AimsTo assess the tolerability of initiating/uptitrating sacubitril/valsartan (LCZ696) from 50 to 200 mg twice daily (target dose) over 3 and 6 weeks in heart failure (HF) patients (ejection fraction ≤35%).Methods and resultsA 5‐day open‐label run‐in (sacubitril/valsartan 50 mg twice daily) preceded an 11‐week, double‐blind, randomization period [100 mg twice daily for 2 weeks followed by 200 mg twice daily (‘condensed’ regimen) vs. 50 mg twice daily for 2 weeks, 100 mg twice daily for 3 weeks, followed by 200 mg twice daily (‘conservative’ regimen)]. Patients were stratified by pre‐study dose of angiotensin‐converting enzyme inhibitor/angiotensin‐receptor blocker (ACEI/ARB; low‐dose stratum included ACEI/ARB‐naïve patients). Of 540 patients entering run‐in, 498 (92%) were randomized and 429 (86.1% of randomized) completed the study. Pre‐defined tolerability criteria were hypotension, renal dysfunction and hyperkalaemia; and adjudicated angioedema, which occurred in (‘condensed’ vs. ‘conservative’) 9.7% vs. 8.4% (P = 0.570), 7.3% vs. 7.6% (P = 0.990), 7.7% vs. 4.4% (P = 0.114), and 0.0% vs. 0.8% of patients, respectively. Corresponding proportions for pre‐defined systolic blood pressure <95 mmHg, serum potassium >5.5 mmol/L, and serum creatinine >3.0 mg/dL were 8.9% vs. 5.2% (P = 0.102), 7.3% vs. 4.0% (P = 0.097), and 0.4% vs. 0%, respectively. In total, 378 (76%) patients achieved and maintained sacubitril/valsartan 200 mg twice daily without dose interruption/down‐titration over 12 weeks (77.8% vs. 84.3% for ‘condensed’ vs. ‘conservative’; P = 0.078). Rates by ACEI/ARB pre‐study dose stratification were 82.6% vs. 83.8% (P = 0.783) for high‐dose/‘condensed’ vs. high‐dose/‘conservative’ and 84.9% vs. 73.6% (P = 0.030) for low‐dose/‘conservative’ vs. low‐dose/‘condensed’.ConclusionsInitiation/uptitration of sacubitril/valsartan from 50 to 200 mg twice daily over 3 or 6 weeks had a tolerability profile in line with other HF treatments. More gradual initiation/uptitration maximized attainment of target dose in the low‐dose ACEI/ARB group.

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The majority of patients (>80%) with SBP of ≥100 mmHg achieved and maintained the target dose of sacubitril/valsartan if the treatment was titrated gradually. These findings suggest that low SBP should not prevent clinicians from considering the initiation of sacubitril/valsartan.

Air impingement technology is gaining popularity in food-processing operations such as baking, freezing, drying, and toasting. In this article, physical characteristics of impinging jets, such as turbulent mixing in the free jet region, stagnation, boundary-layer formation, recirculation, and their interactions with food products in terms of heat and mass transfer have been reviewed. The discussion includes experimental methods used for measurement of heat and mass transfer for single and multiple slot and circular jets. Procedures used for measurement of heat-transfer coefficient such as lumped sensor method, micro-calorimetric approach, and use of flux sensors are presented. Typical qualitative and quantitative flow-field studies using planar visualization and laser Doppler anemometry have been reviewed. Numerical modeling of air impingement systems is discussed with special consideration of problems arising in food-processing systems.

Background:Vitiligo is an idiopathic acquired progressive de/hypopigmentary disorder of skin and mucosae. In Indian skin depigmentaion is very much obvious and can cause psychological distress, low self esteem and social stigmatization.Aims:The primary objective of this study was to evaluate the psychiatric morbidity in vitiligo patients and secondary objective was to assess the morbidity in all eight dimensions of psychosocial and physical aspects, i.e. cognitive, social, discomfort, limitations, depression, fear, embarrassment and anger.Materials and Methods:An institution based case-control study with sixty-one patients of vitiligo and equal number of healthy age and sex matched controls was undertaken. The self-reporting questionnaire-24 (SRQ-24) and skindex (A 61-item survey questionnaire) were used to assess the psychiatric morbidity in both the groups.Results:The SRQ-assessed psychiatric morbidity in the study group was 63.93%, compared with 24.59% in the control group (P<0.0001). Acral vitiligo had maximum association with psychiatric morbidity (86.67%) followed by vitiligo vulgaris (68%), mucosal vitiligo (62.5%) and others. According to the skindex, the most common psychiatric morbidity in vitiligo patients was depression (62.29%) followed by embarrassment (55.73%), social problem (54.09%), cognitive impairment (50.81%), physical limitation (47.54%), discomfort (40.98%), anger (36.06%) and fear (24.59%). The difference in Skindex scoring that marked the psychiatric morbidity among the case and control groups was statistically significant for depression, discomfort, social problem, cognitive impairment, embarrassment (P<0.0001) and physical limitation (P=0.0044).Conclusion:Vitiligo has a high degree of psychiatric morbidity.

Spatial variation of heat transfer is an important factor in air impingement systems. Temperature data were obtained when a jet at room temperature impinged on a flat object initially at -50 °C to estimate heat transfer under freeze-thaw conditions. Single and double circular jets and slot jets were examined. Temperature data were fit into empirical relationships for predicting heat transfer coefficients and their spatial variation for conditions common in impingement freeze-thaw applications. For processing conditions involving cooling, the impingement surface was initially heated to a temperature of 70 °C and allowed to cool when subjected to impingement with room temperature air.

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