Femoral vein pulsatility: a simple tool for venous congestion assessment.

BACKGROUND: Femoral vein Doppler (FVD) is simpler than the VExUS score which is a multimodal scoring system based on combination of IVC diameter, hepatic venous Doppler, portal vein pulsatility and renal vein Doppler, may be useful in assessing right ventricular overload and signs of venous congestion. There is limited data on the relationship between FVD and VExUS score. RESULTS: Adult post-cardiac surgery patients were assessed for venous congestion using the VExUS score and FVD. Agreement between VExUS and FVD was studied using Kappa test, sensitivity, specificity, PPV and NPV for VExUS and FVD was calculated keeping CVP as gold standard. In total, 107 patients were enrolled, with a mean age of 55.67 ± 12.76. The accuracy of VExUS and FVD for detecting venous congestion was 80.37 (95% CI of 71.5 to 87.4) and 74.7 (95% CI of 65.4 to 82.6), respectively. The level of agreement between FVD and VExUS was moderate (Kappa value of 0.62, P < 0.001) while the agreement between FVD and CVP was weak (Kappa value of 0.49, P < 0.001). CONCLUSION: FVD has good accuracy for detecting venous congestion and shows moderate agreement with VExUS grading. With potentially easier physical accessibility and a shorter learning curve for novices, it may be a simple and valuable tool for assessing venous congestion.

Distinguishing in-hospital and out-of-hospital status epilepticus: clinical implications from a 10-year cohort study.

BACKGROUND AND PURPOSE: The aim was to determine differences of clinical, treatment and outcome characteristics between patients with in-hospital and out-of-hospital status epilepticus (SE). METHODS: From 2005 to 2014, clinical data were assessed in adults with SE treated in an academic medical care centre. Clinical characteristics, treatment and outcomes were compared between patients with in-hospital and out-of-hospital SE. RESULTS: Amongst 352 patients, 213 were admitted with SE and 139 developed in-hospital SE. Patients with in-hospital SE had more acute/fatal aetiologies (60% vs. 35%, P < 0.001), fewer previous seizures (33% vs. 50%, P = 0.002), a higher median Charlson Comorbidity Index (3 vs. 2, P < 0.001), longer median SE duration (1 vs. 0.5 days, P = 0.001), more refractory SE (52% vs. 39%, P = 0.022), less return to functional baseline (38% vs. 54%, P = 0.006) and increased mortality (29% vs. 19%, P = 0.001). Whilst in multivariable analyses an increasing Status Epilepticus Severity Score (STESS) was an independent predictor for death in both groups, increased Charlson Comorbidity Index and treatment refractory SE were associated with death only in patients with in-hospital SE. Continuous anaesthesia for refractory SE was associated with increased mortality only in patients with out-of-hospital SE. The area under the receiver operating curve was 0.717 for prediction of death by STESS in patients with in-hospital SE and 0.811 in patients with out-of-hospital SE. CONCLUSIONS: Patients with in-hospital SE had more fatal aetiologies and comorbidities, refractory SE, less return to functional baseline, and increased mortality compared to patients with out-of-hospital SE. Whilst the STESS was a robust predictor for death in both groups, the association between continuous anaesthesia and death was limited to out-of-hospital SE.

[Male osteoporosis]. / Männliche Osteoporose.

