Dvopulsni sustav za isporuku amoksicilina: Pokušaj sprečavanja bakterijske rezistencije na antibiotike

Bearing in mind the present scenario of the increasing biological tolerance of bacteria against antibiotics, a time controlled two pulse dosage form of amoxicillin was developed. The compression coating inlay tablet approach was used to deliver the drug in two pulses to different parts of the GIT after a well defined lag time between the two releases. This was made possible by formulating a core containing one of the two drug fractions (intended to be delivered as the second pulse), which was spray coated with a suspension of ethyl cellulose and a hydrophilic but water insoluble agent as a pore former (microcrystalline cellulose). Coating of 1 up to 5 % (m/m) was applied over the core tablet, giving a corresponding lag of 3, 5, 7 and 12 h. Increasing the level of coating led to retardation of the water uptake capacity of the core, leading to prolongation of the lag time. Microcrystalline cellulose was used as a hydrophilic but water insoluble porosity modifier in the barrier layer, varying the concentration of which had a significant effect on shortening or prolongation of the lag time. This coated system was further partially compression coated with the remaining drug fraction (to be released as the first immediate release pulse) with a disintegrant, giving a final tablet. The core tablet and the final two pulse inlay tablet were further investigated for the in vitro performance.Zbog sve učestalije pojave rezistencije bakterija na antibiotike, razvijen je dvopulsni sustav s vremenskom kontrolom za isporuku amoksicilina. Sustav čine slojevite tablete s obloženim slojem dobivenim metodom kompresije, koji omogućavaju isporuku lijeka u dva pulsa u različite dijelove gastrointestinalnog trakta, s utvrđenom odgodom između dva oslobađanja. Ovakav način oslobađanja postignut je s pripravkom koji u jezgri tablete sadrži jednu frakciju lijeka (koja se oslobađa kao drugi puls), a u oblozi drugu. Obloženi dio dobiven je sprejanjem sa suspenzijom etilceluloze i hidrofilnog, ali vodonetopljivog sredstva koji tvori pore (mikrokristalinična celuloza). Oblaganje sa slojem koji čini 1 do 5 % (m/m) mase jezgre postignut je vremenski odmak drugog pulsa od 3, 5, 7 i 12 h. Povećanjem mase obložnog sloja smanjuje se kapacitet prodiranja vode u jezgru tablete, što produljuje vrijeme drugog pulsa. Mikrokristalinična celuloza uporijebljena je kao hidrofilno, vodonetopljivo sredstvo za kotrolu poroznosti u barijernom sloju. Promjena koncentracije celuloze značajno je utjecala na skraćenje ili produljenje vremenskog odmaka. Obloženi sustav je potom djelomično obložen s preostalom frakcijom lijeka (koja se oslobađa odmah u prvom pulsu) pomiješanom s dezintegratorom. Tableta s jezgrom i dvopulsna slojevita tableta ispitivane su in vitro

Completed Beltrami-Michell formulation for analyzing mixed boundary value problems in elasticity

In elasticity, the method of forces, wherein stress parameters are considered as the primary unknowns, is known as the Beltrami-Michell formulation (BMF). The existing BMF can only solve stress boundary value problems; it cannot handle the more prevalent displacement of mixed boundary value problems of elasticity. Therefore, this formulation, which has restricted application, could not become a true alternative to the Navier's displacement method, which can solve all three types of boundary value problems. The restrictions in the BMF have been alleviated by augmenting the classical formulation with a novel set of conditions identified as the boundary compatibility conditions. This new method, which completes the classical force formulation, has been termed the completed Beltrami-Michell formulation (CBMF). The CBMF can solve general elasticity problems with stress, displacement, and mixed boundary conditions in terms of stresses as the primary unknowns. The CBMF is derived from the stationary condition of the variational functional of the integrated force method. In the CBMF, stresses for kinematically stable structures can be obtained without any reference to the displacements either in the field or on the boundary. This paper presents the CBMF and its derivation from the variational functional of the integrated force method. Several examples are presented to demonstrate the applicability of the completed formulation for analyzing mixed boundary value problems under thermomechanical loads. Selected example problems include a cylindrical shell wherein membrane and bending responses are coupled, and a composite circular plate

