Study protocol for a non-inferiority trial of cytisine versus nicotine replacement therapy in people motivated to stop smoking

<p>Abstract</p> <p>Background</p> <p>Smokers need effective support to maximise the chances of successful quit attempts. Current smoking cessation medications, such as nicotine replacement therapy (NRT), bupropion, nortriptyline or varenicline, have been shown to be effective in clinical trials but are underused by smokers attempting to quit due to adverse effects, contraindications, low acceptability and/or high cost. Cytisine is a low-cost, plant-based alkaloid that has been sold as a smoking cessation aid in Eastern Europe for 50 years. A systematic review of trial evidence suggests that cytisine has a positive impact on both short- and long-term abstinence rates compared to placebo. However, the quality of the evidence is poor and insufficient for licensing purposes in many Western countries. A large, well-conducted placebo-controlled trial (n = 740) of cytisine for smoking cessation has recently been published and confirms the findings of earlier studies, with 12-month continuous abstinence rates of 8.4% in the cytisine group compared to 2.4% in the placebo group (Relative risk = 3.4, 95% confidence intervals 1.7-7.1). No research has yet been undertaken to determine the effectiveness of cytisine relative to that of NRT.</p> <p>Methods/design</p> <p>A single-blind, randomised controlled, non-inferiority trial has been designed to determine whether cytisine is at least as effective as NRT in assisting smokers to remain abstinent for at least one month. Participants (n = 1,310) will be recruited through the national telephone-based Quitline service in New Zealand and randomised to receive a standard 25-day course of cytisine tablets (Tabex^®) or usual care (eight weeks of NRT patch and/or gum or lozenge). Participants in both study arms will also receive a behavioural support programme comprising an average of three follow-up telephone calls delivered over an eight-week period by Quitline. The primary outcome is continuous abstinence from smoking at one month, defined as not smoking more than five cigarettes since quit date. Outcome data will also be collected at one week, two months and six months post-quit date.</p> <p>Discussion</p> <p>Cytisine appears to be effective compared with placebo, and given its (current) relative low cost may be an acceptable smoking cessation treatment for smokers, particularly those in low- and middle-income countries. Cytisine's 'natural' product status may also increase its acceptability and use among certain groups of smokers, such as indigenous people, smokers in countries where the use of natural medicines is widespread (e.g. China, India), and in those people who do not want to use NRT or anti-depressants to help them quit smoking. However it is important to ascertain the effectiveness of cytisine compared with that of existing cessation treatments.</p> <p>Trial registration</p> <p>Australian New Zealand Clinical Trials Registry (<a href="http://www.anzctr.org.au/ACTRN12610000590066.aspx">ACTRN12610000590066</a>)</p

Genomic epidemiology of SARS-CoV-2 in a UK university identifies dynamics of transmission

AbstractUnderstanding SARS-CoV-2 transmission in higher education settings is important to limit spread between students, and into at-risk populations. In this study, we sequenced 482 SARS-CoV-2 isolates from the University of Cambridge from 5 October to 6 December 2020. We perform a detailed phylogenetic comparison with 972 isolates from the surrounding community, complemented with epidemiological and contact tracing data, to determine transmission dynamics. We observe limited viral introductions into the university; the majority of student cases were linked to a single genetic cluster, likely following social gatherings at a venue outside the university. We identify considerable onward transmission associated with student accommodation and courses; this was effectively contained using local infection control measures and following a national lockdown. Transmission clusters were largely segregated within the university or the community. Our study highlights key determinants of SARS-CoV-2 transmission and effective interventions in a higher education setting that will inform public health policy during pandemics.</jats:p

Potential Risk Factors for the Onset of Complex Regional Pain Syndrome Type 1: A Systematic Literature Review

