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BACKGROUND: Crohn's disease (CD) is a debilitating gastrointestinal disease with complex etiology. Although effective, recipients of anti-tumor necrosis factor (TNF) agents may experience primary or secondary nonresponse, necessitating alternative treatments. This study is intended to compare the short-term effectiveness of ustekinumab and vedolizumab in treating CD after failure of multiple lines of anti-TNF therapy using real-world data. METHODS: A retrospective study was conducted at a tertiary hospital in Dammam, Saudi Arabia, including adults (≥18 years old) with CD who did not respond to anti-TNF therapy. Primary endpoints were clinical improvement per the Harvey-Bradshaw Index (HBI) scores and remission at 12 weeks on an ordinal outcome scale. Secondary endpoints included clinical, biochemical, and endoscopic remission; clinical response; corticosteroid-free days; and cumulative steroid dose. Proportional odds and logistic regression Bayesian models were used to analyze outcomes, and the probability of treatment effectiveness was calculated from the posterior distribution. RESULTS: The study included 101 patients (ustekinumab, n = 71 and vedolizumab, n = 30) with a median age of 32 years (IQR: 26.0-38.0); 54.4% were male. At 12 weeks, the HBI endpoint showed an adjusted odds ratio (aOR) = 0.60 (95% confidence interval [CI]: 0.25-1.31), favoring ustekinumab, with a 75% probability of treatment effectiveness over vedolizumab. The clinical ordinal scale had an aOR = 0.61 (95% CI: 0.26-1.35) with a 73% probability of effectiveness for ustekinumab. Ustekinumab was also associated with favorable outcomes in secondary endpoints, reaching up to a 90% probability of effectiveness. CONCLUSION: In CD patients with anti-TNF failure, ustekinumab was more effective than vedolizumab in the short term. These real-world insights contribute to understanding CD management but require validation in larger prospective studies and randomized controlled trials.
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BACKGROUND: There are concerns about indiscriminate prescriptions and the inappropriate use of proton pump inhibitors (PPIs) without any clear indications, especially among noncritically hospitalized patients. OBJECTIVE: This study aimed to characterize PPI prescriptions among non-critically hospitalized patients in a tertiary care hospital in Saudi Arabia. METHODS: A retrospective cross-sectional study was conducted at the King Abdulaziz University Hospital between June and August 2021. The data of adult patients who received PPIs on hospital admission in the medical and surgical wards were collected and analyzed for appropriateness based on the current international guidelines and recommendations. RESULTS: A total of 174 patient records were included in this study. The proportion of patients with appropriate and inappropriate PPI prescriptions was 67.24% (n=117) and 32.76% (n=57), respectively. Female patients (risk=50.00%, 95% CI: 36.89-63.11, p<0.001) were more likely to receive an inappropriate PPI prescription than their male counterparts (risk=33.33%, 95% CI: 24.56-43.43, p<0.001). Intravenous omeprazole 40 mg once daily was the most frequently prescribed PPI (n=62). The hospital length of stay differed significantly between the groups of patients who received appropriate and inappropriate PPIs (24.56 ± 47.14 vs. 13.50 ± 13.84; t=2.34, 95% CI: 1.72-20.4; p=0.02). However, there was no significant difference in the total therapy duration in both the groups (3.76 ± 2.50 vs. 4.75 ± 3.32, t=-1.62, 95%CI: -1.79-0.17; p=0.11). CONCLUSION: The findings show a high trend of inappropriate PPI prescriptions. Hence, educational programs are recommended to encourage healthcare professionals to stick to the approved guidelines when prescribing PPIs.
