To evaluate the applicability and compliance with guidelines for early initiation of long-term prophylaxis in infants with severe hemophilia A and to identify factors associated with guideline ...compliance.
This real-world, prospective, multicenter, population-based FranceCoag study included almost all French boys with severe hemophilia A, born between 2000 and 2009 (ie, after guideline implementation).
We included 333 boys in the study cohort. The cumulative incidence of long-term prophylaxis use was 61.2% at 3 years of age vs 9.5% in a historical cohort of 39 boys born in 1996 (ie, before guideline implementation). The guidelines were not applicable in 23.1% of patients due to an early intracranial bleeding or inhibitor development. Long-term prophylaxis was delayed in 10.8% of patients. In the multivariate analysis, 2 variables were significantly associated with “timely long-term prophylaxis” as compared with “delayed long-term prophylaxis”: hemophilia treating center location in the southern regions of France (OR 23.6, 95% CI 1.9-286.7, P = .013 vs Paris area) and older age at long-term prophylaxis indication (OR 7.2 for each additional year, 95% CI 1.2-43.2, P = .031). Long-term prophylaxis anticipation was observed in 39.0% of patients. Earlier birth year (OR 0.5, 95% CI 0.3-0.8, P = .010 for birth years 2005-2009 vs 2000-2004) and age at first factor replacement (OR 1.9 for each additional year, 95% CI 1.2-3.0, P = .005) were significantly associated with “long-term prophylaxis guideline compliance” vs “long-term prophylaxis anticipation.”
This study suggests that long-term prophylaxis guidelines are associated with increased long-term prophylaxis use. However, early initiation of long-term prophylaxis remains a challenge.
Intracranial haemorrhage (ICH) is known to be a severe although uncommon complication of haemophilia. A national survey has been conducted in France in order to collect information about ICHs which ...occurred in haemophiliacs between 1991 and 2001 and to propose recommendations for the diagnostic and treatment of ICH. Within this period, 123 episodes of ICH were recorded from 106 patients. Two‐thirds of ICH concerned patients with severe haemophilia. Half of the cases occurred in patients under 15 years of age, 67.2% of which were post‐traumatic. Ten cases occurred in neonates with three fatal outcomes. Overall mortality was high (21.9%) suggesting that availability of clotting factor concentrates has not improved the prognosis of this event. Morbidity was also high with 60% of long‐term sequelae. The following parameters have been identified as prognostic factors for death: thrombocytopenia, HCV infection, intraventricular or intraparenchymatous haemorrhage. A delay in diagnosis was mentioned in 43.3% of cases, often related to the lack of recognition of the initial symptoms, which may be very common (apathy, tearfulness in young children and headache in elder patients). Delayed replacement therapy was recorded in 37.2% of cases. Emergency units initially dealt with half of these patients. Information concerning recognition and management of these episodes, not only in severe haemophilia, but also in moderate and mild forms, should be regularly supplied to paediatricians in maternity and physicians from emergency units, as well as to patients and their relatives.
Real-life data on inflammatory bowel disease (IBD) prevalence and costs are scarce. The aims of this study were to provide an overview of the prevalence, mortality, health care utilization and costs ...of IBD patients in Switzerland in the years 2010, 2012, and 2014.
Based on claims data of the Helsana-Group, prevalence of IBD was assessed for 2010, 2012 and 2014. Mortality rates, costs (inpatient, outpatient, medication costs) and utilization (visits, hospitalizations) were compared between patients with and without IBD, and between IBD patients treated with and without biologics. Results were extrapolated to the Swiss general population using national census data. Multivariate linear regression was used to identify socio-demographic and regional factors influencing total costs.
The overall extrapolated prevalence rates of IBD were 0.32% in 2010, 0.38% in 2012, and 0.41% in 2014. Mortality rate didn't differ between the IBD and non-IBD population. Costs increased annually by 6% in IBD versus 2.4% in non-IBD subjects, which was solely due to increased outpatient costs. Almost one-fourth of IBD patients were hospitalized at least once a year. Costs were higher in IBD patients treated with biologics (OR = 3.98, CI: 3.72-4.27, p < 0.001) when compared to IBD patients without biologic therapies. Over 70% of the total costs in IBD patients treated with biologics were due to drug costs, compared with 28% in patients without use of biologic therapies, whereas inpatient costs didn't differ.
The prevalence of IBD seems to be increasing in Switzerland. Outpatient costs increased substantially, while no decrease in inpatient costs was found. Treatment of IBD is more and more based on biologic therapies.
Inflammatory bowel disease (IBD) was shown to be associated with a variety of chronic comorbidities. We aimed to evaluate the frequency of 21 chronic conditions and compared frequencies in IBD and ...non-IBD populations. Further, healthcare costs of those (additional) chronic conditions were calculated.
