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ObjectivesPrison populations around the world are ageing and numbers are rising, leading to greater demand for palliative care for prisoners approaching the end of life. This paper reports a survey that was undertaken by the European Association for Palliative Care Task Force on mapping palliative care provision for prisoners in Europe. The Task Force was established to begin to address the gap in research knowledge by exploring prison systems and care provision across different countries.MethodsThe survey, developed by the Task Force Steering Committee, consisted of 40 questions in six sections. It was completed through online searches; only data that were publicly available on the internet were included. Numerical data were analysed using descriptive statistics, and thematic comparisons were made of free-text data.FindingsThe survey was completed for eight countries: Australia, Belgium, Czech Republic, England and Wales, France, Portugal, Scotland and Slovakia. Three main findings are reported here: healthcare and palliative care provision in prisons, deaths in custody and compassionate release. Despite increasing numbers of older prisoners, relatively few prisons provide inpatient care, and only one country has any prisons that provide dedicated palliative care services. Early release on compassionate grounds is extremely rare in most countries.ConclusionFor the principle of equivalence to be adhered to, facilities for sick and dying prisoners need to be improved, or many more people need to be released on compassionate grounds at the end of life. This mapping study has identified key issues in relation to palliative care in prison and provides the basis for further international research.

The use of e-cigarettes has risen rapidly in recent years. Joanne Brookand Dr Mary Turnerperformed a systematic review to identify if e-cigarettes are appropriate for patients with COPDBackground:A high smoking-related burden is placed on health services in diagnosing, treating and managing associated long-term illnesses such as chronic obstructive pulmonary disease (COPD). While there are many smoking cessation options available, the use of e-cigarettes has risen rapidly.Aim:To identify if the promotion of e-cigarettes is an appropriate intervention for patients with COPD.Methods:A systematic process was used to search databases and identify research papers detailing the effects of e-cigarettes on pulmonary health outcomes in COPD; analysis identified five main themes.Findings:Eight papers were reviewed. Findings support current clinical guidance endorsing the use of e-cigarettes for smoking cessation; however, COPD patients may be at greater risk of inflammatory responses, exacerbation, disease progression and worsening general health.Conclusion:The effects of e-cigarettes are not fully understood, but they are not risk-free. More evidence is needed about both the short and long-term impact of their use in this cohort.

Purpose Trichotillomania (TTM) is characterised by the recurrent pulling out of one’s own hair, resulting in hair loss. It is a poorly understood disorder with no consensus on aetiology or epidemiology. Nested within a larger qualitative study exploring a wide range of TTM topics, the aim of this paper is to report and consider participant views on the acceptability and feasibility of the asynchronous email interview method.Method Cross-cultural qualitative research on TTM is sparse; therefore, an international qualitative study with a geographically diverse sample was conducted using an asynchronous email interview method.Results Participant perspectives highlighted three themes related to the study method: the value in creating personal connections, cathartic reflections, and perceived strengths and weaknesses. This paper highlights the potential of the asynchronous email interview method for sustaining remote research across multiple locations, using a sample of 20 adults with TTM (18–55 years) from 15 different countries.Conclusions This was an acceptable and feasible method for data collection, facilitating remote access while yielding rich data from an often hidden and hard-to-reach population.

Background: Parkinson’s disease-related psychosis increases patients’ risk of falls. Pimavanserin is an atypical antipsychotic approved in the USA in 2016 for the treatment of hallucinations and delusions associated with Parkinson’s disease-related psychosis. Objective: We aimed to compare the risk of falls/fractures among patients with Parkinson’s disease-related psychosis treated with pimavanserin vs other atypical antipsychotics. Patients and Methods: We identified a cohort of patients with Parkinson’s disease-related psychosis aged ≥ 40 years initiating either pimavanserin or a comparator antipsychotic (clozapine, quetiapine, risperidone, olanzapine, aripiprazole, brexpiprazole) in US commercial insurance and supplementary Medicare claims (2015–2019). Comparators were propensity score matched 2:1 with pimavanserin initiators; incidence rates of falls/fractures were compared using incidence rate ratios (IRRs) and 95% confidence intervals (CIs). Results: We identified 112 eligible pimavanserin initiators and 982 comparators. Pimavanserin initiators were younger and had fewer severe comorbidities, indicators of impairment, and healthcare encounters, though they had higher Parkinson’s disease medication use. The crude incidence rates [cases/100 person-years] (95% CI) for composite falls/fractures were 17.8 (7.7–35.0) for pimavanserin and 40.8 (35.0–47.4) for comparators. Matching retained 108 pimavanserin initiators and 216 comparators—all characteristics were well balanced after matching—with a matched IRR (pimavanserin vs comparator) of 0.71 (95% CI 0.27–1.67). Sensitivity analysis IRR estimates were consistently below 1.00, with a sensitivity analysis not requiring a diagnosis of psychosis resulting in an IRR estimate of 0.55 (95% CI 0.34–0.86). Conclusions: The results of this study do not suggest an increase in the risk of falls or fractures associated with pimavanserin compared with other antipsychotics in patients with Parkinson’s disease-related psychosis. Sensitivity analyses suggest a decreased risk.

