Debilitating abdominal pain is a common symptom affecting most patients with chronic pancreatitis (CP). There are multiple underlying mechanisms that contribute to CP-related pain, which makes ...successful treatment difficult. The identification of biomarkers for subtypes of pain could provide viable targets for nonopioid interventions and the development of mechanistic approaches to pain management in CP. Nineteen inflammation- and nociception-associated proteins were measured in serum collected from 358 subjects with definite CP enrolled in PROspective Evaluation of Chronic Pancreatitis for EpidEmiologic and Translational StuDies, a prospective observational study of pancreatitis in US adult subjects. First, serum levels of putative biomarkers were compared between CP subjects with and without pain. Only platelet-derived growth factor B (PDGF-B) stood out, with levels significantly higher in the CP pain group as compared to subjects with no pain. Subjects with pain were then stratified into 4 pain subtypes (Neuropathic, Nociceptive, Mixed, and Unclassified). A comparison of putative biomarker concentration among 5 groups (no pain and 4 pain subtypes) identified unique proteins that were correlated with pain subtypes. Serum transforming growth factor beta 1 (TGFβ1) level was significantly higher in the Nociceptive pain group compared to the No pain group, suggesting that TGFβ1 may be a biomarker for nociceptive pain. The Neuropathic pain only group was too small to detect statistical differences. However, glycoprotein 130 (GP130), a coreceptor for interleukin 6, was significantly higher in the Mixed pain group compared to the groups lacking a neuropathic pain component. These data suggest that GP130 may be a biomarker for neuropathic pain in CP. PERSPECTIVE: Serum TGFβ1 and GP130 may be biomarkers for nociceptive and neuropathic CP pain, respectively. Preclinical data suggest inhibiting TGFβ1 or GP130 reduces CP pain in rodent models, indicating that additional translational and clinical studies may be warranted to develop a precision medicine approach to the management of pain in CP.
Objectives:
Drug‐associated acute pancreatitis (DAP) studies typically focus on single acute pancreatitis (AP) cases. We aimed to analyze the (1) characteristics, (2) co‐risk factors, and (3) ...reliability of the Naranjo scoring system for DAP using INSPPIRE‐2 (the INternational Study group of Pediatric Pancreatitis: In search for a cuRE‐2) cohort study of acute recurrent pancreatitis (ARP) and chronic pancreatitis (CP) in children.
Methods:
Data were obtained from ARP group with ≥1 episode of DAP and CP group with medication exposure ± DAP. Physicians could report multiple risk factors. Pancreatitis associated with Medication (Med) (ARP+CP) was compared to Non‐Medication cases, and ARP‐Med vs CP‐Med groups. Naranjo score was calculated for each DAP episode.
Results:
Of 726 children, 392 had ARP and 334 had CP; 51 children (39 ARP and 12 CP) had ≥1 AP associated with a medication; 61% had ≥1 AP without concurrent medication exposure. The Med group had other risk factors present (where tested): 10 of 35 (28.6%) genetic, 1 of 48 (2.1%) autoimmune pancreatitis, 13 of 51 (25.5%) immune‐mediated conditions, 11 of 50 (22.0%) obstructive/anatomic, and 28 of 51 (54.9%) systemic risk factors. In Med group, 24 of 51 (47%) had involvement of >1 medication, simultaneously or over different AP episodes. There were 20 ARP and 4 CP cases in “probable” category and 19 ARP and 7 CP in “possible” category by Naranjo scores.
Conclusions:
Medications were involved in 51 of 726 (7%) of ARP or CP patients in INSPPIRE‐2 cohort; other pancreatitis risk factors were present in most, suggesting a potential additive role of different risks. The Naranjo scoring system failed to identify any cases as “definitive,” raising questions about its reliability for DAP.
The synthesis of published research in systematic reviews is essential when providing evidence to inform clinical and health policy decision-making. However, the validity of systematic reviews is ...threatened if journal publications represent a biased selection of all studies that have been conducted (dissemination bias). To investigate the extent of dissemination bias we conducted a systematic review that determined the proportion of studies published as peer-reviewed journal articles and investigated factors associated with full publication in cohorts of studies (i) approved by research ethics committees (RECs) or (ii) included in trial registries.
