A qualitative research on co-creating care pathways for Sarcoma and GIST by stimulating reflection

Introduction: Care Pathway Management intends to enhance the quality of care by restructuring care services. As recipients of care, patients have relevant experiential knowledge on the provision of care, but they are rarely involved in Care Pathway Management due to various barriers. This study aims to acquire insights into how patients can be meaningfully involved in Care Pathway Management. Methods: A case study was cond

Endoscopic and surgical treatment outcomes of colitis-associated advanced colorectal neoplasia:a multicenter cohort study

BACKGROUND: Inflammatory bowel disease (IBD) patients are at increased risk of advanced neoplasia (high-grade dysplasia or colorectal cancer). The authors aimed to (1) assess synchronous and metachronous neoplasia following (sub)total or proctocolectomy, partial colectomy or endoscopic resection for advanced neoplasia in IBD, and (2) identify factors associated with treatment choice.MATERIAL AND METHODS: In this retrospective multicenter cohort study, the authors used the Dutch nationwide pathology databank (PALGA) to identify patients diagnosed with IBD and colonic advanced neoplasia (AN) between 1991 and 2020 in seven hospitals in the Netherlands. Logistic and Fine &amp; Gray's subdistribution hazard models were used to assess adjusted subdistribution hazard ratios for metachronous neoplasia and associations with treatment choice.RESULTS: The authors included 189 patients (high-grade dysplasia n =81; colorectal cancer n =108). Patients were treated with proctocolectomy ( n =33), (sub)total colectomy ( n =45), partial colectomy ( n =56) and endoscopic resection ( n =38). Partial colectomy was more frequently performed in patients with limited disease and older age, with similar patient characteristics between Crohn's disease and ulcerative colitis. Synchronous neoplasia was found in 43 patients (25.0%; (sub)total or proctocolectomy n =22, partial colectomy n =8, endoscopic resection n =13). The authors found a metachronous neoplasia rate of 6.1, 11.5 and 13.7 per 100 patient-years after (sub)total colectomy, partial colectomy and endoscopic resection, respectively. Endoscopic resection, but not partial colectomy, was associated with an increased metachronous neoplasia risk (adjusted subdistribution hazard ratios 4.16, 95% CI 1.64-10.54, P &lt;0.01) compared with (sub)total colectomy.CONCLUSION: After confounder adjustment, partial colectomy yielded a similar metachronous neoplasia risk compared to (sub)total colectomy. High metachronous neoplasia rates after endoscopic resection underline the importance of strict subsequent endoscopic surveillance.</p

CONFIRM: a double-blind, placebo controlled phase III clinical trial investigating the effect of nivolumab in patients with relapsed mesothelioma: study protocol for a randomised controlled trial

Background: Mesothelioma is an incurable, apoptosis-resistant cancer caused in most cases by previous exposure to asbestos and is increasing in incidence. It represents a growing health burden but remains under-researched, with limited treatment options. Early promising signals of activity relating to both PD-L1- and PD-1-targeted treatment in mesothelioma implicate a dependency of mesothelioma on this immune checkpoint. There is a need to evaluate checkpoint inhibitors in patients with relapsed mesothelioma where treatment options are limited. Methods: The addition of 12 months of nivolumab (anti-PD1 antibody) to standard practice will be conducted in the UK using a randomised, placebo-controlled phase III trial (the Cancer Research UK CONFIRM trial). A total of 336 patients with pleural or peritoneal mesothelioma who have received at least two prior lines of therapy will be recruited from UK secondary care sites. Patients will be randomised 2:1 (nivolumab:placebo), stratified according to epithelioid/non-epithelioid, to receive either 240 mg nivolumab monotherapy or saline placebo as a 30-min intravenous infusion. Treatment will be for up to 12 months. We will determine whether the use of nivolumab increases overall survival (the primary efficacy endpoint). Secondary endpoints will include progression-free survival, objective response rate, toxicity, quality of life and cost-effectiveness. Analysis will be performed according to the intention-to-treat principle using a Cox regression analysis for the primary endpoint (and for other time-to-event endpoints). Discussion: The outcome of this trial will provide evidence of the potential benefit of the use of nivolumab in the treatment of relapsed mesothelioma. If found to be clinically effective, safe and cost-effective it is likely to become the new standard of care in the UK

Designing a package of sexual and reproductive health and HIV outreach services to meet the heterogeneous preferences of young people in Malawi: results from a discrete choice experiment.

