Association between coronary artery vitamin D receptor expression and select systemic risks factors for coronary artery atherosclerosis.

OBJECTIVE: The aim of this study is to analyze the association between coronary artery vitamin D receptor (VDR) expression and systemic coronary artery atherosclerosis (CAA) risk factors. METHODS: Female cynomolgus monkeys (n = 39) consumed atherogenic diets containing the women's equivalent of 1000 IU/day of vitamin D3. After 32 months consuming the diets, each monkey underwent surgical menopause. After 32 postmenopausal months, CAA and VDR expression were quantified in the left anterior descending coronary artery. Plasma 25OHD3, lipid profiles and serum monocyte chemotactic protein-1 (MCP-1) were measured. RESULTS: In postmenopausal monkeys receiving atherogenic diets, serum MCP-1 was significantly elevated compared with baseline (482.2 ± 174.2 pg/ml vs. 349.1 ± 163.2 pg/ml, respectively; p < 0.001; d = 0.79) and at the start of menopause (363.4 ± 117.2 pg/ml; p < 0.001; d = 0.80). Coronary VDR expression was inversely correlated with serum MCP-1 (p = 0.042). Additionally, the change of postmenopausal MCP-1 (from baseline to necropsy) was significantly reduced in the group with higher, compared to below the median, VDR expression (p = 0.038). The combination of plasma 25OHD3 and total plasma cholesterol/high-density lipoprotein cholesterol was subsequently broken into low-risk, moderate-risk and high-risk groups; as the risk increased, the VDR quantity decreased (p = 0.04). CAA was not associated with various atherogenic diets. CONCLUSION: Coronary artery VDR expression was inversely correlated with markers of CAA risk and inflammation, including MCP-1, suggesting that systemic and perhaps local inflammation in the artery may be associated with reduced arterial VDR expression.

Meta-analysis of the effect of extending the interval after long-course chemoradiotherapy before surgery in locally advanced rectal cancer.

BACKGROUND: The current standard of care in locally advanced rectal cancer (LARC) is neoadjuvant long-course chemoradiotherapy (nCRT) followed by total mesorectal excision (TME). Surgery is conventionally performed approximately 6-8 weeks after nCRT. This study aimed to determine the effect on outcomes of extending this interval. METHODS: A systematic search was performed for studies reporting oncological results that compared the classical interval (less than 8 weeks) from the end of nCRT to TME with a minimum 8-week interval in patients with LARC. The primary endpoint was the rate of pathological complete response (pCR). Secondary endpoints were recurrence-free survival, local recurrence and distant metastasis rates, R0 resection rates, completeness of TME, margin positivity, sphincter preservation, stoma formation, anastomotic leak and other complications. A meta-analysis was performed using the Mantel-Haenszel method. RESULTS: Twenty-six publications, including four RCTs, with 25 445 patients were identified. A minimum 8-week interval was associated with increased odds of pCR (odds ratio (OR) 1·41, 95 per cent c.i. 1·30 to 1·52; P < 0·001) and tumour downstaging (OR 1·18, 1·05 to 1·32; P = 0·004). R0 resection rates, TME completeness, lymph node yield, sphincter preservation, stoma formation and complication rates were similar between the two groups. The increased rate of pCR translated to reduced distant metastasis (OR 0·71, 0·54 to 0·93; P = 0·01) and overall recurrence (OR 0·76, 0·58 to 0·98; P = 0·04), but not local recurrence (OR 0·83, 0·49 to 1·42; P = 0·50). CONCLUSION: A minimum 8-week interval from the end of nCRT to TME increases pCR and downstaging rates, and improves recurrence-free survival without compromising surgical morbidity.

