Difference in patterns of prescribing antidepressants known for their weight-modulating and cardiovascular side effects for patients with obesity compared to patients with normal weight.

BACKGROUND: Patients with depression and comorbid obesity may be more prone to weight modulating and cardiovascular side effects of selected antidepressants (AD). It is important to ascertain whether these AD prescriptions differ by patient weight status. METHODS: Canadian Primary Care Sentinel Surveillance Network (CPCSSN) electronic medical records were used. Participants were adults with depression prescribed an AD in 2000-2016, with weight categories established before the first prescription. Logistic regression and mixed effects models were applied to examine associations between obesity and AD prescribing, adjusted for sex, age, and comorbidities. Machine learning algorithm random forest (RF) was used to evaluate the importance of weight in predicting prescribing patterns. RESULTS: Of 26,571 participants, 72.4% were women, mean age was 38.9 years (standard deviation (SD)=14.2) and mean BMI 27.0 kg/m2 (SD = 6.5); 9.5% had ≥ 1 comorbidity. Patients with obesity, compared to normal weight patients, were more likely to receive bupropion (adjusted odds ratio (aOR) 1.24, 95%CI: 1.09,1.42), fluoxetine (aOR 1.14, 95%CI: 0.97,1.34), and amitriptyline (aOR 1.13, 95%CI: 0.93,1.36), and less likely to receive mirtazapine (aOR 0.55, 95%CI: 0.44,0.68) and escitalopram (aOR 0.88, 95%CI: 0.80, 0.97). RF analysis showed that weight was among the most important predictors of prescribing patterns, equivalent to age and more important than sex. CONCLUSIONS: AD prescribing patterns for patients with obesity appear to be different for selected AD types, including AD known for their weight-modulating and cardiovascular side effects. Longitudinal studies are needed to examine whether these prescribing patterns are associated with significant health outcomes.

Automatic depletion with Spectra Optia allows a safe 16% reduction of red blood cell pack consumption in exchanged sickle cell anemia patients.

BACKGROUND: Chronic red blood cell exchanges (RBCXs) are frequently used to prevent complications in patients with sickle cell anemia, but the scarcity of matched red blood cell packs (RBCPs) is a serious concern. The main goal of this study was to compare the number of RBCPs used during RBCXs between the Spectra Optia (SO) device (with the automatic depletion step) and the former Cobe Spectra (CSP) device. STUDY DESIGN AND METHODS: The performances and safety of 300 SO sessions using the automatic depletion step (SO/DE) in 50 patients with sickle cell anemia under a chronic transfusion program over a 1-year period were prospectively analyzed. The numbers of RBCPs saved using this protocol compared to the SO device without depletion and to the CSP device were determined. RESULTS: The SO/DE protocol appeared to be safe, as only 5% and 17% of the sessions were characterized by a significant decrease in blood pressure and increase in heart rate (grade 2 adverse events), respectively. Postapheresis hematocrit and fraction of cells remaining reached expected values. The SO/DE protocol required 16% fewer RBCPs compared to SO without depletion, allowing a mean saving of 12 RBCPs per patient and per year and 13% fewer compared to CSP device. Interestingly, the saving was more important for patients with high total blood volume and/or high preapheresis hematocrit. CONCLUSION: The SO/DE protocol is an efficient, safe and cost-effective procedure for patients with sickle cell anemia under a chronic transfusion program.

Eryptosis and hemorheological responses to maximal exercise in athletes: Comparison between running and cycling.

We compared the effects of cycling and running exercise on hemorheological and hematological properties, as well as eryptosis markers. Seven endurance-trained subjects randomly performed a progressive and maximal exercise test on a cycle ergometer and a treadmill. Blood was sampled at rest and at the end of the exercise to analyze hematological and blood rheological parameters including hematocrit (Hct), red blood cell (RBC) deformability, aggregation, and blood viscosity. Hemoglobin saturation (SpO2), blood lactate, and glucose levels were also monitored. Red blood cell oxidative stress, calcium content, and phosphatidylserine exposure were determined by flow cytometry to assess eryptosis level. Cycling exercise increased blood viscosity and RBC aggregation whereas it had no significant effect on RBC deformability. In contrast, blood viscosity remained unchanged and RBC deformability increased with running. The increase in Hct, lactate, and glucose concentrations and the loss of weight at the end of exercise were not different between running and cycling. Eryptosis markers were not affected by exercise. A significant drop in SpO2 was noted during running but not during cycling. Our study showed that a progressive and maximal exercise test conducted on a cycle ergometer increased blood viscosity while the same test conducted on a treadmill did not change this parameter because of different RBC rheological behavior between the 2 tests. We also demonstrated that a short maximal exercise does not alter RBC physiology in trained athletes. We suspect that exercise-induced hypoxemia occurring during running could be at the origin of the RBC rheological behavior differences with cycling.

Hormone replacement therapy and the risk of venous thromboembolism: a population-based study.

