ResearchPad - nsaids https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Dialysis timing may be deferred toward very late initiation: An observational study]]> https://www.researchpad.co/article/elastic_article_14499 The optimal timing to initiate dialysis among patients with an estimated glomerular filtration rate (eGFR) of <5 mL/min/1.73 m2 is unknown. We hypothesized that dialysis initiation time can be deferred in this population even with high uremic burden. A case-crossover study with case (0–30 days before dialysis initiation [DI]) and control (90–120 days before DI) periods was conducted in 1,079 hemodialysis patients aged 18–90 years at China Medical University Hospital between 2006 and 2015. The uremic burden was quantified based on 7 uremic indicators that reached the predefined threshold in case period, namely hemoglobin, serum albumin, blood urea nitrogen, serum creatinine, potassium, phosphorus, and bicarbonate. Dialysis timing was classified as standard (met 0–2 uremic indicators), late (3–5 indicators), and very late (6–7 indicators). Median eGFR-DI of the 1,079 patients was 3.4 mL/min/1.73 m2 and was 2.7 mL/min/1.73 m2 in patients with very late initiation. The median follow-up duration was 2.42 years. Antibiotics, diuretics, antihypertensive medications, and non-steroidal anti-inflammatory drugs (NSAIDs) were more prevalently used during the case period. The fully adjusted hazards ratios of all-cause mortality for the late and very late groups were 0.97 (95% confidence interval 0.76–1.24) and 0.83 (0.61–1.15) compared with the standard group. It is safe to defer dialysis initiation among patients with chronic kidney disease (CKD) having an eGFR of <5 mL/min/1.73 m2 even when patients having multiple biochemical uremic burdens. Coordinated efforts in acute infection prevention, optimal fluid management, and prevention of accidental exposure to NSAIDs are crucial to prolong the dialysis-free survival.

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<![CDATA[Severe hyperbilirubinemia is associated with higher risk of contrast-related acute kidney injury following contrast-enhanced computed tomography]]> https://www.researchpad.co/article/N624c57d4-8983-4ece-aecc-e0e7860066cf

Introduction

Contrast-induced acute kidney injury (CI-AKI) is associated with high risks of morbidity and mortality. Hyperbilirubinemia might have some renal protection but with no clear cutoff value for protection. Related studies are typically on limited numbers of patients and only in conditions of vascular intervention.

Methods

We performed this study to elucidate CI-AKI in patients after contrast-enhanced computed tomography (CCT). The outcomes were CI-AKI, dialysis and mortality. Patients were divided to three groups based on their serum levels of total bilirubin: ≤1.2 mg/dl, 1.3–2.0 mg/dl, and >2.0 mg/dl.

Results

We enrolled a total of 9,496 patients who had received CCT. Patients with serum total bilirubin >2.0 mg/dl were associated with CI-AKI. Those undergoing dialysis had the highest incidence of PC-AKI (p<0.001). No difference was found between the two groups of total bilirubin ≤1.2 and 1.3–2.0 mg/dl. Patients with total bilirubin >2mg/dl were associated with CI-AKI (OR = 1.89, 1.53–2.33 of 95% CI), dialysis (OR = 1.40, 1.01–1.95 of 95% CI) and mortality (OR = 1.63, 1.38–1.93 of 95% CI) after adjusting for laboratory data and all comorbidities (i.e., cerebrovascular disease, coronary artery disease, peripheral arterial disease, and acute myocardial infarction, diabetes mellitus, hypertension, gastrointestinal bleeding, cirrhosis, peritonitis, ascites, hepatoma, shock lung and colon cancer). We concluded that total bilirubin level >2 mg/dl is an independent risk factor for CI-AKI, dialysis and mortality after CCT. These patients also had high risks for cirrhosis or hepatoma.

Conclusion

This is the first study providing evidence that hyperbilirubinemia (total bilirubin >2.0 mg/dl) being an independent risk factor for CI-AKI, dialysis and mortality after receiving CCT. Most patients with total bilirubin >2.0mg/dl had cirrhosis or hepatoma.