Four bibliographic databases were searched for methodological research projects (MRPs) without limitations for publication year, language or study location. The searches were supplemented by handsearching the references of included MRPs. We estimated the proportion of studies published using prediction intervals (PI) and a random effects meta-analysis. Pooled odds ratios (OR) were used to express associations between study characteristics and journal publication. Seventeen MRPs (23 publications) evaluated cohorts of studies approved by RECs; the proportion of published studies had a PI between 22% and 72% and the weighted pooled proportion when combining estimates would be 46.2% (95% CI 40.2%-52.4%, I2 = 94.4%). Twenty-two MRPs (22 publications) evaluated cohorts of studies included in trial registries; the PI of the proportion published ranged from 13% to 90% and the weighted pooled proportion would be 54.2% (95% CI 42.0%-65.9%, I2 = 98.9%). REC-approved studies with statistically significant results (compared with those without statistically significant results) were more likely to be published (pooled OR 2.8; 95% CI 2.2-3.5). Phase-III trials were also more likely to be published than phase II trials (pooled OR 2.0; 95% CI 1.6-2.5). The probability of publication within two years after study completion ranged from 7% to 30%.
A substantial part of the studies approved by RECs or included in trial registries remains unpublished. Due to the large heterogeneity a prediction of the publication probability for a future study is very uncertain. Non-publication of research is not a random process, e.g., it is associated with the direction of study findings. Our findings suggest that the dissemination of research findings is biased.
People with dementia and informal carers often access formal care late in the process of dementia. The barriers and facilitators to service use from the perspectives of different stakeholders ...involved are not well understood. Thus, we aimed to explore the barriers and facilitators of access to and utilisation of formal care from the perspectives of people with dementia, their informal carers and health and social care professionals.
Focus groups with people with dementia, informal carers and professionals were conducted in eight European countries. Recruitment targeted people with dementia, informal carers with experience of formal care and professionals involved in providing (access to) formal care. Qualitative content analysis using open coding was used on a national level. Cross-national synthesis was based on the translated national reports.
Overall, 55 focus groups with 261 participants were conducted, involving 51 people with dementia, 96 informal carers and 114 professionals. Sixteen categories describing barriers and facilitators were identified, referring to three global themes: Aspects related to 1) individuals involved, 2) the system or 3) overarching aspects. The attitudes and beliefs of people with dementia and their carers may have a major impact, and they often serve as barriers. Formal care was perceived as a threat to the individual independence of people with dementia and was thus avoided as long as possible. A healthcare professional serving as a constant key contact person could be an essential facilitator to overcome these barriers. Contact should be initiated proactively, as early as possible, and a trusting and consistent relationship needs to be established. Beyond that, the findings largely confirm former research and show that barriers to accessing and using formal care still exist across Europe despite a number of national and European initiatives.
Further investigations are needed to elaborate how the concept of a key contact person could be integrated with existing case management approaches and how the independence and autonomy of people with dementia can be strengthened when formal care needs to be accessed and used. These may be meaningful facilitators regarding enhanced access to formal care for people with dementia and their families.
Malnutrition is widespread among older people and related to poor outcome. Reported prevalences vary widely, also because of different diagnostic criteria used. This study aimed to describe ...prevalences in several populations of older persons in different settings using harmonized definitions.
Available studies within the Joint Programming Initiative (JPI) Knowledge Hub ‘Malnutrition in the Elderly’ (MaNuEL) were used to calculate and compare prevalences of malnutrition indicators: low BMI (<20 kg/m2; age-specific BMI <20 if age 65–<70 and <22 kg/m2 if age ≥70 years), previous weight loss (WL), moderate and severe decrease in food intake, and combined BMI <20 kg/m2 and/or WL in participants aged ≥65 years.
Fifteen samples with in total 5956 participants (59.3% women) were included: 7 consisting of community-dwelling persons, 2 studies in geriatric day hospitals, 3 studies in hospitalized patients and 3 in nursing homes. Mean age of participants ranged between 67 and 87 years. Up to 4.2% of community-dwelling persons had a BMI <20 kg/m2, 1.6 and 9% of geriatric day hospital patients, 4.5–9.4% of hospital patients and 3.8–18.2% of nursing home residents. Using age-specific cut-offs doubled these prevalences. WL was reported in 2.3–10.5% of community-dwelling persons, 6% and 12.6% of geriatric day hospital patients, 5–14% of hospitalized patients and 4.5–7.7% of nursing home residents. Severe decrease in food intake was recorded in up to 9.6% of community-dwelling persons, 1.5% and 12% of geriatric day hospital patients, 3.4–34.2% of hospitalized patients and 1.5–8.2% of nursing home residents. The criteria age-specific BMI and WL showed opposing prevalences across all settings. Compared to women, low BMI and moderate decrease in food intake showed low prevalences in men but similar prevalences were observed for weight loss and severe decrease in food intake. In half of the study samples, participants in a younger age group had a higher prevalence of WL compared to those of an older age group. Prevalence of BMI <20 kg/m2 and WL at the same time did not exceed 2.6% in all samples. The highest prevalences were observed based on combined definitions when only one of the three criteria had to be present.