BACKGROUND: This article examines young people's preferences for integrated family planning (FP) and HIV services in rural Malawi. Different hypothetical configurations for outreach services are presented using a Discrete Choice Experiment (DCE). Responses are analysed using Random Parameters Logit and Generalised Mixed Logit (GMXL) models in preference space and a GMXL model parameterised in willingness-to-pay space. Simulations are used to estimate the proportion of respondents expected to choose different service packages as elements are varied individually and in combination. RESULTS: Responses were collected from 537 young people aged 15-24. Results show that when considering attending an outreach service to access family planning young people value confidentiality and the availability of HIV services including HIV counselling and testing (HCT) and HIV treatment, though significant observable and unobservable heterogeneity is present. Female respondents and those aged 20-24 were less concerned with service confidentiality compared to male respondents and those aged 15-19; respondents who were in a relationship at the time of the survey valued confidentiality more than those who reported being single. The addition of sports and recreation for young people may also be an attractive feature of a youth-friendly service; however, preferences for this attribute vary according to respondent gender. Results of the simulation modelling indicate that the most preferred service package is one that offers confidential services, both HCT and HIV treatment and sports for youth, with up to 32% of respondents expected to choose this service over a service where clients may have concerns over confidentiality, only HCT is available and there are no additional activities for young people. Estimates of willingness-to-pay for service attributes indicate that respondents were willing to pay up to USD$1.76 for confidentiality, USD$0.65 for a service offering both HCT and HIV treatment and USD$0.26 for a service including sports for youth. CONCLUSIONS: Young people were able to complete a complex DCE and appeared to trade between the different characteristics used to describe the outreach services. These findings may offer important insight to policy makers designing youth friendly SRH outreach services and providers aiming to improve the acceptability and uptake of FP services

An Early Cambrian Rift to Post-Rift Transition in the Cordillera of Western North America

The upper Proterozoic and lower Palaeozoic wedge of miogeoclinal strata in the North American Cordillera is widely regarded as evidence for a proto-Pacific passive margin. The rifting history of this margin appears to have been protracted, possibly spanning more than 200 Myr in a tectonic setting that is not well understood. Quantitative subsidence analyses of lower Palaeozoic strata between British Columbia and Utah, however, provide indirect evidence that the transition from rifting to post-rift cooling occurred within a relatively short interval of time, although probably not synchronously, between 600 and 555 Myr. This age is significantly younger than that implied in previous studies. We describe here new field data, which, together with published geological data, provide direct evidence of a latest Proterozoic or early Cambrian age for the rift to post-rift transition. The data support recent arguments for widespread initiation of passive margins around the edge of the North American craton close to the Cambrian-Precambrian boundary

Effectiveness of ophthalmic solution preservatives: a comparison of latanoprost with 0.02% benzalkonium chloride and travoprost with the sofZia preservative system

