Estimating the cost-effectiveness of detecting cases of chronic hepatitis C infection on reception into prison

Background In England and Wales where less than 1% of the population are Injecting drug users (IDUs), 97% of HCV reports are attributed to injecting drug use. As over 60% of the IDU population will have been imprisoned by the age of 30 years, prison may provide a good location in which to offer HCV screening and treatment. The aim of this work is to examine the cost effectiveness of a number of alternative HCV case-finding strategies on prison reception Methods A decision analysis model embedded in a model of the flow of IDUs through prison was used to estimate the cost effectiveness of a number of alternative case-finding strategies. The model estimates the average cost of identifying a new case of HCV from the perspective of the health care provider and how these estimates may evolve over time. Results The results suggest that administering verbal screening for a past positive HCV test and for ever having engaged in illicit drug use prior to the administering of ELISA and PCR tests can have a significant impact on the cost effectiveness of HCV case-finding strategies on prison reception; the discounted cost in 2017 being £2,102 per new HCV case detected compared to £3,107 when no verbal screening is employed. Conclusion The work here demonstrates the importance of targeting those individuals that have ever engaged in illicit drug use for HCV testing in prisons, these individuals can then be targeted for future intervention measures such as treatment or monitored to prevent future transmission

Children's Medicines in Tanzania: A National Survey of Administration Practices and Preferences.

The dearth of age-appropriate formulations of many medicines for children poses a major challenge to pediatric therapeutic practice, adherence, and health care delivery worldwide. We provide information on current administration practices of pediatric medicines and describe key stakeholder preferences for new formulation characteristics. We surveyed children aged 6-12 years, parents/caregivers over age 18 with children under age 12, and healthcare workers in 10 regions of Tanzania to determine current pediatric medicine prescription and administration practices as well as preferences for new formulations. Analyses were stratified by setting, pediatric age group, parent/caregiver education, and healthcare worker cadre. Complete data were available for 206 children, 202 parents/caregivers, and 202 healthcare workers. Swallowing oral solid dosage forms whole or crushing/dissolving them and mixing with water were the two most frequently reported methods of administration. Children frequently reported disliking medication taste, and many had vomited doses. Healthcare workers reported medicine availability most significantly influences prescribing practices. Most parents/caregivers and children prefer sweet-tasting medicine. Parents/caregivers and healthcare workers prefer oral liquid dosage forms for young children, and had similar thresholds for the maximum number of oral solid dosage forms children at different ages can take. There are many impediments to acceptable and accurate administration of medicines to children. Current practices are associated with poor tolerability and the potential for under- or over-dosing. Children, parents/caregivers, and healthcare workers in Tanzania have clear preferences for tastes and formulations, which should inform the development, manufacturing, and marketing of pediatric medications for resource-limited settings

Case report: Rare skeletal manifestations in a child with primary hyperparathyroidism

Background: Primary hyperparathyroidism (PHPT) is uncommon among children with an incidence of 1:300,000. This diagnosis is often missed in children in contrast to adults where it is detected at a pre symptomatic stage due to routine blood investigations. Etiology of PHPT can be due to adenoma, hyperplasia or rarely carcinoma. Case presentation: A 12year old Sri Lankan girl presented with progressive difficulty in walking since 1year. On examination she had bilateral genu valgum. Skeletal survey revealed valgus deformity of knee joints, bilateral subluxation of upper femoral epiphysis(SUFE), epiphyseal displacement of bilateral humeri, rugger jersey spine and subperiosteal bone resorptions in lateral aspects of 2nd and 3rd middle phalanges. There were no radiological manifestations of rickets. Metabolic profile revealed hypercalcemia with hypophosphatemia. Intact parathyroid hormone levels were elevated at 790pg/ml. Vitamin D levels were deficient. She had low bone mineral density with Z score of -3.4. Vitamin D supplementation resulted in worsening of hypercalcemia without reduction in PTH levels. Tc 99 Sestamibi uptake scan showed abnormal tracer retention in left inferior pole of thyroid. A large parathyroid gland was removed with histology favoring parathyroid adenoma. Post operatively she developed hypocalcemia. Bilateral osteotomy was done for SUFE and further surgeries for correction of limb deformities planned. Conclusion: PHPT in children is usually diagnosed late when irreversible organ damage has occurred. Children can present with non specific symptoms involving gastrointestinal, musculoskeletal, renal and neurological systems. PHPT can cause disarray in bone and epiphysis in children during pubertal growth spurt. Genu valgum and SUFE are rare skeletal manifestations in PHPT and only 10 cases of genu valgum and 9 cases of SUFE have been reported up to now. So far no cases have been reported on epiphyseal displacement of humeri. Awareness regarding the occurrence of these rare skeletal manifestations especially during puberty is important for early diagnosis to prevent irreversible outcomes

