Long-term therapies such as disease modifying therapy for Multiple Sclerosis (MS) demand high levels of medication adherence in order to reach acceptable outcomes. The objective of this study was to ...describe adherence to four disease modifying drugs (DMDs) among statutorily insured patients within two years following treatment initiation. These drugs were interferon beta-1a i.m. (Avonex), interferon beta-1a s.c. (Rebif), interferon beta-1b s.c. (Betaferon) and glatiramer acetate s.c. (Copaxone).
This retrospective cohort study used pharmacy claims data from the data warehouse of the German Institute for Drug Use Evaluation (DAPI) from 2001 through 2009. New or renewed DMD prescriptions in the years 2002 to 2006 were identified and adherence was estimated during 730 days of follow-up by analyzing the medication possession ratio (MPR) as proxy for compliance and persistence defined as number of days from initiation of DMD therapy until discontinuation or interruption.
A total of 52,516 medication profiles or therapy cycles (11,891 Avonex, 14,060 Betaferon, 12,353 Copaxone and 14,212 Rebif) from 50,057 patients were included into the analysis. Among the 4 cohorts, no clinically relevant differences were found in available covariates. The Medication Possession Ratio (MPR) measured overall compliance, which was 39.9% with a threshold MPR≥0.8. There were small differences in the proportion of therapy cycles during which a patient was compliant for the following medications: Avonex (42.8%), Betaferon (40.6%), Rebif (39.2%), and Copaxone (37%). Overall persistence was 32.3% at the end of the 24 months observation period, i.e. during only one third of all included therapy cycles patients did not discontinue or interrupt DMD therapy. There were also small differences in the proportion of therapy cycles during which a patient was persistent as follows: Avonex (34.2%), Betaferon (33.4%), Rebif (31.7%) and Copaxone (29.8%).
Two years after initiating MS-modifying therapy, only 30-40% of patients were adherent to DMDs.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Depression and diabetes are independent risk factors for one another, and both are associated with increased risk of cognitive decline. Diabetes patients with lower cognitive function are more likely ...to suffer poorer health outcomes. However, the role of depression in cognitive decline among people with diabetes is not well understood. This systematic review assessed whether adults with comorbid diabetes and depression or depressive symptoms exhibit greater cognitive decline relative to individuals with diabetes alone. Searches were run in CINAHL, the Cochrane Central Register of Controlled Trials, EMBASE, PsycINFO, and PubMed (MEDLINE) with no time or language restrictions. Studies were eligible for inclusion if they were of any quantitative study design, included participants aged 18 years or older with diabetes mellitus of which some must have presented with current depression, and measured cognition as an outcome. The Cochrane Collaboration's Risk Of Bias In Non-randomized Studies-of Interventions tool was used for quality assessment of each study and its collected outcome. Fifteen articles were included in the final analysis. The high degree of heterogeneity in exposures, outcomes, and participant characteristics precluded a meta-analysis of any of the studies, and the risk of bias observed in these studies limits the strength of the evidence. Nonetheless, this review found the presence of comorbid depression was associated with poorer cognitive outcomes than for persons with diabetes alone. While large-scale preventive efforts must address epidemic levels of diabetes and its comorbidities, on the patient level healthcare professionals must be cognizant of the added difficulties that depression poses to patients and the extra support required to management diabetes in these cases. This systematic review is registered with the University of York Centre for Reviews and Dissemination under registration number 2015:CRD42015025122.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Summary
Male sex is associated with unfavourable pharmacokinetics and prognosis in elderly patients with diffuse large B‐cell lymphoma (DLBCL). We investigated higher rituximab doses for elderly male ...DLBCL patients. Elderly patients (61–80 years) received 6 cycles CHOP‐14 (cyclophosphamide, doxorubicin, vincristine and prednisone at 14‐day intervals) and were randomized to 8 cycles rituximab (males 500 mg/m2, females 375 mg/m2) every 2 weeks or according to an upfront dose‐dense schedule. In 268 (120 females, 148 males) no difference between the standard and the upfront dose‐dense rituximab schedule was found (3‐year PFS 72% vs. 74%; OS 74% vs. 77%; P = 0.651). The 500 mg/m2 dose of rituximab for male patients was associated with serum levels and exposure times slightly better than in females and a male/female hazard ratio of 0.9 for progression‐free survival (PFS) and 0.8 for overall survival. For elderly males, 500 mg/m2 was not more toxic than 375 mg/m2 rituximab, but improved PFS by 32.5% (P = 0.039), with a trend for a (30%) better overall survival (P = 0.076) in a planned subgroup analysis adjusting for International Prognostic Index risk factors. We conclude that the higher rituximab dose for elderly male patients abrogated the adverse prognosis of male sex without increasing toxicity. In the era of personalized medicine, sex‐specific pharmacokinetics and toxicities should be investigated for all drugs where these parameters impact on outcome.
