A real world experience with fingolimod in active RRMS patients naïve to second-line agents: a 2 years, intention-to-treat, observational, single center study

Fingolimod is approved by EMA as a second-line treatment for relapsing-remitting multiple sclerosis (RRMS). Experience with fingolimod in real life is still limited. Aim of our study was to report data on fingolimod effectiveness in a real life cohort of Italian active RRMS patients, naive to second-line agents, followed for 2 years. Fingolimod was a part of the patients' regular treatment and is produced by Novartis. We included all consecutive RRMS patients starting fingolimod at our center according to EMA criteria before January 1st 2013. Exclusion criteria were a previous treatment with natalizumab or an immunosuppressant therapy in the previous 12 months. All patients were clinically evaluated quarterly, and performed brain MRI yearly. Definition of "no evidence of disease activity" (NEDA-3): no relapses, no brain MRI activity and no 6-months confirmed worsening in EDSS score. We included 38 RRMS patients, 35 switched from first-line injectable therapies. Six patients were also previously treated with immunosuppressants (5 mitoxantrone, 1 cyclophosphamide). At 24th month 34 patients continued fingolimod treatment. Main adverse events were infections (18 %), liver-enzymes elevation (8 %), and leukopenia (8 %). After 12 and 24 months 79 and 63 % of patients were relapses-free. Fingolimod significantly reduced ARR compared to the previous year (0.3 ± 0.6 vs 1.2 ± 0.5; p < 0.001). After 12 and 24 months 63 and 37 % of patients had NEDA-3. Previous use of immunosuppressants and an ARR ≥1 in the 2 years predicted disease activity. Fingolimod significantly reduce disease activity in active RRMS patients, with no severe/unexpected safety issues. Patients previously treated with immunosuppressants and with a higher ARR at baseline may respond less to fingolimod treatment

Autonomic abnormalities in patients with primary Sjogren&#8217;s syndrome &#8211; Preliminary results

Primary Sjogren's syndrome (pSS) is an autoimmune disease affecting exocrine glands and extra-glandular organs. There are conflicting reports on the presence of autonomic dysfunction in pSS and no data are available on the functional status of sympathetic outflow to the vessels and baroreceptor [baroreflex sensitivity (BRS)] control mechanisms. We investigated the cardiac (cBRS) and sympathetic (sBRS) baroreceptor modulation in both time and frequency domains and the cardiovascular autonomic profile in pSS patients compared to healthy controls. Autonomic symptoms were quantified by the Composite Autonomic Symptom Scale (COMPASS31) three-item questionnaire. The EULAR Sjogren's syndrome patient reported index (ESSPRI) questionnaire evaluated the magnitude of pSS clinical symptoms, i.e., fatigue, pain, and sicca symptoms. Electrocardiogram, beat-by-beat arterial pressure (AP) and respiratory activity were continuously recorded in 17 pSS patients and 16 healthy controls, while supine and during 75 degrees head-up tilt. In seven patients and seven controls, muscle sympathetic nerve activity (MSNA) was measured. Spectrum analysis of RR variability provided markers of cardiac vagal modulation (HFRR nu) and sympatho-vagal balance [low frequency (LF)/high frequency (HF)]. The power of LF (0.1 Hz) oscillations of systolic arterial pressure (SAP) variability (LFSAP) evaluated the vasomotor response to sympathetic stimulation. Compared to controls, pSS patients scored higher in total COMPASS31 (p &lt; 0.0001) and all ESSPRI subdomains (fatigue, p = 0.005; pain, p = 0.0057; dryness, p &lt; 0.0001). Abnormal scialometry (&lt;1.5 ml/15 min) and Schirmer tests (&lt;5 mm/5 min) were found in pSS patients and salivary flow rate was negatively associated with ESSPRI dryness (p = 0.0014). While supine, pSS patients had lower SEQ(cBRs) index of cardiac baroreceptor sensitivity, higher HFRRnu (p = 0.021), lower LF/HF (p = 0.007), and greater MSNA (p = 0.038) than controls. No differences were observed in LFSAP between groups. During orthostatic challenge, although LFSAP increased similarly in both groups, MSNA was greater in pSS patients (p = 0.003). At rest pSS patients showed lower cBR control and greater parasympathetic modulation. Furthermore, greater sympathetic nerve activity was observed in pSS patients while supine and in response to gravitational challenge. We hypothesized that such enhanced sympathetic vasoconstrictor activity might reflect an attempt to maintain blood pressure in a setting of likely reduced vascular responsiveness

Myalgia, Obtundity and Fever in a Patient with a Prosthesis

Objective: We describe a rare case of group G streptococcus (GGS) sepsis complicated by bacterial toxin myopathy. Case: A 65-year-old man, with a history of infection of his shoulder prosthesis, presented with multiorgan failure and notable myalgia likely caused by toxins. The patient was treated successfully with antibiotics and prosthesis removal. Conclusion: This case suggests infection by GGS should be considered in a patient presenting with myalgia associated with sepsis