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Background The Screening Tool to Alert to Right Treatment (START) criteria for older adults was developed to recognize potential prescribing omissions (PPOs) of clinically indicated medications. According to these criteria, statins and antiplatelets should be prescribed for older adults with a documented history of coronary artery, cerebral, or peripheral vascular disease unless contraindicated. Aim This study aimed to investigate physicians' adherence to START criteria and identify the prevalence of PPO, considering the prescription of statins and antiplatelets in older patients with a history of coronary artery, cerebral, or peripheral vascular disease. Methods In this single-center, cohort, retrospective study, patients aged >65 years with a history of coronary artery, cerebral, or peripheral vascular disease were included. The prevalence of PPO for statins and antiplatelet therapy was identified. This study was guided by the screening Tool of Older Persons' Prescriptions (STOPP)/START criteria published in 2016. Results A total of 244 patients with a history of coronary, cerebral, or peripheral vascular disease were included in this study. Statin use was appropriately observed in 131/220 (59.5%) while antiplatelets were appropriately observed in 219/237 (92.4%). Therefore, the PPO for statins and antiplatelets was 40.5% and 7.6%, respectively. Conclusion The results of this study identified that the prevalence of PPO for statins and antiplatelets for older adults was high. We encourage prescribers to utilize tools such as Beer's criteria or STOPP/START, which may assist their decision in addition to their clinical judgment in weighing the benefit to the risk of starting or stopping antiplatelets or statins in older adult patients.
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OBJECTIVES: To compare the effectiveness of aspirin-clopidogrel dual antiplatelet therapy (DAPT) with aspirin or clopidogrel antiplatelet monotherapy (AM) in patients with ischemic stroke. METHODS: It was a single-center, retrospective cross-sectional study of medical records of ischemic stroke patients admitted at King Abdulaziz University Hospital between January 2015 and October 2019. The primary endpoints were ischemic stroke recurrence, rehospitalization, and all-cause mortality between DAPT and AM. Kaplan-Meier and Cox proportional hazard analyses were employed in univariate and multivariate time-to-event analyses. RESULTS: The median time to recurrence of ischemic stroke was 15.0 months (95% confidence interval [CI], 8.586-23.01) for DAPT and 20.4 months (95% CI, 9.872-30.928) for the AM. The median survival time until all-cause mortality was 8.0 months (95% CI, 2.893-13.107) for DAPT and 14.1 months (95% CI, 8.173-19.97) for the AM. No statistically significant reductions in the instantaneous risks of recurrence (hazard ratio [HR], 1.27; 95% CI, 0.59-2.72; p=0.54), re-hospitalization (HR, 0.95; 95% CI, 0.59-1.48; p= 0.77), and mortality (HR, 1.04; 95% CI, 0.48-2.26; p=0.92) were found between the DAPT and AM groups. CONCLUSION: The DAPT was not superior to AM in reducing recurrence and mortality events in patients with ischemic stroke. Rehospitalization due to the sequelae of the composite of stroke, angina, and myocardial infarction was higher in the DAPT group.
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Ischemic Stroke , Stroke , Humans , Platelet Aggregation Inhibitors/therapeutic use , Clopidogrel/therapeutic use , Ticlopidine/therapeutic use , Ischemic Stroke/drug therapy , Retrospective Studies , Cross-Sectional Studies , Drug Therapy, Combination , Aspirin/therapeutic use , Treatment OutcomeABSTRACT
INTRODUCTION: The administration of multiple medications and complex drug regimens has increased medication-related problems (MRPs) and associated factors. MRPs can occur at any stage of the medication process and are common after hospital discharge. Understanding and managing these problems are crucial for promoting safe and effective medication use. OBJECTIVE: This study aimed to evaluate the prevalence of MRPs among post-discharge patients with high medication risk in the academic tertiary care hospital of King Abdulaziz University (KAUH) in Jeddah, Saudi Arabia. METHODS: A prospective cross-sectional study was conducted, and data were collected through phone calls to discharged patients using validated questions. MRPs were identified based on the classification of the Pharmaceutical Care Network Europe (PCNE), and data analysis was performed using descriptive statistics. RESULTS: Out of 287 screened participants, 201 fulfilled the inclusion criteria. The prevalence of MRPs among high-medication-risk patients after hospital discharge was substantial, with 519 MRPs identified. The most common types of MRPs were the need for medication information, untreated symptoms or indications, and nonadherence. CONCLUSION: The most prevalent MRPs among patients in our hospital were the need for education and untreated symptoms or indications. Future studies should investigate MRPs in larger samples and explore interventions by pharmacists.