A total of 4791 IBD patients, who were insured at Helsana Insurance Group in 2014, were compared with 1 114 638 individuals without IBD. Entropy balancing was performed to create balanced samples. Chronic conditions were identified by means of the updated Pharmacy-based Cost Group model. Multivariate log-transformed linear regression modeling was performed to estimate the effect of the morbidity status (non-IBD +none, +1, +2, and +3 or more chronic conditions) on the healthcare costs.
Overall, 78% of IBD patients had at least one comorbidity, with a median of three comorbidities. Largest differences between individuals with and without IBD were found for rheumatologic conditions, acid-related disorders, pain, bone diseases, migraines, cancer, and iron-deficiency anemia, whereas no significant differences between the two groups were found for diabetes, dementia, hyperlipidemia, glaucoma, gout, HIV, psychoses, and Parkinson's disease after adjustments for a variety of covariates. Each increase in the morbidity status led to increased healthcare costs; rheumatologic conditions, acid-related disorders, and pain as the most frequent comorbidities more than doubled total costs in IBD patients.
We found a considerably high prevalence of concomitant chronic diseases in IBD patients. This was associated with considerably higher healthcare costs, especially in the outpatient setting.
Subanesthetic ketamine (KET) elicits rapid, robust, but transient antidepressant effects. KET's antidepressant actions can be augmented and maintained for a longer duration when repeatedly delivered. ...However, KET is recreationally abused, raising long-term treatment safety concerns. Women are more likely than men to seek treatment for depression, escalate from casual to compulsive drug use, and are more sensitive to antidepressants. Similarly, female rodents are more sensitive than males to KET's rapid antidepressant-like behavioral effects; dose-response thresholds in these assays equal 2.5 and 5.0mg/kg (i.p.), respectively. This suggests the utility of preclinical rodent models in optimizing sex-differential KET therapy protocols and minimizing adverse drug reactions.
Here, we assessed behavioral and biochemical correlates of abuse liability following six serial KET treatments on alternating days at three subanesthetic, antidepressant-like doses (2.5, 5.0, or 10mg/kg, i.p.) in adult male and female rats. A potential role for ΔFosB-mediated transcription in the nucleus accumbens is outlined in the context of KET-mediated locomotor sensitization.
Antidepressant-like threshold doses (2.5, 5.0mg/kg KET) failed to evoke a conditioned place preference in all animals, but only males positively responded to a higher dose (10mg/kg). Behavioral sensitization to 5.0 or 10mg/kg KET's locomotor-activating effects was established in both sexes, and females' sensitized response to 5.0mg/kg was greater than males'. KET-induced hyperlocomotion positively correlated with ΔFosB protein expression in the nucleus accumbens. rAAV-ΔJunD inhibition of ΔFosB-mediated transcription in the accumbens failed to block locomotor sensitization to 10mg/kg KET.
These data suggest that in rats, six alternating-day treatments with 2.5mg/kg KET do not induce apparent behavioral signatures of abuse liability despite accumulation of ΔFosB protein in the accumbens. Additionally, females are more sensitive than males to KET's locomotor-stimulant properties, both acutely and after repeated treatments. More studies are needed to determine brain regions and neural mechanisms responsible for KET-induced behavioral adaptations and to extrapolate these data to inform sex-dependent strategies for long-term KET therapy protocols for depression.
•Alternating-day low-dose ketamine is not rewarding.•Dose-dependent repeated ketamine sensitizes locomotor activity.•Females are more sensitive than males to ketamine's stimulant properties.•ΔFosB expression in the nucleus accumbens correlates with sensitized locomotion.
Introduction: Medical care and surveillance of inflammatory bowel disease (IBD) patients have been shown to be far from satisfactory. Data on therapy patterns and surveillance measures in IBD ...patients are scarce. We, therefore, aimed to compare the therapy patterns and surveillance management of IBD patients in the year before and after IBD-related hospitalization. Methods: We examined medical therapy, surveillance management (influenza vaccination, dermatologist visits, Pap smear screening, creatinine measurements, iron measurements, and ophthalmologist visits) and healthcare utilization in 214 ulcerative colitis (UC) and 259 Crohn’s disease (CD) patients who underwent IBD-related hospitalization from 2012 to 2014. Results: IBD-related drug classes changed in 64.5% of IBD patients following hospitalization. During the 1-year follow-up period, biological treatment increased in UC and CD patients, while steroid use decreased. Following hospitalization, 63.1% of UC and 27.0% of CD patients received 5-ASA. Only 21.6% of all IBD patients had a flu shot, and 19.6% of immunosuppressed IBD patients were seen by a dermatologist in the follow-up; other surveillance measures were more frequent. Surveillance before hospital admission and consultations by gastroenterologists were strongly correlated with surveillance during the postoperative follow-up, while gender and diagnosis (UC vs. CD) were not. During the 1-year follow-up, 20.5% of all IBD patients had no diagnostic or disease-monitoring procedure. Discussion/Conclusion: Surveillance measures for IBD patients are underused in Switzerland. Further research is needed to examine the impact of annual screenings and surveillance on patient outcomes.