ObjectiveTo explore how bereaved family members recall managing end of life medications when delivering care to a patient dying at home in England.DesignQualitative study.SettingDomestic homes in two contrasting areas in England.Participants59 bereaved family carers who have delivered care to a patient who spent a minimum of 2 weeks at home prior to their death from cancer or other non-malignant condition. Cases were excluded if the place of death was: a hospice, nursing home or National Health Service (NHS) hospital.ResultsParticipants identified a number of important concerns about managing end of life medication for the dying person at home. Although some support with medications is provided by general practitioners and nurses in the community, family carers take primary responsibility for drug administration and storage. They reported anxiety about giving correct and timely dosages, and concerns about keeping the patient comfortable without overdosing them or risking shortening their lives. In particular, they reported that certain analgesic medications, especially opioids, were considered to have a symbolic significance increasing analgesia requirements, and the use of a syringe driver was associated with deterioration and approaching death. Key barriers to managing end of life medications at home included: complex regimes; unwanted responsibility in deciding when to use ‘as needed’ medication; disagreements with professional staff, and anxiety about medication errors, especially if perceived to have implications for survival.ConclusionsFamily carers require more information about end of life drugs and their effects, support and training in managing medication for a dying person.

Aims and objectivesThe involvement of patients in the design and conduct of research is increasingly promoted by policy and research bodies. The experiences of individuals who become involved in research in this way are not well understood. This study aims to describe the experiences of people's participation in patient and public involvement (PPI) in supportive and palliative care research, specifically with respect to the benefits and challenges of participation for the individuals and the broader research support structures.MethodsIn this qualitative exploratory study, semistructured interviews were undertaken with individuals who had a cancer diagnosis and were involved in a supportive and palliative care research collaborative over a period of 6 years. Recruitment was through the host university organisations involved in the research collaborative. A thematic analysis was undertaken to identify commonalities and differences across their experiences.FindingsThe eight participants in the study were highly motivated and undertook PPI in research alongside other voluntary activities. They identified a number of research and personal benefits: bringing a lay perspective into research, making a difference and personal gains. Personal gains concerned support, new knowledge and skills and greater confidence. The challenges to participation that were identified included the emotional and practical nature of the work, issues of language and identifying the difference made.ConclusionsInvolvement in supportive and palliative care research is valued by people with a cancer diagnosis, but there are ongoing issues of emotional support and good communication through the use of appropriate language in documentation.

Dysphagia is discussed in terms of techniques for imaging evaluation, common and uncommon or unexpected causes, and relevant imaging findings.

SHIP-TO-CLASSROOM INTERACTIONS ARE INCREASINGLY COMMON ON SCIENTIFIC research cruises, as are other informal marine education outreach programs. However, very rarely (if at all) are the materials developed by these interactions and programs accessible to students with learning disabilities. These students often find the material "cool" and intriguing but are not able to do the activities or read the material posted for a number of reasons: their reading level is too low, their attention span is not long enough to read paragraphs of information, and/or they do not understand the concept being communicated. Building off of lessons learned in an earlier ship-toclassroom education program (Orcutt et al. 2011), we launched the Classroom Connection (CC) program to include students with all learning levels in education outreach efforts by creating accessible reading materials and modified hands-on, student-led activities. The CC program targeted elementary and middle school children with learning disabilities but it was open to students of alI ages and academic levels. Here, we present an overview of the CC program operated during two ocean research expeditions, highlighting steps taken to make material accessible to all classrooms. In particular, we address the importance of "accessible" lesson plans, measurable evaluation, and advance promotion of the program. It is our hope that the CC program becomes a widely used template for marine outreach and education as it is inclusive of all students regardless of their learning level. [ABSTRACT FROM AUTHOR]

