Urban attributes and the spread of COVID-19: The effects of density, compliance and socio-political factors in Israel.

Current debates identifying urban population density as a major catalyst for the spread of COVID-19, and the praise for de-densification and urban sprawl that they entail, may have dire environmental consequences. Juxtaposing competing theories about the urban antecedents of COVID-19, our key argument is that urban political attributes overshadow the effects of cities' spatial characteristics. This is true even when considering levels of compliance with movement restrictions and controlling for demographic and socio-economic conditions. Taking advantage of Israel as a living lab for studying COVID-19, we examine 271 localities during the first 3 months of the outbreak in Israel, a country where over 90% of the population is urban. Rather than density, we find social makeup and politics to have a critical effect. Cities with some types of political minority groups, but not others, exhibit higher infection rates. Compliance has a significant effect and density's influence on the spread of the disease is contingent on urban political attributes. We conclude with assessing how the relationship between the politics of cities and the spread of contagious diseases sheds new light on tensions between neo-Malthusian sentiments and concerns about urban sprawl and environmental degradation.

Topical Oxymetazoline for Fecal Incontinence in Patients with Spinal Cord Injury: A Double-Blind Randomized Controlled Crossover Study.

BACKGROUND: Topical α-agonists contract the internal anal sphincter muscle; therefore, they may serve as treatment for fecal incontinence. OBJECTIVES: The aim of this study was to investigate the effect of the α-agonist oxymetazoline 1.0% on fecal incontinence in patients with spinal cord injury. DESIGN: This was a double-blind, crossover study. Before randomization, all patients underwent a 1-day, open-label anal manometry and pharmacokinetic study. SETTINGS: The study was conducted at the Department of Internal Medicine, Semmelweis University, Hungary. PATIENTS: Nineteen patients were enrolled into a randomized double-blind, placebo-controlled clinical trial with 2 arms: placebo for 4 weeks followed by oxymetazoline for 4 weeks, or vice versa, with an interval 2-week washout period, in a crossover trial design. Treatment order was randomly assigned, and fecal incontinence was captured with daily diaries. MAIN OUTCOME MEASURES: The primary outcome measured was the number of fecal incontinence episodes in the 8 and 12 hours after drug administration. RESULTS: Resting anal pressure increased in response to oxymetzoline (25.2%). The change in the mean fecal incontinence episodes per month (12 hours post drug application) favored oxymetazoline over placebo: 26.3 (SD ±28.4) versus 36 (SD ±39.8) (p = 0.021). When only nongas episodes were included, the mean number of episodes decreased from 10.1 (+4.3) to 6.3 (±2.1) fecal incontinence episodes per month (p = 0.022). No difference was observed in adverse events between treatment and placebo periods. All pharmacokinetic samples were below the detection limit. LIMITATIONS: The study was limited by the small number of participants. CONCLUSIONS: In this study, oxymetazoline gel presented a clear clinical beneficial effect accompanied by a favorable safety and tolerability profile. Results of the pharmacokinetic analysis indicate that the clinical benefit was mainly due to a local effect of oxymetazoline. Future studies are planned to investigate higher doses of oxymetazoline for this indication. See Video Abstract at http://links.lww.com/DCR/A797.

A Randomized, Double-Blind, Placebo-Controlled Pilot Study of Betahistine to Counteract Olanzapine-Associated Weight Gain.

Patients with schizophrenia experience higher rates of obesity and related morbidity and mortality than the general population does. Given preclinical studies revealing the role of histamine H1 receptor in human eating behavior, and the potential of olanzapine to block with this system, we hypothesized that histamine H1 receptor agonists may be beneficial in reducing antipsychotic-associated weight gain. In the present study, 36 patients with a diagnosis of schizophrenia or schizoaffective disorder and treated with olanzapine were randomized to betahistine (48 mg/d) or matching placebo for 16 weeks. Study outcomes were change in body weight from baseline and effect on antipsychotic efficacy of olanzapine. The patients in the betahistine group had less weight gain (-1.95 kg) compared with placebo group (5.6 + 5.5 kg vs 6.9 + 5.6 kg, respectively). Positive and Negative Syndrome Scale Questionnaire showed improvement within each group and that subjects treated with betahistine enjoyed an improvement (reduction) by a mean of 35.7 points, higher when compared with placebo subjects who had a reduction of 26.6 points (P = 0.233). An almost equal amount of subjects in both groups experienced adverse effects during the course of this study (87.5% of betahistine vs 85.0% of placebo-treated subjects). Overall, there were no clinically marked differences in safety signals between both groups. A larger study addressing the weaknesses of this pilot study is warranted.

Betahistine decreases olanzapine-induced weight gain and somnolence in humans.