ANTECEDENTES: El tratamiento estándar actual del cáncer de recto localmente avanzado (locally advanced rectal cancer, LARC) consiste en quimiorradioterapia neoadyuvante de ciclo largo (neoadjuvant, long-course chemoradiation, nCRT) seguida de exéresis total del mesorrecto (total mesorectal excision, TME). De forma convencional, la cirugía se realiza a las 6-8 semanas después de la nCRT. Este estudio tuvo como objetivo determinar el efecto sobre los resultados de ampliar este intervalo. MÉTODOS: Se realizó una búsqueda sistemática de los estudios que analizaban los resultados oncológicos, comparando el intervalo clásico (< 8 semanas) desde el final de la nCRT hasta la TME con un intervalo mínimo de 8 semanas, en pacientes con LARC. El criterio de valoración principal fue la tasa de respuesta patológica completa (pathologic complete response, pCR). Los criterios de valoración secundarios fueron las tasas de supervivencia sin recidiva (recurrence-free survival, RFS), recidiva local (local recurrence, LR) y metástasis a distancia (distant metastasis, DM), tasas de resección R0, integridad (completeness) del mesorrecto, afectación del margen de resección, preservación esfinteriana, formación de estoma, fuga anastomótica y otras complicaciones. Se realizó un metaanálisis utilizando el método de Mantel-Haenszel. RESULTADOS: Se identificaron 26 publicaciones, incluidos cuatro ensayos clínicos aleatorizados, con 17.220 pacientes. Un intervalo mínimo de 8 semanas se asoció con un aumento de la razón de oportunidades (odds ratio, OR) de pCR (OR, 1,68, i.c. del 95% 1,37-2,06, P < 0,001) y de disminución del estadio tumoral (OR 1,18, i.c. del 95% 1,05-1,32, P = 0,004). Los porcentajes de resección R0, integridad del mesorrecto, ganglios linfáticos identificados, preservación esfinteriana, formación de estoma y complicaciones fueron similares entre los dos grupos. El aumento del porcentaje de pCR se tradujo en una disminución de las DM (OR 0,71, i.c. del 95% 0,54-0,93, P = 0,01) y de la recidiva global (OR 0,76, i.c. del 95% 0,58-0,98, P = 0,04), pero no de la LR (OR 0,83, i.c. del 95% 0,49-1,42, P = 0,50). CONCLUSIÓN: Un intervalo mínimo de 8 semanas entre el final de la nCRT y la TME aumenta las tasas de pCR y la reducción del estadio tumoral, así como mejora la RFS sin comprometer la morbilidad quirúrgica.

Immobilization of whole cells of Lactococcus lactis containing high levels of a hyperthermostable ß-galactosidase enzyme in chitosan beads for efficient galacto-oligosaccharide production.

Galacto-oligosaccharides (GOS) are prebiotic food ingredients that are proposed to stimulate the growth of beneficial gut microorganisms, particularly bifidobacteria. Previously, we developed a method for efficient GOS production using whole cells of Lactococcus lactis containing high levels of a hyper-thermostable ß-galactosidase enzyme from Sulfolobus solfataricus. In this study, a recombinant DNA removal and whole-cell enzyme immobilization process was developed to produce GOS from lactose before removal of the immobilized whole-cell enzyme, which could be reused for subsequent applications. Chitosan was found to be a superior immobilization material compared with alginate, as it retained its bead structure during the high temperature (90°C) used here for GOS production. Prior to immobilization, the recombinant DNA was degraded in the whole cells using UV treatment, resulting in an immobilized whole-cell enzyme that was free of recombinant DNA and with minimum effect on the efficiency of the enzyme. The optimum pH and temperature for GOS synthesis using the chitosan beads was pH = 5.5 and 90°C. The highest GOS production using the chitosan beads occurred with 40% initial lactose resulting in 150 g/L of GOS (tri-oligosaccharides and tetra-oligosaccharides) in addition to di-oligosaccharide GOS products that were not quantified. Notably, the highest lactose conversion rate was found using lower starting lactose concentrations, with more than 60% conversion into tri-oligosaccharides and tetra-oligosaccharides. The immobilized enzyme retained ∼50% activity after 2 cycles of GOS production. In conclusion, the chitosan-immobilized whole-cell enzyme can be used for efficient GOS production that is free of the whole-cell enzyme as well as detectable recombinant DNA.

Analysis of head impacts during sub-elite hurling practice sessions.