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Tamarindus indica Linn (tamarind, F. Leguminosae) is one of the most widely consumed edible fruits in the world. Phytochemical investigation of tamarind pulp n-butanol fraction yielded one new (+)-pinitol glycoside compound 1 (25% w/w), and 1D, 2D NMR, and HRESIMS investigation were used to confirm the new compound's structure. (+)-Pinitol glycoside showed anti-Alzheimer potential that was confirmed in prophylactic and treatment groups by decreasing time for the T-maze test; decreased TAO, brain and serum AChE, MDA, tau protein levels, and ß amyloid peptide protein levels; and increasing GPX, SOD levels, and in vivo regression of the neurodegenerative features of Alzheimer's dementia in an aluminum-intoxicated rat model. The reported molecular targets for human Alzheimer's disease were then used in a network pharmacology investigation to examine their complex interactions and identify the key targets in the disease pathogenesis. An in silico-based analysis (molecular docking, binding free energy calculation (ΔGBinding), and molecular dynamics simulation) was performed to identify the potential targets for compound 1. The findings of this study may lead to the development of dietary supplements for the treatment of Alzheimer's disease.
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Background/purpose Self-medication is a public health concern because of the potential for medication overuse or abuse, as well as the physical, social, and psychological consequences. In Saudi Arabia, self-medication is common, especially among health science students. Inappropriate self-medication can cause several adverse effects, such as increasing the risk of medication abuse or delaying hospital appointments due to concealing specific symptoms with some medications. Therefore, our study aims to investigate and evaluate health science students' practices, awareness, and attitudes towards self-medication in the Faculty of Pharmacy at King Abdulaziz University, Jeddah, Saudi Arabia. Materials and methods A cross-sectional study was conducted using an online self-administered survey to measure the attitude, awareness, and prevalence of self-medication among pharmacy students at King Abdulaziz University in Jeddah, Saudi Arabia. Students in the pharmacy program from the first to the sixth year were invited to participate in the study from April 2019 to June 2019. Raosoft was used to compute the sample size (n = 235) with a 5% margin of error and a 95% confidence range. Results The factors associated with significant effects were an academic year (p = 0.001), smoking (p = 0.018), average sleeping time (p = 0.032), having any headache (p = 0.022), and their opinion about self-medication (p < 0.0001). Conclusion According to the study, the self-medication of analgesics is common among pharmacy students, and the most used medication was paracetamol.
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Background: Poor waste management of unused or expired medications jeopardizes healthcare staff, employees who oversee medical waste, patients and their families, the neighboring population, and environmental contamination. In addition, the inappropriate treatment or disposal of that waste leads to. In addition, medical waste disposal exerts an intolerable burden on the economy of health care facilities. Currently, there is a lack of data in community settings regarding adequate methods of medication disposal in Saudi Arabia. Aim of the Study: The current study aimed to evaluate current knowledge and awareness of the safe disposal of unused or expired medicines in the Saudi Arabia. Method: A survey study was conducted in Saudi Arabia within 5 months from October 2021-February 2022. The survey was distributed to participants via social media channels. The questionnaire was constituted of 16 items divided into three sections: demographic information, quantification, and characterization of unused and expired medication at home, and practice and attitude regarding the disposal of unused or expired medication. Results: The survey was taken by 1105 participants and 1100 (99.54%) participants completed the survey. The study found that (49.1%) of participants stored medicines at home and these medicines were mainly stored in the refrigerator (64.4%). Household trash was the most frequent method of disposal (79.5%). Non-prescribed medicines (67%) were mainly stored as unused or expiry medicines at home followed by prescribed medicines (51.9%). The main reason for the storage of unused/expired medicines at home was stopped medication after recovery (68.5%). Only 8.4% of participants had received appropriate education or training related to the correct disposal of medication. The best-practiced method to increase community awareness regarding the disposal of unused or expiry medicine was awareness through social networking (70.3%). In conclusion, patients' education regarding safe medication disposal and availability of medication disposal program is necessary to improve appropriate medication waste methods and decrease possible environmental harm.
