•Patients who had SGLT2i (with insulin) had higher HbA1c than those who had insulin.•Patients who had SGLT2i (with insulin) had higher BMI than those who had insulin.•Total daily doses of insulin ...decreased after the first SGLT2i prescription.•HbA1c, BMI, HDL, and SBP improved after the first SGLT2i prescription.
To investigate the baseline demographic and clinical characteristics of patients with type 1 diabetes mellitus (T1DM) newly treated with a sodium-glucose cotransporter 2 inhibitor (SGLT2i) as an add-on to insulin, or treated with insulin alone or in combination with oral anti-diabetic drugs other than an SGLT2i.
Retrospective study using data from the JMDC database (December 21, 2018, to October 31, 2020). Included patients with T1DM treated with an SGLT2i (add-on to insulin) (n = 1027) or with insulin (n = 4320). Baseline demographic and clinical characteristics were summarized, and change in insulin dose and efficacy outcomes, including hemoglobin A1c (HbA1c) and body mass index (BMI), before and after the first SGLT2i or insulin prescription were evaluated.
The SGLT2i add-on group had higher HbA1c and BMI than the insulin group. Daily insulin doses decreased from immediately before to after the first SGLT2i prescription. HbA1c and BMI improved from baseline to after the first SGLT2i prescription.
This large real-world study reported the baseline demographic and clinical characteristics of patients with T1DM newly treated with an SGLT2i in Japan. The findings may guide the appropriate use of SGLT2i and support large-scale database studies in T1DM research.
Background
Limited data are available on the epidemiology and clinical management of anaemia in patients with non-dialysis-dependent chronic kidney disease (NDD-CKD).
Methods
This retrospective ...observational study was based on records from databases of five Local Health Units across Italy. Adults with reported NDD-CKD stage 3a–5 between 1 January 2014 and 31 December 2016 were identified. Annual prevalence and incidence of anaemia (age- and sex-standardised) and clinical management (erythropoiesis-stimulating agents ESAs, intravenous IV iron, and blood transfusions) were evaluated. Eligibility for ESAs was defined by ≥ 2 records of Hb < 10 g/dL, or < 11 g/dL over 6 months.
Results
Overall, 101,143 individuals with NDD-CKD (3a–5) recorded between 2014 and 2016 were identified, of whom 40,020 (39.6%) were anaemic. Prevalence of anaemia was 33.8% in 2016 and incidence of anaemia was stable (11.4–12.4%) from 2014 to 2016. Prevalence and incidence of anaemia increased with CKD stage. Among eligible patients, 12.8% with Hb < 11 g/dL and 15.5% with Hb < 10 g/dL received ESAs, and the proportion treated increased with CKD stage. Among ESA-treated patients with at least 2 years of follow up, 18.4% and 19.3% received IV iron in the Hb < 11 and < 10 g/dL groups, respectively, and 16.5% and 19.4% received blood transfusions. Corresponding proportions for the overall anaemic cohort were 9.0% and 11.3%, respectively.
Conclusions
Anaemia is a significant issue in patients with NDD-CKD. Low rates of ESA treatment indicate a potential treatment gap and suggest that anaemia may not be adequately controlled in many patients.
Graphical abstract
Abstract
Background and Aims
Anaemia is a common complication in patients with NDD-CKD, and its prevalence increases with advancing CKD stage.1,2 It is a risk factor for both CKD progression and ...other adverse outcomes, including major adverse cardiac events, hospitalisation and all-cause mortality.1 We aim to report the prevalence of NDD-CKD stage 3a–5 in Italy, and to evaluate the prevalence and incidence of anaemia among patients with NDD-CKD. Of those patients with anaemia, we seek to establish the size of the patient pool eligible for ESAs, and consequently, the proportion of patients treated with ESAs.
Method
Patients ≥18 years of age with a record of NDD-CKD stage 3a–5 between 1 January 2014 and 31 December 2016 were identified from databases of five Local Health Units (LHUs) across Italy. NDD-CKD stage 3a–5 in our study was defined as either ≥1 hospitalisation record with discharge diagnosis of CKD (ICD-9-CM 585.x, where x = 3, 4, or 5) or ≥1 record of estimated glomerular filtration rate (eGFR) <60 mL/min. eGFR values were estimated using the Modification of Diet in Renal Disease method and were as reported by LHUs. Patient classification into CKD stage 3a–5 based on eGFR was done according to KDIGO guidelines.3 Anaemia was defined as Hb <13 g/dL (males) or <12 g/dL (females). Prevalence was defined as the presence of ≥1 record of NDD-CKD stage 3a–5 or anaemia in the entire period preceding the timepoint of interest, or as incident NDD-CKD/anaemia; incidence was defined as a first record of the condition in the year of interest (no record of the condition in the patient’s history). Point prevalence (at 31 December of each reported year) and annual incidence were age- and sex-standardised using census data from 1 January of the following year. Among patients with anaemia of NDD-CKD stage 3a–5, eligibility for ESA was defined as at least one record of Hb <10 g/dL,4 and patients with a record of ESA prescription were categorised as ESA treated.