The reported incidence of head and neck injuries in hurling is 0.12 per 1000 hours, but no previous research has quantified head impact characteristics in this sport. Here, a wireless accelerometer and gyroscope captured head impacts, in 20 senior club level hurling players. Peak linear and rotational acceleration and impact location were recorded during three hurling training sessions, each player participating once. A mean of 27.9 impacts (linear acceleration >10g) per player, per session were recorded; 1314 impacts during a total exposure time of 247 minutes. Only 2.6% impacts had peak linear acceleration of >70g and 6.2% had peak rotational acceleration >7900 rad/s2. There were significant differences in the number and magnitude of impacts, quantified by the accelerometer, between three training sessions of differing intensity (ŋ2 0.03-0.09, p < 0.001). This study represents a first step in quantifying head impacts during hurling, demonstrating the feasibility of this technology in the field. The sensors were able to discriminate between sessions of varying intensity. These data can be used to develop athlete monitoring protocols and may be useful in developing innovative helmet-testing standards for hurling. The potential for this technology to provide feedback has clinical utility for team medical personnel.

Phenotype-driven molecular autopsy for sudden cardiac death.

A phenotype-driven approach to molecular autopsy based in a multidisciplinary team comprising clinical and laboratory genetics, forensic medicine and cardiology is described. Over a 13 year period, molecular autopsy was undertaken in 96 sudden cardiac death cases. A total of 46 cases aged 1-40 years had normal hearts and suspected arrhythmic death. Seven (15%) had likely pathogenic variants in ion channelopathy genes [KCNQ1 (1), KCNH2 (4), SCN5A (1), RyR2(1)]. Fifty cases aged between 2 and 67 had a cardiomyopathy. Twenty-five had arrhythmogenic right ventricular cardiomyopathy (ARVC), 10 dilated cardiomyopathy (DCM) and 15 hypertrophic cardiomyopathy (HCM). Likely pathogenic variants were found in three ARVC cases (12%) in PKP2, DSC2 or DSP, two DCM cases (20%) in MYH7, and four HCM cases (27%) in MYBPC3 (3) or MYH7 (1). Uptake of cascade screening in relatives was higher when a molecular diagnosis was made at autopsy. In three families, variants previously published as pathogenic were detected, but clinical investigation revealed no abnormalities in carrier relatives. With a conservative approach to defining pathogenicity of sequence variants incorporating family phenotype information and population genomic data, a molecular diagnosis was made in 15% of sudden arrhythmic deaths and 18% of cardiomyopathy deaths.

Anticholinergic burden in schizophrenia and ability to benefit from psychosocial treatment programmes: a 3-year prospective cohort study.

BACKGROUND: Many medications administered to patients with schizophrenia possess anticholinergic properties. When aggregated, pharmacological treatments may result in a considerable anticholinergic burden. The extent to which anticholinergic burden has a deleterious effect on cognition and impairs ability to participate in and benefit from psychosocial treatments is unknown. METHOD: Seventy patients were followed for approximately 3 years. The MATRICS consensus cognitive battery (MCCB) was administered at baseline. Anticholinergic burden was measured with the Anticholinergic Cognitive Burden (ACB) scale. Ability to benefit from psychosocial programmes was measured using the DUNDRUM-3 Programme Completion Scale (D-3) at baseline and follow-up. Psychiatric symptoms were measured using the PANSS. Total antipsychotic dose was measured using chlorpromazine equivalents. Functioning was measured using the Social and Occupational Functioning Assessment Scale (SOFAS). RESULTS: Mediation analysis found that the influence of anticholinergic burden on ability to participate and benefit from psychosocial programmes was completely mediated by the MCCB. For every 1-unit increase on the ACB scale, change scores for DUNDRUM-3 decreased by -0.27 points. This relationship appears specific to anticholinergic burden and not total antipsychotic dose. Moreover, mediation appears to be specific to cognition and not psychopathology. Baseline functioning also acted as mediator but only when MCCB was not controlled for. CONCLUSIONS: Anticholinergic burden has a significant impact on patients' ability to participate in and benefit from psychosocial treatment programmes. Physicians need to be mindful of the cumulative effect that medications can have on patient cognition, functional capacity and ability to benefit from psychosocial treatments.

British Dietetic Association evidence-based guidelines for the dietary management of Crohn's disease in adults.

