ABSTRACT
Idiopathic pulmonary fibrosis (IPF) is a chronic lung disease that leads to respiratory decline due to scarring and thickening of lung tissues. Multiple pathways contribute to the fibrotic process in this disease, such as inflammation, epithelial to mesenchymal transition and oxidative stress. The RhoA/ROCK signaling pathway is a key regulator of profibrotic signaling, as it affects the organization of actin-myosin and the remodeling of the extracellular matrix. ROCK1/2, a downstream effector of RhoA, is overexpressed in IPF patients and is a promising target for IPF therapy. However, due to hypotensive side effects of ROCK1/2 inhibitors, selective ROCK2 compounds are being explored. In this study, we report the discovery of GNS-3595, a potent and selective ROCK2 inhibitor that has ~80-fold selectivity over ROCK1 at physiological concentrations of ATP. GNS-3595 effectively inhibited ROCK2-mediated phosphorylation of myosin light chain (p-MLC) and reduced the expression of fibrosis-related proteins, such as collagen, fibronectin, and alpha-smooth muscle actin (α-SMA) in various in vitro cellular models. GNS-3595 also prevented transforming growth factor beta (TGF-ß)-induced fibroblast-to-myofibroblast transition (FMT). Additionally, in a bleomycin-induced mouse model of pulmonary fibrosis, therapeutic exposure to GNS-3595, suppressed lung fibrosis, stabilized body weight loss, and prevented fibrosis-induced lung weight gain. Transcriptome and protein expression analysis from lung tissues showed that GNS-3595 can revert the fibrosis-related gene expression induced by bleomycin. These results indicate that GNS-3595 is a highly potent, selective, and orally active ROCK2 inhibitor with promising therapeutic efficacy against pulmonary fibrosis.
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OBJECTIVE: To describe adherence to daily somatropin treatment and impact on height velocity within 1 year of treatment start among patients with pediatric growth hormone deficiency in a real-world US population. METHODS: This retrospective cohort study included pediatric patients aged ≥3 years to <16 years with pediatric growth hormone deficiency prescribed somatropin by a pediatric endocrinologist at a US-based center of excellence between January 1, 2015 and December 31, 2020. Patient data were collected using hospital electronic health records linked to a specialty pharmacy patient prescription records. Adherence, evaluated over 12 months, was measured using the proportion of days covered metric and patients were categorized as adherent if their proportion of days covered ≥80%. Height velocity was annualized to compare across adherent and nonadherent patients. RESULTS: One hundred eighty-one patients were identified and included in this study, of which 70.2% were male,73.5% were white, and mean age (standard deviation [SD]) at index was 12.1 (2.8). In the height velocity analysis, 174 patients were included and the mean (SD) annualized change in height was 10.2 (5.7) cm/y in the adherent group (n = 108) and 9.8 (7.6) in the nonadherent group (n = 66). The difference in height velocity between the groups was not statistically significant. CONCLUSIONS: Minor improvements in average height velocity were observed in the patient group who were adherent to somatropin therapy, although not statistically significant. Lack of observed significance may be due to small sample sizes, short observation period, a likely heterogenous population in terms of growth hormone prescribing, data bias due to single-center origin, or potential patient misclassification.