Prevalences for different criteria vary between and within the settings which might be explained by varying functional status. The criteria used strongly affect prevalence and it may be preferable to look at each criterion separately as each may indicate a nutritional problem.
Taxation of sugar-sweetened beverages (SSBs), as a component of a comprehensive strategy, has emerged as an apparent effective intervention to counteract the rising prevalence of overweight and ...obesity. Insight into the political and public acceptability may help adoption and implementation in countries with governments that are considering an SSBs tax. Hence, we aimed to conduct a systematic review and meta-analysis to synthesize the existing qualitative and quantitative literature on political and public acceptability of an SSBs tax.
Four electronic databases (PubMed, Embase, Scopus, Web of Science) were searched until November 2018. The methodological quality of the included studies was assessed using the Mixed Methods Appraisal Tool. Qualitative studies were analyzed using a thematic synthesis. Quantitative studies were analyzed using a random-effects meta-analysis for the pooling of proportions.
Thirty-seven articles reporting on forty studies were eligible for inclusion. Five themes derived from the thematic synthesis: (i) beliefs about effectiveness and cost-effectiveness, (ii) appropriateness, (iii) economic and socioeconomic benefit, (iv) policy adoption and implementation, and (v) public mistrust of the industry, government and public health experts. Results of the meta-analysis indicated that of the public 42% (95% CI = 0.38-0.47) supports an SSBs tax, 39% (0.29-0.50) supports an SSBs tax as a strategy to reduce obesity, and 66% (0.60-0.72) supports an SSBs tax if revenue is used for health initiatives.
Beliefs about effectiveness and cost-effectiveness, appropriateness, economic and socioeconomic benefit, policy adoption and implementation, and public mistrust of the industry, government and public health experts have important implications for the political and public acceptability of an SSBs tax. We provide recommendations to increase acceptability and enhance successful adoption and implementation of an SSBs tax: (i) address inconsistencies between identified beliefs and scientific literature, (ii) use raised revenue for health initiatives, (iii) communicate transparently about the true purpose of the tax, and (iv) generate political priority for solutions to the challenges to implementation.
Common mental disorders are frequently experienced by refugees. This study evaluates the impact of a brief, lay provider delivered group-based psychological intervention Group Problem Management Plus ...(gPM+) on the mental health of refugees in a camp, as well as on parenting behavior and children's mental health.
In this single-blind, parallel, randomized controlled trial, 410 adult Syrian refugees (300 females, 110 males) in Azraq Refugee Camp (Jordan) were identified through screening of psychological distress (≥16 on the Kessler Psychological Distress Scale) and impaired functioning (≥17 on the WHO Disability Assessment Schedule). Participants were randomly allocated to gPM+ or enhanced usual care (EUC) involving referral information for psychosocial services on a 1:1 ratio. Participants were aware of treatment allocation, but assessors were blinded to treatment condition. Primary outcomes were scores on the Hopkins Symptom Checklist-25 (HSCL; depression and anxiety scales) assessed at baseline, 6 weeks, and 3 months follow-up as the primary outcome time point. It was hypothesized that gPM+ would result in greater reductions of scores on the HSCL than EUC. Secondary outcomes were disability, posttraumatic stress, personally identified problems, prolonged grief, prodromal psychotic symptoms, parenting behavior, and children's mental health. Between October 15, 2019 and March 2, 2020, 624 refugees were screened for eligibility, 462 (74.0%) screened positive, of whom 204 were assigned to gPM+ and 206 to EUC. There were 168 (82.4%) participants in gPM+ and 189 (91.7%) in EUC assessed at follow-up. Intent-to-treat analyses indicated that at follow-up, participants in gPM+ showed greater reduction on HSCL depression scale than those receiving EUC (mean difference, 3.69 95% CI 1.90 to 5.48, p = .001; effect size, 0.40). There was no difference between conditions in anxiety (mean difference -0.56, 95% CI -2.09 to 0.96; p = .47; effect size, -0.03). Relative to EUC, participants in gPM+ had greater reductions in severity of personally identified problems (mean difference 0.88, 95% CI 0.07 to 1.69; p = .03), and inconsistent disciplinary parenting (mean difference 1.54, 95% CI 1.03 to 2.05; p < .001). There were no significant differences between conditions for changes in PTSD, disability, grief, prodromal symptoms, or childhood mental health outcomes. Mediation analysis indicated the change in inconsistent disciplinary parenting was associated with reduced attentional (β = 0.11, SE .07; 95% CI .003 to .274) and internalizing (β = 0.08, SE .05; 95% CI .003 to 0.19) problems in children. No adverse events were attributable to the interventions or the trial. Major limitations included only one-quarter of participants being male, and measures of personally identified problems, grief, prodromal psychotic symptoms, inconsistent parenting behavior, and children's mental health have not been validated with Syrians.