BACKGROUND: Crohn's disease is a debilitating chronic inflammatory bowel disease. Appropriate use of diet and nutritional therapy is integral to the overall management strategy of Crohn's disease. The aim was to develop evidence-based guidelines on the dietary management of Crohn's disease in adults. METHODS: Questions relating to the dietary management of Crohn's disease were developed. These included the roles of enteral nutrition to induce remission, food re-introduction diets to structure food re-introduction and maintain remission, and dietary management of stricturing disease, as well as whether probiotics or prebiotics induce or maintain remission. A comprehensive literature search was conducted and relevant studies from January 1985 to November 2009 were identified using the electronic database search engines CINAHL, Cochrane Library, EMBASE, MEDLINE, Scopus and Web of Science. Evidence statements, recommendations, practical considerations and research recommendations were developed. RESULTS: Fifteen research papers were critically appraised and the evidence formed the basis of these guidelines. Although corticosteroids appear to be more effective, enteral nutrition (elemental or non-elemental) can be offered as an alternative option to induce disease remission. After a course of enteral nutrition, food re-introduction diets may be useful to structure food re-introduction and help maintain disease remission. Dietary fibre is contraindicated in the presence of strictures as a result of the risk of mechanical obstruction. The use of probiotics and prebiotics is not currently supported. CONCLUSIONS: As an alternative to corticosteroids, evidence supports enteral nutrition to induce disease remission. Food re-introduction diets provide structure to food re-introduction and help maintain disease remission. These guidelines aim to reduce variation in clinical practice.

Production of galactooligosaccharides using a hyperthermophilic ß-galactosidase in permeabilized whole cells of Lactococcus lactis.

Galactooligosaccharides (GOS) are novel prebiotic food ingredients that can be produced from lactose using ß-galactosidase, but the process is more efficient at higher temperatures. To efficiently express the lacS gene from the hyperthermophile Sulfolobus solfataricus, in Lactococcus lactis a synthetic gene (lacSt) with optimized codon usage for Lc. lactis was designed and synthesized. This hyperthermostable ß-galactosidase enzyme was successfully overexpressed in Lc. lactis LM0230 using a nisin-controlled gene expression system. Enzyme-containing cells were then killed and permeabilized using 50% ethanol and were used to determine both hydrolysis and transgalactosylation activity. The optimum conditions for GOS synthesis was found to be at pH 6.0 and 85 °C. A maximum production of 197 g/L of GOS tri- and tetrasaccharides was obtained from 40% initial lactose, after 55 h of incubation. The total GOS yield increased with the initial lactose concentration, whereas the highest lactose conversion rate (72%) was achieved from a low lactose solution (5%). Given that a significant proportion of the remaining lactose would be expected to be converted into disaccharide GOS, this should enable the future development of a cost-effective approach for the conversion of whey-based substrates into GOS-enriched food ingredients using this cell-based technology.

Application of the STOPP/START criteria: a systematic review of the prevalence of potentially inappropriate prescribing in older adults, and evidence of clinical, humanistic and economic impact.

WHAT IS KNOWN AND OBJECTIVE: Potentially inappropriate prescribing (PIP) has significant clinical, humanistic and economic impacts. Identifying PIP in older adults may reduce their burden of adverse drug events. Tools with explicit criteria are being developed to screen for PIP in this population. These tools vary in their ability to identify PIP in specific care settings and jurisdictions due to such factors as local prescribing practices and formularies. One promising set of screening tools are the STOPP (Screening Tool of Older Person's potentially inappropriate Prescriptions) and START (Screening Tool of Alert doctors to the Right Treatment) criteria. We conducted a systematic review of research studies that describe the application of the STOPP/START criteria and examined the evidence of the impact of STOPP/START on clinical, humanistic and economic outcomes in older adults. METHODS: We performed a systematic review of studies from relevant biomedical databases and grey literature sources published from January 2007 to January 2012. We searched citation and reference lists and contacted content experts to identify additional studies. Two authors independently selected studies using a predefined protocol. We did not restrict selection to particular study designs; however, non-English studies were excluded during the selection process. Independent extraction of articles by two authors used predefined data fields. For randomized controlled trials and observational studies comparing STOPP/START to other explicit criteria, we assessed risk of bias using an adapted tool. RESULTS AND DISCUSSION: We included 13 studies: a single randomized controlled trial and 12 observational studies. We performed a descriptive analysis as heterogeneity of study populations, interventions and study design precluded meta-analysis. All observational studies reported the prevalence of PIP; however, the application of the criteria was not consistent across all studies. Seven of the observational studies compared STOPP/START with other explicit criteria. The STOPP/START criteria were reported to be more sensitive than the more-frequently-cited Beers criteria in six studies, but less sensitive than a set of criteria developed in Australia. The STOPP criteria identified more medications associated with adverse drug events than the 2002 version of the Beers criteria. Patients with PIP, as identified by STOPP, had an 85% increased risk of adverse drug events in one study (OR = 1·85, 95% CI: 1·51-2·26; P < 0·001). There was limited evidence that the application of STOPP/START criteria optimized prescribing. Research involving the application of STOPP/START on the impact on the quality of life was not found. The direct costs of PIP were documented in three studies from Ireland, but more extensive analyses on the economic impact or studies from other jurisdictions were not found. WHAT IS NEW AND CONCLUSION: The STOPP/START criteria have been used to review the medication profiles of community-dwelling, acute care and long-term care older patients in Europe, Asia and North America. Observational studies have reported the prevalence and predictors of PIP. The STOPP/START criteria appear to be more sensitive than the 2002 version of the Beers criteria. Limited evidence was found related to the clinical and economic impact of the STOPP/START criteria.