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Withanolides are steroidal lactones with diverse bioactive potential and their production from plant sources varies with genotype, age, culture conditions, and geographical region. Endophytic fungi serve as an alternative source to produce withanolides, like their host plant, Withania somnifera (L.) Dunal. The present study aimed to isolate endophytic fungi capable of producing withanolides, characterization and investigation of biological activities of these molecules. The methanolic fungal crude extract of one of the fungal isolates WSE16 showed maximum withanolide production (219 mg/L). The fungal isolate WSE16 was identified as Penicillium oxalicum based on its morphological and internal transcribed spacer (ITS) sequence analysis and submitted in NCBI (accession number OR888725). The methanolic crude extract of P. oxalicum was further purified by column chromatography, and collected fractions were assessed for the presence of withanolides. Fractions F3 and F4 showed a higher content of withanolides (51.8 and 59.1 mg/L, respectively) than other fractions. Fractions F3 and F4 exhibited antibacterial activity against Staphylococcus aureus with an IC50 of 23.52 and 17.39 µg/ml, respectively. These fractions also showed antioxidant activity (DPPH assay with IC50 of 39.42 and 38.71 µg/ml, superoxide anion scavenging assay with IC50 of 41.10 and 38.84 µg/ml, and reducing power assay with IC50 of 42.61 and 41.40 µg/ml, respectively) and acetylcholinesterase inhibitory activity (IC50 of 30.34 and 22.05 µg/ml, respectively). The withanolides present in fraction 3 and fraction 4 were identified as (20S, 22R)-1a-Acetoxy-27-hydroxywitha-5, 24-dienolide-3b-(O-b-D-glucopyranoside) and withanamide A, respectively, using UV, FTIR, HRMS, and NMR analysis. These results suggest that P. oxalicum, an endophytic fungus isolated from W. somnifera, is a potential source for producing bioactive withanolides.
Subject(s)
Endophytes , Penicillium , Withania , Withanolides , Withania/microbiology , Withania/chemistry , Withanolides/metabolism , Withanolides/isolation & purification , Withanolides/pharmacology , Penicillium/metabolism , Penicillium/genetics , Endophytes/metabolism , Endophytes/isolation & purification , Endophytes/genetics , Endophytes/classification , Antioxidants/pharmacology , Antioxidants/metabolism , Antioxidants/isolation & purification , Antioxidants/chemistry , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/biosynthesis , Anti-Bacterial Agents/isolation & purification , Phylogeny , Cholinesterase Inhibitors/pharmacology , Cholinesterase Inhibitors/isolation & purification , Microbial Sensitivity TestsABSTRACT
The purpose of the study is to explore the antecedents of minimalism and, further, to study the impact of minimalism on millennials' well-being via a sense of fulfilment. To understand the origins of minimalism and its following effects on well-being, a theoretical framework is created. An online survey with a structured questionnaire was created to collect the necessary data from respondents. SMART PLS was used to analyse the suggested framework. This research establishes the mediating role of a sense of fulfilment in the interactions between minimalism and well-being and shows how environmental awareness, contemporary aesthetics, voluntary simplicity, normative influence, and resource sharing positively lead to minimalism. A minimalist lifestyle will help to preserve precious resources, reduce waste, and lower carbon emissions, all of which will have a significant positive influence on the environment. Additionally, clearing up clutter will give them more room and time, which will improve their well-being because they will have more time for their family and interests. The study suggests a thorough model to comprehend the origins of minimalism. Additionally, it established a connection between well-being and minimalism.
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OBJECTIVE: The aim of the TOP-PRO-study, a double-blind randomized controlled trial, was to assess the efficacy (non-inferiority) and tolerability of propranolol compared to topiramate for the prevention of chronic migraine. BACKGROUND: Except for topiramate, oral preventive treatment for chronic migraine lacks credible evidence. METHODS: Chronic migraine patients aged above 18 years and less than 65 years of age, not on any preventive treatment were randomly allocated to receive topiramate (100 mg/day) or propranolol (160 mg/day). The primary efficacy outcome was the mean change in migraine days per 28 days at the end of 24 weeks from baseline. A mean difference of 1.5 days per four weeks was chosen as the cut-off delta value. Multiple secondary efficacy outcomes and treatment emergent adverse events were also assessed. RESULTS: As against the planned sample size of 244, only 175 patients could be enrolled before the spread of the corona virus disease-2019 pandemic and enforcement of lockdown in India. Of the 175 randomized patients, 95 (topiramate 46 and propranolol 49) completed the trial. The mean change in migraine days was -5.3 ± 1.2 vs -7.3 ± 1.1 days (p = 0.226) for topiramate and propranolol groups respectively. Propranolol was found to be non-inferior and not superior to topiramate (point estimate of -1.99 with a 95% confidence interval of -5.23 to 1.25 days). Multiple secondary outcomes also did not differ between the two groups. Intention to treat analysis of 175 patients and per-protocol analysis of 95 patients yielded concordant results. There was no significant difference in the incidence of adverse events between the two groups. CONCLUSION: Propranolol (160mg/day) was non-inferior, non-superior to topiramate (100mg/day) for the preventive treatment of chronic migraine and had a comparable tolerability profile.Trial Registration: Clinical Trials Registry-India CTRI/2019/05/018997).