Olanzapine's efficacy in schizophrenia is attributed to antagonism of dopamine and serotonin receptors. Olanzapine is also a potent histamine-H1 antagonist that results in weight gain and somnolence. Betahistine is a centrally acting histamine-H1 agonist, and therefore may reduce olanzapine's effect on histamine receptors in the brain. Olanzapine's high affinity for the histamine-H1 receptor warrants the use of high doses of betahistine. Forty-eight healthy women were recruited and randomized to receive either betahistine 144 mg/day or matching placebo for 4 weeks. Due to the high dose of betahistine, olanzapine was started only on the second week and titrated up to 10 mg/day, and co-administration continued for an additional 2 weeks. Only nominal differences in adverse events were noted between the treatment groups. Betahistine caused a 37% reduction in mean weight gain (1.24 kg in the betahistine arm vs. 1.93 kg in the placebo arm; p=.049) and 60% reduction in the mean increase in daytime Epworth sleepiness scores (1.82 units in the betahistine group vs. 3.57 units in the placebo group; p=.042). The present study suggests that betahistine-olanzapine co-administration, in healthy female subjects, yields an acceptable safety profile with mitigation of weight gain and somnolence. This should be further tested in a patient cohort.

Acute effects of betahistine hydrochloride on food intake and appetite in obese women: a randomized, placebo-controlled trial.

BACKGROUND: Central nervous system histaminergic tone is thought to play a role in appetite regulation. In animal models, histamine receptor 1 (HRH1) agonists and histamine receptor 3 (HRH3) antagonists decrease food intake. OBJECTIVE: The objective of this study was to examine the acute effects of betahistine hydrochloride (an HRH1 agonist and HRH3 antagonist) on food intakes and appetites. DESIGN: The study was a proof-of-concept, randomized, double-blinded, placebo-controlled, dose-ranging study performed to examine the effects of betahistine in women with class I or II obesity [body mass index (BMI; in kg/m²) of 30-39.99]. After a 24-h placebo run-in period, subjects received a placebo (n = 19) or 48 (n = 19), 96 (n = 17), or 144 (n = 21) mg betahistine/d for 24 h. Treatment was followed by a buffet test meal to assess energy intake. Hunger, satiety, and desire to eat were measured after consuming the meal by using visual analog scales. Data were analyzed by using regression models with the assumption that there would be an increasing effect of betahistine doses. Analyses were adjusted for age, log fat and lean mass, food preferences, and intake during a buffet test meal obtained during the placebo run-in period. RESULTS: Of the 79 obese women (mean ± SD age: 42 ± 11 y; BMI: 35 ± 3) enrolled in the study, 76 women completed the study. The betahistine dose did not significantly change intakes from those observed during the run-in period of the buffet test meal (P = 0.78). Hunger, fullness, and desire to eat (all P > 0.62) similarly showed no differences according to the betahistine dose. CONCLUSIONS: Betahistine did not produce an effect on food intakes or appetites. More potent histaminergic modulators may be required to elucidate the possible role of histaminergic pathways in human obesity. This trial was registered at clinicaltrials.gov as NCT00459992.

Serum protein N-glycans profiling for the discovery of potential biomarkers for nonalcoholic steatohepatitis.

The hepatic histology in nonalcoholic fatty liver disease can vary from isolated hepatic steatosis to steatohepatitis can progress to cirrhosis and liver-related death. The aim was to evaluate the use of blood serum N-glycan fingerprinting as a tool for differential diagnosis of nonalcoholic steatohepatitis from steatosis. A group of 47 patients with NAFLD was diagnosed by clinical laboratory analysis and ultrasonography, and was studied histologically using the Brunt's scoring system. The control group included 13 healthy individuals. N-glycan profiles of serum proteins were determined by DNA sequencer-based carbohydrate analytical profiling. We have found that the concentrations of two glycans (NGA2F and NA2) and their logarithm ratio of NGA2F versus NA2 (named GlycoNashTest) were associated with the degree of NASH-related fibrosis, but had no correlation with the grade of inflammation nor steatosis severity. When used to screen NAFLD patients, GlycoNashTest could identify advanced NASH-related fibrosis (F3-F4) with the diagnosis sensitivity of 89.5% and specificity of 71.4%. The serum N-glycan profile is a promising noninvasive method for detecting NASH or NASH-related fibrosis in NAFLD patients, which could be a valuable supplement to other markers currently used in diagnosis of NASH.

Betahistine: what's new on the agenda?

BACKGROUND: Betahistine is an orally administered, centrally acting histamine H(1) receptor agonist with partial H(3) antagonistic activity and no H(2)-binding effects. In the past betahistine was clinically studied mainly as a vasodilator for conditions such as cluster headaches, vascular dementia and Meniere's disease, for which it is still used. In recent years, histamine was found to be a key neurotransmitter in the regulation of feeding behavior. OBJECTIVE: To provide a review of the developmental history and current research interests of betahistine. METHODS: All reports of betahistine use in animals and humans were retrieved and reviewed. RESULTS/CONCLUSION: The unique pharmacologic properties of betahistine point to its potential future use as an antiobesity agent.

The 13C-caffeine breath test detects significant fibrosis in patients with nonalcoholic steatohepatitis.