Mitogenic CD28 (or Superagonistic CD28) antibodies activate CTL functions by human CD4+ T cells—functions previously unknown to be induced by these stimulatory antibodies. Some human memory CD4+T cells have cytotoxic functions best understood in the context of viral infections; however, their possible role in pathologic processes is understudied. The novel discovery that mitogenic CD28 antibodies induced proliferation and expansion of Tregs offered therapeutic promise for autoimmune disorders. However, the failed TGN1412 trial forced reassessment of this concept. As memory CD4+T cells are known to produce toxic molecules, including granzyme B (GrzB) and FasL, we wondered whether mitogenic CD28 was able to induce these cytotoxic molecules. A commercially available mitogenic human CD28 mAb (clone ANC28.1) was used to determine whether mitogenic CD28 induces cytotoxic function from human memory CD4+T cells. We found that stimulation of memory CD4+T cells by ANC28.1, as well as by conventional costimulation (CD3/CD28 mAb), robustly induced enzymatically active GrzB, along with increased surface expression of FasL. These functional phenotypes were induced in association with increased expression of T cell activation markers CD69 and CD25, and elimination of target cells by ANC28.1‐activated memory CD4+T cells involved both GrzB and FasL. Additionally, ANC28.1‐activated memory CD4+T cells caused disruption of epithelial cell monolayer integrity, which was partially mediated by GrzB. These findings reveal functions of memory CD4+T cells previously unknown to be induced by mitogenic CD28, and suggest that these pathogenic mechanisms may have been responsible for some of the widespread tissue destruction that occurred in the TGN1412 trial recipients.

A volunteer workgroup of public health personnel and parish nurses in Wisconsin collaborated to develop theInfection Control and Emergency Preparedness Toolkit for the Faith Communityto help prepare congregations for health emergencies and prevent the spread of disease. This article reports a pilot study of the toolkit with 30 parishes/churches, focusing on the infection control portion of the materials.

Hwang et al.1recently published a retrospective analysis of the risk of hospitalization or mortality in patients with Parkinson disease (PD) using pimavanserin in long-term care facilities. However, the study design and cohort selection do not support the authors' conclusions.

Under normal physiological conditions, gastric acid production is controlled by a negative feedback mechanism. Proton pump inhibitors, such as pantoprazole, inhibit gastric acid secretion by irreversibly binding and inactivating luminally active hydrogen potassium ATPase. Recovery of acid production after treatment with a proton pump inhibitor is driven by new pump synthesis, activation of existing cytoplasmic pumps, or reversal of proton pump inhibition. The authors measured the time course of the inhibition and recovery of acid secretion in healthy volunteers following intravenous administration of pantoprazole to determine the rate of proton pump activation under maximally stimulated conditions. Gastric acid production was measured in 27 Helicobacter pylori negative healthy volunteers (mean age = 31± 7 years; 17 men, 10 women) who received single doses of intravenous pantoprazole (20, 40, 80, or 120 mg) in the presence of a continuous intravenous infusion of 1 ug/kg/h of pentagastrin. From the time profile of acid secretion, the authors described the rate of change of acid output using an irreversible pharmacodynamic response model represented by the equation dR/dt = −k ṁ R ṁ Cpanto+ Ln2/PPR ṁ (Ro‐R) and correlated the parameter values with demographic factors and gastric acid measurements. Mean stimulated acid output secretion was 21.6 ± 18.4 mEq/h (range: 1.6–90.5) prior to the administration of pantoprazole and remained steady for 25 hours after placebo administration. Intravenous pantoprazole inhibited acid output in a dose‐response fashion, with maximal inhibition (99.9%) occurring after an 80 mg dose. Mean proton pump recovery time was 37.1 ± 21.0 hours (range: 6.7–75), and recovery was independent of the dose of pantoprazole. There was no association noted between proton pump recovery time and gender, age, race, body weight, or pantoprazole dose. However, there was an inverse correlation between acid output during baseline stimulation and recovery of acid secretion. Mean proton pump recovery time in stimulated normal human volunteers was 37.1 ± 21.0 hours, with a range of 6.7 to 75 hours. The authors hypothesize that there may be a normal homeostatic mechanism that maintains acid secretory capability within a normal range by altering the rate of proton pump activation dependent on the individual's parietal cell mass. Abnormalities of this process may be responsible for the development of acid peptic disease in susceptible individuals.