Background
Ketamine has rapid antidepressant effects and shows great promise as a novel treatment for depression, but its limitations including its abuse potential are poorly understood. Given that ...the prevalence of depression is twice as high in women as in men and that depression and substance use disorders are highly comorbid, we hypothesized that a sex-specific responsivity to behavioral assays that characterize addiction-like behavior may arise in rats with prior exposure to chronic stress and therapeutically relevant ketamine.
Methods
Male and female rats that underwent chronic mild stress were treated with four 1.47 mg/kg intravenous ketamine infusions once every fourth day and underwent operant self-administration of 0.5 mg/kg/infusion ketamine. Measures of anhedonia (or lack of pleasure, a signature feature of depression), anxiety-induced neophagia, motivation to obtain ketamine, and craving were assessed using the sucrose intake test, novelty-suppressed feeding test, progressive ratio schedule of reinforcement, and incubation of craving following abstinence, respectively. Finally, dendritic spine density in the nucleus accumbens core was measured.
Results
Ketamine infusions reduced anxiety-induced neophagia in both male rats and female rats but had no effect on measures of anhedonia. Female rats with prior exposure to chronic mild stress had greater motivation to obtain ketamine compared to nonstressed female rats, an effect not observed in male rats. Additionally, female rats who received antidepressant ketamine infusions had a higher threshold for displaying ketamine addiction-like behavior than saline-treated female rats as well as increased thin spine density in the nucleus accumbens core. These effects were not observed in male rats.
Conclusion
This study shows that repeated low-dose ketamine does not increase abuse potential of subsequent ketamine. It also highlights an important female-specific effect of stress to increase ketamine addiction-like behavior, which requires further investigation for clinical populations.
Postoperative recurrence is frequently observed after ileocecal resection in Crohn's disease (CD) patients. Since 2010, endoscopy within 1 year is considered the gold standard for its diagnosis. ...However, if and how frequent such endoscopies are performed in clinical practice remains unknown.
We analyzed 1-year follow-up data on CD patients who underwent ileocecal resection between 2012 and 2014 and compared them with hospitalized, non-resected CD controls. Data were extracted from the Helsana database. Helsana is one of the largest Swiss health insurance companies providing coverage for 1.2 million individuals.
A total of 645 CD patients were identified with ≥1 hospitalization between 2012 and 2014 and a follow-up of 1 year. Of these, 79 (12.2%) underwent ileocecal resection. Although endoscopy rates increased over time and were higher in patients with resection versus controls (
= 0.029), in only 54.4% a 1-year follow-up ileocolonoscopy was performed. Postoperative prophylaxis with anti-tumor necrosis factor or azathioprine was prescribed in 63.3%. Female sex and age >60 years were independent predictors for not receiving prophylaxis (odds ratio OR 0.36,
= 0.048, and OR 0.2,
= 0.022). Patients with resection had significantly lower numbers of rehospitalizations (1.2 vs. 1.8,
= 0.021), with resection being an independent negative predictor for number of rehospitalizations in a Poisson regression model (incident risk ratio 0.64,
= 0.029). However, disease-related surgery was more often the cause for rehospitalization after resection versus controls (47.6 vs. 22.1%,
= 0.015). Total and inpatient health-care costs were higher in these patients.
Endoscopies are underused after ileocecal resection. This contrasts current guidelines. Physicians should be aware of this underuse and perform follow-up examinations more often.
Real-life data on health resource utilization and costs of hospitalized patients with inflammatory bowel disease are lacking in Switzerland. We aimed to assess health resource utilization and costs ...during a 1-year follow-up period starting with an index hospitalization.
On the basis of claims data of the Helsana health insurance group, health resource utilization was assessed and costs reimbursed by mandatory basic health insurance in Swiss Francs (CHF); 1 CHF=0.991 US$ were calculated during a 1-year follow-up period starting with an index hospitalization in the time period between 1 January 2013 and 31 December 2014.
Of 202 002 patients with at least one hospitalization in 2013-2014, a total of 270 (0.13%) patients had inflammatory bowel disease as main diagnosis 112 (41.5%) ulcerative colitis (UC), 158 (58.5%) Crohn's disease (CD), 154/270 (57.0%) females. In comparison with patients with UC, patients with CD were significantly more frequently treated with biologics (45.6 vs. 20.5%, P<0.001) and more frequently underwent surgery during index hospitalization (27.8 vs. 9.8%, P=0.002). Compared with patients with UC, those with CD had significantly more consultations odds ratio (OR): 1.06, 95% confidence interval (CI): 1.01-1.12, P=0.016, higher median annual total costs (OR: 1.25, 95% CI: 1.05-1.48, P=0.012), and higher outpatient costs (OR: 1.33, 95% CI: 1.07-1.66, P=0.011). In the bivariate model, median total costs for patients with CD and those with UC were 24 270 and 17 270 CHF, respectively (P=0.032).
When compared with patients with UC, hospitalized patients with CD have during a 1-year follow-up a higher rate of outpatient consultations and generate higher costs.
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