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Background: Electroconvulsive therapy (ECT) is a highly efficacious treatment modality used to produce seizures in patients diagnosed with major depressive disorders and psychotic episodes. In general, ECT treatment is successful in most patients; however, in some populations, ECT fails to produce adequate response. Caffeine, theophylline, and aminophylline are documented to augment seizure activity in ECT. By inhibiting adenosine, these medications can improve ECT response rate in a certain patient population. Caffeine and aminophylline have been documented to prolong seizure duration. Theophylline has been shown to improve seizure duration along with decreasing seizure threshold. All of these medications have very minimal side effect profiles. This review will discuss up-to-date evidence on the effects of xanthine derivatives in patients receiving ECT treatment. Methods: A literature review of PubMed and EMBASE was performed for related studies. Results: Eight studies were included in our review. Premedication with caffeine, theophylline, or aminophylline was associated with increased seizure duration in patients suffering from mental disorders and were indicated to manage ECT. Conclusion: Xanthine derivatives prolong seizure duration in patients treated with ECT.
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BACKGROUND: Diabetes is a health problem that has an enormous and intolerable public health burden on the individual, family, and community. Diabetes affects nearly one-fifth of adults in Saudi Arabia and is expected to double by 2030. AIM OF THE STUDY: The study aims to evaluate the impact of switching patients from conventional basal insulin analogues to insulin degludec during a 90-day follow-up period. METHODS: This was a retrospective observational pretest-posttest cohort study conducted at King Abdulaziz University Hospital between June 2019 and August 2020. Adult patients with diabetes who switched their basal insulin to insulin degludec were included and evaluated for its impact on insulin doses, hemoglobin A1c (HbA1c), hypoglycemic events, and/or body weight changes during a 90-day follow-up period. RESULTS: Out of 718 patients, 107 patients were included in the study, with 60.7% being females and their mean (± SD) age was 62.2 ± 14.6 years. There was a significant decrease in the mean baseline of HbA1c from 9.2% to 8.7% after 90 days of follow-up (P<0.001). A statistically significant reduction was noted in the total insulin requirements from a baseline of 71.70 (± 42.4) units to 46.5 (± 29) units, P=0.001, after switching to insulin degludec. However, there were no statistically significant differences in the body weight from the baseline mean (± SD) of 80.5 kg (± 19.4) to 79.9 kg (± 19.9), P=0.68, after switching to insulin degludec. Lastly, there were no statistically significant differences in the reported hypoglycemic episodes from a baseline of 48.7% vs 37.3% after 90 days of follow-up (P = 0.166). CONCLUSION: Switching to the novel insulin degludec conferred better blood glucose control and dose reduction. There was no increase in the frequency of hypoglycemic episodes or body weight.
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Two series of chalcone/aryl carboximidamide hybrids 4a-f and 6a-f were synthesised and evaluated for their inhibitory activity against iNOS and PGE2. The most potent derivatives were further checked for their in vivo anti-inflammatory activity utilising carrageenan-induced rat paw oedema model. Compounds 4c, 4d, 6c and 6d were proved to be the most effective inhibitors of PGE2, LPS-induced NO production, iNOS activity. Moreover, 4c, 4d, 6c and 6d showed significant oedema inhibition ranging from 62.21% to 78.51%, compared to indomethacin (56.27 ± 2.14%) and celecoxib (12.32%). Additionally, 4c, 6a and 6e displayed good COX2 inhibitory activity while 4c, 6a and 6c exhibited the highest 5LOX inhibitory activity. Compounds 4c, 4d, 6c and 6d fit nicely into the pocket of iNOS protein (PDB ID: 1r35) via the important amino acid residues. Prediction of physicochemical parameters exhibited that 4c, 4d, 6c and 6d had acceptable physicochemical parameters and drug-likeness. The results indicated that chalcone/aryl carboximidamides 4c, 4d, 6c and 6d, in particular 4d and 6d, could be used as promising lead candidates as potent anti-inflammatory agents.