Subject(s)
COVID-19 , Migraine Disorders , Aged , Communicable Disease Control , Double-Blind Method , Fructose/therapeutic use , Humans , Migraine Disorders/drug therapy , Propranolol/therapeutic use , Topiramate/therapeutic use , Treatment OutcomeABSTRACT
Magnetism induced by defects in nominally non-magnetic solids has attracted intense scientific interest in recent years. The local magnetism in highly disordered undoped and Co-doped topological insulator (TI) Bi2Se3nanoplates has been investigated by muon spin relaxation (µSR). UsingµSR spectroscopy, together with other macroscopic characterizations, we find that these nanoplates are composed of a core with both static fields and dynamically fluctuating moments, and a shell with purely dynamically fluctuating moments. The fluctuations in the core die out at low temperatures, while those in the shell continue till 2 K. When Bi2Se3is doped with Co, the static magnetic component increases, whilst keeping the dual (static-plus-dynamic) nature intact. The findings indicate that highly disordered TI's could constitute a new class of promising magnetic materials that can be engineered by magnetic impurity doping.
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OBJECTIVE: Recombinant human growth hormone (somatropin) is recommended for children with growth hormone deficiency (GHD) to normalize adult height. Prior research has indicated an association between adherence to somatropin and height velocity. Further research is needed using real-world data to quantify this relationship; hence the objective of this study was to investigate the association between adherence to somatropin and change in height among children with GHD. METHODS: This retrospective cohort study included patients in the IQVIA PharMetrics Plus and Ambulatory Electronic Medical Records databases aged 3 to 15 years, with ≥1 GHD diagnosis code claim and newly initiated on somatropin between January 1, 2007 and November 30, 2019. Adherence was measured over the follow-up using the medication possession ratio (MPR); patients were classified as adherent (MPR ≥ 0.8) or nonadherent (MPR < 0.8). RESULTS: Among 201 patients initiated on somatropin, 74.6% were male, mean age was 11.4 years, and the mean follow-up was 343.3 days. Approximately 76.6% of patients were adherent to somatropin over the follow-up period. Adjusted growth trajectories were similar between adherent and nonadherent patients pre-treatment initiation (P = .15). Growth trajectories post-initiation were significantly different (P = .001). On average, adherent patients gained an additional 1.8 cm over 1 year compared with nonadherent patients, adjusted for covariates. CONCLUSION: Greater adherence to somatropin therapy is associated with improved height velocity. As suboptimal adherence to daily somatropin therapy is an issue for children with GHD, novel strategies to improve adherence may improve growth outcomes.