Factors influencing the stability of freeze-dried stress-resilient and stress-sensitive strains of bifidobacteria.

Freeze-drying is a common method for preservation of probiotics, including bifidobacteria, for further industrial applications. However, the stability of freeze-dried bifidobacteria varies depending on the freeze-drying method and subsequent storage conditions. The primary goals of this study were to develop an optimized freeze-drying procedure and to determine the effects of temperature, water activity, and atmosphere on survival of freeze-dried bifidobacteria. To address these goals, a commercially used bifidobacteria strain that is resilient to stress, Bifidobacterium animalis ssp. lactis Bb-12, and a characterized intestinal strain that is more sensitive to stress conditions, Bifidobacterium longum DJO10A, were used. A freeze-drying protocol was developed using trehalose as the cryoprotectant, which resulted in almost no loss of viability during freeze-drying. Resuscitation medium, temperature, and time did not significantly influence recovery rates when this cryoprotectant was used. The effects of temperature (-80 to 45°C), water activity (0.02 to 0.92), and atmosphere (air, vacuum, and nitrogen) were evaluated for the stability of the freeze-dried powders during storage. Freeze-dried B. animalis ssp. lactis Bb-12 was found to survive under all conditions tested, with optimum survival at temperatures up to 21°C, water activities up to 0.44, and all 3 atmospheres tested. The intestinal-adapted strain B. longum DJO10A was much more sensitive to the different storage conditions, but could be adequately maintained using optimum conditions. These optimum storage conditions included frozen storage, replacement of oxygen with nitrogen, and water activities between 0.11 and 0.22. These results indicated that an optimized storage environment is required to maintain viability of stress-sensitive bifidobacteria strains, whereas stress-resilient bifidobacteria strains can maintain viability over a wide range of storage conditions, which is practical in countries where controlled cold storage conditions may not be readily available.

Ice nucleation by particles immersed in supercooled cloud droplets.

The formation of ice particles in the Earth's atmosphere strongly affects the properties of clouds and their impact on climate. Despite the importance of ice formation in determining the properties of clouds, the Intergovernmental Panel on Climate Change (IPCC, 2007) was unable to assess the impact of atmospheric ice formation in their most recent report because our basic knowledge is insufficient. Part of the problem is the paucity of quantitative information on the ability of various atmospheric aerosol species to initiate ice formation. Here we review and assess the existing quantitative knowledge of ice nucleation by particles immersed within supercooled water droplets. We introduce aerosol species which have been identified in the past as potentially important ice nuclei and address their ice-nucleating ability when immersed in a supercooled droplet. We focus on mineral dusts, biological species (pollen, bacteria, fungal spores and plankton), carbonaceous combustion products and volcanic ash. In order to make a quantitative comparison we first introduce several ways of describing ice nucleation and then summarise the existing information according to the time-independent (singular) approximation. Using this approximation in combination with typical atmospheric loadings, we estimate the importance of ice nucleation by different aerosol types. According to these estimates we find that ice nucleation below about -15 °C is dominated by soot and mineral dusts. Above this temperature the only materials known to nucleate ice are biological, with quantitative data for other materials absent from the literature. We conclude with a summary of the challenges our community faces.