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<![CDATA[Low dose naltrexone: Effects on medication in rheumatoid and seropositive arthritis. A nationwide register-based controlled quasi-experimental before-after study]]> https://www.researchpad.co/article/5c6f14fad5eed0c48467abf4

In recent years, low dose naltrexone (LDN) has been used as an off-label therapy for several chronic diseases. Results from small laboratory and clinical studies indicate some beneficial effects of LDN in autoimmune diseases, but clinical research on LDN in rheumatic disease is limited. Using a pharmacoepidemiological approach, we wanted to test the hypothesis that starting LDN leads to reduced dispensing of medicines used in the treatment of rheumatic disease. We performed a controlled before-after study based on the Norwegian Prescription Database (NorPD) to compare prescriptions to patients one year before and one year after starting LDN in 2013. The identified patients (n = 360) were stratified into three groups based on LDN exposure. Outcomes were differences in dispensing of medicines used in rheumatic disease. In persistent LDN users, there was a 13% relative reduction in cumulative defined daily doses (DDD) of all medicines examined corresponding to -73.3 DDD per patient (95% CI -120,2 to -26.4, p = 0.003), and 23% reduction of analgesics (-21.6 DDD (95% CI -35.5 to -7.6, p<0.009)). There was no significant DDD change in patients with lower LDN exposure. Persistent LDN users had significantly reduced DDDs of NSAID and opioids, and a lower proportion of users of DMARDs (-6.7 percentage points, 95% CI -12.3 to-1.0, p = 0.028), TNF-α antagonists and opioids. There was a decrease in the number of NSAID users among patients with the least LDN exposure. Important limitations are that prescription data are proxies for clinical effects and that a control group unexposed to LDN is lacking. The results support the hypothesis that persistent use of LDN reduces the need for medication used in the treatment of rheumatic and seropositive arthritis. Randomised clinical trials on LDN in rheumatic disease are warranted.

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<![CDATA[Involvement of gliadin, a component of wheat gluten, in increased intestinal permeability leading to non-steroidal anti-inflammatory drug-induced small-intestinal damage]]> https://www.researchpad.co/article/5c76fe30d5eed0c484e5b699

Gliadin, a component of wheat gluten known to be an important factor in the etiology of celiac disease, is related to several other diseases through its enhancing effect on intestinal paracellular permeability. We investigated the significance of gliadin in non-steroidal anti-inflammatory drug (NSAID)-induced small-intestinal damage in mice. 7-week-old C57BL/6 male mice were divided into the following groups: standard diet group, in which mice were fed with wheat-containing standard rodent diet (CE-2); gluten-free diet group, in which mice were fed with gluten-free diet (AIN-76A); and gliadin-administered group, in which mice fed with gluten-free diet were administered with gliadin (~250 mg/kg BW). Each group was subdivided into negative, healthy control group and NSAID-treated group. To some mice fed with gluten-free diet and administered with gliadin, epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor was administered for clarification of the significance of EGFR in NSAID-induced small intestinal damage and intestinal permeability. In mice fed with a gluten-free diet, indomethacin or diclofenac induced very mild mucosal damage in the small intestine compared with that in mice fed with a wheat-containing standard diet. Gliadin exacerbated the NSAID-induced small-intestinal damage in mice fed with a gluten-free diet. With the administration of indomethacin, MPO activity, a marker of neutrophil infiltration into the mucosa and mRNA expression level of tumor necrosis factor α and interleukin-1β in the small intestine were higher in the gliadin-administered mice. Gliadin increased the intestinal paracellular permeability without indomethacin administration (4.3-fold) and further increased the permeability after indomethacin administration (2.1-fold). Gliadin induced phosphorylation of epidermal growth factor receptor (EGFR) in small-intestinal tissues, and erlotinib (an EGFR tyrosine kinase inhibitor) attenuated the indomethacin-induced intestinal damage and permeability exacerbated by gliadin, accompanied by inhibition of EGFR phosphorylation. These results suggest that gliadin plays an important role in the induction and exacerbation of NSAID-induced small-intestinal damage, and that increase in intestinal permeability via the EGFR signalling pathway is involved in its mechanism.

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<![CDATA[Patterns of multimorbidity and polypharmacy in young and adult population: Systematic associations among chronic diseases and drugs using factor analysis]]> https://www.researchpad.co/article/5c648d0cd5eed0c484c81e2d

Objectives

The objective was to identify the systematic associations among chronic diseases and drugs in the form of patterns and to describe and clinically interpret the constituted patterns with a focus on exploring the existence of potential drug-drug and drug-disease interactions and prescribing cascades.

Methods

This observational, cross-sectional study used the demographic and clinical information from electronic medical databases and the pharmacy billing records of all users of the public health system of the Spanish region of Aragon in 2015. An exploratory factor analysis was conducted based on the tetra-choric correlations among the diagnoses of chronic diseases and the dispensed drugs in 887,572 patients aged ≤65 years. The analysis was stratified by age and sex. To name the constituted patterns, assess their clinical nature, and identify potential interactions among diseases and drugs, the associations found in each pattern were independently reviewed by two pharmacists and two doctors and tested against the literature and the information reported in the technical medicinal forms.