Subject(s)
Dwarfism, Pituitary , Human Growth Hormone , Adult , Body Height , Child , Dwarfism, Pituitary/drug therapy , Female , Growth Hormone , Human Growth Hormone/therapeutic use , Humans , Male , Medication Adherence , Recombinant Proteins/therapeutic use , Retrospective StudiesABSTRACT
OBJECTIVES: Stroke constitutes a significant public health problem in developing countries. Caregivers provide an important support system for patient care but usually lack knowledge and skill to attend their stroke patients. We assessed whether a caregiver-directed educational intervention would reduce hospital-acquired complications and improve stroke patients' outcomes. MATERIALS AND METHODS: We randomly assigned two Neurology inpatient wards to receive either standard care or an educational intervention. The coprimary outcomes included incidence of hospital-acquired complications and in-hospital mortality. Secondary outcomes included the modified Rankin Scale and mortality at three months. RESULTS: Among 164 patients recruited, 82 received intervention, and standard care each. The mean (Standard deviation) Glasgow coma scale of patients was 11.01 (3.4), and National Institute of Health Stroke Scale was 19.17 (8.54). The incidence of complications (72 in the intervention versus 81 in the control group; p=0.56) was not different. Ten patients (12.2%) in the intervention group and 16 (19.5%) in the control group (p=0.20) died in-hospital. Twenty patients (27.8%) in the intervention and twelve (18.2%) in the control group attained modified Rankin Scale 0-2 at three months (p=0.12). The mortality at three months (20 [24.4%] in the intervention versus 25 [30.5%] in the control group) was not different (p=0.38). The intervention group had fewer complications (42 versus 68 in the control group; p=0.01) during the initial ten days of hospital stay, but adjusted analysis revealed no difference. CONCLUSION: A structured educational intervention did not reduce the incidence of hospital-acquired complications, mortality, or morbidity. However, there was a trend towards fewer complications in the initial days of hospital stay. Extended hospital stay, caregiver fatigue, and dilution of the intervention over time might be reasons for the apparent lack of effect. CLINICAL TRIAL REGISTRATION-URL: http://www.ctri.nic.in. Unique identifier: CTRI/2018/11/016312.
Subject(s)
Caregivers/education , Health Education , Stroke Rehabilitation , Stroke/therapy , Adult , Aged , Disability Evaluation , Female , Health Knowledge, Attitudes, Practice , Hospital Mortality , Humans , India , Length of Stay , Male , Middle Aged , Recovery of Function , Risk Factors , Stroke/complications , Stroke/diagnosis , Stroke/mortality , Stroke Rehabilitation/adverse effects , Time Factors , Treatment OutcomeABSTRACT
The plasmon-enhanced photoresponse properties of a Ag nanoparticle decorated Bi2Se3 nanosheet (AGBS)/p-Si heterojunction device have been studied. The Ag nanoparticles, Bi2Se3 nanosheets, and AGBS nanocomposite are synthesized chemically. Microscopic investigations, ultimately of the AGBS nanocomposite, reveal that the Bi2Se3 nanosheets of thickness â¼20 nm and lateral dimension â¼1 µm are decorated with Ag nanoparticles of sizes 20-40 nm in the nanocomposite. The x-ray diffraction pattern of AGBS shows that apart from being in a metallic state, the Ag in the AGBS is also in the form of compounds with Bi, Se, and additionally O. This observation is further complemented by the x-ray photoelectron spectrum, which shows the presence of Ag0 and Ag+ states of Ag in AGBS. The UV-visible absorption spectra show the plasmonic peak of the Ag nanoparticles occurs at 420 nm; the peak is shifted to â¼500 nm in AGBS due to the modified dielectric environment of the nanoparticles. The AGBS/p-Si heterojunction shows excellent photoresponse properties, with a responsivity of 0.28 A/W, a fairly high detectivity of 4 × 1010 Jones, and an EQE of 71% under 10 V reverse bias at a 500 nm wavelength. The plasmon enhanced photoresponse at the selective wavelength makes this material attractive for high performance optoelectronic devices.
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BACKGROUND: Reproductive function in women with end stage renal disease generally improves after kidney transplant. However, pregnancy remains challenging due to the risk of adverse clinical outcomes. METHODS: We searched PubMed/MEDLINE, Elsevier EMBASE, Scopus, BIOSIS Previews, ISI Science Citation Index Expanded, and the Cochrane Central Register of Controlled Trials from date of inception through August 2017 for studies reporting pregnancy with kidney transplant. RESULTS: Of 1343 unique studies, 87 met inclusion criteria, representing 6712 pregnancies in 4174 kidney transplant recipients. Mean maternal age was 29.6 ± 2.4 years. The live-birth rate was 72.9% (95% CI, 70.0-75.6). The rate of other pregnancy outcomes was as follows: induced abortions (12.4%; 95% CI, 10.4-14.7), miscarriages (15.4%; 95% CI, 13.8-17.2), stillbirths (5.1%; 95% CI, 4.0-6.5), ectopic pregnancies (2.4%; 95% CI, 1.5-3.7), preeclampsia (21.5%; 95% CI, 18.5-24.9), gestational diabetes (5.7%; 95% CI, 3.7-8.9), pregnancy induced hypertension (24.1%; 95% CI, 18.1-31.5), cesarean section (62.6, 95% CI 57.6-67.3), and preterm delivery was 43.1% (95% CI, 38.7-47.6). Mean gestational age was 34.9 weeks, and mean birth weight was 2470 g. The 2-3-year interval following kidney transplant had higher neonatal mortality, and lower rates of live births as compared to > 3 year, and < 2-year interval. The rate of spontaneous abortion was higher in women with mean maternal age < 25 years and > 35 years as compared to women aged 25-34 years. CONCLUSION: Although the outcome of live births is favorable, the risks of maternal and fetal complications are high in kidney transplant recipients and should be considered in patient counseling and clinical decision making.
