Solriamfetol real world experience study (SURWEY): Initiation, titration, safety, effectiveness, and experience during follow-up for patients with narcolepsy from Germany.

BACKGROUND: Excessive daytime sleepiness (EDS) is a core narcolepsy symptom, for which solriamfetol (Sunosi®) was recently approved in the European Union. SURWEY characterises real-world strategies used by physicians when initiating solriamfetol, and patient outcomes after follow-up. METHODS: SURWEY is an ongoing retrospective chart review conducted by physicians in Germany/France/Italy. Here, data are reported from 70 German patients with EDS and narcolepsy. Eligibility included age ≥18 years, reached a stable solriamfetol dose, and completed ≥6 weeks of treatment. Patients were classified (based on existing EDS treatment) into changeover, add-on, or new-to-therapy subgroups. RESULTS: Patients' mean ± SD age was 36.9 ± 13.9 years. Changeover from prior EDS medication was the most common initiation strategy. Initial solriamfetol dose was typically 75 mg/day (69%). In 30 patients (43%), solriamfetol was titrated; 27/30 (90%) completed titration as prescribed, most within 7 days. Mean ± SD Epworth Sleepiness Scale (ESS) score was 17.6 ± 3.1 at initiation (n = 61) and 13.6 ± 3.8 at follow-up (n = 51). Slight/strong improvements in EDS were perceived for >90% of patients (patient and physician report). Sixty-two percent reported an effect duration of 6 to <10 h; 72% reported no change in perceived nighttime sleep quality. Common adverse events included headache (9%), decreased appetite (6%), and insomnia (6%); no cardiovascular events were reported. CONCLUSIONS: Most patients in this study were switched from a prior EDS medication to solriamfetol. Solriamfetol was typically initiated at 75 mg/day; titration was common. ESS scores improved after initiation, and most patients perceived improvement in EDS. Common adverse events were consistent with those reported in clinical trials. GOV REGISTRATION: N/A.

Increased renal papillary density in kidney stone formers detectable by CT scan is a potential marker of stone risk, but is unrelated to underlying hypercalciuria.

Several previous studies have reported an increase in Hounsfield unit density of the renal papillae in patients with nephrolithiasis compared with controls. Kidney stone formers (KSF) were found to have higher papillary and cortical density in both kidneys, irrespective of which side had calculi, and it was proposed that this might be related to the presence of underlying hypercalciuria. The current study was designed: (1) to determine whether recurrent KSF do have higher papillary density compared with healthy controls; (2) to test an association between higher renal papillary density and the presence of hypercalciuria in KSF. This retrospective case-matched controlled study was carried out at the Royal Free Hospital, London, UK. We investigated 111 patients, 57 of whom were KSF and 54 healthy controls. The CT attenuation values were measured within a 0.2 cm(2) area of the renal papilla in the upper, middle, and lower segments of each kidney, and were compared between KSF and non-stone formers, and between KSF with and without hypercalciuria. There were no significant differences in age and sex between groups. Papillary density was significantly higher in KSF by both crude and adjusted analyses (p < 0.001). However, there was no association between higher papillary density and hypercalciuria in KSF. The papillary density measured by CT is a useful, non-invasive tool to differentiate between KSF and healthy controls. The absence of any correlation between papillary density and hypercalciuria suggests that the presence of clinically significant underlying renal stone disease, rather than urinary metabolic abnormalities, correlates with radiologically detectable increased papillary density.

Vascular calcification and bone mineral density in recurrent kidney stone formers.

BACKGROUND AND OBJECTIVES: Recent epidemiologic studies have provided evidence for an association between nephrolithiasis and cardiovascular disease, although the underlying mechanism is still unclear. Vascular calcification (VC) is a strong predictor of cardiovascular morbidity and the hypothesis explored in this study is that VC is more prevalent in calcium kidney stone formers (KSFs). The aims of this study were to determine (1) whether recurrent calcium KSFs have more VC and osteoporosis compared with controls and (2) whether hypercalciuria is related to VC in KSFs. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: This is a retrospective, matched case-control study that included KSFs attending an outpatient nephrology clinic of the Royal Free Hospital (London, UK) from 2011 to 2014. Age- and sex-matched non-stone formers were drawn from a list of potential living kidney donors from the same hospital. A total of 111 patients were investigated, of which 57 were KSFs and 54 were healthy controls. Abdominal aortic calcification (AAC) and vertebral bone mineral density (BMD) were assessed using available computed tomography (CT) imaging. The prevalence, severity, and associations of AAC and CT BMD between KSFs and non-stone formers were compared. RESULTS: Mean age was 47±14 years in KSFs and 47±13 in non-stone formers. Men represented 56% and 57% of KSFs and non-stone formers, respectively. The prevalence of AAC was similar in both groups (38% in KSFs versus 35% in controls, P=0.69). However, the AAC severity score (median [25th percentile, 75th percentile]) was significantly higher in KSFs compared with the control group (0 [0, 43] versus 0 [0, 10], P<0.001). In addition, the average CT BMD was significantly lower in KSFs (159±53 versus 194 ±48 Hounsfield units, P<0.001). A multivariate model adjusted for age, sex, high BP, diabetes, smoking status, and eGFR confirmed that KSFs have higher AAC scores and lower CT BMD compared with non-stone formers (P<0.001 for both). Among stone formers, the association between AAC score and hypercalciuria was not statistically significant (P=0.86). CONCLUSIONS: This study demonstrates that patients with calcium kidney stones suffer from significantly higher degrees of aortic calcification than age- and sex-matched non-stone formers, suggesting that VC may be an underlying mechanism explaining reported associations between nephrolithiasis and cardiovascular disease. Moreover, bone demineralization is more prominent in KSFs. However, more data are needed to confirm the possibility of potentially common underlying mechanisms leading to extraosseous calcium deposition and osteoporosis in KSFs.