Results

Six multimorbidity-polypharmacy patterns were found in this large-scale population study, named as respiratory, mental health, cardiometabolic, endocrinological, osteometabolic, and mechanical-pain. The nature of the patterns in terms of diseases and drugs differed by sex and age and became more complex as age advanced.

Conclusions

The six clinically sound multimorbidity-polypharmacy patterns described in this non-elderly population confirmed the existence of systematic associations among chronic diseases and medications, and revealed some unexpected associations suggesting the prescribing cascade phenomenon as a potential underlying factor. These findings may help to broaden the focus and orient the early identification of potential interactions when caring for multimorbid patients at high risk of adverse health outcomes due to polypharmacy.

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<![CDATA[Dietary supplementation of Scutellaria baicalensis extract during early lactation decreases milk somatic cells and increases whole lactation milk yield in dairy cattle]]> https://www.researchpad.co/article/5c5217abd5eed0c484794341

Systemic inflammation is common in early lactation dairy cows and is associated with decreased milk production. The Scutellaria baicalensis plant contains flavonoids with anti-inflammatory and anti-oxidative properties, which may counteract the inflammatory state in early lactation dairy cows. The objective of this experiment was to determine whether Scutellaria baicalensis extract (SBE), a source of bioactive flavonoids, would alter the adaptation to lactation. Multiparous Holstein cows (n = 122) were used in a randomized block design to determine the effect of short-term and long-term postpartum administration of SBE on 305-d milk yield, 120-d milk component yield, and early lactation milk markers of inflammation and metabolic function. Treatments were 1) control, 2) short term (5-d) administration of the SBE (SBE5), and 3) long term (60-d) administration of the SBE (SBE60). Treatments were included in a treatment pellet that was identical to a control pellet in ingredient source and composition except for the extract (10 g/d SBE providing 3.3 g/d of the flavonoid baicalin), both provided via an automated milking system beginning on d 1 of lactation. Milk samples were collected on d 1, 3, and once during d 5–12 of lactation, followed by weekly sampling until 120 days in milk (DIM). Milk samples collected in the first 2 wk were used for biomarker analysis (haptoglobin, β-hydroxybutyrate [BHB], and glucose-6-phosphate [G6P]), and all samples were used for composition analysis. Cows were body condition scored every 2 wk prepartum and postpartum. Milk production, programmed pellet allocation, and actual provision of both pelleted feeds were recorded daily. Treatment effects were evaluated by contrasts between control and SBE5 and control and SBE60 for both the treatment (TP; wk 1–9) and carryover periods (CP; wk 10–37). Total pellet offered was greater for SBE60 in both the TP (P < 0.01) and CP (P = 0.02) but was not different for SBE5 during either period (P ≥ 0.13). No treatment effects were observed for body condition score (BCS), milk haptoglobin, BHB, or G6P. SBE5 did not alter milk yield or milk components. SBE60 increased whole-lactation milk yield by 1,419 kg (13%; P = 0.03). SBE60 increased milk lactose and fat yields (P ≤ 0.04) and tended to increase milk protein yield (P = 0.09) during TP, and each increased during CP (P ≤ 0.04). Somatic cell count decreased by 10% in SBE60 during TP (P = 0.02) but not CP (P = 0.13). Mastitis incidence tended to differ by treatment, being lesser for both SBE5 and SBE60 vs. control (14 and 15% vs. 33%). SBE supplementation did not impact time to pregnancy or hazard of leaving the herd. In conclusion, despite no detected treatment effects on BCS or milk biomarkers of inflammation and metabolic status, supplementation of postpartum dairy cows with Scutellaria baicalensis extract for 60 d was effective at increasing whole lactation milk yield.

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<![CDATA[Prevalence and treatment of gout among patients with chronic kidney disease in the Irish health system: A national study]]> https://www.researchpad.co/article/5c644870d5eed0c484c2e6d4

Background

Gout is a common inflammatory arthritis associated with adverse clinical outcomes. Under treatment is common in the general population. The aim of this study was to determine the prevalence of gout and its treatment among patients with chronic kidney disease (CKD).

Methods

We conducted a multi-centre cross sectional study of patients (n = 522) who attended specialist nephrology clinics in Ireland. Standardized data collection tool recorded clinical characteristics and medication use at clinic visits and kidney function was assessed with standardised creatinine measurements and Estimated Glomerular Filtration Rate (eGFR). The prevalence of gout and the corresponding use of urate lowering therapies (ULT) were determined. Multivariate logistic regression explored correlates of gout expressed as Odds Ratios (OR) and 95% Confidence Intervals (CI) adjusting for demographic and clinical characteristics.