Completed Beltrami-Michell Formulation for Analyzing Radially Symmetrical Bodies

A force method formulation, the completed Beltrami-Michell formulation (CBMF), has been developed for analyzing boundary value problems in elastic continua. The CBMF is obtained by augmenting the classical Beltrami-Michell formulation with novel boundary compatibility conditions. It can analyze general elastic continua with stress, displacement, or mixed boundary conditions. The CBMF alleviates the limitations of the classical formulation, which can solve stress boundary value problems only. In this report, the CBMF is specialized for plates and shells. All equations of the CBMF, including the boundary compatibility conditions, are derived from the variational formulation of the integrated force method (IFM). These equations are defined only in terms of stresses. Their solution for kinematically stable elastic continua provides stress fields without any reference to displacements. In addition, a stress function formulation for plates and shells is developed by augmenting the classical Airy's formulation with boundary compatibility conditions expressed in terms of the stress function. The versatility of the CBMF and the augmented stress function formulation is demonstrated through analytical solutions of several mixed boundary value problems. The example problems include a composite circular plate and a composite circular cylindrical shell under the simultaneous actions of mechanical and thermal loads

Migratory winter bag-net fishery in coastal waters of the Hooghly estuary

The migratory winter big-net fishery is a typical feature of the coastal waters of the Hooghly estuary, 4,000 man with about 800 bag-nets migrated from different estuarine areas and established fishing camps In different islands during 1934 85 and 1985-86. Three and a half months seasonal fishery accounted for an average estimated fish yield of 17,872 t, forming about 71% of the total fish yield from the estuary as against 29% to 33% about 15 year* ago. An average catch per unit of effort of 152 kg was about 18 to 36 times that obtained in the upper and middle stretches and about 3 times more than that 15 years ago in the lower coastal waters. Harpodon nehereus, Trichlurus spp., Psma pama, Setipinna spp. and different species of prawns dominated in the catches. The bulk of the catches are tundrlsd and exported to marketing centres. The reasons for tremendous increase in the winter migratory bag-net catches have been discusse

Cord pilot trial - immediate versus deferred cord clamping for very preterm birth (before 32 weeks gestation): study protocol for a randomized controlled trial

Background: Preterm birth is the most important single determinant of adverse outcome in the United Kingdom; one in every 70 babies (1.4%) is born before 32 weeks (very preterm), yet these births account for over half of infant deaths. Deferring cord clamping allows blood flow between baby and placenta to continue for a short time. This often leads to increased neonatal blood volume at birth and may allow longer for transition to the neonatal circulation. Optimal timing for clamping the cord remains uncertain, however. The Cochrane Review suggests that deferring umbilical cord clamping for preterm births may improve outcome, but larger studies reporting substantive outcomes and with long-term follow-up are needed. Studies of the physiology of placental transfusion suggest that flow in the umbilical cord at very preterm birth may continue for several minutes. This pilot trial aims to assess the feasibility of conducting a large randomised trial comparing immediate and deferred cord clamping in the UK. Methods/Design: Women are eligible for the trial if they are expected to have a live birth before 32 weeks gestation. Exclusion criteria are known monochorionic twins or clinical evidence of twin-twin transfusion syndrome, triplet or higher order multiple pregnancy, and known major congenital malformation. The interventions will be cord clamping within 20 seconds compared with cord clamping after at least two minutes. For births with cord clamping after at least two minutes, initial neonatal care is at the bedside. For the pilot trial, outcomes include measures of recruitment, compliance with the intervention, retention of participants and data quality for the clinical outcomes. Information about the trial is available to women during their antenatal care. Women considered likely to have a very preterm birth are approached for informed consent. Randomisation is close to the time of birth. Follow-up for the women is for one year, and for the children to two years of age (corrected for gestation at birth). The target sample size is 100 to 110 mother-infant pairs recruited over 12 months at eight sites. Trial registration: ISRCTN21456601, registered on 28 February 2013