BACKGROUND: Osteoporosis in men is an important public health problem with more than 1 million cases in Germany. Although osteoporotic fractures have a much higher mortality in men than in women, male patients are still underdiagnosed and undertreated. OBJECTIVE: Epidemiology of male osteoporosis and current treatment situation, pathophysiological aspects at the hormonal level, risk factors, diagnostic work-up and therapeutic options. MATERIAL AND METHODS: Overview of data concerning male osteoporosis, recommendations for diagnostic work-up and presentation of the study situation on pharmaceutical therapies. RESULTS: As risk factors for osteoporosis are present in 50-70 % of male patients, a detailed patient history is necessary for assessment of the risk factors. Radiological imaging of the spine is primarily recommended to identify individuals with prevalent vertebral fractures, as approximately 10 % of males above the age of 50 years have suffered a vertebral fracture. Laboratory testing of relevant parameters helps to rule out other metabolic bone diseases. In Germany, specific medications available for the treatment of male osteoporosis comprise the active vitamin D analogue alfacalcidol, the oral bisphosphonates alendronate and risedronate, the intravenous biphosphonate zoledronic acid, the anti- receptor activator of NF-κB ligand (RANKL) antibody denosumab, which can be given as intravenous injection and strontium ranelate, a drug with a complex mode of action. Teriparatide, a recombinant form of the 34 N-terminal amino acid sequence of parathyroid hormone is the only anabolic agent approved for male osteoporosis. CONCLUSION: Osteoporosis in men is increasingly being recognized as an important public health problem and affected patients need to be adequately diagnosed and treated. Nowadays, a broad spectrum of well-proven therapeutic options with different modes of action allow individual treatment strategies for male osteoporosis patients.

Sports injuries and illnesses during the 2015 Winter European Youth Olympic Festival.

BACKGROUND: The prevention of injury and illness remains an important issue among young elite athletes. Systematic surveillance of injuries and illnesses during multi-sport events might provide a valuable basis to develop preventive measures, focusing especially on adequate information for youth athletes. AIM: To analyse the frequencies and characteristics of injuries and illnesses during the 2015 Winter European Youth Olympic Festival (W-EYOF). METHODS: All National Olympic Committees were asked to report daily the occurrence or non-occurrence of newly sustained injuries and illnesses on a standardised reporting form. RESULTS: Among the 899 registered athletes (37% female) with a mean age of 17.1±0.8 years, a total of 38 injuries and 34 illnesses during the 5 competition days of the W-EYOF were reported, resulting in an incidence of 42.3 injuries and 37.8 illnesses per 1000 athletes, respectively. Injury frequency was highest in snowboard cross (11%), Nordic combined (9%), alpine skiing (6%), and ice hockey (6%), taking into account the respective number of registered athletes. In snowboard cross, females showed a significant higher injury frequency compared to males (22% vs 4%, p=0.033). The lower back (16%), the pelvis (13%), the knee (11%), and the face (11%) were the most common injury locations. About 58% of injuries occurred in competition and about 42% in training. In total, 42% of injuries resulted in an absence of training or competition. The prevalence of illness was highest in figure skating (10%) and Nordic combined (9%), and the respiratory system was affected most often (53%). CONCLUSIONS: Four per cent of the athletes suffered from an injury and 4% from illnesses during the 2015 W-EYOF, which is about twofold lower compared to the first Winter Youth Olympic Games in 2012.

A Novel Study Paradigm for Long-term Prevention Trials in Alzheimer Disease: The Placebo Group Simulation Approach (PGSA): Application to MCI data from the NACC database.

INTRODUCTION: The PGSA (Placebo Group Simulation Approach) aims at avoiding problems of sample representativeness and ethical issues typical of placebo-controlled secondary prevention trials with MCI patients. The PGSA uses mathematical modeling to forecast the distribution of quantified outcomes of MCI patient groups based on their own baseline data established at the outset of clinical trials. These forecasted distributions are then compared with the distribution of actual outcomes observed on candidate treatments, thus substituting for a concomitant placebo group. Here we investigate whether a PGSA algorithm that was developed from the MCI population of ADNI 1*, can reliably simulate the distribution of composite neuropsychological outcomes from a larger, independently selected MCI subject sample. METHODS: Data available from the National Alzheimer's Coordinating Center (NACC) were used. We included 1523 patients with single or multiple domain amnestic mild cognitive impairment (aMCI) and at least two follow-ups after baseline. In order to strengthen the analysis and to verify whether there was a drift over time in the neuropsychological outcomes, the NACC subject sample was split into 3 subsamples of similar size. The previously described PGSA algorithm for the trajectory of a composite neuropsychological test battery (NTB) score was adapted to the test battery used in NACC. Nine demographic, clinical, biological and neuropsychological candidate predictors were included in a mixed model; this model and its error terms were used to simulate trajectories of the adapted NTB. RESULTS: The distributions of empirically observed and simulated data after 1, 2 and 3 years were very similar, with some over-estimation of decline in all 3 subgroups. The by far most important predictor of the NTB trajectories is the baseline NTB score. Other significant predictors are the MMSE baseline score and the interactions of time with ApoE4 and FAQ (functional abilities). These are essentially the same predictors as determined for the original NTB score. CONCLUSION: An algorithm comprising a small number of baseline variables, notably cognitive performance at baseline, forecasts the group trajectory of cognitive decline in subsequent years with high accuracy. The current analysis of 3 independent subgroups of aMCI patients from the NACC database supports the validity of the PGSA longitudinal algorithm for a NTB. Use of the PGSA in long-term secondary AD prevention trials deserves consideration.