Subject(s)
Kidney Transplantation , Pregnancy Outcome , Pregnancy, High-Risk , Abortion, Induced/statistics & numerical data , Abortion, Spontaneous/epidemiology , Adult , Birth Weight , Cesarean Section/statistics & numerical data , Female , Gestational Age , Humans , Infant, Newborn , Postoperative Complications/epidemiology , Pregnancy , Pregnancy Complications/epidemiology , Procedures and Techniques Utilization , Stillbirth/epidemiology , Young AdultABSTRACT
Peripheral neuropathy is a common reason for referral to neurology. Chronic acquired demyelinating neuropathies are an important and varied group with overlapping presentations, and may have an immune-mediated cause. Their correct diagnosis is important as they respond to different treatments; timely intervention can prevent irreversible axonal degeneration. We present a case that highlights the approach to an adult presenting with a chronic demyelinating neuropathy.
Subject(s)
Castleman Disease/complications , Castleman Disease/diagnostic imaging , Muscle Weakness/complications , Muscle Weakness/diagnostic imaging , POEMS Syndrome/complications , POEMS Syndrome/diagnostic imaging , Diagnosis, Differential , Humans , Male , Middle Aged , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/complications , Polyradiculoneuropathy, Chronic Inflammatory Demyelinating/diagnostic imagingABSTRACT
BACKGROUND AND AIM: Endoscopic ultrasound (EUS) aspiration needles are single-use devices. However, in many centers, because of cost-constraints, these devices are reused multiple times. We studied microbiological contamination and bioburden on reprocessed needles to evaluate whether these devices can be successfully sterilized. METHODS: We studied 10 EUS needles each of 19 G, 22 G, and 25 G in size, and five 22-G ProCore needles. After initial use, each needle was reprocessed by a standardized protocol. We used standard microbiological cultures, as well as ATP bioluminescence technique to quantify bioburden as relative light units (RLU). We defined significant soil contamination by RLU values >200. We also used extractant fluid to disrupt cell membranes in an attempt to enhance ATP detection. RESULTS: We found culture positivity in 3/34 (8.8%), and detectable bioburden on the exposed surface of 33/35 (94.3%), and inside lumen of 29 (82.9%) reprocessed FNA needles. Significant bioburden was found in three (8.6%) and two (5.7%) needles on the surface and lumen, respectively. We found that use of extractant fluid enhanced detection of bioburden. Larger (19 G) needles had higher surface contamination (P = 0.016), but there was no relation of luminal contamination with needle diameter (P = 0.138). Sheath design and presence of side bevel did not influence extent of contamination. There was significant correlation between the surface and intraluminal bioburden (P < 0.001). CONCLUSIONS: There is significant bioburden in reprocessed EUS needles; standard microbiological cultures have low sensitivity for detection of needle contamination. We have provided objective evidence for the futility of reprocessing attempts, and practice of EUS needle reuse should be discontinued.