Results
For 2016, the prevalence of NDD-CKD stage 3a–5 in the population aged ≥18 years was 5.6% (83,625/1,507,391): CKD stage 3a was the most common (4.2%; 62,683/1,507,391), while the prevalence of each of the stages 3b–5 was ≤1.0% (Table). The prevalence and incidence of anaemia among patients with NDD-CKD stage 3a–5 in 2016 was 33.8% and 11.4%, respectively. The prevalence of anaemia increased with CKD stage: from 28.2% among patients with stage 3a to 78.9% among those with stage 5. A similar trend was observed for incidence, which increased from 9.3% for stage 3a to 32.8% for stage 5. The proportion of patients with NDD-CKD stage 3a–5 and anaemia who were eligible for ESA treatment from 2014–2016 ranged from 51.9% to 75.6% across the CKD stages. In 2016, the proportion of patients with incident NDD-CKD anaemia who were eligible for ESAs but not treated was 42.3%. This proportion was similar across the CKD stages, except for stage 5, for which the proportion of patients who were eligible but not ESA treated was 51.1%.
Conclusion
In Italy, we found that higher CKD stages are associated with increased prevalence and incidence of anaemia in NDD-CKD, a finding which is supported by previous research in other countries worldwide.1,2 Despite this, almost half of patients with anaemia of NDD-CKD stage 3a–5 were eligible for ESA treatment but did not receive ESAs. This suggests that anaemia may not be adequately controlled in patients with NDD-CKD stage 3a–5, and may need further attention and treatment.
This post hoc Poisson regression analysis investigated the relationship between mean volume voided and incontinence episodes/24 h after fixed frequency adjustment in children with overactive bladder ...from the LION study, a phase 3, double-blind, randomised, placebo-controlled, sequential, dose-titration solifenacin trial. Patients were aged 5–< 12 years with ≥ 4 episodes of daytime incontinence during a 7-day pre-baseline diary period. The dependent variable was the mean number of incontinence episodes/24 h at the end of study. Explanatory variables included treatment, mean number of incontinence episodes/24 h at baseline, and change from baseline to end of study in mean volume voided. Statistical significance and goodness of fit were analysed using the Pearson’s chi-square test. A negative estimate was found between the dependent variable ‘incontinence’ and both mean volume voided and daytime maximum volume voided/micturition (an increase in mean volume voided or daytime maximum volume voided/micturition would lead to a reduction in incontinence;
P
= 0.0014 and
P
= 0.0317, respectively). The model was a good fit to the data in both analyses with a Pearson’s chi-square goodness-of-fit criteria of 0.8.
Conclusion
: Increase in mean volume voided was significantly correlated to reduction in incontinence episodes/24 h in children with overactive bladder treated with solifenacin.
This study is registered at
ClinicalTrials.gov
:
NCT01565707.
What is known:
• Mean volume voided per micturition is used as an indicator of treatment efficacy, with increases noted as number of incontinence episodes (and micturition frequency) decrease.
• The relationship between mean volume voided and incontinence episodes is not clearly understood.
What is new:
• Increase in mean volume voided significantly correlated to reduction in incontinence in solifenacin-treated children with overactive bladder (Poisson regression model analysis).
• Compared with placebo, solifenacin-treated children had a lower predicted number of incontinence episodes/24 h.
Objective To assess the hypothesis that patients receiving placebo in overactive bladder (OAB) trials who experience less benefit from “treatment” continue with behavioral modifications such as fluid ...restriction, whereas those on active treatment adopt more normal drinking patterns. This may manifest itself as a reduction in micturition frequency (MF). Materials and Methods We interrogated a large integrated database containing pooled patient data from 4 randomized, placebo-controlled phase III OAB solifenacin studies. A statistical correction was applied to MF to remove the influence of fluid intake. Results Pooled analysis using patient-level data from 3011 patients and accounting for the studies within the models showed that all patients voided progressively less total urine per 24 hours during treatment than at baseline. However, reduction in total urine volume voided per 24 hours was larger in patients receiving placebo vs those on solifenacin; with a substantial decrease in 24-hour urine output in the placebo group from baseline to week 4, which was not the case in active groups. After correcting MF for volume voided for each patient using the statistical correction and averaging the corrected MF per treatment arm, the placebo effect almost disappeared. Patients on solifenacin voided less often, with a statistically significant increase in volume voided each time they voided, vs placebo. Conclusion Assuming volume voided is a good surrogate measure for fluid intake, this analysis shows that fluid restriction almost completely explains the reduction in MF in the placebo group. In contrast, patients receiving active treatment adopt more normal drinking patterns once they start to perceive improvement in their OAB symptoms.