Birth weight and cognitive performance in older women: the Rancho Bernardo study

Low birth weight is associated with poorer cognitive function from infancy through early adulthood, but little is known about low birth weight and cognitive performance in the elderly. This study examines the association of birth weight with cognitive function in community-dwelling older women. Participants were 292 community-dwelling women aged 55–89 (median = 71 years) who attended a 1988–91 clinic visit when cognitive function was assessed, and responded to a 1991 mailed questionnaire assessing birth weight. All analyses were adjusted for age and education. Birth weight ranged from 2 to 12 pounds (lbs; mean = 7.4 ± 1.9). When birth weight was categorized into tertiles (2–6.9 lbs, 7–8 lbs, and 8.1–12.4 lbs), women in the lowest tertile had significantly lower (“poorer”) scores on Serial 7’s, a test of concentration and calculation (p < 0.05). Other birth weight categorizations (lowest quartile or quintile, or birth weight <5.5 lbs vs. 5.6–8.9 lbs and ≥9 lbs) did not improve the prediction of poor performance on Serial 7’s. Birth weight as a continuous variable was significantly and positively associated with Serial 7’s test scores (p = 0.04). Results suggest that small decrements in cognitive function tasks involving calculation may persist throughout life in women who were of relatively low birth weight. Although this association could be spurious, it deserves further evaluation

Psychiatric disorders in individuals born very preterm / very low-birth weight: An individual participant data (IPD) meta-analysis

Background: Data on psychiatric disorders in survivors born very preterm (VP; <32 weeks) or very low birthweight (VLBW; <1500 g) are sparse. We compared rates of psychiatric diagnoses between VP/VLBW and term-born, normal birthweight (term/NBW) control participants. / Methods: This individual participant data (IPD) meta-analysis pooled data from eligible groups in the Adults born Preterm International Collaboration (APIC). Inclusion criteria included: 1) VP/VLBW group (birth weight 2499 g and/or gestational age ≥37 weeks), and 3) structured measure of psychiatric diagnoses using DSM or ICD criteria. Diagnoses of interest were Attention Deficit Hyperactivity Disorder (ADHD), Autism Spectrum Disorder (ASD), Anxiety Disorder, Mood Disorder, Disruptive Behaviour Disorder (DBD), Eating Disorder, and Psychotic Disorder. A systematic search for eligible studies was conducted (PROSPERO Registration Number 47555). / Findings: Data were obtained from 10 studies (1385 VP/VLBW participants, 1780 controls), using a range of instruments and approaches to assigning diagnoses. Those born VP/VLBW had ten times higher odds of meeting criteria for ASD (odds ratio [OR] 10·6, 95% confidence interval [CI] 2·50, 44·7), five times higher odds of meeting criteria for ADHD (OR 5·42, 95% CI 3·10, 9·46), twice the odds of meeting criteria for Anxiety Disorder (OR 1·91, 95% CI 1·36, 2·69), and 1·5 times the odds of meeting criteria for Mood Disorder (OR 1·51, 95% CI 1·08, 2·12) than controls. This pattern of findings was consistent within age (<18 years vs. ≥18 years) and sex subgroups. / Interpretation: Our data suggests that individuals born VP/VLBW might have higher odds of meeting criteria for certain psychiatric disorders through childhood and into adulthood than term/NBW controls. Further research is needed to corroborate our results and identify factors associated with psychiatric disorders in individuals born VP/VLBW. / Funding: Australia's National Health & Medical Research Council; CAPES (Coordenação de Aperfeiçoamento de Pessoal deNível Superior) - International Cooperation General Program; Canadian Institutes of Health Research Team Grant; National Council for Scientific and Technological Development (CNPq); Academy of Finland; Sigrid Juselius Foundation; Signe and Ane Gyllenberg Foundation; European Union's Horizon 2020 research and innovation programme: Project RECAP-Preterm; European Commission Dynamics of Inequality Across the Life-course: structures and processes (DIAL); Neurologic Foundation of New Zealand; MRC programme grant; Health Research Council of New Zealand; National Institutes of Health, USA; The Research Council of Norway; Joint Research Committee between St. Olavs Hospital and Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU); Liaison Committee between Central Norway Regional Health Authority and NTNU