BACKGROUND: The C-caffeine breath test (CBT) is a noninvasive tool for the evaluation of the cytochrome P450 system, implicated in the development of nonalcoholic steatohepatitis. GOAL: To apply the CBT to assess the extent of hepatic fibrosis in patients with nonalcoholic fatty liver disease (NAFLD). METHODS: Twenty-six consecutive patients (mean age 56.1+/-6.85 y, 69.2% women) with NAFLD underwent the CBT, in addition to the clinical and laboratory evaluations and liver biopsy. Ten healthy individuals matched for age served as controls. RESULTS: Mean delta over baseline values differed significantly between patients and controls (1.51+/-0.9 vs. 2.37+/-0.8 Delta per thousand/mg, respectively) (P=0.01) and were significantly higher in patients with fibrosis stage <2 (Brunt's system) (2.0+/-0.77 vs. 1.3+/-0.9 for stage > or =2, P=0.05). Mean delta over baseline values correlated highly with fibrosis stage (P=0.01), albumin (P=0.007), international normalized ratio (P=0.04), bilirubin (P=0.0008), and platelet count (P=0.0001). On multivariate stepwise logistic regression analysis, CBT was the best predictor of severe fibrosis (stage > or =2) (odds ratio 0.274, 95% confidence interval 0.086-0.872, P=0.028), with an area under the curve of 0.788. CONCLUSIONS: The CBT is safe and easy to perform. It can reliably predict severe hepatic fibrosis in patients with NAFLD. Further large-scale studies are still needed.

[Vitamin B6 (Pyridoxine)--excessive dosage in food supplements and OTC medications].

Vitamin B6 (Pyridoxine) is sold in Israel as a supplement and is available over-the-counter (OTC) without regulation. High intake of this vitamin is found in patients with premenstrual syndrome, carpal tunnel syndrome, pregnancy associated nausea and vomiting, decreasing homocysteine levels and improving cognitive function. Mega-doses of this vitamin may result in intoxication. In this review we will outline vitamin B6 function, daily recommended intake, deficiency signs and patients in deficiency risk, and the clinical spectrum of vitamin B6 intoxication.

Use of bioelectrical impedance analysis to predict energy expenditure of hospitalized patients receiving nutrition support.

BACKGROUND: The energy requirement of a patient receiving nutrition support is typically estimated by calculating the basal energy expenditure (BEE) using the Harris-Benedict equations and multiplying by stress and activity factors. Because fat-free mass (FFM) and fat mass (FM) are important determinants of BEE, we hypothesized that body composition estimates derived from bioelectrical impedance analysis (BIA) could be used to develop predictive equations for resting energy expenditure (REE) that were more accurate than those calculated using the Harris-Benedict equations. METHODS: Seventy-six adults referred to the nutrition support service were studied. REE was measured by indirect calorimetry, and single-frequency BIA was used to estimate FFM and FM. Using the first 20 male and 20 female patients, predictive equations for REE were developed by multiple regression analysis, using BIA-derived body composition values, age, and gender. The next 36 patients were used to compare the accuracy of these equations with the Harris-Benedict equations in estimating REE. RESULTS: Using BLA-derived body composition values, gender, and age, predictive equations were developed for REE that explained approximately 65% of the variance. Inclusion of other BIA or anthropometric parameters did not improve the equations. When compared with the Harris-Benedict equations, the equations developed in this study were significantly more accurate, providing an REE estimate that was closer to the measured value in about 75% of patients. CONCLUSIONS: These results indicate that BLA-derived body composition estimates may be used to more accurately predict the energy requirements of patients receiving nutrition support than calculations based on the Harris-Benedict equations.

Evaluation of stress factors and body weight adjustments currently used to estimate energy expenditure in hospitalized patients.

BACKGROUND: The purpose of this study was to critically examine current approaches for estimating energy expenditure and requirements of hospitalized patients requiring nutrition support. METHODS: All indirect calorimetry tests performed by our adult nutrition support service from 1991 to 2000 were reviewed. Stress factors were calculated as the measured energy expenditure divided by the predicted energy expenditure using the Harris-Benedict equation. Various methods for adjusting the body weights of obese subjects for use in the Harris-Benedict equation were evaluated. RESULTS: The average stress factor for these hospitalized patients was 1.25, and there were no differences in the stress factors between men and women. For obese subjects, using an adjusted body weight equal to ideal body weight plus 50% of the difference between ideal and actual body weight in the Harris-Benedict equation gave stress factors comparable with normal weight subjects. For underweight subjects, using the actual rather than ideal body weight gave stress factors that were most similar to normal weight patients. Disease-specific stress factors were calculated and compared with literature values. Mechanical ventilation, recent feeding, fever, and restlessness during the indirect calorimetry measurement increased the measured energy expenditure. CONCLUSIONS: Our findings provide nutrition support services with updated information on disease-specific stress factors that can be used for estimating energy expenditure in hospitalized patients. An adjusted body weight equal to ideal body weight plus 50% of the excess body weight should be used for estimating the energy requirements of obese patients requiring nutrition support.