Abstract Purpose To evaluate long-term safety and efficacy of once-daily oral solifenacin suspension in children (aged 5–<12 years) and adolescents (aged 12–<18 years) with overactive bladder. ...Materials and Methods 40-week, open-label extension of a 12-week double-blind, placebo-controlled trial. Outcome measures: incidence and severity of adverse events (primary endpoint), laboratory variables, vital signs, 12-lead electrocardiogram, post-void residual volume, change from baseline to end of treatment in: mean number of micturitions and incontinence episodes/24 hours, number of incontinence-free days/7 days, number of grade 3 or 4 urgency episodes/24 hours (adolescents only). Results Patients enrolled: 119 children, 29 adolescents. Incidence of drug-related treatment-emergent adverse events: 34.7% (children), 37.9% (adolescents), the most common of which were: children, constipation (11.9%), electrocardiogram QT prolonged (8.5%), dry mouth (4.2%); adolescents, electrocardiogram QT prolonged (13.8%), nausea (6.9%). Adverse events resulted in 10.2% (children) and 13.8% (adolescents) discontinuing treatment. No cases of urinary retention or increase in post-void residual volume, and no clinically relevant changes in laboratory variables or vital signs. Two cases of dizziness but no other CNS drug-related treatment-emergent adverse events reported. Improvements in all efficacy parameters and grade 3 or 4 urgencies observed by 3 weeks were improved and/or maintained during the study. Conclusions Once-daily solifenacin oral suspension was well tolerated for up to 52 weeks in children aged 5–<12 years and adolescents aged 12–<18 years diagnosed with overactive bladder, with constipation and electrocardiogram QT prolonged the most common adverse reactions, respectively. Improvements in efficacy at 3 weeks were sustained over the study.
Introduction and Hypothesis
Pooled data from seven randomized placebo-controlled trials were analysed to evaluate relationships between baseline body mass index (BMI), gender or age and the ...efficacy/tolerability of solifenacin (5 – 10 mg daily) in patients with overactive bladder (OAB).
Methods
Changes in efficacy variables from baseline to 12 weeks were compared in patients with symptoms at baseline between solifenacin-treated and placebo-treated groups. Normalization rates were calculated (no more than eight micturitions in 24 h, no more than one episode of nocturia per night, zero values for other variables over 24 h). Treatment-emergent adverse events (TEAEs) were recorded.
Results
The baseline incidence of incontinence and urgency incontinence increased with increasing BMI and age; relatively more women than men were incontinent. The baseline incidence of urgency was similar between genders and among age groups, but tended to increase with increasing BMI. The baseline frequencies of micturition and nocturia were similar in all BMI categories, between genders and in all age groups. The results from this meta-analysis of an integrated database of data from trials investigating solifenacin showed that solifenacin was more efficacious than placebo for all OAB symptoms across all BMI and age categories, and between genders. Normalization rates for micturition frequency, incontinence and urgency were greater in patients receiving solifenacin than in those receiving placebo across all categories. The overall incidence of TEAEs was higher in patients receiving solifenacin than in those receiving placebo; solifenacin was generally well tolerated in both groups. The overall frequency of TEAEs for solifenacin and placebo was slightly higher in women than in men and in older than in younger patients. The most commonly reported TEAEs were dry mouth and constipation.
Conclusions
Regardless of BMI, gender or age, all patients with OAB can be considered candidates for solifenacin treatment.
Up to 25% of prostate cancer (PCa) patients managed conservatively experienced hospitalization and emergency department visits within 12 mo after diagnosis; 6% experienced PCa-related symptomatic ...progression. The probabilities of receiving therapies for PCa decreased according to the time elapsed after the diagnosis.
Conservative management is an option for prostate cancer (PCa) patients either with the objective of delaying or even avoiding curative therapy, or to wait until palliative treatment is needed. PIONEER, funded by the European Commission Innovative Medicines Initiative, aims at improving PCa care across Europe through the application of big data analytics.
To describe the clinical characteristics and long-term outcomes of PCa patients on conservative management by using an international large network of real-world data.
From an initial cohort of >100 000 000 adult individuals included in eight databases evaluated during a virtual study-a-thon hosted by PIONEER, we identified newly diagnosed PCa cases (n = 527 311). Among those, we selected patients who did not receive curative or palliative treatment within 6 mo from diagnosis (n = 123 146).