Subject(s)
Endoscopic Ultrasound-Guided Fine Needle Aspiration/instrumentation , Equipment Contamination , Needles/microbiology , Sterilization , Humans , Luminescent Measurements , Pancreatic Pseudocyst/pathologyABSTRACT
BACKGROUND & AIMS: In gastrointestinal muscles, v-kit Hardy-Zuckerman 4 feline sarcoma viral oncogene homolog (KIT) is predominantly expressed by interstitial cells of Cajal (ICC) and platelet-derived growth factor receptor-α (PDGFRA) polypeptide is expressed by so-called fibroblast-like cells. KIT and PDGFRA have been reported to be coexpressed in ICC precursors and gastrointestinal stromal tumors (GISTs), which originate from the ICC lineage. PDGFRA signaling has been proposed to stimulate growth of GISTs that express mutant KIT, but the effects and mechanisms of selective blockade of PDGFRA are unclear. We investigated whether inhibiting PDGFRA could reduce proliferation of GIST cells with mutant KIT via effects on the KIT-dependent transcription factor ETV1. METHODS: We studied 53 gastric, small intestinal, rectal, or abdominal GISTs collected immediately after surgery or archived as fixed blocks at the Mayo Clinic and University of California, San Diego. In human GIST cells carrying imatinib-sensitive and imatinib-resistant mutations in KIT, PDGFRA was reduced by RNA interference (knockdown) or inhibited with crenolanib besylate (a selective inhibitor of PDGFRA and PDGFRB). Mouse ICC precursors were retrovirally transduced to overexpress wild-type Kit. Cell proliferation was analyzed by methyltetrazolium, 5-ethynyl-2'-deoxyuridine incorporation, and Ki-67 immunofluorescence assays; we also analyzed growth of xenograft tumors in mice. Gastric ICC and ICC precursors, and their PDGFRA(+) subsets, were analyzed by flow cytometry and immunohistochemistry in wild-type, Kit(+/copGFP), Pdgfra(+/eGFP), and NOD/ShiLtJ mice. Immunoblots were used to quantify protein expression and phosphorylation. RESULTS: KIT and PDGFRA were coexpressed in 3%-5% of mouse ICC, 35%-44% of ICC precursors, and most human GIST samples and cell lines. PDGFRA knockdown or inhibition with crenolanib efficiently reduced proliferation of imatinib-sensitive and imatinib-resistant KIT(+)ETV1(+)PDGFRA(+) GIST cells (50% maximal inhibitory concentration = 5-32 nM), but not of cells lacking KIT, ETV1, or PDGFRA (50% maximal inhibitory concentration >230 nM). Crenolanib inhibited phosphorylation of PDGFRA and PDGFRB, but not KIT. However, Kit overexpression sensitized mouse ICC precursors to crenolanib. ETV1 knockdown reduced KIT expression and GIST proliferation. Crenolanib down-regulated ETV1 by inhibiting extracellular-signal-regulated kinase (ERK)-dependent stabilization of ETV1 protein and also reduced expression of KIT and PDGFRA. CONCLUSIONS: In KIT-mutant GIST, inhibition of PDGFRA disrupts a KIT-ERK-ETV1-KIT signaling loop by inhibiting ERK activation. The PDGFRA inhibitor crenolanib might be used to treat patients with imatinib-resistant, KIT-mutant GIST.