The effect of zoledronic acid on the fracture risk in men with osteoporosis.

BACKGROUND: Prospective, placebo-controlled, double-blind, randomized studies on osteoporosis treatment with bisphosphonates in men are rare. This review focuses on a recent trial and compares the results with other studies. METHODS: This review provides a summary of recent literature on fracture risk in men following treatment with zoledronic acid. According to a recent clinical study with 1,199 men, zoledronic acid was linked to a lower risk of vertebral fractures. In this manuscript, a re-analysis of the presented statistical data will be demonstrated by performing a Bonferroni-correction to adjust for type 1 error accumulation in multiple statistical tests. RESULTS: It will be shown that the provided evidence linking zoledronic acid to a lower fracture risk in male osteoporosis is true, but less pronounced than originally assumed. CONCLUSION: Comparative clinical studies are recommended, where the benefits of different bisphosphonates are compared to each other under the same experimental conditions.

Progress and problems in muscle glycogenoses.

In this selective review, we consider a number of unsolved questions regarding the glycogen storage diseases (GSD). Thus, the pathogenesis of Pompe disease (GSD II) is not simply explained by excessive intralysosomal glycogen storage and may relate to a more general dysfunction of autophagy. It is not clear why debrancher deficiency (GSD III) causes fixed myopathy rather than exercise intolerance, unless this is due to the frequent accompanying neuropathy. The infantile neuromuscular presentation of branching enzyme deficiency (GSD IV) is underdiagnosed and is finally getting the attention it deserves. On the other hand, the late-onset variant of GSD IV (adult polyglucosan body disease APBD) is one of several polyglucosan disorders (including Lafora disease) due to different etiologies. We still do not understand the clinical heterogeneity of McArdle disease (GSD V) or the molecular basis of the rare fatal infantile form. Similarly, the multisystemic infantile presentation of phosphofructokinase deficiency (GSD VII) is a conundrum. We observed an interesting association between phosphoglycerate kinase deficiency (GSD IX) and juvenile Parkinsonism, which is probably causal rather than casual. Also unexplained is the frequent and apparently specific association of phosphoglycerate mutase deficiency (GSD X) and tubular aggregates. By paying more attention to problems than to progress, we aimed to look to the future rather than to the past.

A randomized trial of 4-aminopyridine in EA2 and related familial episodic ataxias.

OBJECTIVE: The therapeutic effects of 4-aminopyridine (4AP) were investigated in a randomized, double-blind, crossover trial in 10 subjects with familial episodic ataxia with nystagmus. METHODS: After randomization, placebo or 4AP (5 mg 3 times daily) was administered for 2 3-month-long treatment periods separated by a 1-month-long washout period. The primary outcome measure was the number of ataxia attacks per month; the secondary outcome measures were the attack duration and patient-reported quality of life (Vestibular Disorders Activities of Daily Living Scale [VDADL]). Nonparametric tests and a random-effects model were used for statistical analysis. RESULTS: The diagnosis of episodic ataxia type 2 (EA2) was genetically confirmed in 7 subjects. Patients receiving placebo had a median monthly attack frequency of 6.50, whereas patients taking 4AP had a frequency of 1.65 (p = 0.03). Median monthly attack duration decreased from 13.65 hours with placebo to 4.45 hours with 4AP (p = 0.08). The VDADL score decreased from 6.00 to 1.50 (p = 0.02). 4AP was well-tolerated. CONCLUSIONS: This controlled trial on EA2 and familial episodic ataxia with nystagmus demonstrated that 4AP decreases attack frequency and improves quality of life. LEVEL OF EVIDENCE: This crossover study provides Class II evidence that 4AP decreases attack frequency and improves the patient-reported quality of life in patients with episodic ataxia and related familial ataxias.