Biomechanics of head injury in olympic taekwondo and boxing.

OBJECTIVE: The purpose was to examine differences between taekwondo kicks and boxing punches in resultant linear head acceleration (RLA), head injury criterion (HIC15), peak head velocity, and peak foot and fist velocities. Data from two existing publications on boxing punches and taekwondo kicks were compared. METHODS: For taekwondo head impacts a Hybrid II Crash Dummy (Hybrid II) head was instrumented with a tri-axial accelerometer mounted inside the Hybrid II head. The Hybrid II was fixed to a height-adjustable frame and fitted with a protective taekwondo helmet. For boxing testing, a Hybrid III Crash Dummy head was instrumented with an array of tri-axial accelerometers mounted at the head centre of gravity. RESULTS: Differences in RLA between the roundhouse kick (130.11±51.67 g) and hook punch (71.23±32.19 g, d = 1.39) and in HIC15 (clench axe kick: 162.63±104.10; uppercut: 24.10±12.54, d = 2.29) were observed. CONCLUSIONS: Taekwondo kicks demonstrated significantly larger magnitudes than boxing punches for both RLA and HIC.

Development and evaluation of a novel taekwondo chest protector to improve mobility when performing axe kicks.

The axe kick, in Olympic style taekwondo, has been identified as the most popular scoring technique aimed to the head during full contact competition. The first purpose of this study was to identify and investigate design issues with the current World Taekwondo Federation approved chest protector. A secondary purpose was to develop a novel chest protector addressing the identified design issues and to conduct a biomechanical analysis. Fifteen male elite Taekwondo players were selected to perform three different styles of the axe kick, i.e., front, in-out, and out-in axe kick five times each for a total of 45 kicks. Two-way repeated measures ANOVA showed significant differences between the novel and existing chest protector conditions for vertical height of the toe, downward kicking foot speed, hip flexion angle and ipsilateral shoulder flexion extension range of motion (ROM) (p < 0.05). There were no significant differences between the control condition (no chest protector) and the novel chest protector condition for these variables (p > 0.05). These results indicate that the novel chest protector interferes less with both the lower and upper limbs during the performance of the axe kick and provides a more natural, free-moving alternative to the current equipment used.

Daily opioid and stimulant co-use and nonfatal overdoses in the context of social disadvantage: Findings on marginalized populations.

OBJECTIVE: Opioids and stimulants are increasingly implicated in overdose deaths, particularly among minoritized groups. We examined daily opioid and cocaine co-use, nonfatal overdoses, and naloxone carrying among minoritized people who inject drugs (PWID). METHODS: The study derived data from 499 PWID in Baltimore City, MD, recruited using street-based outreach between 2016 and 2019. Participants reported overdoses; sociodemographic characteristics; and use of nonmedical prescription opioids, heroin, cocaine, and naloxone. RESULTS: Among the participants, the mean age was 46, 34 % were female, 64 % self-identified as Black, and 53 % experienced recent homelessness. Black PWID, compared to White PWID, were as likely to use opioids and cocaine daily but were 61 % less likely to have naloxone. After controlling for sociodemographic characteristics, women (aOR:1.88, 95%CI: 1.14, 3.11), persons experiencing homelessness (aOR:3.07, 95%CI: 1.79, 5.24), and those who experienced a recent overdose (aOR:2.14, 95%CI: 1.29, 3.58) were significantly more likely to use opioids and any form of cocaine every day. In a subanalysis of only female PWID, females engaged in sex work (aOR:2.27, 95%CI: 1.02, 5.07) and females experiencing recent homelessness (aOR:5.82, 95%CI: 2.50, 13.52) were significantly more likely to use opioids and cocaine daily. Furthermore, females (aOR:1.69, 95%CI:1.03, 2.77), persons experiencing homelessness (aOR:1.94, 95%CI:1.16, 3.24), and those with higher educational attainment (aOR:2.06, 95%CI:1.09, 3.91) were more likely to often/always carry naloxone, while Black PWID were less likely to have naloxone (aOR:0.39, 95%CI:0.22, 0.69). CONCLUSIONS: These findings highlight the need for targeted naloxone distribution and other harm-reduction interventions among minoritized groups in urban areas.