Anaesthetists in the acute and chronic pain teams are often involved in treating Complex Regional Pain Syndromes. Current literature about the risk factors for the onset of Complex Regional Pain Syndrome Type 1 (CRPS 1) remains sparse. This syndrome has a low prevalence, a highly variable presentation, and no gold standard for diagnosis. In the research setting, the pathogenesis of the syndrome continues to be elusive. There is a growing body of literature that addresses efficacy of a wide range of interventions as well as the likely mechanisms that contribute to the onset of CRPS 1. The objective for this systematic search of the literature focuses on determining the potential risk factors for the onset of CRPS 1. Eligible articles were analysed, dated 1996 to April 2014, and potential risk factors for the onset of CRPS 1 were identified from 10 prospective and 6 retrospective studies. Potential risk factors for the onset of CRPS 1 were found to include being female, particularly postmenopausal female, ankle dislocation or intra-articular fracture, immobilisation, and a report of higher than usual levels of pain in the early phases of trauma. It is not possible to draw definite conclusions as this evidence is heterogeneous and of mixed quality, relevance, and weighting strength against bias and has not been confirmed across multiple trials or in homogenous studies

The epidemiology of non-viral gastroenteritis in New Zealand children from 1997 to 2015: an observational study

Abstract Background Acute gastroenteritis is a substantial cause of hospitalization in children. Shigella, Salmonella, Campylobacter, Yersinia, enterotoxigenic Escherichia coli (ETEC), Giardia and Cryptosporidium are gastrointestinal pathogens that are notifiable in New Zealand (NZ). The impact of these infections in the pediatric population has not yet been analyzed. The aim of this study was to describe the epidemiological trends in disease notifications and hospital admissions due to non-viral gastroenteritis in NZ children. Methods In this population-based descriptive study, age-specific and age-standardized notification and hospital admission rates were analyzed from 1997-to-2015 for Shigella, Salmonella, Campylobacter, Yersinia, ETEC, Giardia and Cryptosporidium infections in children < 15 years of age. Variations in disease by gender, age, ethnicity and geography were described. Results From 1997-to-2015 there were 74,454 notifications (57.6% male) and 3192 hospitalizations (56.4% male) due to non-viral gastroenteritis in NZ children aged < 15 years. There was an overall trend towards a reduction in disease notifications and hospitalizations, however each disease showed a unique pattern of change over time. Campylobacter was the pathogen most frequently notified, accounting for 51.7% of notifications and 43.4% of hospitalizations. The hospitalization-to-notification ratios were, from highest to lowest, Salmonella typhi (1:1.09), Shigella (1:4.0), ETEC (1:7.81), nontyphoidal Salmonella (1:13.1), Campylobacter (1:27.8), Yersinia (1:29.2), Cryptosporidium (1,33.4), and Giardia (1,72.5). Compared to females, male notification rates were approximately 40% higher for Campylobacter, 25% higher for Giardia and Yersinia, and 15% higher for Cryptosporidium and nontyphoidal Salmonella (p < 0.001). Notification rates were highest in children 1–4 years, with the exceptions of nontyphoidal Salmonella, Salmonella typhi and Yersinia. Notification rates for nontyphoidal Salmonella and Yersinia were highest in children < 1 year, and for Salmonella typhi those aged 5–9 years. Children < 1 year were most likely to be hospitalized. Conclusions The incidence of non-viral gastroenteritis in NZ children reduced during the 19-year period considered. The burden of disease was highest in the community, with only a small percentage of cases requiring hospitalization. This study provides important insight into the non-viral causes of gastroenteritis in NZ children and how environmental influences and changes in food safety practices may have helped to reduce the burden of these diseases in children

Inequity in dialysis related practices and outcomes in Aotearoa/New Zealand: a Kaupapa Māori analysis