Results

Overall prevalence of gout was 16.6% and increased significantly from 7.5% in Stage 1–2 CKD to 22.8% in stage 4–5 CKD, P< 0.005. Prevalence increased with age (P < 0.005) and was higher in men than women (19.1% versus 10.3% P< 0.005). Overall, 67.9% of gout patients with CKD were treated with ULT, and the percentage increased with advancing stage of CKD from 55.6% in Stage 1–2 to 77.4% in Stage 4–5, P<0.005. Multivariable modelling identified men (vs women), OR, 1.95 (0.95–4.03), serum albumin, OR 1.09 (1.02–1.16) per 1 g/L lower, poorer kidney function, OR 1.11 (1.01–1.22) per 5 ml/min/1.73m2 lower, and rising parathyroid hormone levels, OR 1.38 (1.08–1.77) per 50 pg/ml higher as disease correlates.

Conclusions

Gout is common in CKD and increases with worsening kidney function in the Irish health system. Over two thirds of patients with gout were receiving ULT, increasing to 77% of patients with advanced CKD. Greater awareness of gout in CKD, its treatment and the effectiveness of treatment strategies should be vigorously monitored to improve patient outcomes.

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<![CDATA[A test of positive suggestions about side effects as a way of enhancing the analgesic response to NSAIDs]]> https://www.researchpad.co/article/5c37b79dd5eed0c48449066e

Side effects are frequent in pharmacological pain management, potentially preceding analgesia and limiting drug tolerability. Discussing side effects is part of informed consent, yet can favor nocebo effects. This study aimed to test whether a positive suggestion regarding side effects, which could act as reminders of the medication having been absorbed, might favor analgesia in a clinical interaction model. Sixty-six healthy males participated in a study “to validate pupillometry as an objective measure of analgesia”. Participants were unknowingly randomized double-blind to positive vs control information about side effects embedded in a video regarding the study drugs. Sequences of moderately painful heat stimuli applied before and after treatment with diclofenac and atropine served to evaluate analgesia. Atropine was deceptively presented as a co-analgesic, but used to induce side effects. Adverse events (AE) were collected with the General Assessment of Side Effects (GASE) questionnaire prior to the second induced pain sequence. Debriefing fully informed participants regarding the purpose of the study and showed them the two videos.The combination of medication led to significant analgesia, without a between-group difference. Positive information about side effects increased the attribution of AE to the treatment compared to the control information. The total GASE score was correlated with analgesia, i.e., the more AEs reported, the stronger the analgesia. Interestingly, there was a significant between-groups difference on this correlation: the GASE score and analgesia correlated only in the positive information group. This provides evidence for a selective link between AEs and pain relief in the group who received the suggestion that AEs could be taken as a sign “that help was on the way”. During debriefing, 65% of participants said they would prefer to receive the positive message in a clinical context. Although the present results cannot be translated immediately to clinical pain conditions, they do indicate the importance of testing this type of modulation in a clinical context.

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<![CDATA[Development and evaluation of user-tested Thai patient information leaflets for non-steroidal anti-inflammatory drugs: Effect on patients’ knowledge]]> https://www.researchpad.co/article/5c3fa57bd5eed0c484ca4def

Introduction

Thai patients do not routinely receive patient information leaflets (PILs) with medicines, so awareness of safety issues is low. This study aimed: i) to develop Thai PILs for NSAIDs and subject these to user-testing, and ii) to assess the potential value of PILs from the patient perspective and effect on patient knowledge.

Methods

Four PILs for NSAIDs were developed and subjected to multiple rounds of user-testing by the general public. Self-administered questionnaires were distributed to orthopaedic out-patients prescribed one of these NSAIDs, assessing knowledge before and after providing a PIL. The follow-up questionnaire also sought use of and views on the PILs using a visual analogue scale (VAS).

Results

1,240 baseline questionnaires were completed; only 13.5% of patients had good knowledge. 688 patients returned follow-up questionnaires (55.5%), of whom75% had good knowledge. In patients completing both questionnaires, mean knowledge score increased from 6.22±1.40 to 8.42±1.41 (p<0.001). Patients with high educational levels had high baseline scores (OR = 2.728) and showed greatest improvement in knowledge (OR = 5.628). 90% (625) of follow-up respondents indicated they read all information in the PILs. All also agreed that these PILs should distributed to all patients taking NSAIDs. The median VAS score for usefulness was 9.3 (IQR 8.6–10.0).

Conclusions

User-testing of PILs was feasible in a Thai population and enabled the development of acceptable and desirable PILs. PILs could improve patients' knowledge about their medicine, particularly among those with higher educational level. User-tested PILS could meet the need for more written medicine information.