Distinguishing objective from subjective assessments of the severity of medication-related safety events among people with Parkinson's disease: a qualitative study.

WHAT IS KNOWN AND OBJECTIVE: Safety events indicating medication-related errors in Parkinson's disease (PD) are common but seldom studied, particularly from lay perspectives. Our objective was to study the meaning and significance to people living with PD of their experience of safety events. METHODS: Twenty qualitative interviews were conducted by telephone with purposively sampled individuals with PD, a proxy, or both, throughout New Zealand. Themes identified from the data included joint assessments of the objective and subjective severity of the individual safety events. RESULTS AND DISCUSSION: Most of the events indicated minor objective errors, whose severity was sometimes perceived as major, especially in the face of callous communication. WHAT IS NEW AND CONCLUSION: Variation between objective and subjective assessments of the severity of possible errors indicated by safety events highlight the importance of distinguishing between, and using, both forms of assessment.

Osteoporotic fracture admissions compared to other major medical admissions in Irish public hospitals.

Multinational reports suggest Ireland has one of the greatest illness burdens related to osteoporosis. Hospital care represents the costliest portion of health services. We found public hospital bed days for fragility fractures in Ireland increased by 43% between 2008 and 2017 which exceeded those for other common diseases. INTRODUCTION: Recent multinational reports suggest Ireland has one of the greatest illness burdens related to osteoporosis, manifesting clinically as fragility fractures (FF). International reports show that FF incidence, rate of hospital admission and cost are similar or greater than those for breast cancer, myocardial infarction and stroke. Studies addressing the illness burden of osteoporosis in Ireland are few, and none compares fragility fractures to other common chronic diseases. METHODS: A retrospective analysis of national administrative data for all public hospital admissions was performed on adults aged 50 years and older from January 2008 to December 2017. RESULTS: In 2017, public hospital bed days for FF totalled 249,887 outnumbering Chronic Obstructive Pulmonary Disease (COPD): 131,897; 6 solid cancers (CA): 118,098; myocardial infarction (MI): 83,477; and diabetes mellitus (DM): 31,044. Bed days for FF increased by 43% between 2008 and 2017, in contrast to a 32%, 28% and 31% reduction for CA, MI and DM, respectively, and a 12% increase for COPD. Public hospital bed days for FF in 2016 were greater than MI, stroke, atrial fibrillation and chest pain combined but less than a combination of COPD, pneumonia and lower respiratory tract infection. CONCLUSION: Osteoporotic fractures represent a large and rapidly increasing illness burden amongst older Irish adults, with substantial care requirements and the resulting onus on our healthcare system. Urgent action is needed to address this public health issue and the services for those at risk of fracture.

Association between proton pump inhibitors and spontaneous bacterial peritonitis in cirrhotic patients - a systematic review and meta-analysis.

Acid suppressive therapy, in the form of proton pump inhibitor (PPI), is widely used in cirrhotic patients, often in indications which are not clearly justified. PPI facilitates enteric bacterial colonisation, overgrowth and translocation, which might predispose to spontaneous bacterial peritonitis. However, observational studies evaluating the association of PPI and SBP in cirrhotic patients have yielded inconsistent results. We therefore conducted a meta-analysis of relevant clinical studies to determine the nature of this association. Observational studies assessing the association between SBP and PPI in cirrhosis, conducted in adult population and published in all languages, were identified through systematic search in the MEDLINE, EMBASE and manual reviews of all major gastroenterology meeting proceedings up to May 2010. The relevant studies were pooled using traditional meta-analytic techniques with a random-effects model. Four studies were identified and included in the meta-analysis. The pooled analysis, involving a total of 772 patients, found a significant association between the use of PPI and the development of SBP (OR 2.77, 95% CI 1.82-4.23). There was very little degree of heterogeneity as reflected by an I(2) value of 22% and the visual inspection of the funnel plot. There is a potential association between use of PPI and development of SBP. Therefore, PPIs should be used judiciously and only when clearly indicated in cirrhotics. Further studies are essential to clarify this relationship and elucidate the underlying mechanisms.