Exploring the pharmacokinetics of second-generation cephalosporin, cefaclor: a systematic review in healthy and diseased populations.

Cefaclor is a bactericidal antibiotic recommended for treating diverse types of infections. This review aims to comprehensively assess the pharmacokinetic (PK) data on cefaclor in humans.Google Scholar, PubMed, Cochrane Library, and EBSCO databases were systematically performed to identify all the relevant studies containing at least one reported PK parameter of cefaclor.Cefaclor shows the linear PK profile as the area under the plasma concentration-time curve from 0 to t (AUC0-t) and maximum plasma concentration (Cmax) increase in a dose-dependent manner. The AUC0-t of cefaclor in the rice diet was found to be higher than that of bread food, i.e. 19.9 ± 2.6 ug/ml.hr vs 15.4 ± 4 ug/ml.hr. The AUC in paediatrics during the fed state was significantly higher compared to that in adults. Patients with renal impairments showed a Cmax 2.2 times higher than that of normal subjects. A significant increase in Cmax was depicted among individuals following a vegetarian diet in comparison with the non-vegetarian diet. Moreover, cefaclor exhibits time-dependent killing above the minimum inhibitory concentration (MIC < 2 ug), favouring its use in treating infections caused by specific pathogens.This systematic review summarises all the reported PK parameters of cefaclor in healthy and diseased subjects in the literature. This data can help practitioners in adjusting cefaclor doses among different diseases and populations to avoid drug interactions and adverse effects.

Influence of milling pH and storage on quality characteristics, mineral and fatty acid profile of buffalo Mozzarella cheese.

BACKGROUND: Currently, cheese fat is a major component of human diet due to change in eating habits. It contains a number of health destroying as well as health promoting fatty acids. Bovine milk cheese fatty acid composition is regulating by many factors. These may be breed of animal, animal health condition like mastitis and stage of lactation. It also differs with feed and dietary fat intake and seasons. Many studies demonstrated physicochemical, textural and sensory characteristics of Mozzarella cheese with variation in technological process but no literature found about the fatty acid profile and potential influence of milling pH on the fatty acid composition of buffalo Mozzarella cheese. METHODS: Buffalo Mozzarella cheeses were manufactured at 5.2, 5.1, 5.0, 4.9 and 4.8 milling pH, vacuum packaged and stored at 4 °C and analyzed for quality characteristics, mineral composition and fatty acid profile on days 1, 45, and 90. Results were analyzed by ANOVA according to complete randomized design. RESULTS: This study evaluated the effect of milling pH on chemical composition, mineral and fatty acid profile of buffalo Mozzarella cheese. Experimentally induced milling pH differences persisted and significantly affected chemical composition during first day of manufacturing but have no effect on fatty acid profile of cheese. However, storage effects significantly on chemical composition and fatty acid profile of cheese. Decreasing milling pH from 5.2-4.9 resulted in decrease in moisture content of cheese. As a result of changes in milling pH, all the cheeses experienced a significant loss in protein content. In contrast to protein content, fat content of cheese increases with decreasing milling pH. Ash contents of cheese decreased with decreasing milling pH. The level of calcium decreases from 77.82 mg/g to 69.1 mg/g with decreasing milling pH while there is no clear trend observed for potassium and sodium during change in milling pH. Saturated fatty acids presented higher concentrations reaching values of about 71.38 g/100 g throughout storage while monounsaturated fatty acids decreases with storage from 26.72 to 22.06 g/100 g. On the other hand, total polyunsaturated fatty acids exhibited lower concentrations than total monounsaturated fatty acids reaching values of 3.2 g/100 g and its value also decreased with ripening and reached to 1.6 g/100 g. Concentration of C18:1 t10-11 was observed 1.89% in freshly prepared cheese. Milling pH did not influence C18:1 t10-11 concentration but storage days significantly (p < 0.05) decreased its concentration. CONCLUSION: In modern era, Mozzarella cheese is major source of dietary fatty acids. The study demonstrated that Mozzarella cheese is a rich source of saturated fatty acids that has detrimental effect on health but it is also observed that it is also a major source of essential fatty acids that has beneficial impact on health. It is concluded that technological conditions like milling pH minimally influence cheese fatty acid profile but after manufacturing treatments and conditions like packaging and storage greatly influence fatty acid profile of cheese. It was concluded that cheese may get oxidized if it is packed in inappropriate packaging material that have reduced air barrier resistance. Moreover, cheese storage under light may also become oxidized which is also harmful for health.