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<![CDATA[Thiazide-associated hyponatremia attenuates the fracture-protective effect of thiazide: A population-based study]]> https://www.researchpad.co/article/5c141eecd5eed0c484d28d87

Background

Thiazide, a first-line therapy for hypertension, lowers blood pressure, increases bone mineral density, and reduces the risk of fractures. However, hyponatremia, an adverse effect of thiazide, is associated with increased risk of osteoporosis and fractures. It is currently unclear whether thiazide-associated hyponatremia (TAH) outweighs the protective effects of thiazide.

Methods

Using data from Taiwan’s National Health Insurance Research Database, we identified patients who were prescribed thiazide between 1998 and 2010. Those diagnosed with hyponatremia within three years after initiation of thiazide were selected for the TAH group. Thiazide users without hyponatremia were selected for the control group. The association between TAH and fracture risk was further evaluated using multivariable Cox regression models adjusted for comorbidities and medications. Subjects were followed up from the index date until the appearance of a fracture, death, or the end of a 3-year period.

Results

A total of 1212 patients were included in the TAH group, matched with 4848 patients in the control group. The incidence rate of fracture was higher in the TAH group than in the control group (31.4 versus 20.6 per 1000 person-years). TAH was associated with a higher risk of total fractures (adjusted hazard ratio [aHR]: 1.47, 95% confidence interval [CI] = 1.15–1.88), vertebra fractures (aHR: 1.84, 95% CI = 1.12–3.01), and hip fractures (aHR: 1.66, 95% CI = 1.12–2.46) after controlling for comorbidities and other medications.

Conclusions

Thiazide users with hyponatremia have a higher risk of fracture than thiazide users without hyponatremia. The fracture-protective effect of thiazide is attenuated by TAH.

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<![CDATA[Use of statins or NSAIDs and survival of patients with high-grade glioma]]> https://www.researchpad.co/article/5c0ed763d5eed0c484f14054

Background

High-grade glioma (HGG) is associated with a limited prognosis. Drug repurposing has become of increasing interest to improve standard therapy. Statins and NSAIDs inhibit glioma cell growth in vitro and in vivo, but data on statin and NSAID treatment in relation to survival of patients with HGG are sparse.

Methods

We performed multivariable adjusted Cox-regression analyses among 1,093 patients with HGG from a regional cancer registry to obtain Hazard Ratios (HRs) with 95% Confidence Intervals (CIs) for overall survival (OS) and progression-free survival (PFS) according to treatment with statins or NSAIDs. Data on dose and duration of treatment was mostly lacking in our analysis, therefore we were not able to perform dose-response analyses.

Results

Use of statins was unrelated to OS or PFS of glioma patients. Use of aspirin was associated with prolonged OS and PFS in patients with WHO grade III, but not WHO grade IV glioma. Use of other NSAIDs (diclofenac, ibuprofen) or non-NSAID analgesics (paracetamol) was mostly unrelated to survival of glioma patients. Use of selective COX-2 inhibitors and metamizol was related to inferior patient survival in parts of the analyses.

Conclusions

Use of statins or NSAIDS, including aspirin, was not associated with prolonged OS or PFS of patients with WHO grade IV glioma in our selected cohort. There was an indication for improved survival in patients with WHO grade III glioma using aspirin, but further studies are needed to confirm our first observation.

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<![CDATA[A cross-sectional study of national outpatient gastric acid suppressant prescribing in the United States between 2009 and 2015]]> https://www.researchpad.co/article/5c0ae47bd5eed0c484589cbc

Purpose

Gastric acid suppressants are commonly used in the United States, and while generally well-tolerated, long-term use has been associated with infection, bone fractures, and nutrient malabsorption. The purpose of this study was to describe national trends in gastric acid suppressant use over a 7-year period.

Methods

This was a cross-sectional study using data from the National Ambulatory Medical Care Survey from 2009 to 2015. Gastric acid suppressant use was defined as any outpatient visit with a documented prescription for a proton pump inhibitor or histamine-2 receptor antagonist documented during the outpatient visit. Sample data weights were used to extrapolate to national estimates. Use was calculated as the number of prescriptions per total outpatient visits per year. Appropriateness of prescribing was assessed using FDA-approved indications listed in each visit.

Results

These data represent 6.8 billion patient outpatient visits between 2009 and 2015, of which nearly 600 million (8.8%) had documented gastric acid suppressant use. The median (IQR) age of gastric acid suppressant users and non-gastric acid suppressant users was 62 (50–73) and 49 (25–65), respectively. Gastric acid suppressant use decreased from 9.0% in 2009 to 7.7% in 2012, and then increased to 9.7% in 2015. Proton pump inhibitor use was slightly higher in the Midwest (8.3%). Only 15.8% of gastric acid suppressant users had a documented indication.