Head position during resting modifies spontaneous daytime decrease of downbeat nystagmus.

BACKGROUND: The intensity of downbeat nystagmus (DBN) decreases during the daytime when the head is in upright position. OBJECTIVE: This prospective study investigated whether resting in different head positions (upright, supine, prone) modulates the intensity of DBN after resting. METHODS: Eye movements of 9 patients with DBN due to cerebellar (n = 2) or unknown etiology (n = 7) were recorded with video-oculography. Mean slow-phase velocities (SPV) of DBN were determined in the upright position before resting at 9 am and then after 2 hours (11 am) and after 4 hours (1 pm) of resting. Whole-body positions during resting were upright, supine, or prone. The effects of all 3 resting positions were assessed on 3 separate days in each patient. RESULTS: Before resting (9 am), the average SPV ranged from 3.05 °/s to 3.6 °/s on the separate days of measurement. After resting in an upright position, the average SPV at 11 am and 1 pm was 0.65 °/sec, which was less (p < 0.05) than after resting in supine (2.1 °/sec) or prone (2.22 °/sec) positions. CONCLUSION: DBN measured during the daytime in an upright position becomes minimal after the patient has rested upright. The spontaneous decrease of DBN is less pronounced when patients lie down to rest. This indicates a modulation by otolithic input. We recommend that patients with DBN rest in an upright position during the daytime. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that for patients with DBN 2 hours of rest in the upright position decreases nystagmus more than 2 hours of rest in the supine or prone positions (relative improvement 79% upright, 33% supine, and 38% prone: p < 0.05).

[Pharmacotherapy of central oculomotor disorders]. / Pharmakotherapie zentraler Nystagmusformen.

Nystagmus causes blurred vision due to oscillopsia, as well as impaired balance. Depending on etiology, additional cerebellar and brain stem signs may occur. We present the current pharmacotherapy of the most common forms of central nystagmus: downbeat nystagmus (DBN), upbeat nystagmus (UBN), acquired pendular nystagmus (APN), and congenital nystagmus (CGN). Recommended medical therapies are aminopyridines (4-AP) for DBN and UBN, gabapentin and memantine for CGN and APN, and baclofen for periodic alternating nystagmus (PAN).

Severe infantile type of carnitine palmitoyltransferase II (CPT II) deficiency due to homozygous R503C mutation.

We report a patient with severe infantile carnitine palmitoyltransferase II (CPT II) deficiency who died at the age of 3 months. Genetic analysis of the CPT2 gene revealed that the patient was homozygous, and her parents were heterozygous, for a R503C missense mutation. Heterozygosity for R503C, without a second mutation, has previously been reported in symptomatic patients from two families, one with the mild adult myopathic form and one with malignant hyperthermia. In contrast, the R503C heterozygous parents of the patient were entirely asymptomatic, suggesting that additional genetic and/or environmental factors must have contributed to the occurrence of symptoms in previously reported carriers. Our findings indicate that the mutation R503C should be added to the handful of mutations associated with the severe phenotype when present in the homozygous state or combined with another severe mutation.

The variable clinical phenotype of liver glycogen synthase deficiency.