SUMMARY BACKGROUND: Hormone replacement therapy (HRT) using oral estrogen alone or combined with a progestogen is associated with an increased risk of venous thromboembolism (VTE) in postmenopausal women. This risk may differ for tibolone and transdermal HRT. METHODS: Among the United Kingdom's General Practice Research Database, we identified the cohort of all women aged 50-79 between 1 January 1987 and 1 March 2008. Using a nested case-control approach, all incident cases of VTE occurring during the study period were identified and matched with up to 10 controls selected from the cohort members. Rate ratios (RR) of VTE with current use of tibolone, transdermal and oral HRT were estimated using conditional logistic regression. RESULTS: The cohort of 955 582 postmenopausal women included 23 505 cases of VTE matched with 231 562 controls. The risk of VTE was not increased with current use of transdermal estrogen alone (RR 1.01; 95% CI, 0.89-1.16) or combined with a progestogen (RR 0.96; 95% CI, 0.77-1.20), or with current use of tibolone (RR 0.92; 95% CI: 0.77-1.10), relative to non-use. On the other hand, the risk was increased with current use of oral estrogen (RR 1.49; 95% CI, 1.37-1.63) and oral estrogen-progestogen (RR 1.54; 95% CI, 1.44-1.65), and increased with estrogen dosage. The risks with oral formulations were particularly elevated during the first year of use but disappeared 4 months after discontinuation. CONCLUSION: Transdermal HRT and tibolone were not associated with an increased risk of VTE in postmenopausal women.

Primary angiitis of the central nervous system: response to mycophenolate mofetil.

Primary angiitis of the central nervous system (PACNS) is a rare inflammatory disease restricted to the CNS of unknown cause. Clinical presentation and evolution are highly variable with potentially fluctuating signs and symptoms. Brain imaging often shows supratentorial ischaemic lesions. Definite diagnosis is established by brain biopsy. Treatment usually combines glucocorticosteroids and cyclophosphamide. A case of PACNS is reported here, which was proved by a brain biopsy and characterised by unusually prominent involvement of the posterior cerebral fossa. Successful treatment with mycophenolate mofetil in combination with steroids is described.

Serial combination therapy: is immune modulation in multiple sclerosis enhanced by initial immune suppression?

BACKGROUND: Although the concept that an initial course of immune-suppression facilitates subsequent immune-modulation (such as Th1 to Th2 deviation) is attractive for several autoimmune diseases, such a mechanism for serial-combination therapy has never been formally demonstrated. Recently, brief mitoxantrone induction-chemotherapy followed by immune-modulation with glatiramer acetate (GA) was significantly more effective at reducing multiple sclerosis disease activity than with GA alone. OBJECTIVE: To examine whether the benefit of initial immune suppression with mitoxantrone before GA treatment is associated with more efficient immune modulation. METHODS: IgG1/IgG4 GA-reactive antibody profiles, previously established as markers of GA-induced Th2 immune-deviation, were prospectively measured in vivo in patients treated with GA alone or with mitoxantrone induction therapy followed by GA. RESULTS: Significant and sustained increase in IgG4 antibodies (and the anticipated reversal of the IgG1/IgG4 ratio) was seen in patients treated with GA alone. Combination therapy resulted in lesser IgG4 induction (and no reversal of IgG1/IgG4 ratio). Thus, the enhanced efficacy of mitoxantrone-GA combination regimen was associated with decreased, rather than increased, efficiency of shifting the GA-reactive IgG1/IgG4 antibody profile. CONCLUSION: These results provide important insights into mechanisms of combination therapy and therapeutic strategies for autoimmune diseases.

Clinical characteristics of responders to interferon therapy for relapsing MS.

OBJECTIVE: To determine the proportion of patients with multiple sclerosis (MS) who respond to interferon-beta (IFNB) therapy and assess whether clinical characteristics differ in IFNB responders vs nonresponders. METHODS: Data on all patients who received IFNB who were entered in the prospective European Database for Multiple Sclerosis (EDMUS) database in Lyon as of March 31, 2001, were reviewed. Responders were defined as having a lower relapse rate on IFNB compared with the year or 2 years prior to IFNB therapy. RESULTS: Two hundred sixty-two patients with relapsing MS received at least 6 months of IFNB: 200 relapsing remitting (RR) and 62 relapsing secondary progressive (SP). One-third of patients experienced a higher or identical annual relapse rate while on IFNB treatment. Compared with nonresponders, responders were older and had longer disease duration at the time IFNB was initiated. RRMS responders also had a higher relapse rate during the year prior to IFNB therapy and SPMS responders had a higher Disability Status Scale score at initiation of IFNB. CONCLUSION: Clinical profiles of patients with relapsing MS who respond to IFNB may differ from those who do not with a more inflammatory and less neurodegenerative disease at the time IFNB is initiated.

Linkage and association study of the CTLA-4 region in coeliac disease for Italian and Tunisian populations.

Coeliac disease (CD) is a multifactorial disease for which there is an intensive search for genetic risk factors. Some authors found an association between the CTLA-4 region and CD. In the present work, we investigate the possible implication of the CTLA-4 region as a genetic risk factor for CD, through two statistical approaches: the maximum likelihood score (MLS) test in a large Italian sample of affected sib-pairs using polymorphic genetic markers on chromosome 2, and the transmission disequilibrium test (TDT) in continental Italian and Tunisian families using the CTLA-4 exon 1 49 A/G polymorphism. None of these approaches provides evidence for linkage or association between the CTLA-4 region and CD. This might result from a difference in the CTLA-4 region from population to population, either in its involvement as a risk factor or in the strength of linkage disequilibrium.