Abstract Background In Aotearoa/New Zealand, Māori, as the indigenous people, experience chronic kidney disease at three times the rate of non-Māori, non-Pacific New Zealanders. Māori commence dialysis treatment for end-stage kidney disease at three times the rate of New Zealand European adults. To examine for evidence of inequity in dialysis-related incidence, treatment practices, and survival according to indigeneity in Aotearoa/New Zealand, utilising a Kaupapa Māori approach. Methods We conducted a retrospective cohort study involving adults who commenced treatment for end-stage kidney disease in Aotearoa/New Zealand between 2002 and 2011. We extracted data from the Australian and New Zealand Dialysis and Transplant Registry (ANZDATA) linked to the New Zealand National Health Index (NHI). Propensity score methods were used to assemble a cohort of 1039 Māori patients matched 1:1 on clinical and socio-demographic characteristics with a cohort of 1026 non-Māori patients. We compared incidence of end-stage kidney disease and treatment practices. Differences in the risks of all-cause mortality during treatment between propensity-matched cohorts were estimated using Cox proportional hazards and generalised linear models. Results Non-Māori patients were older, more frequently lived in urban areas (83% versus 67% [standardised difference 0.38]) and bore less socioeconomic deprivation (36% living in highest decile areas versus 14% [0.53]). Fewer non-Māori patients had diabetes (35% versus 69%, [− 0.72]) as a cause of kidney failure. Non-Māori patients were more frequently treated with peritoneal dialysis (34% versus 29% [0.11]), received a pre-emptive kidney transplant (4% vs 1% [0.19]), and were referred to specialist care < 3 months before treatment (25% vs 19% [0.15]) than Māori patients. Fewer non-Māori started dialysis with a non-tunnelled dialysis vascular catheter (43% versus 47% [− 0.08]). The indigenous-age standardised incidence rate ratio for non-Māori commencing renal replacement therapy in 2011 was 0.50 (95% CI, 0.40–0.61) compared with Māori. Propensity score matching generated cohorts with similar characteristics, although non-Māori less frequently started dialysis with a non-tunnelled venous catheter (30% versus 47% [− 0.35]) or lived remotely (3% versus 14% [− 0.50]). In matched cohorts, non-Māori experienced lower all-cause mortality at 5 yr. after commencement of treatment (risk ratio 0.78, 95% CI 0.72–0.84). New Zealand European patients experienced lower mortality than Māori patients in indigenous age-standardised analyses (age-standardised mortality rate ratio 0.58, 95% CI 0.51–0.67). Conclusions Non-Māori patients are treated with temporary dialysis vascular access less often than Māori, and experience longer life expectancy with dialysis, even when socioeconomic, demographic, and geographical factors are equivalent. Based on these disparities, health services should monitor and address inequitable treatment practices and outcomes in end-stage kidney disease care

Potential Risk Factors for the Onset of Complex Regional Pain Syndrome Type 1: A Systematic Literature Review

Anaesthetists in the acute and chronic pain teams are often involved in treating Complex Regional Pain Syndromes. Current literature about the risk factors for the onset of Complex Regional Pain Syndrome Type 1 (CRPS 1) remains sparse. This syndrome has a low prevalence, a highly variable presentation, and no gold standard for diagnosis. In the research setting, the pathogenesis of the syndrome continues to be elusive. There is a growing body of literature that addresses efficacy of a wide range of interventions as well as the likely mechanisms that contribute to the onset of CRPS 1. The objective for this systematic search of the literature focuses on determining the potential risk factors for the onset of CRPS 1. Eligible articles were analysed, dated 1996 to April 2014, and potential risk factors for the onset of CRPS 1 were identified from 10 prospective and 6 retrospective studies. Potential risk factors for the onset of CRPS 1 were found to include being female, particularly postmenopausal female, ankle dislocation or intraarticular fracture, immobilisation, and a report of higher than usual levels of pain in the early phases of trauma. It is not possible to draw definite conclusions as this evidence is heterogeneous and of mixed quality, relevance, and weighting strength against bias and has not been confirmed across multiple trials or in homogenous studies

Psychological distress, anxiety, family violence, suicidality, and wellbeing in New Zealand during the COVID-19 lockdown: A cross-sectional study.

New Zealand's early response to the novel coronavirus pandemic included a strict lockdown which eliminated community transmission of COVID-19. However, this success was not without cost, both economic and social. In our study, we examined the psychological wellbeing of New Zealanders during the COVID-19 lockdown when restrictions reduced social contact, limited recreation opportunities, and resulted in job losses and financial insecurity. We conducted an online panel survey of a demographically representative sample of 2010 adult New Zealanders in April 2020. The survey contained three standardised measures-the Kessler Psychological Distress Scale (K10), the GAD-7, and the Well-Being Index (WHO-5)-as well as questions designed specifically to measure family violence, suicidal ideation, and alcohol consumption. It also included items assessing positive aspects of the lockdown. Thirty percent of respondents reported moderate to severe psychological distress (K10), 16% moderate to high levels of anxiety, and 39% low wellbeing; well above baseline measures. Poorer outcomes were seen among young people and those who had lost jobs or had less work, those with poor health status, and who had past diagnoses of mental illness. Suicidal ideation was reported by 6%, with 2% reporting making plans for suicide and 2% reporting suicide attempts. Suicidality was highest in those aged 18-34. Just under 10% of participants had directly experienced some form of family harm over the lockdown period. However, not all consequences of the lockdown were negative, with 62% reporting 'silver linings', which included enjoying working from home, spending more time with family, and a quieter, less polluted environment. New Zealand's lockdown successfully eliminated COVID-19 from the community, but our results show this achievement brought a significant psychological toll. Although much of the debate about lockdown measures has focused on their economic effects, our findings emphasise the need to pay equal attention to their effects on psychological wellbeing