Improving benchmarking by using an explicit framework for the development of composite indicators: an example using pediatric quality of care

<p>Abstract</p> <p>Background</p> <p>The measurement of healthcare provider performance is becoming more widespread. Physicians have been guarded about performance measurement, in part because the methodology for comparative measurement of care quality is underdeveloped. Comprehensive quality improvement will require comprehensive measurement, implying the aggregation of multiple quality metrics into composite indicators.</p> <p>Objective</p> <p>To present a conceptual framework to develop comprehensive, robust, and transparent composite indicators of pediatric care quality, and to highlight aspects specific to quality measurement in children.</p> <p>Methods</p> <p>We reviewed the scientific literature on composite indicator development, health systems, and quality measurement in the pediatric healthcare setting. Frameworks were selected for explicitness and applicability to a hospital-based measurement system.</p> <p>Results</p> <p>We synthesized various frameworks into a comprehensive model for the development of composite indicators of quality of care. Among its key premises, the model proposes identifying structural, process, and outcome metrics for each of the Institute of Medicine's six domains of quality (safety, effectiveness, efficiency, patient-centeredness, timeliness, and equity) and presents a step-by-step framework for embedding the quality of care measurement model into composite indicator development.</p> <p>Conclusions</p> <p>The framework presented offers researchers an explicit path to composite indicator development. Without a scientifically robust and comprehensive approach to measurement of the quality of healthcare, performance measurement will ultimately fail to achieve its quality improvement goals.</p

Hypertensive patients' perceptions of their physicians' knowledge about them: a cross-sectional study in Japan

<p>Abstract</p> <p>Background</p> <p>In order to evaluate the difference in quality of primary care provided by physicians between the types of medical institutions in Japan, we examined whether the physicians' comprehensive knowledge of their patients is perceived differently by the patients seen at clinics and hospitals.</p> <p>Methods</p> <p>Patients with prescriptions for hypertensive drugs were approached sequentially at 13 pharmacies, and were administered a questionnaire on their perception of their physician's knowledge about them. Data were obtained for 687 patients (362 from clinics and 325 from hospitals). A physician's knowledge of his or her patients was assessed according to six aspects: their medical history, their current medications, history of allergy, what worries patients most about their health, patients' values and beliefs on their health, and patients' roles and responsibilities at work, home, or school. Responses were scored from 1 through 6 (1: knows very well; 6: doesn't know at all).</p> <p>Results</p> <p>Patients treated in clinics were seen more frequently, for a longer period, and had fewer complications than the patients who were treated in hospitals. Among the six aspects of physicians' knowledge assessed, 79.3% of the patients reported that their physicians knew their complete list of medications "very well or well," while 28.3% reported the same about their roles and responsibilities at work, home, or school. Physicians in clinics were considered to know their patients' worries about their health (p = 0.004) and the roles and responsibilities of the patients at work, home, or school (p = 0.028) well. Multiple regression analysis showed that the type of medical institutions remained as a significant variable only for the aspect of patients' worries about their health. The factor that consistently affected the patients' perception of physicians' knowledge about them was the patients' age.</p> <p>Conclusions</p> <p>Hypertensive patients' perceptions of their physicians' knowledge about them did not differ significantly between clinics and hospitals in Japan for most of the aspects. In order to differentiate the roles of physicians in hospitals and clinics better and ensure the quality of primary care, the establishment of a standardized educational system to train primary care physicians better is recommended.</p

Post-neonatal Mortality, Morbidity, and Developmental Outcome after Ultrasound-Dated Preterm Birth in Rural Malawi: A Community-Based Cohort Study

Using data collected as a follow-up to a randomized trial, Melissa Gladstone and colleagues show that during the first two years of life, infants born preterm in southern Malawi are disadvantaged in terms of mortality, growth, and development