Abstract Objective To examine the associations between diabetes, disability, and the likelihood of comorbid major depressive disorder (MDD) and generalized anxiety disorder (GAD). Methods Data were ...obtained from the 2012 Canadian Community Health Survey — Mental Health ( N = 17 623). Diabetes assessment consisted of a self-reported diagnosis of diabetes made by a health care professional. Disability was assessed via self-report. 12-Month and lifetime MDD and GAD were assessed with the Composite International Diagnostic Interview 3.0. Results In multinomial logistic regression models adjusted for sociodemographic and health-related factors, having diabetes was associated with a greater likelihood of 12-month comorbid MDD and GAD (OR = 1.99, 95% CI 1.22, 3.25, p = .006), compared with those with neither MDD nor GAD. No significant associations were found for MDD without GAD or GAD without MDD. This pattern of effects held when lifetime diagnoses of MDD and GAD were considered. For individuals with diabetes ( n = 1730), adjusted binary logistic regression models demonstrated that with 12-month diagnoses, MDD without GAD (OR = 2.79, 95% CI 1.39–5.62, p = .004), GAD without MDD (OR = 3.69, 95% CI 1.34–10.11, p = .01), and comorbid MDD and GAD (OR = 4.17, 95% CI 1.66–10.51, p = .002) were associated with greater disability than the control group. Only comorbid MDD and GAD were associated with disability when lifetime diagnoses of MDD and GAD were considered. Conclusions Individuals with diabetes may be particularly vulnerable to comorbid MDD and GAD, and MDD-GAD comorbidity may exacerbate disability in persons with diabetes.
Abstract Objective To examine the potential synergistic associations between prediabetes, depressive and anxiety symptoms, and the risk of incident type 2 diabetes. Methods Data were from the ...Emotional Well-Being, Metabolic Factors and Health Status (EMHS) study and included 2
486 adults between 40
and
69 years without diabetes at baseline. Hemoglobin A1c levels and measures of depressive and anxiety symptoms were collected at baseline and mutually exclusive groups were formed based on the presence/absence of prediabetes and high/low depressive and anxiety symptoms. A follow-up telephone interview conducted approximately 4.6 years later inquired about new diabetes diagnoses. Results 86 participants developed diabetes during the follow-up period. After accounting for sociodemographic, lifestyle, and metabolic characteristics, participants with prediabetes and elevated depressive symptoms had an increased risk of developing diabetes compared to those without prediabetes and with low depressive symptoms (OR = 10.65, 95% CI = 4.60, 24.66). The joint effect of prediabetes and depressive symptoms on diabetes risk was synergistic (Synergy Index = 2.57, 95% CI = 1.02, 6.49). Similar results were found for participants with prediabetes and high symptoms of anxiety (OR = 8.95, 95% CI = 3.54, 22.63), however the joint effect of prediabetes and anxiety symptoms did not significantly exceed additive risk after adjusting for covariates (Synergy Index = 2.39, 95% CI = 0.83, 6.87). Conclusion The combination of prediabetes and depressive or anxiety symptoms was associated with an increased risk of developing diabetes. This study underscores the importance of mental health in the progression from prediabetes to type 2 diabetes.
To study clinical presentation, outcome, and the role of radiotherapy in patients with aggressive B-cell lymphoma and skeletal involvement treated with and without rituximab.
Outcome of patients with ...skeletal involvement was analyzed in a retrospective study of nine consecutive prospective trials of the German High-Grade Non-Hodgkin lymphoma Study Group.
Of 3,840 patients, 292 (7.6%) had skeletal involvement. In the MabThera International Trial (MInT) for young good-prognosis patients and the Rituximab With CHOP Over 60 Years (RICOVER-60) study for elderly patients, the randomized addition of rituximab improved event-free survival (EFS; hazard ratio for MInT HRMInT = 0.4, P > 001; hazard ratio for RICOVER-60 HRRICOVER-60 = 0.6, P > .001) and overall survival (OS; HRMInT = 0.4, P < .001; HRRICOVER-60 = 0.7, P = .002) in patients without skeletal involvement, but failed to improve the outcome of patients with skeletal involvement (EFS: HRMInT = 1.4, P = .444; HRRICOVER-60 = 0.8, P = .449; OS: HRMInT = 0.6, P = .449; HRRICOVER-60 = 1.0, P = .935). Skeletal involvement was associated with a worse outcome after cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) plus rituximab (HREFS = 1.5, P = .048; HROS = 1.1; P = .828), but not after CHOP without rituximab (HREFS = 0.8, P = .181; HROS = 0.7, P = .083). In contrast to rituximab, additive radiotherapy to sites of skeletal involvement was associated with a decreased risk (HREFS = 0.3, P = .001; HROS = 0.5; P = .111).
Rituximab failed to improve the outcome of patients with diffuse large B-cell lymphoma with skeletal involvement, although our data suggest a beneficial effect of radiotherapy to sites of skeletal involvement. Whether radiotherapy to sites of skeletal involvement can be spared in cases with a negative positron emission tomography after immunochemotherapy should be addressed in appropriately designed prospective trials.