Patient and disease characteristics were reported. The number of patients who experienced the main study outcomes was quantified for each stratum and the overall cohort. Kaplan-Meier analyses were used to estimate the distribution of time to event data.
The most common comorbidities were hypertension (35–73%), obesity (9.2–54%), and type 2 diabetes (11–28%). The rate of PCa-related symptomatic progression ranged between 2.6% and 6.2%. Hospitalization (12–25%) and emergency department visits (10–14%) were common events during the 1st year of follow-up. The probability of being free from both palliative and curative treatments decreased during follow-up. Limitations include a lack of information on patients and disease characteristics and on treatment intent.
Our results allow us to better understand the current landscape of patients with PCa managed with conservative treatment. PIONEER offers a unique opportunity to characterize the baseline features and outcomes of PCa patients managed conservatively using real-world data.
Up to 25% of men with prostate cancer (PCa) managed conservatively experienced hospitalization and emergency department visits within the 1st year after diagnosis; 6% experienced PCa-related symptoms. The probability of receiving therapies for PCa decreased according to time elapsed after the diagnosis.
The standard recommended treatment for neurogenic detrusor overactivity (NDO) is clean intermittent catheterization combined with an antimuscarinic agent. However, the adverse systemic side-effects ...of oxybutynin, the most widely used agent, are of concern.
To evaluate the efficacy and safety of solifenacin in pediatric patients with NDO, aged 6 months–<5 years and 5–<18 years.
Two open-label, baseline-controlled, phase 3 studies were conducted in pediatric patients with NDO. Patients were treated with sequential doses of solifenacin oral suspension (pediatric equivalent doses 2.5–10 mg) for 12 weeks to determine each patient's optimal dose, followed by a fixed dose ≥40-week treatment period. Primary efficacy endpoint was change from baseline in maximum cystometric capacity (MCC) after 24 weeks. Secondary endpoints included bladder compliance, bladder volume until first detrusor contraction (>15 cmH2O), number of overactive detrusor contractions (>15 cmH2O), maximum catheterized volume (MCV)/24 h, and incontinence episodes/24 h. Safety parameters were treatment-emergent adverse events (TEAEs), serious adverse events, laboratory variables, vital signs, electrocardiograms, and ocular accommodation and cognitive function assessments.
After 24 weeks, MCC had significantly increased compared with baseline in patients aged 6 months –<5 years and 5–<18 years (37.0 ml and 57.2 ml, respectively; P < 0.001; Fig.). Improvement was also observed after 52 weeks’ treatment. Significant changes were observed from baseline to week 24 in all secondary endpoints in both age groups: increase in bladder compliance, increase in bladder volume to first detrusor contraction as a percentage of expected bladder capacity, reduction in the number of overactive detrusor contractions, increase in MCV, and decreased incontinence episodes. TEAEs were mostly mild or moderate, and there were no new drug-related TEAEs compared with adult studies. Age-related improvements were noted in ocular accommodation and cognitive function.
These long-term multicenter investigations demonstrated the efficacy and safety of solifenacin in pediatric patients with NDO. The observed increases in MCC were clinically relevant and demonstrated that an increase in fluid volume can be accommodated in the bladder prior to reaching intravesical pressures that endanger kidney function and/or are associated with leakage or discomfort. Solifenacin was well tolerated with low incidences of constipation and dry mouth (typically associated with antimuscarinics), central nervous system–related side-effects, and facial flushing.
Solifenacin was effective and well tolerated in pediatric patients with NDO, aged 6 months–<18 years, suggesting that it is a viable alternative to oxybutynin, the current standard of care.
NCT01981954 and NCT01565694. Display omitted
Androgen deprivation therapy-based with or without first-generation anti-androgens, was the standard of care for patients with metastatic hormone-sensitive prostate cancer (mHSPC) for decades. ...However, the development of docetaxel chemotherapy and new androgen receptor-targeted agents, abiraterone acetate and prednisolone, apalutamide , enzalutamide and darolutamide (in combination with docetaxel chemotherapy) has proven that combination of treatments is more effective. Recently, intensification therapy, so-called “triplets”, have emerged in the armamentarium of mHSPC treatment. Metastatic disease is a clinical state that remains poorly understood. The optimal diagnostic and management of patients with mHSPC are changing thanks to the development of new imaging techniques and therapies. The primary objective of this study is to develop and validate a predictive model for the occurrence of symptomatic progression, initiation of new treatments and death amongst patients with mHSPC treated with one of the approved treatment plans, on characteristics present at admission.
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