Nonalcoholic Wernicke's Encephalopathy: A Retrospective Study from a Tertiary Care Center in Northern India.

OBJECTIVE: The objective of this study was to describe the demographic features, clinical presentation, and management and outcome of fifty cases of nonalcoholic Wernicke's encephalopathy from a tertiary care hospital of a region with reported incidence of thiamine deficiency disorders. MATERIALS AND METHODS: In a retrospective study, fifty adult cases of Wernicke's encephalopathy were analyzed. The diagnosis of Wernicke's encephalopathy was made according to the European federation of neurological societies guidelines 2010. Response to thiamine replacement and associated brain magnetic resonance imaging (MRI) findings were also considered as supportive evidence. RESULTS: The mean age of patients was 50.38 years with 20 males and 30 females. The most common clinical manifestations were alteration in sensorium in 30 (60%), ataxia in 18 (36%), memory impairment in 15 (30%), nystagmus in 35 (70%), ophthalmoparesis in 11 (22%), and seizures in 4 (8%). A total of 42 patients had a history of recurrent vomiting. All patients had polished rice as their staple diet. Thirty-five patients had associated polyneuropathy and 15 had a gastrointestinal disorder. Twenty patients underwent MRI which showed both typical and atypical lesions. Majority of patients showed partial or complete response to intravenous thiamine. On discharge, the most common residual symptoms were lower limb weakness, ataxia, and memory impairment. CONCLUSION: The study shows high incidence of nonalcoholic Wernicke's encephalopathy in the region with predominant causative factor being a thiamine deficient diet. Recurrent vomiting can be a prominent early symptom of thiamine deficiency and its recognition can help in the early diagnosis of Wernicke's encephalopathy and related thiamine deficiency disorders. Thiamine fortification of food should be done in areas with reported incidence of thiamine deficiency disorders.

Mirabegron as Add-On Treatment to Solifenacin in Patients with Incontinent Overactive Bladder and an Inadequate Response to Solifenacin Monotherapy: Responder Analyses and Patient-Reported Outcomes from the BESIDE Study [corrected].

PURPOSE: We investigated improvements in overactive bladder and patient reported outcomes in patients with overactive bladder and refractory incontinence treated with mirabegron 50 mg plus solifenacin 5 mg vs solifenacin 5 or 10 mg. MATERIALS AND METHODS: Patients with overactive bladder who were incontinent despite 4 weeks of single-blind daily solifenacin 5 mg were randomized 1:1:1 to a double-blind daily combination of mirabegron 50 mg/solifenacin 5 mg, or solifenacin 5 or 10 mg for 12 weeks. The mirabegron dose was increased from 25 to 50 mg after week 4. Symptom bother, health related quality of life and patient perception of bladder condition were assessed by OAB-q (Overactive Bladder Questionnaire) and the PPBC (Patient Perception of Bladder Condition) questionnaire, respectively. Responder rates were based on a 50% reduction in daily incontinence, zero incontinence episodes and fewer than 8 micturitions per 24 hours with minimal important differences in OAB-q and PPBC. RESULTS: Overall 2,174 patients with a median age of 59 years were randomized, including 727 to the combination, 728 to solifenacin 5 mg and 719 to solifenacin 10 mg. Symptom bother, total health related quality of life and its subscales (coping, concern and social), and PPBC were significantly improved with combination vs solifenacin monotherapy (p <0.05). The odds of achieving clinically meaningful improvements in incontinence, micturition frequency, symptom bother, health related quality of life and PPBC were significantly higher for combination than solifenacin monotherapy. The odds of becoming continent was 47% and 28% higher for combination vs solifenacin 5 and 10 mg (OR 1.47, 95% CI 1.17-1.84, p = 0.001 and OR 1.28; 95% CI 1.02-1.61, p = 0.033, respectively). CONCLUSIONS: Significantly more patients on the combination achieved clinically meaningful improvements in incontinence and micturition frequency. Improvements were accompanied by similar improvements in PPBC, symptom bother and health related quality of life.