<p>Abstract</p> <p>Background</p> <p>Although in vitro and in vivo laboratory studies have suggested that benzalkonium chloride (BAK) in topical ophthalmic solutions may be detrimental to corneal epithelial cells, multiple short- and long-term clinical studies have provided evidence supporting the safety of BAK. Despite the conflicting evidence, BAK is the most commonly used preservative in ophthalmic products largely due to its proven antimicrobial efficacy. This study was designed to characterize the antimicrobial performance of two commonly used topical ocular hypotensive agents that employ different preservative systems: latanoprost 0.005% with 0.02% BAK and travoprost 0.004% with sofZia, a proprietary ionic buffer system.</p> <p>Methods</p> <p>Each product was tested for antimicrobial effectiveness by <it>European Pharmacopoeia </it>A (EP-A) standards, the most stringent standards of the three major compendia, which specify two early sampling time points (6 and 24 hours) not required by the <it>United States Pharmacopeia </it>or <it>Japanese Pharmacopoeia</it>. Aliquots were inoculated with between 10⁵and 10⁶colony-forming units of the test organisms: <it>Staphylococcus aureus, Pseudomonas aeruginosa, Escherichia coli, Candida albicans </it>and <it>Aspergillus brasiliensis</it>. Sampling and enumeration were conducted at protocol-defined time points through 28 days.</p> <p>Results</p> <p>BAK-containing latanoprost met EP-A criteria by immediately reducing all bacterial challenge organisms to the test sensitivity and fungal challenges within the first six hours while the preservative activity of travoprost with sofZia did not. Complete bacterial reduction by travoprost with sofZia was not shown until seven days into the test, and fungal reduction never exceeded the requisite 2 logs during the 28-day test. Travoprost with sofZia also did not meet EP-B criteria due to its limited effectiveness against <it>Staphylococcus aureus</it>. Both products satisfied United States and Japanese pharmacopoeial criteria.</p> <p>Conclusions</p> <p>Latanoprost with 0.02% BAK exhibited more effective microbial protection than travoprost with sofZia using rates of microbial reduction, time to no recovery for all challenges and evaluation against EP-A criteria as measures. The rapid and complete reduction of all microbial challenges demonstrates that antimicrobial activity of latanoprost with 0.02% BAK exceeds that of travoprost with sofZia preservative system in these products and provides a more protective environment in the event of contamination and subsequent exposure to microorganisms during use.</p

Spike firing and IPSPs in layer V pyramidal neurons during beta oscillations in rat primary motor cortex (M1) in vitro

Beta frequency oscillations (10-35 Hz) in motor regions of cerebral cortex play an important role in stabilising and suppressing unwanted movements, and become intensified during the pathological akinesia of Parkinson's Disease. We have used a cortical slice preparation of rat brain, combined with concurrent intracellular and field recordings from the primary motor cortex (M1), to explore the cellular basis of the persistent beta frequency (27-30 Hz) oscillations manifest in local field potentials (LFP) in layers II and V of M1 produced by continuous perfusion of kainic acid (100 nM) and carbachol (5 µM). Spontaneous depolarizing GABA-ergic IPSPs in layer V cells, intracellularly dialyzed with KCl and IEM1460 (to block glutamatergic EPSCs), were recorded at -80 mV. IPSPs showed a highly significant (P< 0.01) beta frequency component, which was highly significantly coherent with both the Layer II and V LFP oscillation (which were in antiphase to each other). Both IPSPs and the LFP beta oscillations were abolished by the GABAA antagonist bicuculline. Layer V cells at rest fired spontaneous action potentials at sub-beta frequencies (mean of 7.1+1.2 Hz; n = 27) which were phase-locked to the layer V LFP beta oscillation, preceding the peak of the LFP beta oscillation by some 20 ms. We propose that M1 beta oscillations, in common with other oscillations in other brain regions, can arise from synchronous hyperpolarization of pyramidal cells driven by synaptic inputs from a GABA-ergic interneuronal network (or networks) entrained by recurrent excitation derived from pyramidal cells. This mechanism plays an important role in both the physiology and pathophysiology of control of voluntary movement generation

Women's Preferences for Treatment of Perinatal Depression and Anxiety : A Discrete Choice Experiment

Perinatal depression and anxiety (PNDA) are an international healthcare priority, associated with significant short- and long-term problems for women, their children and families. Effective treatment is available but uptake is suboptimal: some women go untreated whilst others choose treatments without strong evidence of efficacy. Better understanding of women's preferences for treatment is needed to facilitate uptake of effective treatment. To address this issue, a discrete choice experiment (DCE) was administered to 217 pregnant or postnatal women in Australia, who were recruited through an online research company and had similar sociodemographic characteristics to Australian data for perinatal women. The DCE investigated preferences regarding cost, treatment type, availability of childcare, modality and efficacy. Data were analysed using logit-based models accounting for preference and scale heterogeneity. Predicted probability analysis was used to explore relative attribute importance and policy change scenarios, including how these differed by women's sociodemographic characteristics. Cost and treatment type had the greatest impact on choice, such that a policy of subsidising effective treatments was predicted to double their uptake compared with the base case. There were differences in predicted uptake associated with certain sociodemographic characteristics: for example, women with higher educational attainment were more likely to choose effective treatment. The findings suggest policy directions for decision makers whose goal is to reduce the burden of PNDA on women, their children and families