Subject(s)
Cell Proliferation/genetics , DNA-Binding Proteins/genetics , Gastrointestinal Stromal Tumors/metabolism , Proto-Oncogene Proteins c-kit/metabolism , Receptor, Platelet-Derived Growth Factor alpha/metabolism , Signal Transduction/genetics , Transcription Factors/genetics , Animals , Benzamides/metabolism , Benzimidazoles/metabolism , Biomarkers, Tumor/metabolism , Cell Line, Tumor , Flow Cytometry , Gastrointestinal Stromal Tumors/genetics , Gene Knockdown Techniques/methods , Humans , Imatinib Mesylate , Immunohistochemistry , Mice , Mice, Inbred BALB C , Mutation , Nucleic Acid Precursors/genetics , Phosphorylation/genetics , Piperazines/metabolism , Piperidines/metabolism , Proto-Oncogene Proteins c-kit/genetics , Pyrimidines/metabolism , Receptor, Platelet-Derived Growth Factor alpha/genetics , Receptor, Platelet-Derived Growth Factor beta/metabolismABSTRACT
BACKGROUND: Acute interstitial nephritis secondary to proton pump inhibitors (PPIs) frequently goes undiagnosed due to its subacute clinical presentation, which may later present as chronic kidney disease (CKD). We investigated the association of PPI use with the development of CKD and death. METHODS: Two separate retrospective case-control study designs were employed with a prospective logistic regression analysis of data to evaluate the association of development of CKD and death with PPI use. The population included 99,269 patients who were seen in primary care VISN2 clinics from 4/2001 until 4/2008. For evaluation of the CKD outcome, 22,807 with preexisting CKD at the first observation in Veterans Affairs Health Care Upstate New York (VISN2) network data system were excluded. Data obtained included use of PPI (Yes/No), demographics, laboratory data, pre-PPI comorbidity variables. RESULTS: A total of 19,311/76,462 patients developed CKD. Of those who developed CKD 24.4 % were on PPI. Patients receiving PPI were less likely to have vascular disease, COPD, cancer and diabetes. Of the total of 99,269 patients analyzed for mortality outcome, 11,758 died. A prospective logistic analysis of case-control data showed higher odds for development of CKD (OR 1.10 95 % CI 1.05-1.16) and mortality (OR 1.76, 95 % CI 1.67-1.84) among patients taking PPIs versus those not on PPIs. CONCLUSIONS: Use of proton pump inhibitors is associated with increased risk of development of CKD and death. With the large number of patients being treated with proton pump inhibitors, healthcare providers need to be better educated about the potential side effects of these medications.
Subject(s)
Proton Pump Inhibitors/adverse effects , Renal Insufficiency, Chronic/etiology , Renal Insufficiency, Chronic/mortality , Aged , Case-Control Studies , Female , Humans , Male , Middle Aged , Mortality/trends , Nephritis, Interstitial/diagnosis , Nephritis, Interstitial/etiology , Nephritis, Interstitial/mortality , Prospective Studies , Renal Insufficiency, Chronic/diagnosis , Retrospective Studies , Risk FactorsABSTRACT
BACKGROUND AND AIMS: Vitamin D deficiency is a common problem in stroke survivors. Observational studies have reported an association of low vitamin D levels with greater stroke severity, poststroke mortality and functional disability. Randomised clinical trials are lacking. We sought to assess the effect of calcium and vitamin D supplementation in ischaemic stroke survivors with vitamin D deficiency/insufficiency on disability/mortality outcomes. METHODS: In this randomised controlled open-label trial, 73 patients of acute ischaemic stroke were screened for serum 25 hydroxy Vitamin D (25(OH)D) levels. A total of 53 patients with baseline 25(OH)D <75 nmol/L were randomised into two arms. One received vitamin D and calcium supplementation along with usual care (n=25) and the other received usual care alone (n=28). Primary outcome was the proportion of patients achieving a good outcome [modified Rankin Scale score 0-2] at 6 months and all cause mortality at 6 months. RESULTS: The age (mean±SD) of participants was 60.4±11.3 years, 69.8% were males. The proportion of patients achieving good outcome was higher in the intervention arm (Adjusted OR 1.9, 95% CI 0.6-6.4; P=.31). The survival probability was greater in the intervention arm (83.8%, CI 62.4-93.6) as compared with the control arm (59.5%, CI 38.8-75.2; P=.049) with adjusted Hazard ratio (HR) of 0.26 (95% CI 0.08-0.9; P=.03). CONCLUSIONS: This is the first randomised controlled study assessing the effect of vitamin D and calcium supplementation on ischaemic stroke outcomes and points towards a potential benefit. Findings need to be validated by a larger trial.