Efficacy and Safety of Mirabegron Add-on Therapy to Solifenacin in Incontinent Overactive Bladder Patients with an Inadequate Response to Initial 4-Week Solifenacin Monotherapy: A Randomised Double-blind Multicentre Phase 3B Study (BESIDE).

BACKGROUND: Incontinence has a greater detrimental effect on quality of life than other symptoms of overactive bladder (OAB) and is often difficult to treat with antimuscarinic monotherapy. OBJECTIVE: To evaluate the efficacy and the safety and tolerability of combination (solifenacin 5mg and mirabegron 50mg) versus solifenacin 5 or 10mg in OAB patients remaining incontinent after 4 wk of solifenacin 5mg. DESIGN, SETTING, AND PARTICIPANTS: OAB patients remaining incontinent despite daily solifenacin 5mg during 4-wk single-blind run-in were randomised 1:1:1 to double-blind daily combination or solifenacin 5 or 10mg for 12 wk. Patients receiving the combination were initiated on mirabegron 25mg increasing to 50mg after week 4. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS: The primary end point was a change from baseline to end of treatment (EOT) in the mean number of incontinence episodes per 24h (stratified rank analysis of covariance [ANCOVA]). Key secondary end points were a change from baseline to EOT in the mean number of micturitions per 24h (ANCOVA) and number of incontinence episodes noted in a 3-d diary at EOT (mixed-effects Poisson regression). A trial (BESIDE) comparing combination treatment (solifenacin plus mirabegron) with one treatment alone (solifenacin) tested the superiority of combination versus solifenacin 5mg, noninferiority (and potential superiority) of combination versus solifenacin 10mg (key secondary end points), and the safety and tolerability of combination therapy versus solifenacin monotherapy. RESULTS AND LIMITATIONS: A total of 2174 patients were randomised to combination (n=727), solifenacin 5mg (n=728), or solifenacin 10mg (n=719). At EOT, combination was superior to solifenacin 5mg, with significant improvements in daily incontinence (p=0.001), daily micturitions (p<0.001), and incontinence noted in a 3-d diary (p=0.014). Combination was noninferior to solifenacin 10mg for key secondary end points and superior to solifenacin 10mg for improving daily micturitions. All treatments were well tolerated. CONCLUSIONS: Adding mirabegron 50mg to solifenacin 5mg further improved OAB symptoms versus solifenacin 5 or 10mg, and it was well tolerated in OAB patients remaining incontinent after initial solifenacin 5mg. PATIENT SUMMARY: In this 12-wk study, overactive bladder patients who remained incontinent despite initial solifenacin 5mg treatment received additional treatment with mirabegron 50mg. Combining mirabegron 50mg with solifenacin 5mg was superior to solifenacin 5mg alone in improving symptoms of incontinence and frequent urination, and it was well tolerated. TRIAL REGISTRATION: ClinicalTrials.gov NCT01908829.

Cardiovascular Safety of ß3-adrenoceptor Agonists for the Treatment of Patients with Overactive Bladder Syndrome.