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Amides/pharmacology , Anti-Inflammatory Agents, Non-Steroidal/pharmacology , Chalcone/pharmacology , Dinoprostone/antagonists & inhibitors , Drug Design , Edema/drug therapy , Enzyme Inhibitors/pharmacology , Molecular Docking Simulation , Nitric Oxide Synthase Type II/antagonists & inhibitors , Amides/chemical synthesis , Amides/chemistry , Animals , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Anti-Inflammatory Agents, Non-Steroidal/chemistry , Carrageenan , Cells, Cultured , Chalcone/chemical synthesis , Chalcone/chemistry , Dinoprostone/metabolism , Dose-Response Relationship, Drug , Edema/chemically induced , Enzyme Inhibitors/chemical synthesis , Enzyme Inhibitors/chemistry , Mice , Molecular Structure , Nitric Oxide Synthase Type II/metabolism , RAW 264.7 Cells , Structure-Activity RelationshipABSTRACT
BACKGROUND: Because of the uncertainty in the appropriate initial loop diuretic dose in acute decompensated heart failure (ADHF), the risk of acute kidney injury (AKI) is believed to be increased with the high dose of initial intravenous (IV) loop diuretic. AIMS: The purpose of this study is to examine the impact of the first 24-h IV diuretic on kidney function in ADHF. METHODS: A retrospective cohort study included patients with ADHF. These patients were divided into two groups: the first group received an initial total IV diuretic dose that was equal to or 2.5 times less than the home dose in the first 24 h (low dose), while the second group received 2.5 times more than the home dose in the first 24 h (high dose). The primary outcome was the incidence of developing AKI within 48 h of first IV diuretic. The secondary outcomes were total hospital length of stay and all-cause 30-day readmission rates. RESULTS: A total of 252 patients were available for analysis; 172 patients received a low dose in the first 24 h, while 80 patients received a high dose. The incidence of AKI was higher in the high-dose group compared to that in the low-dose group (25% vs. 9.9%, P = 0.002). There was no significant difference between the two groups in terms of hospital stay and all-cause 30-day readmission. CONCLUSION: In patients with ADHF, the initial high dose of IV loop diuretics is associated with an increased risk of developing AKI.
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Heart Failure , Sodium Potassium Chloride Symporter Inhibitors , Acute Disease , Diuretics/adverse effects , Heart Failure/drug therapy , Humans , Kidney , Retrospective Studies , Sodium Potassium Chloride Symporter Inhibitors/adverse effectsABSTRACT
Objectives: To estimate the pancreatic cancer risk among subjects exposed versus not exposed to proton pump inhibitors.Methods: The authors searched PubMed, EMBASE, Scopus, Cochrane Library, and clinicaltrials.gov to identify relevant studies. The authors quantified pancreatic cancer risk among subjects exposed versus not exposed to PPIs, expressed as the pooled (adjusted) odds ratio (OR/aOR) and 95% confidence interval (95%CI) in overall and sensitivity analyses.Results: One randomized trial, two cohort, four case-control, and five nested case-control studies with 700,178 subjects (73,985 cases; 626,193 controls) were retained. PPI exposure was associated with pancreatic cancer risk (OR = 1.75, 95%CI = 1.12-2.72, I2 = 99%); confirmed in sensitivity analyses for high-quality studies, observational studies, case-control studies, studies with pancreatic cancer as the primary outcome, and in sensitivity analyses for diabetes and obesity but not for pancreatitis and smoking. This association was independent of the duration and Defined Daily Dose of PPI exposure. Rabeprazole had a singular significant association with pancreatic cancer (OR = 5.40, 95%CI = 1.98-14.703, I2 = 87.9%).Conclusion: The class of PPIs is associated with a 1.75-fold increase in pancreatic cancer risk, confirmed in sensitivity analyses.