We report two new cases of liver glycogen synthase deficiency (GSD0). The first patient presented at the age of 8 months with recurrent hypoglycemic seizures. The second patient presented at 14 months with asymptomatic incidental hyperglycemia. Glucose monitoring in both patients revealed daily fluctuations from fasting hypoglycemia to postprandial hyperglycemia. Genetic analysis of the GYS2 gene confirmed the diagnosis. GSD0 is more common than previously assumed. Recognition of the variable phenotype spectrum of GSD0 and routine analysis of GYS2 are essential for the correct diagnosis.

Encysted peritoneal hydatidosis in a child -- the effectiveness of pre-operative therapy with a combination of praziquantel and albendazole.

A child with encysted peritoneal hydatidosis was found to be completely cured after 3 months of combined therapy with praziquantel and albendazole followed by resection of a huge peritoneal cyst and the removal of numerous, dead, daughter cysts.

Leptospirosis among patients presenting with dengue-like illness in Puerto Rico.

Leptospirosis is difficult to distinguish from dengue fever without laboratory confirmation. Sporadic cases/clusters of leptospirosis occur in Puerto Rico, but surveillance is passive and laboratory confirmation is rare. We tested for leptospirosis using an IgM ELISA on sera testing negative for dengue virus IgM antibody and conducted a case-control study assessing risk factors for leptospirosis, comparing clinical/laboratory findings between leptospirosis (case-patients) and dengue patients (controls). Among 730 dengue-negative sera, 36 (5%) were positive for leptospirosis. We performed post mortem testing for leptospirosis on 12 available specimens from suspected dengue-related fatalities; 10 (83%) tested positive. Among these 10 fatal cases, pulmonary hemorrhage and renal failure were the most common causes of death. We enrolled 42 case-patients and 84 controls. Jaundice, elevated BUN, hyperbilirubinemia, anemia, and leukocytosis were associated with leptospirosis (p < .01 for all). Male sex, walking in puddles, rural habitation, and owning horses were independently associated with leptospirosis. Epidemiological, clinical, and laboratory criteria may help distinguish leptospirosis from dengue and identify patients who would benefit from early antibiotic treatment.

Cognitive performance in Alzheimer's disease patients receiving rivastigmine for up to 5 years.

This analysis aimed to assess mini-mental state examination (MMSE) scores in patients with Alzheimer's disease who received rivastigmine, an inhibitor of acetylcholinesterase and butyrylcholinesterase, for up to 5 years. Rivastigmine data came from two pooled open-label extensions of four 6-month, randomised, placebo-controlled trials. Projections of decline, had the same patients not been treated, were made using a baseline-dependent mathematical model. MMSE data were available for 1998 rivastigmine-treated patients and 657, 298 and 83 were still on treatment at 3, 4 and 5 years, respectively. The mean (+/-SD) baseline MMSE score was 19.3 (+/-4.9). Projected mean scores in model-based untreated patients declined below 10 points on the MMSE at about 3 years, while the mean MMSE score of patients who remained on rivastigmine stayed above 10 points for 5 years.

Preserved cognitive function after 12 months of treatment with rivastigmine in mild Alzheimer's disease in comparison with untreated AD and MCI patients.

Cholinesterase inhibitors (ChEIs) have shown positive symptomatic effects on cognition, activities of daily living, and behavior in patients with Alzheimer's disease (AD). Rivastigmine is a slowly reversible ChEI that inhibits acetylcholinesterase and butyrylcholinesterase. We evaluated the effects of long-term rivastigmine treatment on cognitive function and plasma levels of ChE activity, and the relationship between ChE activity and cognition. Patients with mild AD (n = 11) treated with rivastigmine for 12 months were compared with matched groups of untreated patients with AD (n = 21) or mild cognitive impairment (MCI; n = 22) representing the natural course of the pre-clinical and very early stage of disease. For untreated AD patients, neuropsychological assessment was made at baseline and 12 months. Determination of ChE activity in plasma and assessment of global cognition, episodic memory, visuospatial ability, and attention were performed at 0 (baseline), 3, 6, and 12 months for treated AD patients and untreated MCI patients. At 12 months, cognitive function was slightly improved or maintained in mild AD patients treated with rivastigmine. In contrast, cognition was markedly worsened in untreated AD patients and unchanged or slightly worsened in untreated MCI patients. In the group of treated AD patients, there was a significant correlation between plasma ChE inhibition and cognition, particularly in relation to attention. This effect was most apparent at 3 months of treatment. In conclusion, a clear beneficial effect of rivastigmine was shown on cognitive function for patients with mild AD and plasma values of ChE inhibition were associated with attention.