CONTEXT: Mirabegron, the first ß3-adrenoceptor agonist in clinical practice, is approved for treatment of overactive bladder (OAB) syndrome symptoms. Because ß3-adrenoceptors are expressed in cardiovascular (CV) tissues, there are concerns that OAB treatment with ß3-adrenoceptor agonists may affect the heart and vasculature. OBJECTIVE: To provide a summary of CV effects of ß3-adrenoceptor agonists in clinical studies. EVIDENCE ACQUISITION: A systematic literature search from inception until November 2014 was performed on studies in PubMed and Medline. EVIDENCE SYNTHESIS: Twenty papers, published between 1994 and 2014, were identified: mirabegron (16), solabegron (2), AK-677 (1), and BRL35135 (1). More detailed CV data from mirabegron studies were available in online regulatory documents filed with the US Food and Drug Administration and the UK National Institute for Health and Care Excellence. CONCLUSIONS: The CV safety of mirabegron appears to be acceptable at therapeutic doses and comparable with that of antimuscarinic agents, currently first-line therapy for OAB. PATIENT SUMMARY: In this review we looked at the cardiovascular (CV) effects of ß3-adrenoceptor agonists used for the treatment of overactive bladder (OAB). The CV safety of mirabegron (the only clinically approved ß3-adrenoceptor agonist) appears to be acceptable at therapeutic doses and comparable with that of antimuscarinic agents, the current first-line therapy for OAB.

Association of glycosylated haemoglobin level and diabetes mellitus duration with the severity of coronary artery disease.

Diabetes mellitus (DM) is known to cause microvascular and possibly macrovascular complications. This study was performed to find the association between glycosylated haemoglobin (HbA1C) level and the severity of coronary artery disease. One hundred and ten consecutive patients admitted to hospital with acute myocardial infarction were studied. Seventy-eight patients (70.9%) had DM, 73 (93.58%) had HbA1C > 7%, 52 (47.3%) were hypertensive, 19 (17.3%) had a history of smoking and 37 (33.6%) had raised cholesterol. Coronary angiography was carried out in 87 (79.1%) patients and the severity of disease was assessed using the Gensini score. The mean Gensini score was 53.36+/-36.94 and the mean HbA1C was 8.4+/-2.39%. There was a significant association between Gensini score and DM (p=0.003) and between Gensini score and hypertension (p=0.018). HbA1C (r=0.427, p=0.001) and duration of DM (r=0.362, p=0.004) had a positive linear correlation with the Gensini score. Multiple regression analysis showed HbA1C to be an independent factor that influenced the Gensini score (p=0.021).

Exercise capacity of Saudi with symptoms suggestive of cardiovascular disease in a military hospital in Western Saudi Arabia.

OBJECTIVE: To analyze the results of exercise tolerance test (ETT) of Saudi women and assess their exercise capacity. METHODS: A hospital based retrospective cohort analysis was carried out on all Saudi women referred to the Cardiology Department for ETT from February 2005 to June 2007. They underwent symptom limited treadmill test according to the standard Bruce protocol with exercise electrocardiogram monitoring. RESULTS: One hundred and seventy-six women were included in the study. Fifty-one (31.9%) patients did not achieve target heart rate. The mean age +/- SD was 48.3 +/- 9.3 years. There was no association of age, diabetes mellitus, hypertension, positive family history of ischemic heart disease (IHD) and hyperlipidemia to achieve target heart rate (p>0.05). Exercise time was influenced by diabetes mellitus (p=0.054) and hyperlipidemia (p=0.044). The mean exercise time +/-SD was 5.15 +/- 2.63 minutes and the mean exercise capacity +/-SD was 6.29+/-2.52. metabolic equivalent. Sensitivity was 36.4% (95% CI 29.3-44.6), specificity 92.3% (95% CI 80.5-96.8), positive predictive value 26.7% (95% CI 21.3-31.4), negative predictive value 95.4% (95% CI 90.9-98.3), likelihood ratio for positive result was 4.7 (95% CI 3.1-6.2) and likelihood ratio for negative result was 0.69 (95% CI 0.48-0.81). CONCLUSION: Exercise capacity of Saudi women is less when compared to similar studies in women from other regions. Exercise tolerance test can be used to rule out presence of IHD in Saudi women, but value of a positive test is less likely to predict the presence of IHD.