Lack of reduction of left ventricular mass in treated hypertension: the strong heart study.

BACKGROUND: Hypertensive left ventricular mass (LVM) is expected to decrease during antihypertensive therapy, based on results of clinical trials. METHODS AND RESULTS: We assessed 4-year change of echocardiographic LVM in 851 hypertensive free-living participants of the Strong Heart Study (57% women, 81% treated). Variations of 5% or more of the initial systolic blood pressure (SBP) and LVM were categorized for analysis. At baseline, 23% of men and 36% of women exhibited LV hypertrophy (LVH, P<0.0001). At the follow-up, 3% of men and 10% of women had regression of LVH (P<0.0001 between genders); 14% of men and 15% of women, free of baseline LVH, developed LVH. There was an increase in LVM over time, more in men than in women (P<0.001). Participants whose LVM did not decrease had similar baseline SBP and diastolic BP, but higher body mass index (BMI), waist/hip ratio, heart rate (all P<0.008), and urinary albumin/creatinine excretion (P<0.001) than those whose LVM decreased. After adjusting for field center, initial LVM index, target BP, and kinship degree, lack of decrease in LVM was predicted by higher baseline BMI and urinary albumin/creatinine excretion, independently of classes of antihypertensive medications, and significant effects of older age, male gender, and percentage increase in BP over time. Similar findings were obtained in the subpopulation (n=526) with normal BP at follow-up. CONCLUSIONS: In a free-living population, higher BMI is associated with less reduction of hypertensive LVH; lack of reduction of LVM is independent of BP control and of types of antihypertensive treatment, but is associated with renal damage.

Left ventricular dysfunction and outcome at two-year follow-up in patients with type 2 diabetes: The DYDA study.

AIMS: Left ventricular dysfunction (LVD) in type 2 diabetes mellitus (DM) (DYDA) study is a prospective investigation enrolling 960 with DM without overt cardiac disease. At baseline, a high prevalence of LVD was detected by analysing midwall shortening. We report here the incidence of clinical events in DYDA patients after 2-year follow-up and the frequency of LVD detected at baseline and 2-year evaluation. METHODS: Systolic LVD was defined as midwall shortening ≤15%, diastolic LVD as any condition different from "normal diastolic function" identified as E/A ratio on Doppler mitral flow between 0.75 and 1.5 and deceleration time of E wave >140 ms. Major outcome was a composite of major events, including all-causes death and hospital admissions. RESULTS: During the study period, any systolic/diastolic LVD was found in 616 of 699 patients (88.1%) in whom LVD function could be measured at baseline or at 2 years. Older age and high HbA1c predicted the occurrence of LVD. During the follow-up 15 patients died (1.6%), 3 for cardiovascular causes, 139 were hospitalized (14.5%, 43 of them for cardiovascular causes, 20 for a new cancer). CONCLUSIONS: During a 2-year follow-up any LVD is detectable in a large majority of patients with DM without overt cardiac disease. Older age and higher HbA1c predict LVD. All-cause death or hospitalization occurred in 15% of patients, cardiovascular cause was uncommon. Independent predictors of events were older age, pathologic lipid profile, high HbA1c, claudicatio and repaglinide therapy. Echo-assessed LVD at baseline was not prognosticator of events.

Does information on systolic and diastolic function improve prediction of a cardiovascular event by left ventricular hypertrophy in arterial hypertension?