Supplementation with Oral Vitamin C Prior to and during Myeloablative Chemotherapy and Autologous Haematopoietic Stem Cell Transplantation: A Pilot Study

Chemotherapy-related side effects are common in patients undergoing myeloablative chemotherapy and haematopoietic stem cell transplantation. Some, such as oral mucositis, are believed to be due to enhanced oxidative stress and inflammation. Vitamin C, a potent antioxidant with anti-inflammatory properties, becomes severely depleted following myeloablative chemotherapy. The aim of our study was to assess the feasibility and efficacy of oral vitamin C supplementation to restore and maintain adequate vitamin C concentrations in patients undergoing myeloablative chemotherapy and stem cell transplantation. We carried out a pilot randomized controlled trial in 20 patients with myeloma and lymphoma. Placebo or vitamin C tablets (1 g twice daily) were initiated one week prior to transplantation and continued for 4 weeks post-transplantation. Blood samples were collected weekly for analysis of plasma vitamin C concentrations using high-performance liquid chromatography. The patients&rsquo; symptoms and quality of life parameters were monitored using the World Health Organization oral toxicity scale and the European Organization for the Research and Treatment of Cancer Quality of Life Questionnaire (EORTC QLQ). Pre-supplementation with oral vitamin C doubled vitamin C concentrations relative to placebo by day 0 (median 61 vs. 31 &micro;mol/L), with 60% of those in the vitamin C group achieving concentrations &ge; 50 &micro;mol/L, compared with only 10% in the placebo group. Following chemotherapy and transplantation, significance between the vitamin C and placebo groups was lost by day 7, with only 30% of the patients in the vitamin C group having plasma concentrations &ge; 50 &micro;mol/L. This was partly due to intolerance of the oral intervention due to nausea/vomiting and diarrhoea (40% of the participants in each group). Oral mucositis was also observed in 40% of the participants at day 7 or 14. Overall, our study showed that whilst short-term oral vitamin C pre-supplementation was able to restore adequate vitamin C status by day 0, ongoing supplementation could not maintain adequate vitamin C concentrations following chemotherapy and transplantation. Thus, intravenous vitamin C should be trialled as this bypasses the gastrointestinal system, negating intolerance issues and improving bioavailability of the vitamin

Deaths from Opioid Overdosing: Implications of Coroners’ Inquest Reports 2008–2012 and Annual Rise in Opioid Prescription Rates: A Population-Based Cohort Study

<p><b>Article full text</b></p> <p><br></p> <p>The full text of this article can be found here<b>.</b></p><p><a href="https://link.springer.com/article/10.1007/s40122-017-0080-7">https://link.springer.com/article/10.1007/s40122-017-0080-7</a></p><p></p> <p><br></p> <p><b>Provide enhanced content for this article</b></p> <p><br></p> <p>If you are an author of this publication and would like to provide additional enhanced content for your article then please contact <a href="http://www.medengine.com/Redeem/”mailto:[email protected]”"><b>[email protected]</b></a>.</p> <p> </p> <p>The journal offers a range of additional features designed to increase visibility and readership. All features will be thoroughly peer reviewed to ensure the content is of the highest scientific standard and all features are marked as ‘peer reviewed’ to ensure readers are aware that the content has been reviewed to the same level as the articles they are being presented alongside. Moreover, all sponsorship and disclosure information is included to provide complete transparency and adherence to good publication practices. This ensures that however the content is reached the reader has a full understanding of its origin. No fees are charged for hosting additional open access content.</p> <p><br></p> <p>Other enhanced features include, but are not limited to:</p> <p><br></p> <p>• Slide decks</p> <p>• Videos and animations</p> <p>• Audio abstracts</p> <p>• Audio slides</p