Src Dependent Pancreatic Acinar Injury Can Be Initiated Independent of an Increase in Cytosolic Calcium

Several deleterious intra-acinar phenomena are simultaneously triggered on initiating acute pancreatitis. These culminate in acinar injury or inflammatory mediator generation in vitro and parenchymal damage in vivo. Supraphysiologic caerulein is one such initiator which simultaneously activates numerous signaling pathways including non-receptor tyrosine kinases such as of the Src family. It also causes a sustained increase in cytosolic calcium- a player thought to be crucial in regulating deleterious phenomena. We have shown Src to be involved in caerulein induced actin remodeling, and caerulein induced changes in the Golgi and post-Golgi trafficking to be involved in trypsinogen activation, which initiates acinar cell injury. However, it remains unclear whether an increase in cytosolic calcium is necessary to initiate acinar injury or if injury can be initiated at basal cytosolic calcium levels by an alternate pathway. To study the interplay between tyrosine kinase signaling and calcium, we treated mouse pancreatic acinar cells with the tyrosine phosphatase inhibitor pervanadate. We studied the effect of the clinically used Src inhibitor Dasatinib (BMS-354825) on pervanadate or caerulein induced changes in Src activation, trypsinogen activation, cell injury, upstream cytosolic calcium, actin and Golgi morphology. Pervanadate, like supraphysiologic caerulein, induced Src activation, redistribution of the F-actin from its normal location in the sub-apical area to the basolateral areas, and caused antegrade fragmentation of the Golgi. These changes, like those induced by supraphysiologic caerulein, were associated with trypsinogen activation and acinar injury, all of which were prevented by Dasatinib. Interestingly, however, pervanadate did not cause an increase in cytosolic calcium, and the caerulein induced increase in cytosolic calcium was not affected by Dasatinib. These findings suggest that intra-acinar deleterious phenomena may be initiated independent of an increase in cytosolic calcium. Other players resulting in acinar injury along with the Src family of tyrosine kinases remain to be explored. © 2013 Mishra et al

Inhibition of invasion and induction of apoptotic cell death of cancer cell lines by overexpression of TIMP-3

Dysregulation of matrix degrading metalloproteinase enzymes (MMPs) leads to increased extracellular matrix turnover, a key event in the local invasion and metastasis of many tumours. The tissue inhibitors of metalloproteinases (TIMPs) limit the activity of MMPs, which suggests their use in gene therapy. We have previously shown that overexpression of TIMP-1, -2 or -3 inhibits vascular smooth muscle and melanoma cell invasion, while TIMP-3 uniquely promotes apoptosis. We have therefore sought to determine whether TIMP-3 can inhibit invasion and promote apoptosis in other cancer cell types. Adenoviral-mediated overexpression of TIMP-3 inhibited invasion of HeLa and HT1080 cells through artificial basement membrane to similar levels as that achieved by TIMP-1 and -2. However, TIMP-3 uniquely promoted cell cycle entry and subsequent death by apoptosis. Apoptosis was confirmed by morphological analysis, terminal dUTP nick end labelling (TUNEL) and flow cytometry. The apoptotic phenotype was mimicked by addition of exogenous recombinant TIMP-3 to uninfected cultures demonstrating that the death signal is initiated extracellularly and that a bystander effect exists. These results show that TIMP-3 inhibits invasion in vitro and promotes apoptosis in cancer cell type of differing origin. This clearly identifies the potential of TIMP-3 for gene therapy of multiple cancer types. © 1999 Cancer Research Campaig