In camp-based Syrian refugees, a brief group behavioral intervention led to reduced depressive symptoms, personally identified problems, and disciplinary parenting compared to usual care, and this may have indirect benefits for refugees' children. The limited capacity of the intervention to reduce PTSD, disability, or children's psychological problems points to the need for development of more effective treatments for refugees in camp settings.
Prospectively registered at Australian and New Zealand Clinical Trials Registry: ACTRN12619001386123.
Recently, myocardial work analysis as an echocardiographic tool to non-invasively determine LV work has been introduced and validated against invasive measurements. Based on systolic blood pressure ...and speckle-tracking derived longitudinal strain (GLS) during systole and isovolumic relaxation, it is considered less load-dependent than LV ejection fraction (LVEF) or GLS and to integrate information on LV active systolic and diastolic work. We aimed to establish reference values for global constructive (GCW) and global wasted work (GWW) as well as of global work index (GWI) and global work efficiency (GWE) across a wide age range and to assess the association with standard echocardiography parameters to estimate the potential additional information provided by myocardial work (MyW). The Characteristics and Course of Heart Failure STAges A/B and Determinants of Progression (STAAB) cohort study carefully characterized a representative sample of the population of the City of Würzburg, Germany, aged 30-79 years. We performed myocardial work analysis using the standardized, quality-controlled transthoracic echocardiograms of all individuals lacking any cardiovascular risk factor. Out of 4965 participants, 779 (49±10 years, 59% women) were eligible for the present analysis. Levels of GCW, GWW, and GWE were independent of sex and body mass index, and were stable until the age of 45 years. Thereafter, we observed an upward shift to further stable values of GCW and a linear increase of GWW with advancing age, resulting in lower GWE. Age-adjusted percentiles for GCW, GWW, GWI, and GWE were derived. Higher levels of blood pressure or LV mass were associated with higher GCW, GWI, and GWW, resulting in lower GWE; higher LVEF correlated with higher GCW and GWI, but lower GWW. Higher E/e' correlated with higher GWW, higher e' with lower GWW. Derived from a large sample of apparently healthy individuals from a population based-cohort, we provide age-adjusted reference values for myocardial work indices, applicable for either sex. Weak correlations with common echocardiographic parameters suggest MyW indices to potentially provide additional information, which has to be evaluated in diseased patient cohorts.
The aim of this study was to report 36-month longitudinal changes using the North Star Ambulatory Assessment (NSAA) in ambulant patients affected by Duchenne muscular dystrophy amenable to skip exons ...44, 45, 51 or 53. We included 101 patients, 34 had deletions amenable to skip exon 44, 25 exon 45, 19 exon 51, and 28 exon 53, not recruited in any ongoing clinical trials. Five patients were counted to skip exon 51 and 53 since they had a single deletion of exon 52. The difference between subgroups (skip 44, 45, 51 and 53) was significant at 12 (p = 0.043), 24 (p = 0.005) and 36 months (pless than or equal to0.001). Mutations amenable to skip exons 53 and 51 had lower baseline values and more negative changes than the other subgroups while those amenable to skip exon 44 had higher scores both at baseline and at follow up. Our results confirm different progression of disease in subgroups of patients with deletions amenable to skip different exons. This information is relevant as current long term clinical trials are using the NSAA in these subgroups of mutations.
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