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Pancreatic Neoplasms/chemically induced , Proton Pump Inhibitors/adverse effects , Humans , Risk FactorsABSTRACT
Fluvastatin (FLV) is a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor often used to lower total and low-density lipoprotein (LDL) cholesterol and for the prevention of adverse cardiovascular events. This drug as well as melittin (MEL), the major component of honeybee venom (Apis mellifera), has shown antineoplastic activity, then representing promising approaches for cancer therapy. However, adverse effects related to the use of FLV and MEL have been reported and very few studies have been carried out to obtain an optimized formulation allowing for combining the two drugs and then maximizing the anticancer activity, then minimizing the needed dosage. In the present study, an optimized formulation in terms of minimized particle size and maximized zeta potential was investigated for its cytotoxic potential in human OVCAR3 ovarian cancer cells. FLV-MEL nano-conjugates, containing a sub-toxic concentration of drug, demonstrated an improved cytotoxic potential (IC50 = 2.5 µM), about 18-fold lower, compared to the free drug (IC50 = 45.7 µM). Cell cycle analysis studies demonstrated the significant inhibition of the OVCAR3 cells proliferation exerted by FLV-MEL nano-conjugates compared to all the other treatments, with a higher percentage of cells accumulating on G2/M and pre-G1 phases, paralleled by lower percentage of cells in G0/G1 and S phases. The synergistic antineoplastic activity of FLV and MEL combined in the optimized formula was also showed by the marked pronecrotic and pro-apoptotic activities, the latter mediated by the modulation of BAX/BCL-2 ratio in favor of BAX. Our optimized FLV-MEL formulation might therefore represents a novel path for the development of specific and more effective antineoplastic drugs directed against ovarian cancer.
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BACKGROUND: A prior meta-analysis found no association between BRCA1 mutation and prostate cancer (PCa). Subsequent BRCA2 mutation studies have shown an association with PCa risk and mortality. We conducted a meta-analysis of overall BRCA mutation carriers and in subgroups to (1) estimate PCa risk in BRCA mutation carriers, (2) evaluate the frequency of BRCA mutation carriers in patients with PCa, and (3) compare cancer-specific survival (CSS) and overall survival (OS) among BRCA mutation carriers and noncarriers. METHODS: We searched the PubMed/MEDLINE, Embase, and Cochrane databases. Unadjusted odds ratio (OR), percentage (%), and hazard ratio (HR) were used to calculate pooled estimates for PCa risk, frequency, and survival, respectively. Subgroup analyses by mutation type ( BRCA1 or BRCA2) were conducted for the three objectives. Further subgroup analyses by study design (age-sex-adjusted or crude), ascertainment method (ascertained or inferred genotyping), population (Ashkenazi Jewish or general population), and survival outcomes (CSS or OS) were conducted. The associations were evaluated using random-effects models, in two-sided statistical tests. RESULTS: A total of 8 cohort, 7 case-control, 4 case-series, 28 frequency, and 11 survival studies were included. Being a BRCA mutation carrier ( BRCA1 and/or BRCA2) was associated with a significant increase in PCa risk (OR = 1.90, 95% CI = 1.58-2.29), with BRCA2 mutation being associated with a greater risk of PCa (OR = 2.64, 95% CI = 2.03-3.47) than BRCA1 (OR = 1.35, 95% CI = 1.03-1.76). The frequency of BRCA1 and BRCA2 carriers in patients with PCa was 0.9% and 2.2%, respectively. OS (HR = 2.21, 95% CI = 1.64-2.30) and CSS (HR = 2.63, 95% CI = 2.00-3.45) were significantly worse among BRCA2 carriers compared to noncarriers, whereas OS (HR = 0.47, 95% CI = 0.11-1.99) and CSS (HR = 1.07, 95% CI = 0.38-2.96) were statistically not significant when comparing BRCA1 carriers and noncarriers. CONCLUSIONS: There is a 1.90-fold greater risk of PCa in overall BRCA mutation carriers. This elevated PCa risk is attributable mainly to a 2.64-fold greater risk of PCa in BRCA2 carriers compared to a moderate 1.35-fold greater risk in BRCA1 carriers. The frequency of BRCA2 mutations was higher than BRCA1 mutations among patients with PCa. BRCA2 but not BRCA1 mutations were associated with higher PCa mortality. The BRCA mutation may be a clinical factor to stratify high-risk patients and guide clinical strategies for more effective treatments for patients with PCa.