Effects of clockwise and counterclockwise job shift work rotation on sleep and work-life balance on hospital nurses

Rotational shift work is associated with sleep disturbances, increased risk of cardiovascular and psychological disorders, and may negatively impact work\u2013life balance. The direction of shift rotation (Clockwise, CW or counterclockwise, CCW) and its role in these disorders are poorly understood. The aim of the study was to investigate the effect of the shift schedule direction on sleep quantity and quality, alertness and work performance, and on work\u2013life balance on hospital nurses. One-hundred female nurses, working a continuous rapid shift schedule in hospitals in the north of Italy, participated in this cross-sectional study. Fifty worked on CW rotation schedule (Morning: 6 a.m.\u20132 p.m., Afternoon: 2 p.m.\u201310 p.m., Night: 10 p.m.\u20136 a.m., 2 rest days) and fifty on CCW rotation (Afternoon, Morning, Morning, Night, 3 rest days). Data were collected by ad hoc questionnaire and daily diary. During the shift cycle CW nurses slept longer (7.40 \ub1 2.24 h) than CCW (6.09 \ub1 1.73; p < 0.001). CW nurses reported less frequently than CCW awakening during sleep (40% vs. 80%; p < 0.001), attention disturbance during work (20% vs. 64%; p < 0.001), and interference with social and family life (60% vs. 96% and 20% vs. 70%, respectively; p < 0.001). CCW rotating shift schedule seems to be characterized by higher sleep disturbances and a worse work\u2013life balance

Syncope in a Working-Age Population: Recurrence Risk and Related Risk Factors

Syncope in a worker undertaking risky tasks may result in fatalities for the individual or for third parties. We aimed at assessing the rate of syncope recurrence and the risk factors underlying the likelihood of syncope relapse in a working-age population. A prospective cohort of all patients aged 18\u207b65 years consecutively admitted to the Emergency Department for syncope was enrolled. Risk of syncope relapse was assessed at a six-month, 1-year, and 5-year follow-up. Predictors of syncope recurrence have been evaluated at six months and 1 year from the syncope index by a multivariable logistic regression analysis. 348 patients were enrolled. Risk of syncope relapse was 9.2% at 6 months, 11.8% at 1 year, and 23.4% at 5 years. At 6-month follow-up, predictor of syncope recurrence was 653 prior lifetime syncope episodes. At 1-year, 653 prior lifetime syncope episodes, diabetes mellitus, and anaemia were risk factors for syncope relapse. There was an exceeding risk of recurrence in the first 6 months and a reduced risk of 3.5% per year after the first year. Anaemia, diabetes mellitus, and prior lifetime syncope burden are of importance when giving advice about the resumption of "high risk" jobs following a syncope episode

Effects of prolonged head-down bed rest on sympathetic baroreflex control and orthostatic tolerance

Orthostatic intolerance has been described after prolonged bed confinement in several clinical settings. This may impact patients’ quality of life and increase risk of falls. Standing is associated with unloading of baroreceptor activity controlling heart rate (HR) and sympathetic vasomotor discharge assessed by muscle sympathetic nerve activity (MSNA). In the present study we evaluated the changes in baroreceptor response and in orthostatic tolerance induced by controlled long lasting bed rest in healthy volunteers. As part of the European Space Agency Medium-term Bed Rest protocol, eight volunteers (33 ±1yrs) were studied before and after 21-days of -6º head down bed rest (HDBR). Subjects underwent ECG, beat-by-beat blood pressure, respiratory activity and MSNA recordings during 15-minutes of 80 head-up tilt (HUT) followed by a 3-minute –10mmHg stepwise increase of lower body negative pressure, up to pre-syncope. The α index obtained in the low frequency band (0.1 Hz) by cross-spectrum analysis of RR and systolic arterial pressure (SAP) variability quantified the cardiac baroreflex sensitivity. The percentage of MSNA burst occurrence for different diastolic pressure values (grouped in bins of 1 mmHg) was assessed. The slope of the regression line between MSNA Bursts % and diastolic pressure was assumed to represent the gain of sympathetic baroreflex control (sBRS). the subjects orthostatic tolerance was decreased after HDBR(12±0.6min) compared to baseline (21±0.6min). In the supine position HR, SAP and α index were unchanged before and after HDBR. During HUT, HR and SAP were unmodified, α index was lower after (3.4±0.7) compared to before HDBR (6.4±1.0). While supine, sBRS was lower after (-2.9±1.5 %mmHg) compared to before HDBR (-6.0±1.1 %/mmHg). Similarly, during HUT sBRS was lower after HDBR (-2.2±0.6 %/mmHg) compared to before (-4.4±0.4%mmHg). These data suggest that prolonged bed confinement decreased the overall baroreceptor sensitivity.These alterations may be involved in the reduction of orthostatic tolerance