Effect of Early Intervention with Combination Ledipasvir/Sofosbuvir (Harvoni®) in Patients with Chronic Hepatitis C Virus Infection

In the United States, hepatitis C virus (HCV) is the most common bloodborne infection with an estimated prevalence of 3.2 million people. Although new cases of HCV are declining since the 1980s there are still approximately 17,000 new cases diagnosed each year. There are multiple risk factors, however, in the United States the most common mode of transmission is intravenous drug use. Among infected individuals, approximately 55-85% will develop a chronic HCV infection. In this population, the risk of cirrhosis of the liver is 15-30% within 20 years and morbidity can be significant. HCV infection has become the most frequent reason for hepatologic consultation and the single leading indication for hepatic transplantation, accounting for 30% of such procedures in the United States. Until late 2013, the treatment of choice for chronic HCV was pegylated interferon-α plus ribavirin, which achieved a cure rate of 54%-63%. Recently, novel antiviral drugs that specifically target HCV have provided better options in HCV treatment. Use of ledipasvir, an HCV NS5A replication complex inhibitor in combination with sofosbuvir, a nucleotide analog HCV NS5B polymerase inhibitor, in patients with chronic HCV, achieves high rates of sustained viral response (SVR) with just 12-weeks of treatment. A fixed-dose combination of ledipasvir-sofosbuvir (90mg/400mg), or Harvoni® was approved for treatment of chronic HCV genotypes 1,4,5, and 6. Although extremely successful, the use of this medication is inhibited by high costs, upwards of $90,000 for each 12-week treatment

International collaboration: developing an international nursing module through the use of Wiki technology

The internationalisation of education gathered momentum with the Bologna process initiated in 1998, which focused upon lifelong learning, involvement of students into HEI’s (Higher Education Institutions), and easing mobility of students for job placements by 2010 (Davies, 2008). This goal for globalization continues to be unmet due to obstacles related to migration and language. Other barriers exist with cultural, social, and ethical factors. Educators are seeking creative virtual learning environments (VLE) to augment the learning experience for all students to help meet these goals by 2020. With shrinking of the world economies and technological revolutions of the past ten years, educators desire innovative methodologies enhancing students’ international experiences. Traditionally, nursing students were encouraged to engage in overseas clinical placements to gain cultural and diverse experiences. Due to increased costs of overseas travel, these types of culturally enriching experiences are waning. With increased global migration, students must be prepared to become active world citizens in the care for their patients. Regardless of background of the student, educators want technologies to enable culturally authentic experiences that simulate the previous era. The authors of this paper sought to utilize Wiki technology to broaden the global learning experiences for students from three higher education institutions (HEIs)

The Diabetes Remission Clinical Trial (DiRECT): protocol for a cluster randomised trial

Background: Despite improving evidence-based practice following clinical guidelines to optimise drug therapy, Type 2 diabetes (T2DM) still exerts a devastating toll from vascular complications and premature death. Biochemical remission of T2DM has been demonstrated with weight loss around 15kg following bariatric surgery and in several small studies of non-surgical energy-restriction treatments. The non-surgical Counterweight-Plus programme, running in Primary Care where obesity and T2DM are routinely managed, produces >15 kg weight loss in 33 % of all enrolled patients. The Diabetes UK-funded Counterpoint study suggested that this should be sufficient to reverse T2DM by removing ectopic fat in liver and pancreas, restoring first-phase insulin secretion. The Diabetes Remission Clinical Trial (DiRECT) was designed to determine whether a structured, intensive, weight management programme, delivered in a routine Primary Care setting, is a viable treatment for achieving durable normoglycaemia. Other aims are to understand the mechanistic basis of remission and to identify psychological predictors of response. Methods/Design: Cluster-randomised design with GP practice as the unit of randomisation: 280 participants from around 30 practices in Scotland and England will be allocated either to continue usual guideline-based care or to add the Counterweight-Plus weight management programme, which includes primary care nurse or dietitian delivery of 12-20weeks low calorie diet replacement, food reintroduction, and long-term weight loss maintenance. Main inclusion criteria: men and women aged 20-65years, all ethnicities, T2DM 0-6years duration, BMI 27-45 kg/m2. Tyneside participants will undergo Magnetic Resonance (MR) studies of pancreatic and hepatic fat, and metabolic studies to determine mechanisms underlying T2DM remission. Co-primary endpoints: weight reduction ≥ 15 kg and HbA1c <48 mmol/mol at one year. Further follow-up at 2 years. Discussion: This study will establish whether a structured weight management programme, delivered in Primary Care by practice nurses or dietitians, is a viable treatment to achieve T2DM remission. Results, available from 2018 onwards, will inform future service strategy