In mammals, S-adenosylhomocysteine hydrolase (AdoHcyase) is the only known enzyme to catalyze the breakdown of S-adenosylhomocysteine (AdoHcy) to homocysteine and adenosine. AdoHcy is the product of all adenosylmethionine (AdoMet)-dependent biological transmethylations. These reactions have a wide range of products, and are common in all facets of biometabolism. As a product inhibitor, elevated levels of AdoHcy suppress AdoMet-dependent transmethylations. Thus, AdoHcyase is a regulator of biological transmethylation in general. The three-dimensional structure of AdoHcyase complexed with reduced nicotinamide adenine dinucleotide phosphate (NADH) and the inhibitor (1′R, 2′S, 3′R)-9-(2′,3′-dihyroxycyclopenten-1-yl)adenine (DHCeA) was solved by a combination of the crystallographic direct methods program, SnB, to determine the selenium atom substructure and by treating the multiwavelength anomalous diffraction data as a special case of multiple isomorphous replacement. The enzyme architecture resembles that observed for NAD-dependent dehydrogenases, with the catalytic domain and the cofactor binding domain each containing a modified Rossmann fold. The two domains form a deep active site cleft containing the cofactor and bound inhibitor molecule. A comparison of the inhibitor complex of the human enzyme and the structure of the rat enzyme, solved without inhibitor, suggests that a 17° rigid body movement of the catalytic domain occurs upon inhibitor/substrate binding.

A 24-year-old female patient who had suffered from recurrent bouts of acute pancreatitis for over 3 years was found on endoscopic retrograde cholangiopancreatography to have an aberrant pancreatic duct that terminated in a cyst. An aberrant lobe of pancreas had been discovered at exploratory laparotomy 3 years previously and was left untreated. Excision of the aberrant lobe of pancreas and accompanying gastric duplication cyst was curative. This case illustrates the importance of obtaining endoscopic retrograde cholangiopancreatography in all young individuals with recurrent pancreatitis to detect this rare, but curable, cause of pancreatitis.

The appropriate use of serum creatinine level as a surrogate for time in the course of renal failure when dialysis commences requires it to be a significant predictor of mortality in incident patients with end-stage renal disease (ESRD). This study evaluated factors that account for variations in creatinine level before the initiation of dialysis and whether incident creatinine level after controlling for these factors was a risk factor for mortality. This is a retrospective cohort study of patients from Maryland and Virginia who initiated dialysis between April 1, 1995, and December 31, 1996, with data ascertained from the Health Care Financing Administration Form 2728. Multivariate models were used to evaluate both the factors that predict incident serum creatinine level and the association between creatinine level and mortality. There were 5,388 patients followed up for an average of 23.6 ± 0.2 months. Mean creatinine level was 9.2 ± 0.1 mg/dL, with case-mix factors most predictive of serum creatinine level and accounting for 9% of its variance. Hematocrit and blood urea nitrogen levels as additional surrogates for progression of renal disease accounted for 7.4% of the variance, whereas the nutritional parameters, body mass index, and albumin level only explained an additional 1% of the total variance in creatinine level. Creatinine level was inversely correlated with mortality risk, and this relationship was sustained both with transformation into an estimated glomerular filtration rate and multivariate adjustment for confounders (relative risk = 0.96; P< 0.0001). Creatinine values from an incident ESRD population have a weak relationship with the timing of dialysis initiation but represent a strong measure of health status.