Optimization of flow shop scheduling through a hybrid genetic algorithm for manufacturing companies

A task scheduling problem is a process of assigning tasks to a limited set of resources available in a time interval, where certain criteria are optimized. In this way, the sequencing of tasks is directly associated with the executability and optimality of a preset plan and can be found in a wide range of applications, such as: programming flight dispatch at airports, programming production lines in a factory, programming of surgeries in a hospital, repair of equipment or machinery in a workshop, among others. The objective of this study is to analyze the effect of the inclusion of several restrictions that negatively influence the production programming in a real manufacturing environment. For this purpose, an efficient Genetic Algorithm combined with a Local Search of Variable Neighborhood for problems of n tasks and m machines is introduced, minimizing the time of total completion of the tasks. The computational experiments carried out on a set of problem instances with different sizes of complexity show that the proposed hybrid metaheuristics achieves high quality solutions compared to the reported optimal cases

Monitoring the early signs of cognitive decline in elderly by computer games: an MRI study

BACKGROUND: It is anticipated that current and future preventive therapies will likely be more effective in the early stages of dementia, when everyday functioning is not affected. Accordingly the early identification of people at risk is particularly important. In most cases, when subjects visit an expert and are examined using neuropsychological tests, the disease has already been developed. Contrary to this cognitive games are played by healthy, well functioning elderly people, subjects who should be monitored for early signs. Further advantages of cognitive games are their accessibility and their cost-effectiveness. PURPOSE: The aim of the investigation was to show that computer games can help to identify those who are at risk. In order to validate games analysis was completed which measured the correlations between results of the 'Find the Pairs' memory game and the volumes of the temporal brain regions previously found to be good predictors of later cognitive decline. PARTICIPANTS AND METHODS: 34 healthy elderly subjects were enrolled in the study. The volume of the cerebral structures was measured by MRI. Cortical reconstruction and volumetric segmentation were performed by Freesurfer. RESULTS: There was a correlation between the number of attempts and the time required to complete the memory game and the volume of the entorhinal cortex, the temporal pole, and the hippocampus. There was also a correlation between the results of the Paired Associates Learning (PAL) test and the memory game. CONCLUSIONS: The results gathered support the initial hypothesis that healthy elderly subjects achieving lower scores in the memory game have increased level of atrophy in the temporal brain structures and showed a decreased performance in the PAL test. Based on these results it can be concluded that memory games may be useful in early screening for cognitive decline

Periodontal treatment to improve glycaemic control in diabetic patients: study protocol of the randomized, controlled DIAPERIO trial

<p>Abstract</p> <p>Background</p> <p>Periodontitis is a common, chronic inflammatory disease caused by gram-negative bacteria leading to destruction of tissues supporting the teeth. Epidemiological studies have consistently shown increased frequency, extent and severity of periodontitis among diabetic adults. More recently, some controlled clinical trials have also suggested that periodontal treatment could improve glycaemic control in diabetic patients. However current evidence does not provide sufficient information on which to confidently base any clinical recommendations. The main objective of this clinical trial is to assess whether periodontal treatment could lead to a decrease in glycated haemoglobin levels in metabolically unbalanced diabetic patients suffering from chronic periodontitis.</p> <p>Methods</p> <p>The DIAPERIO trial is an open-label, 13-week follow-up, randomized, controlled trial. The total target sample size is planned at 150 participants, with a balanced (1:1) treatment allocation (immediate treatment vs delayed treatment). Periodontal treatment will include full mouth non-surgical scaling and root planing, systemic antibiotherapy, local antiseptics (chlorhexidine 0.12%) and oral health instructions. The primary outcome will be the difference in change of HbA1c between the two groups after the 13-weeks' follow-up. Secondary outcomes will be the difference in change of fructosamine levels and quality of life between the two groups.</p> <p>Discussion</p> <p>The DIAPERIO trial will provide insight into the question of whether periodontal treatment could lead to an improvement in glycaemic control in metabolically unbalanced diabetic patients suffering from periodontitis. The results of this trial will help to provide evidence-based recommendations for clinicians and a draft framework for designing national health policies.</p> <p>Trial registration</p> <p>Current Controlled Trials ISRCTN15334496</p