Conclusions

Proton pump inhibitor use increased after 2012, and the majority of gastric acid suppressant users did not have a documented indication. Judicious gastric acid suppressant prescribing needs to be exercised, especially in the context of new safety data regarding long-term proton pump inhibitor use.

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<![CDATA[Association between fibromyalgia syndrome and peptic ulcer disease development]]> https://www.researchpad.co/article/5989db50ab0ee8fa60bdc1ab

Purpose

The correlation of fibromyalgia syndrome (FMS) with peptic ulcer disease (PUD) is unclear. We therefore conducted a cohort study to investigate whether FMS is correlated with an increased risk of PUD.

Methods

In this study, we established an FMS cohort comprising 26068 patients aged more than 20 years who were diagnosed with FMS from 2000 to 2011. Furthermore, we established a control cohort by randomly choosing 104269 people without FMS who were matched to the FMS patients by gender, age, and index year. All patients were free of PUD at the baseline. Cox proportional hazard regressions were performed to compute the hazard ratio of PUD after adjustment for demographic characteristics and comorbidities.

Results

The prevalence of comorbidities was significantly higher in the FMS patients than in the controls. The incidence of PUD was 29.8 and 19.4 per 1000 person-years in the FMS and control cohorts, respectively. In addition, the FMS cohort exhibited a 1.40-fold higher risk of PUD (95% confidence interval = 1.35–1.45) compared with the control cohort. After control for confounding factors, the medications (selective serotonin reuptake inhibitors, serotonin–norepinephrine reuptake inhibitors, and antidepressants) taken by the FMS patients did not increase the risk of PUD.

Conclusion

FMS patients exhibit a higher risk of PUD than that of patients without FMS.

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<![CDATA[Acute Kidney Injury Treated with Dialysis outside the Intensive Care Unit: A Retrospective Observational Single-Center Study]]> https://www.researchpad.co/article/5989db2dab0ee8fa60bd1a7a

Introduction

The number of patients suffering from acute kidney injury requiring dialysis (AKI-D) is increasing. Whereas causes and outcome of AKI-D in the intensive care unit (ICU) are described extensively, few data exist about AKI-D patients treated outside the ICU. Aim of this study was to identify the causes of AKI-D, determine in-depth the comorbid conditions and outcome of this particular patient group and identify possibilities for its prevention.

Methods

We retrospectively studied all AKI-D patients treated outside the ICU in a single nephrology referral center between January 2010 and June 2015. Data on comorbid conditions, renal function and drug therapy prior to AKI-D, and possible causal events were collected. Patients were grouped into those with renal hypoperfusion as the predominant cause of AKI-D (hemodynamic group) and those with other causes (non-hemodynamic group).

Results

During 66 months 128 patients (57% male, mean age 69.3 years) were treated. AKI-D was community-acquired in 70.3%. The most frequent comorbidities were hypertension (62.5%), chronic kidney disease (CKD) (58.9%), coronary artery disease (CAD) (46.1%), diabetes (35.9%) and heart failure (34.1%). Most patients were prescribed diuretics (61.7%) and inhibitors of the renin-angiotensin-aldosterone system (RASI) (57.8%); 46.1% had a combination of both. In the 88 patients with hemodynamic AKI-D (68.8%) the most frequent initiating events were diarrhea (39.8%), infections (17.0%) and acute heart failure (13.6%). In the 40 patients with non-hemodynamic AKI-D (31.2%) interstitial nephritis (n = 15) was the prominent diagnosis. Patients with hemodynamic AKI-D were older (72.6 vs. 62.1 years, p = 0.001), suffered more often from CKD (68.2% vs. 33.3%, p = 0.003), CAD (54.5% vs. 27.5%, p = 0.004) and diabetes (42.0% vs. 22.5%, p = 0.033), and were more frequently on diuretics (75.0% vs. 32.5%, p<0.001), RASI (67.0% vs. 37.5%, p = 0.002) or their combination (58.0% vs. 20.0%, p<0.001). Twenty-two (17.2%) patients died and 27 (21.1%) patients died or developed end-stage renal disease.

Conclusion

AKI-D treated outside the ICU is most often caused by renal hypoperfusion. It predominantly afflicts elderly patients with one or more comorbid conditions, who are treated with diuretics and RASI and have an acute illness leading to volume depletion. Early discontinuation of these drugs may be a successful strategy to avoid AKI-D in vulnerable patients.