Climate indices in historical climate reconstructions:a global state of the art

Abstract. Narrative evidence contained within historical documents and inscriptions provides an important record of climate variability for periods prior to the onset of systematic meteorological data collection. A common approach used by historical climatologists to convert such qualitative information into continuous quantitative proxy data is through the generation of ordinal-scale climate indices. There is, however, considerable variability in the types of phenomena reconstructed using an index approach and the practice of index development in different parts of the world. This review, written by members of the PAGES (Past Global Changes) CRIAS working group – a collective of climate historians and historical climatologists researching Climate Reconstructions and Impacts from the Archives of Societies – provides the first global synthesis of the use of the index approach in climate reconstruction. We begin by summarising the range of studies that have used indices for climate reconstruction across six continents (Europe, Asia, Africa, the Americas, and Australia) as well as the world's oceans. We then outline the different methods by which indices are developed in each of these regions, including a discussion of the processes adopted to verify and calibrate index series, and the measures used to express confidence and uncertainty. We conclude with a series of recommendations to guide the development of future index-based climate reconstructions to maximise their effectiveness for use by climate modellers and in multiproxy climate reconstructions

Climate indices in historical climate reconstructions: a global state of the art

Narrative evidence contained within historical documents and inscriptions provides an important record of climate variability for periods prior to the onset of systematic meteorological data collection. A common approach used by historical climatologists to convert such qualitative information into continuous quantitative proxy data is through the generation of ordinal-scale climate indices. There is, however, considerable variability in the types of phenomena reconstructed using an index approach and the practice of index development in different parts of the world. This review, written by members of the PAGES (Past Global Changes) CRIAS working group – a collective of climate historians and historical climatologists researching Climate Reconstructions and Impacts from the Archives of Societies – provides the first global synthesis of the use of the index approach in climate reconstruction. We begin by summarising the range of studies that have used indices for climate reconstruction across six continents (Europe, Asia, Africa, the Americas, and Australia) as well as the world's oceans. We then outline the different methods by which indices are developed in each of these regions, including a discussion of the processes adopted to verify and calibrate index series, and the measures used to express confidence and uncertainty. We conclude with a series of recommendations to guide the development of future index-based climate reconstructions to maximise their effectiveness for use by climate modellers and in multiproxy climate reconstructions.The meetings that underpinned this article were supported by PAGES (Past Global Changes). The article processing charges for this open-access publication were covered by the Freigeist Fellowship “The Dantean Anomaly (1309–1321)” (funded by the Volkswagen Foundation) and the Education University of Hong Kong

Durability of a primary care-led weight-management intervention for remission of type 2 diabetes: 2-year results of the DiRECT open-label, cluster-randomised trial

Background: The DiRECT trial assessed remission of type 2 diabetes during a primary care-led weight-management programme. At 1 year, 68 (46%) of 149 intervention participants were in remission and 36 (24%) had achieved at least 15 kg weight loss. The aim of this 2-year analysis is to assess the durability of the intervention effect. Methods: DiRECT is an open-label, cluster-randomised, controlled trial done at primary care practices in the UK. Practices were randomly assigned (1:1) via a computer-generated list to provide an integrated structured weight-management programme (intervention) or best-practice care in accordance with guidelines (control), with stratification for study site (Tyneside or Scotland) and practice list size (>5700 or ≤5700 people). Allocation was concealed from the study statisticians; participants, carers, and study research assistants were aware of allocation. We recruited individuals aged 20–65 years, with less than 6 years' duration of type 2 diabetes, BMI 27–45 kg/m2, and not receiving insulin between July 25, 2014, and Aug 5, 2016. The intervention consisted of withdrawal of antidiabetes and antihypertensive drugs, total diet replacement (825–853 kcal per day formula diet for 12–20 weeks), stepped food reintroduction (2–8 weeks), and then structured support for weight-loss maintenance. The coprimary outcomes, analysed hierarchically in the intention-to-treat population at 24 months, were weight loss of at least 15 kg, and remission of diabetes, defined as HbA1c less than 6·5% (48 mmol/mol) after withdrawal of antidiabetes drugs at baseline (remission was determined independently at 12 and 24 months). The trial is registered with the ISRCTN registry, number 03267836, and follow-up is ongoing. Findings: The intention-to-treat population consisted of 149 participants per group. At 24 months, 17 (11%) intervention participants and three (2%) control participants had weight loss of at least 15 kg (adjusted odds ratio [aOR] 7·49, 95% CI 2·05 to 27·32; p=0·0023) and 53 (36%) intervention participants and five (3%) control participants had remission of diabetes (aOR 25·82, 8·25 to 80·84; p<0·0001). The adjusted mean difference between the control and intervention groups in change in bodyweight was −5·4 kg (95% CI −6·9 to −4·0; p<0·0001) and in HbA1c was −4·8 mmol/mol (–8·3 to −1·4 [–0·44% (–0·76 to −0·13)]; p=0·0063), despite only 51 (40%) of 129 patients in the intervention group using anti-diabetes medication compared with 120 (84%) of 143 in the control group. In a post-hoc analysis of the whole study population, of those participants who maintained at least 10 kg weight loss (45 of 272 with data), 29 (64%) achieved remission; 36 (24%) of 149 participants in the intervention group maintained at least 10 kg weight loss. Serious adverse events were similar to those reported at 12 months, but were fewer in the intervention group than in the control group in the second year of the study (nine vs 22). Interpretation: The DiRECT programme sustained remissions at 24 months for more than a third of people with type 2 diabetes. Sustained remission was linked to the extent of sustained weight loss