Efficacy of rivastigmine in subjects with moderately severe Alzheimer's disease.

BACKGROUND: Cholinesterase (ChE) inhibitors are primarily used in the treatment of mild to moderate Alzheimer's disease (AD), but may also be effective in more severe disease. OBJECTIVE: To evaluate the dual ChE inhibitor, rivastigmine, in more severe dementia. METHODS: We retrospectively analysed pooled data from three randomised, placebo-controlled, double-blind, 6-month trials, involving 2126 AD subjects. Subjects were selected according to baseline Mini-Mental State Examination (MMSE) score to identify subjects with more severe cognitive impairment (10-12 MMSE points). One-hundred-and-seventeen subjects were included who had been treated with rivastigmine 6-12 mg/day or placebo. The AD Assessment Scale-Cognitive Subscale (ADAS-Cog), the MMSE, a six-item subscore of the Progressive Deterioration Scale (PDS) and the BEHAVE-AD assessed efficacy. Tolerability was assessed by recording adverse events (AEs) and the relative risk (RR) of discontinuation. RESULTS: This group of subjects responded well to rivastigmine. After 6 months, the mean ADAS-Cog score declined by 6.3 points in the placebo group and increased by 0.2 points in the rivastigmine group (observed cases; p<0.001). Clinical benefits were also observed with the MMSE, the six-item PDS score and items of the BEHAVE-AD. Rivastigmine showed the same pattern of AEs as in other studies, but the RR of dropping out due to AEs was lower than in subjects with milder AD. CONCLUSION: Current treatment guidelines do not recommend treating individuals with severe AD with ChE inhibitors. However, this retrospective analysis suggests that rivastigmine 6-12 mg/day may benefit subjects with more severe disease, as well as subjects with mild to moderate impairment.

Eosinophilic pericarditis: a rare complication of idiopathic hypereosinophilic syndrome in a child.

We describe an 18-month-old child with idiopathic hypereosinophilic syndrome (IHES) who presented with fever, and cervical lymphadenopathy. Chest X-ray showed marked cardiomegaly, and echocardiogram revealed large pericardial effusion. Other causes of pericarditis were excluded. Despite the initiation of steroid therapy, signs of impending cardiac tamponade developed. Pericardiocentesis yielded bloody fluid with a white blood count of 14,800/mm3, of which 23% were eosinophils. The child recovered after pericardial drainage and prolonged systemic steroid therapy. Eosinophilic pericarditis is a rare but potentially dangerous complication of IHES.

Technical assessment of fuel cell operation on anaerobic digester gas at the Yonkers, NY, wastewater treatment plant.

This paper summarizes the results of a 2-year field test to assess the performance of a specially modified commercial phosphoric acid 200-kW fuel cell power plant to recover energy from anaerobic digester gas (ADG) which has been cleansed of contaminants (sulfur and halide compounds) using a patented gas pretreatment unit (GPU). Specific project goals include characterization of the fuel cell power plant emissions and verification of the GPU performance for removing sulfur contaminants. To remove halide contaminants from the ADG, a halide guard, consisting of a vessel with a metal oxide supported on alumina, was incorporated into the fuel cell reactant supply. This first-of-a-kind demonstration was conducted at the Yonkers, NY, wastewater treatment plant, a sewage processing facility owned and operated by Westchester County. Results have demonstrated that the ADG fuel cell power plant can produce electrical output levels close to full power (200 kW) with negligible air emissions of CO, NO(x), and SO(2). The GPU removed virtually 100% of H(2)S and 88% of organic sulfur, bringing the overall sulfur removal efficiency of the GPU to over 99%. The halide guard removed up to 96% of the halides exiting the GPU.