13%, 39%, 38%, 6%, 4%). After matching (n=347), the response rate was slightly worse (12%, 43%, 36%, 6%, 3%). This can be compared to the response rate from the RCT of (7%, 53%, 33%, 3%, 4%). OS for Nordic MP treated patients was 2.67 years (2.25-3.17). After matching the OS was 3.37 years (2.86-3.96) and this can be compared to the trial with OS 2.40 years (2.23-2.66). Patients treated with MPT (n=283) in the Nordic countries had a response rate of (5%, 14%, 52%, 20%, 9%). After matching (n=179) the response rate was slightly changed to (6%, 20%, 50%, 13% 11%). The corresponding RCT response results were 14%, 29%, 34%, 10%, and 13% respectively. OS for Nordic MPT treated patients was 4.15 years (3.73- 4.74). After matching the OS was 4.28 years (3.98-NA) years and compared to 2.42 years (2.08-3.17) OS observed in the corresponding trial. Patients treated with VMP (n=59) in the Nordic countries had a response rate of (4%, 5%, 40%, 18%, 33%). After matching (n=31) the response rate was improved to (8%, 11%, 28%, 8%, 45%). This corresponding response rates shown in the trial are 1%, 23%, 33%, 8%, and 33% respectively. OS for Nordic MP treated patients was 4.86 years (3.79-NA). After matching the OS was 4.86 years (4.86-NA) and this can be compared to the trial with OS 4.70 years. Summary and Conclusions: Surprisingly Nordic treated MM patients do very well compared to, and even better than, patients treated in RCTs. Since the OS for all tested treatments improves after matching to the RCT baseline characteristics, patients recruited to the RCTs seems to be a bit better than ordinary Nordic patents. The database used in the present study, and the used method, can be valuable for generalizing the results to the Nordic setting and estimating potential difference for future RCTs and Nordic MM treated patients. Future research should include different data cuts to see whether the analyses are biased by differences subsequent treatments applied in RCTs and clinical practice

Micro-costing study of rituximab subcutaneous injection versus intravenous infusion in dutch setting

Background: Rituximab for subcutaneous (SC) administration has recently been approved for use in common forms of diffuse large B-cell lymphoma (DLBCL). This form of rituximab is supplied in ready-to-use vials that do not require individual dose adjustment. It is expected that SC-injection will shorten the treatment time per administration of rituximab in comparison with currently available intravenous (IV) infusion. Aims: The goal of this study is to identify and compare all direct costs of IV and SC rituximab given to the DLBCL patients in the Netherlands. Methods: Using a prospective, observational, bottom up, micro-costing study we collected primary data on the direct medical costs of the preparation, administration and acquisition of rituximab. Drug costs and spillage, labor costs, material costs and remaining daycare costs were identified using standardized forms, structured using guideline prices and compared for the IV and SC forms of rituximab. Results: Measurements were done on 53 administrations (33 IV and 20 SC). The mean total costs of the IV infusion were €2174, and €1907 for the SC injection. The estimated difference of €267 per administration was mainly due to spillage costs and differences in chair time, related daycare costs and drug costs. Summary and Conclusions: Rituximab administered in the form of SC injection is less costly than its IV form. Taking into account their equal effectiveness, favorable pharmacoeconomic profile of SC rituximab can result in significant savings when transferred to the total DLBCL population in the Netherlands