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<![CDATA[Identification of small molecules that disrupt vacuolar function in the pathogen Candida albicans]]> https://www.researchpad.co/article/5989db51ab0ee8fa60bdc421

The fungal vacuole is a large acidified organelle that performs a variety of cellular functions. At least a sub-set of these functions are crucial for pathogenic species of fungi, such as Candida albicans, to survive within and invade mammalian tissue as mutants with severe defects in vacuolar biogenesis are avirulent. We therefore sought to identify chemical probes that disrupt the normal function and/or integrity of the fungal vacuole to provide tools for the functional analysis of this organelle as well as potential experimental therapeutics. A convenient indicator of vacuolar integrity based upon the intracellular accumulation of an endogenously produced pigment was adapted to identify Vacuole Disrupting chemical Agents (VDAs). Several chemical libraries were screened and a set of 29 compounds demonstrated to reproducibly cause loss of pigmentation, including 9 azole antifungals, a statin and 3 NSAIDs. Quantitative analysis of vacuolar morphology revealed that (excluding the azoles) a sub-set of 14 VDAs significantly alter vacuolar number, size and/or shape. Many C. albicans mutants with impaired vacuolar function are deficient in the formation of hyphal elements, a process essential for its pathogenicity. Accordingly, all 14 VDAs negatively impact C. albicans hyphal morphogenesis. Fungal selectivity was observed for approximately half of the VDA compounds identified, since they did not alter the morphology of the equivalent mammalian organelle, the lysosome. Collectively, these compounds comprise of a new collection of chemical probes that directly or indirectly perturb normal vacuolar function in C. albicans.

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<![CDATA[Cyclic Dipeptide Shuttles as a Novel Skin Penetration Enhancement Approach: Preliminary Evaluation with Diclofenac]]> https://www.researchpad.co/article/5989db1fab0ee8fa60bcee63

This study demonstrates the effectiveness of a peptide shuttle in delivering diclofenac into and through human epidermis. Diclofenac was conjugated to a novel phenylalanyl-N-methyl-naphthalenylalanine-derived diketopiperazine (DKP) shuttle and to TAT (a classical cell penetrating peptide), and topically applied to human epidermis in vitro. DKP and TAT effectively permeated into and through human epidermis. When conjugated to diclofenac, both DKP and TAT enhanced delivery into and through human epidermis, though DKP was significantly more effective. Penetration of diclofenac through human epidermis (to receptor) was increased by conjugation to the peptide shuttle and cell penetrating peptide with enhancement of 6x by DKP-diclofenac and 3x by TAT-diclofenac. In addition, the amount of diclofenac retained within the epidermis was significantly increased by peptide conjugation. COX-2 inhibition activity of diclofenac was retained when conjugated to DKP. Our study suggests that the peptide shuttle approach may offer a new strategy for targeted delivery of small therapeutic and diagnostic molecules to the skin.

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<![CDATA[Safety and efficacy of cell-free and concentrated ascites reinfusion therapy (CART) in refractory ascites: Post-marketing surveillance results]]> https://www.researchpad.co/article/5989db5cab0ee8fa60bdfddb

We performed post-marketing surveillance to evaluate the safety and efficacy of cell-free and concentrated ascites reinfusion therapy (CART). In total, 356 CART sessions in 147 patients at 22 centers were performed. The most common primary disease was cancer (128 cases, 300 sessions). Mean amount of ascites collected was 3.7 L, and mean concentration ratio was 9.2. Mean amount of reinfused protein was 67.8 g (recovery rate, 72.0%). Performance status, dietary intake, urine volume, body weight and abdominal circumference were significantly improved after CART. Body temperature increased significantly, by 0.3°C on average. Concomitant steroids and/or NSAIDs use before reinfusion was significantly and negatively associated with increases in body temperature. Most adverse events were fever and chills. This study examined a large number of patients compared with previous studies, and showed that CART is an effective and relatively safe treatment for refractory ascites, such as malignant ascites.

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<![CDATA[Whole-Body Diffusion-Weighted Imaging in Chronic Recurrent Multifocal Osteomyelitis in Children]]> https://www.researchpad.co/article/5989da16ab0ee8fa60b7b57f

Objective

Chronic recurrent multifocal osteomyelitis/ chronic non-bacterial osteomyelitis (CRMO/ CNO) is a rare auto-inflammatory disease and typically manifests in terms of musculoskeletal pain. Because of a high frequency of musculoskeletal disorders in children/ adolescents, it can be quite challenging to distinguish CRMO/ CNO from nonspecific musculosketetal pain or from malignancies. The purpose of this study was to evaluate the visibility of CRMO lesions in a whole-body diffusion-weighted imaging (WB-DWI) technique and its potential clinical value to better characterize MR-visible lesions.