Abstract:  Mineralization of N from organic materials added to soil depends on the quality of the substrate as a carbon, energy and nutrient source for the saprophytic microflora. Quality reflects a combination of biochemical and physical attributes. We investigated how biochemical composition interacts with particle size to affect the soil microflora and N dynamics following incorporation of crop residues into soil. Four fresh shoot and root crop residues were cut into coarse and fine particle sizes, and incorporated into sandy-loam soil which was incubated under controlled environment conditions for 6 months. In the case of the highest biochemical quality material, potato shoot (C/N ratio of 10 : 1), particle size had no effect on microbial respiration or net N mineralization. For lower biochemical quality Brussels sprout shoot (C/N ratio of 15 : 1), reducing particle size caused microbial respiration to peak earlier and increased net mineralization of N during the early stages of decomposition, but reduced net N mineralization at later stages. However, for the lowest biochemical quality residues, rye grass roots (C/N ratio of 38 : 1) and straw (C/N ratio of 91 : 1) reducing particle size caused microbial respiration to peak later and increased net immobilization of N. For Brussels sprout shoot, reducing particle size decreased the C content and the C/N ratio of residue-derived light fraction organic matter (LFOM) 2 months following incorporation. However C and N content of LFOM derived from the other materials was not affected by particle size. For materials of all qualities, particle size had little effect on biomass N. We conclude that the impact of particle size on soil microbial activities, and the protection of senescent microbial tissues from microbial attack, is dependant on the biochemical quality of the substrate.

The purpose of this study was to determine whether an observed difference in hemodialysis adequacy between states in Network 5 was due to variations in patient characteristics and to what extent dialysis center effects played a role in the observed disparity between states. This was a retrospective observational study of 6,969 patients dialyzed at centers in Maryland and Virginia. There were 3,919 patients on hemodialysis at 89 facilities in Virginia and 3,050 subjects dialyzed at 65 centers in Maryland. The mean urea reduction ratio (URR) was higher in Virginia compared with Maryland (68.2 ± 0.1% v66.0 ± 0.2%, P< 0.0001, respectively), and there continued to be a mean difference in URR of 1.8% between VA and MD (P< 0.0001) after adjusting for several covariates. The differences in URR between states varied depending on facility proprietary status, size as measured by number of stations, and relationship to hospital (free-standing or hospital-based). Furthermore, the center where a patient dialyzed, when treated as a fixed effect, accounted for 15% of the variance in URR. The mean difference of 1.8% in URR between states persisted in a mixed-effects model that included all covariates along with adjusting for dialysis centers as a random effect. The disparity in dialysis adequacy between states in Network 5 could not be accounted for by demographic characteristics, case mix factors, or a large center effect observed in the region. Therefore, we conclude that underlying national reports on dialysis adequacy are heterogeneous results related to differences across regions such as states within a given Network. This difference between states is not explained by the strong center effect found on adequacy in this population of hemodialysis patients.

To determine the effects of anemia in children with end-stage renal disease, we studied cardiac performance before and 1 and 6 months after recombinant erythropoietin (Epogen). Children with end-stage renal disease were included if they had significant anemia [hematocrit (Hct)<30%]. Epogen 50 U/kg was given subcutaneously or intravenously three times per week until the Hct was =33%. Echocardiography, cardiac output (acetylene rebreathing), and treadmill (modified Bruce) tests were performed. Boys (9) and girls (9), 11.9±5.6 years, were given Epogen and the Hct increased (from 21.7±2.7% to 33.4±2.1%,P=0.001). Heart rate decreased (P=0.04) and stroke volume did not change. Blood pressure did not change. Cardiac thickness, chamber dimensions, left ventricular wall stress, velocity of circumferential fiber shortening, and indices of diastolic function were normal and did not change after Epogen. Exercise time increased (from 10.3±1.9 to 11.2±1.9 min,P=0.01) after 1 month of Epogen. Resting oxygen consumption (VO2) decreased (from 7.8±1.8 to 6.9±1.4 ml/min per kg,P=0.01) 1 month after Epogen and peak exercise VO2 did not change after Epogen. There were no differences in exercise tests between the 1 and 6 month measurements. Exercise tolerance improves after the short-term correction of anemia and there is no further improvement after long-term correction.

S-Adenosylhomocysteine (AdoHcy) hydrolase regulates all adenosylmethionine-(AdoMet) dependent transmethylations by hydrolyzing the potent feedback inhibitor AdoHcy to homocysteine and adenosine. The crystallographic structure determination of a selenomethionyl-incorporated AdoHcy hydrolase inhibitor complex was accomplished using single wavelength anomalous diffraction data and the direct methods program, Snb v2.0, which produced the positions of all 30 crystallographically distinct selenium atoms. The mode of enzyme–cofactor binding is unique, requiring interactions from two protein monomers. An unusual dual role for a catalytic water molecule in the active site is revealed in the complex with the adenosine analog 2′-hydroxy, 3′-ketocyclopent-4′-enyladenine.