Left ventricular (LV) mass (LVM) is the most important information requested in hypertensive patients referred for echocardiography. However, LV function also predicts cardiovascular (CV) risk independent of LVM. There is no evidence that addition of LV function significantly improves model prediction of CV risk compared with LVM alone. Thus, composite fatal and nonfatal CV or cerebrovascular events were evaluated in 5380 hypertensive outpatients (2336 women, 298 diabetics, and 1315 obese subjects) without prevalent CV disease (follow-up: 3.5+/-2.8 years). We compared 5 risk models using Cox regression and adjusting for age and sex: (1) LV mass normalized for height in meters(2.7) (LVMi); (2) LVMi, concentric LV geometry, by relative wall thickness (>0.43), ejection fraction, and transmitral diastolic pattern (by thirtiles of mitral deceleration index); (3) LVMi, LV geometry, midwall shortening, and mitral deceleration index thirtiles; (4) as No. 2 with the addition of left atrial dilatation (>23 mm); and (5) as No. 3 with the addition of left atrial dilatation. Individual hazard functions were compared using receiving operating characteristic curves and z statistics. Areas under the curves increased from 0.60 in the model with the sole LVMi to 0.62 in the others (all P values for differences were not significant). The additional information on systolic and diastolic function decreased the contribution (Wald statistics) of LVMi in the Cox model without improving the model ability to predict CV risk. We conclude that risk models with inclusion of information on LV geometry and systolic and diastolic function, in addition to LVMi, do not improve the prediction of CV events but rather redistribute the impact of individual predictors within the risk variance.

Inappropriate left ventricular mass in children and young adults with chronic renal insufficiency.

Increased left ventricular (LV) mass (M) in children with chronic renal insufficiency (CRI) might represent an adaptive mechanism to compensate for increased workload. We hypothesized that in children with CRI, pre-dialysis, values of left ventricular mass (LVM) exceed compensatory values for individual cardiac load. Complete anthropometric characteristics, biochemical profile and echocardiograms were obtained for 33 children with CRI, pre-dialysis (age 1-23 years, mean 12.2 +/- 5.0 years), and 33 age- and gender-matched healthy controls. LV dimensions, wall thicknesses and volume were measured. Endocardial and midwall shortening, ejection fraction, LVM, LVM index, relative wall thickness, circumferential wall stress and excess LVM (as ratio of observed LVM to value predicted from body size, gender and cardiac workload) were analysed. Patients with CRI showed higher values of LVM index, resulting in higher prevalence of LV hypertrophy (36.3% vs 9%, P < 0.05). The ratio of excess LVM was greater in patients with CRI than in healthy controls (126 +/- 19% and 103 +/- 13%, respectively, P < 0.001). LV ejection fraction, midwall fractional shortening and stress-corrected midwall shortening were lower in patients with CRI than in controls. We concluded that, in children with CRI, the values of LVM are higher than those needed to sustain individual cardiac load than in healthy controls, a condition associated with LV hypertrophy and reduced systolic performance.

Myocardial mechano-energetic efficiency in hypertensive adults.

BACKGROUND: Myocardial mechanical efficiency can be measured as the ratio between systolic work and energy consumption. We evaluated the relation between myocardial mechanical efficiency and left ventricular (LV) mass in untreated hypertensive patients. METHODS: Myocardial work was estimated in 256 normotensive (35 +/- 12 years) and 306 hypertensive patients (47 +/- 10 years) with normal ejection fraction, as stroke work in gram-meters (stroke work = BPs x SV x 0.0144, where BPs is systolic blood pressure, SV is echocardiographic stroke volume). Myocardial O2 consumption was estimated as the product of heart rate (HR) x BPs (eMVO2). Myocardial mechanical efficiency was estimated as the ratio of stroke work/eMVO2, which can be simplified and expressed as ml/s. RESULTS: LV mass was greater in hypertensive than in normotensive patients (46 +/- 13 vs. 38 +/- 11 g/m2.7, P < 0.0001), but myocardial mechanical efficiency was identical (85 +/- 23 vs. 86 +/- 26 ml/s). Relations between myocardial mechanical efficiency and LV mass were close (both P < 0.0001), but more scattered among hypertensive patients because of 56 patients exhibiting low myocardial mechanical efficiency relative to the magnitude of LV mass. At comparable age and body size, these patients had higher HR, BPs, and pulse pressure than those with normal myocardial mechanical efficiency (all P < 0.001). After adjusting for age and sex, hypertensive patients with low myocardial mechanical efficiency showed greater relative wall thickness and lower ejection fraction and midwall shortening than those with normal myocardial mechanical efficiency (all P < 0.001). Low myocardial mechanical efficiency was also associated with inappropriately high LV mass (P < 0.0001). CONCLUSION: In some hypertensive patients the left ventricle works inefficiently with a high energy wasting, at the same level of LV mass as hypertensive patients with normal myocardial mechanical efficiency. Those patients feature a high cardiovascular risk phenotype, with concentric LV geometry, systolic dysfunction, and indirect signs of more severe vascular impairment.