Access to affordable daycare might improve population mental health. However, evidence is sparse and restricted to middle- and high-income country settings. We conducted a cluster-randomized ...controlled trial in one low-income setting, rural Rajasthan, India. Communities lacking daycare facilities were identified (n = 160) and randomly selected for assistance in setting up a community-based daycare program (n = 80) or not (n = 80). Women eligible for the daycare program living in these communities completed structured interviews before the intervention (participation rate = 89%) and approximately one year after rollout of the intervention (participation rate = 96%), resulting in a final analytic sample of 3041. Mental distress was measured with the Hindi version of the 12-item General Health Questionnaire (score range: 0–12). We modeled the relation between access to daycare and number of mental distress symptoms (GHQ-12 score) with negative binomial regression using an intention-to-treat approach, which groups women according to if they lived in communities randomized to affordable daycare. We also evaluated the effect of access to daycare on secondary outcomes that may be related to mental distress, including women's work burden, agency, and intimate partner violence (IPV). We found that access to daycare resulted in modest reductions in symptoms of mental distress (mean difference = 0.21, 95% CI: −0.43, 0.02). We found some evidence that daycare reduced IPV, but virtually no change in women's work burden or agency. Our results provide some indication that access to affordable daycare might be one policy lever to improve population mental health.
•We assessed the effect of access to daycare using an intention-to-treat approach.•41% of women living in communities randomized to daycare utilized services.•Access to daycare resulted in modest reductions in women's mental distress.•Access to daycare resulted in modest reductions in intimate partner violence.•Access to daycare did not lead to meaningful changes in agency or work amount.
Summary Background Cyclophosphamide, doxorubicin, vincristine, and prednisolone (CHOP) is used to treat patients with non-Hodgkin lymphoma. Interval decrease from 3 weeks of treatment (CHOP-21) to 2 ...weeks (CHOP-14), and addition of rituximab to CHOP-21 (R-CHOP-21) has been shown to improve outcome in elderly patients with diffuse large B-cell lymphoma (DLBCL). This randomised trial assessed whether six or eight cycles of R-CHOP-14 can improve outcome of these patients compared with six or eight cycles of CHOP-14. Methods 1222 elderly patients (aged 61–80 years) were randomly assigned to six or eight cycles of CHOP-14 with or without rituximab. Radiotherapy was planned to sites of initial bulky disease with or without extranodal involvement. The primary endpoint was event-free survival; secondary endpoints were response, progression during treatment, progression-free survival, overall survival, and frequency of toxic effects. Analyses were done by intention to treat. The trial is registered on National Cancer Institute website, number NCT00052936 and as EU-20243. Findings 3-year event-free survival was 47·2% after six cycles of CHOP-14 (95% CI 41·2–53·3), 53·0% (47·0–59·1) after eight cycles of CHOP-14, 66·5% (60·9–72·0) after six cycles of R-CHOP-14, and 63·1% (57·4–68·8) after eight cycles of R-CHOP-14. Compared with six cycles of CHOP-14, the improvement in 3-year event-free survival was 5·8% (−2·8–14·4) for eight cycles of CHOP-14, 19·3% (11·1–27·5) for six cycles of R-CHOP-14, and 15·9% (7·6–24·2) for eight cycles of R-CHOP-14. 3-year overall survival was 67·7% (62·0–73·5) for six cycles of CHOP-14, 66·0% (60·1–71·9) for eight cycles of CHOP-14, 78·1% (73·2–83·0) for six cycles of R-CHOP-14, and 72·5% (67·1–77·9) for eight cycles of R-CHOP-14. Compared with treatment with six cycles of CHOP-14, overall survival improved by −1·7% (−10·0–6·6) after eight cycles of CHOP-14, 10·4% (2·8–18·0) after six cycles of R-CHOP-14, and 4·8% (−3·1–12·7) after eight cycles of R-CHOP-14. In a multivariate analysis that used six cycles of CHOP-14 without rituximab as the reference, and adjusting for known prognostic factors, all three intensified regimens improved 3-year event-free survival (eight cycles of CHOP-14: RR relative risk 0·76 0·60–0·95, p=0·0172; six cycles of R-CHOP-14: RR 0·51 0·40–0·65, p<0·0001; eight cycles of R-CHOP-14: RR 0·54 0·43–0·69, p<0·0001). Progression-free survival improved after six cycles of R-CHOP-14 (RR 0·50 0·38–0·67, p<0·0001), and eight cycles of R-CHOP-14 (RR 0·59 0·45–0·77, p=0·0001). Overall survival improved only after six cycles of R-CHOP-14 (RR 0·63 0·46–0·85, p=0·0031). In patients with a partial response after four cycles of chemotherapy, eight cycles were not better than six cycles. Interpretation Six cycles of R-CHOP-14 significantly improved event-free, progression-free, and overall survival over six cycles of CHOP-14 treatment. Response-adapted addition of chemotherapy beyond six cycles, though widely practiced, is not justified. Of the four regimens assessed in this study, six cycles of R-CHOP-14 is the preferred treatment for elderly patients, with which other approaches should be compared.
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