Material and Methods

Whole-body imaging at 3T was performed in 16 patients (average: 13 years) with confirmed CRMO. The protocol included 2D Short Tau Inversion Recovery (STIR) imaging in coronal and axial orientation as well as diffusion-weighted imaging in axial orientation. Visibility of lesions in DWI and STIR was evaluated by two readers in consensus. The apparent diffusion coefficient (ADC) was measured for every lesion and corresponding reference locations.

Results

A total of 33 lesions (on average 2 per patient) visible in STIR and DWI images (b = 800 s/mm2 and ADC maps) were included, predominantly located in the long bones. With a mean value of 1283 mm2/s in lesions, the ADC was significantly higher than in corresponding reference regions (782 mm2/s). By calculating the ratio (lesion to reference), 82% of all lesions showed a relative signal increase of 10% or higher and 76% (25 lesions) showed a signal increase of more than 15%. The median relative signal increase was 69%.

Conclusion

This study shows that WB-DWI can be reliably performed in children at 3T and predominantly, the ADC values were substantially elevated in CRMO lesions. WB-DWI in conjunction with clinical data is seen as a promising technique to distinguish benign inflammatory processes (in terms of increased ADC values) from particular malignancies.

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<![CDATA[Intervention to Improve Appropriate Prescribing and Reduce Polypharmacy in Elderly Patients Admitted to an Internal Medicine Unit]]> https://www.researchpad.co/article/5989db03ab0ee8fa60bc7499

Background

Polypharmacy and inappropriate medication prescriptions are associated with increased morbidity and mortality. Most interventions proposed to improve appropriate prescribing are time and resource intensive and therefore hardly applicable in daily clinical practice.

Objective

To test the efficacy of an easy-to-use checklist aimed at supporting the therapeutic reasoning of physicians in order to reduce inappropriate prescribing and polypharmacy.

Methods

We assessed the efficacy and safety of a 5-point checklist to be used by all physicians on the internal medicine wards of a Swiss hospital by comparing outcomes in 450 consecutive patients aged ≥65 years hospitalized after the introduction of the checklist, and in 450 consecutive patients ≥65 years hospitalized before the introduction of the checklist. The main measures were the proportion of patients with prescription of potentially inappropriate medications (PIMs) at discharge, according to STOPP criteria, and the number of prescribed medications at discharge, before and after the introduction of the checklist. Secondary outcomes were the prevalence of polypharmacy (≥ 5 drugs) and hyperpolypharmacy (≥ 10 drugs), and the prevalence of potentially inappropriate prescribing omissions (PPOs) according to START criteria.

Results

At admission 59% of the 900 patients were taking > 5 drugs, 13% ≥ 10 drugs, 37% had ≥ 1 PIM and 25% ≥ 1 PPO. The introduction of the checklist was associated with a significant reduction by 22% of the risk of being prescribed ≥ 1 PIM at discharge (adjusted risk ratios [RR] 0.78; 95% CI: 0.68–0.94), but not with a reduction of at least 20% of the number of drugs prescribed at discharge, nor with a reduction of the risk of PPOs at discharge.

Conclusions

The introduction of an easy-to-use 5-point checklist aimed at supporting therapeutic reasoning of physicians on internal medicine wards significantly reduced the risk of prescriptions of inappropriate medications at discharge.

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<![CDATA[Initial systemic inflammatory state perturbs exercise training adaptations in elite Taekwondo athletes]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc897

Purpose

This study examined ten-week TKD-specific training effects on aerobic capacity, body composition, hormone responses and hematological parameters in elite TKD athletes with varied initial inflammatory states.

Methods

Twenty-two elite college TKD athletes were divided into two groups according to their initial neutrophils-to-lymphocytes ratio (NLR) values: Low NLR (N = 11, 9M/2F, age: 21.6 ± 1.0 yrs; NLR: 1.3 ± 0.2) and High NLR (N = 11, 8M/3F, age: 22.0 ± 0.7 yrs, NLR: 2.5 ± 1.3), and participated in a 10-week TKD-specific training program. Aerobic capacity, body composition, hormonal responses and hematological parameters were measured at baseline and 10-weeks after TKD training.

Results

VO2max and shuttle run distance were significantly increased in both groups after training. However, the degree of improvement was greater in the Low NLR group than in the High NLR group. After 10-weeks of exercise training, the High NLR group presented markedly higher fat mass percentage and visceral fat area and significantly lowers DHEA-S to cortisol ratio (D/C ratio) than the Low NRL group. The post-training NLR was negatively correlated with the D/C ratio. Neutrophil counts and NLR were still significantly higher in the High NLR group after training.

Conclusions

This study provides new evidence that young elite TKD athletes with slightly high baseline systemic inflammatory state appear to perturb adaptations to exercise training.

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