The ACCESS study a Zelen randomised controlled trial of a treatment package including problem solving therapy compared to treatment as usual in people who present to hospital after self-harm: study protocol for a randomised controlled trial

<p>Abstract</p> <p>Background</p> <p>People who present to hospital after intentionally harming themselves pose a common and important problem. Previous reviews of interventions have been inconclusive as existing trials have been under powered and done on unrepresentative populations. These reviews have however indicated that problem solving therapy and regular written communications after the self-harm attempt may be an effective treatment. This protocol describes a large pragmatic trial of a package of measures which include problem solving therapy, regular written communication, patient support, cultural assessment, improved access to primary care and a risk management strategy in people who present to hospital after self-harm using a novel design.</p> <p>Methods</p> <p>We propose to use a double consent Zelen design where participants are randomised prior to giving consent to enrol a large representative cohort of patients. The main outcome will be hospital attendance following repetition of self-harm, in the 12 months after recruitment with secondary outcomes of self reported self-harm, hopelessness, anxiety, depression, quality of life, social function and hospital use at three months and one year.</p> <p>Discussion</p> <p>A strength of the study is that it is a pragmatic trial which aims to recruit large numbers and does not exclude people if English is not their first language. A potential limitation is the analysis of the results which is complex and may underestimate any effect if a large number of people refuse their consent in the group randomised to problem solving therapy as they will effectively cross over to the treatment as usual group. However the primary analysis is a true intention to treat analysis of everyone randomised which includes both those who consent and do not consent to participate in the study. This provides information about how the intervention will work in practice in a representative population which is a major advance in this study compared to what has been done before.</p> <p>Trial registration</p> <p>Australia and New Zealand Clinical Trials Register (ANZCTR): <a href="http://www.anzctr.org.au/ACTRN12609000641291.aspx">ACTRN12609000641291</a></p

Substance abuse treatment client experience in an employed population: results of a client survey

<p>Abstract</p> <p>Background</p> <p>Understanding client perspectives on treatment is increasingly recognized as key to improving care. Yet information on the perceptions and experiences of workers with private insurance coverage who receive help for substance use conditions is relatively sparse, particularly in managed behavioral health care organization (MBHO) populations. Furthermore, the role of several factors including prior service use has not been fully explored.</p> <p>Methods</p> <p>Employees covered by a large MBHO who had received substance abuse services in the past year were surveyed (146 respondents completed the telephone survey and self-reported service use).</p> <p>Results</p> <p>The most common reasons for entering treatment were problems with health; home, family or friends; or work. Prior treatment users reported more reasons for entering treatment and more substance use-related work impairment. The majority of all respondents felt treatment helped a lot or some. One quarter reported getting less treatment than they felt they needed.</p> <p>Discussion and conclusions</p> <p>Study findings point to the need to tailor treatment for prior service users and to recognize the role of work in treatment entry and outcomes. Perceived access issues may be present even among insured clients already in treatment.</p

Post-postfeminism? New feminist visibilities in postfeminist times

This article contributes to debates about the value and utility of the notion of postfeminism for a seemingly “new” moment marked by a resurgence of interest in feminism in the media and among young women. The paper reviews current understandings of postfeminism and criticisms of the term’s failure to speak to or connect with contemporary feminism. It offers a defence of the continued importance of a critical notion of postfeminism, used as an analytical category to capture a distinctive contradictory-but-patterned sensibility intimately connected to neoliberalism. The paper raises questions about the meaning of the apparent new visibility of feminism and highlights the multiplicity of different feminisms currently circulating in mainstream media culture – which exist in tension with each other. I argue for the importance of being able to “think together” the rise of popular feminism alongside and in tandem with intensified misogyny. I further show how a postfeminist sensibility informs even those media productions that ostensibly celebrate the new feminism. Ultimately, the paper argues that claims that we have moved “beyond” postfeminism are (sadly) premature, and the notion still has much to offer feminist cultural critics