Subject(s)
Brain Ischemia/diet therapy , Calcium, Dietary/administration & dosage , Stroke/diet therapy , Vitamin D Deficiency/diet therapy , Vitamin D/administration & dosage , Vitamins/administration & dosage , Brain Ischemia/blood , Brain Ischemia/mortality , Dietary Supplements , Female , Follow-Up Studies , Humans , Kaplan-Meier Estimate , Male , Middle Aged , Risk Factors , Stroke/blood , Stroke/mortality , Treatment Outcome , Vitamin D/analogs & derivatives , Vitamin D/blood , Vitamin D Deficiency/mortalitySubject(s)
Hypertension , Rheumatology , Vasculitis , Humans , Hypertension/complications , Hypertension/diagnosisABSTRACT
OBJECTIVE: This study examined the effect of perioperative acute kidney injury (AKI) on long-term kidney dysfunction and death after lower extremity revascularization. Perioperative AKI is commonly seen in the form of mild rises of serum creatinine after major cardiovascular surgeries. Its effect on long-term survival and development of chronic kidney disease (CKD) is well established in cardiac surgery patients. However, there are no data on the effect of AKI on long-term outcomes after revascularization for lower limb ischemia. METHODS: We retrospectively reviewed the patients with peripheral arterial occlusive diseases who underwent endovascular or surgical revascularization of the lower extremities from 2001 through 2010. All demographic and clinical information have been maintained prospectively by the surgeon and followed up by the research team. Perioperative AKI was defined as rises of ≥0.3 mg/dL in serum creatinine from the values measured preoperatively. The primary end points were development of CKD (estimated glomerular filtration rate <60 mL/min) and all-cause mortality. Univariate and multivariate analyses were performed to examine relevant associations. RESULTS: Within the study period, 717 patients underwent 875 procedures. Mean follow-up was 42 ± 14 months. AKI developed in 86 patients after the index procedure. Overall prevalence of CKD diagnosed postoperatively was 14.9%. Overall mortality reported within the follow-up period was 55.9%. Perioperative AKI was a significant predictor of CKD (area under the curve, 0.84 ± 0.13) and all cause mortality (area under the curve, 0.82 ± 0.12). CONCLUSIONS: Perioperative AKI is associated with an increased occurrence of CKD and a higher mortality rate after revascularization procedures of the lower extremities.
Subject(s)
Acute Kidney Injury/etiology , Endovascular Procedures/adverse effects , Ischemia/therapy , Lower Extremity/blood supply , Peripheral Arterial Disease/therapy , Renal Insufficiency, Chronic/etiology , Vascular Surgical Procedures/adverse effects , Acute Kidney Injury/diagnosis , Acute Kidney Injury/mortality , Aged , Aged, 80 and over , Biomarkers/blood , Chi-Square Distribution , Chronic Disease , Creatinine/blood , Endovascular Procedures/mortality , Female , Glomerular Filtration Rate , Humans , Ischemia/diagnosis , Ischemia/mortality , Kaplan-Meier Estimate , Logistic Models , Male , Middle Aged , Multivariate Analysis , Odds Ratio , Peripheral Arterial Disease/diagnosis , Peripheral Arterial Disease/mortality , Proportional Hazards Models , Renal Insufficiency, Chronic/diagnosis , Renal Insufficiency, Chronic/mortality , Retrospective Studies , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , Vascular Surgical Procedures/mortalityABSTRACT
The study aimed to identify desirable social, familial, reproductive, dietary, and lifestyle factors for maintaining normal body mass index (BMI) of urban affluent women (25-45 years) in Delhi, India. A total of 387 urban affluent women with at least one living child participated in this cross-sectional study conducted from March 2008 to April 2010. Women were classified into four BMI categories on the basis of World Health Organization (WHO; 2004) classification for Asians. Significant factors for maintaining normal BMI were: Younger age, less parity, nuclear family, normal weight status of parents, postpartum weight gain between 2 and 3 kg, regularity in taking meals, fixed meal size, self-perceived normal weight, and shorter sitting time and television viewing time. Multivariate regression analysis identified five determining factors for maintaining BMI, which are normal weight of father, self-perceived normal weight, fixed meal size, sitting time less than 6 h/day, and television viewing time less than 1 h/day. By small lifestyle modifications, normal BMI can be maintained.