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Introduction: Warfarin is an anticoagulant whose efficacy depends on reaching and maintaining an INR (International Normalized Ratio) within therapeutic ranges. Up to 60% of interindividual dose-response variability can be explained by pharmacogenes, in this regard there are no studies in Peru. We studied the effect of the CYP4F2 gene on the dose of warfarin in Peruvian patients. Material and Methods: A descriptive and ambispective observational study was carried out with patients seen in the Grau ESSALUD Hospital Hematology Service, Lima, Peru, selected by non-probabilistic convenience sampling. The inclusion criteria were patients anticoagulated for more than three months and with stable doses of warfarin (same dose for at least three outpatient visits and with an INR in therapeutic ranges of 2.5-3.5). Analysis of the CYP4F2 gene was performed by taking a DNA sample from peripheral blood. Results: 70 patients with a mean age of 69.6 + 13.4, male 38 (54.39%) and female 32 (45.7%) entered the study. The mean dose of warfarin was 31.6 + 15.2 mg/week. The genotypic frequency of the CYP4F2 gene, rs2108622 variant (C>T) was 55 (78%), 13 (19%) and 2 (3%) of CC, CT, TT, respectively. No deviation from the Hardy-Weinberg equilibrium was found in the variants studied (p=0.56). Mean warfarin doses/week of the CC, CT, TT genotypes were 30.34 + 11.98; 36.4 + 25.6 and 36.25 + 1.8 mg/week, respectively (p=0.397). Conclusion: In conclusion, it appears that CYP4F2 gene genotypes do not have a significant effect on warfarin dose. [ABSTRACT FROM AUTHOR]

Aims: The aim of this study was to investigate the association between VKORC1 and CYP2C9 genes polymorphisms and the maintenance dose of warfarin in Peruvian patients. Methods: An observational study was conducted on outpatients from the Hospital Grau ESSALUD in Lima, Peru. The participants were selected using nonprobabilistic convenience sampling. Inclusion criteria required patients to have been on anticoagulation therapy for >3 months, maintain stable doses of warfarin (consistent dose for at least 3 outpatient visits), and maintain an international normalized ratio within the therapeutic range of 2.5–3.5. DNA samples were obtained from peripheral blood for gene analysis. Results: Seventy patients (mean age of 69.6 ± 13.4 years, 45.7% female) were included in the study. The average weekly warfarin dose was 31.6 ± 15.2 mg. The genotypic frequencies of VKORC1 were as follows: 7.1% (95% confidence interval, 2.4–15.9) for AA; 44.3% (32.4–56.7) for GA; and 48.6% (36.4–60.8) for GG. No deviation from the Hardy–Weinberg equilibrium was observed in the variants studied (P =.56). The mean weekly warfarin doses for AA, GA and GG genotypes were 16.5 ± 2.9, 26.5 ± 9.5 and 37.9 ± 17.1 mg, respectively (P <.001). The genotypic frequencies of CYP2C9 were as follows: 82.8% (72.0–90.8) for CC (*1/*1); 4.3% (1.0–12.0) for CT (*1/*2); and 12.9% (6.1–23.0) for TT (*2/*2). We did not find a significant association between the CYP2C9 gene polymorphism and the dose of warfarin. Conclusions: The AA genotype of the VKORC1 gene was associated with a lower maintenance dose of warfarin in Peruvian patients. [ABSTRACT FROM AUTHOR]

Background: With the Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic posing a global health emergency, selfmedication with ivermectin has been observed in certain Latin American countries. This study aimed to characterize the clinical features of liver injury associated with ivermectin when used as self-medication for treating coronavirus disease 2019 (COVID-19). Materials and Methods: We reviewed the clinical records of patients diagnosed with severe COVID-19 at the Emergency Room of Rebagliati Hospital in Lima, Peru, in March 2021. The criteria of the Drug-Induced Liver Injury (DILI) Expert Working Group and the Council for International Organizations of Medical Sciences/Roussel Uclaf Causality Assessment Method (CIOMS/RUCAM) were utilized to establish the diagnosis of drug-induced liver injury and assess causality, respectively. Results: We report five cases of ivermectin-induced liver injury (IILI), comprising four men and one woman, with a mean age of 49.3±12.3 years. The mean daily dose, duration, and total dose of ivermectin were 32.9±21.8 mg/day, 2.6 ± 0.6 days, and 89.6±71.4 mg, respectively. On average, IILI occurred 11±3.8 days after the initiation of treatment, and none of the cases developed jaundice. The mean levels of alanine aminotransferase, alkaline phosphatase, and gamma-glutamyl transferase were elevated 8±4.4, 1.7±0.9, and 10.9±5.0 times above the upper limit of normal, respectively. Two patients exhibited a hepatocellular pattern, two had a mixed pattern, and one displayed a cholestatic pattern. All cases were classified as mild and achieved recovery. Causality assessment categorized four cases as "possible" and one case as "highly probable.". Conclusion: The findings emphasize the need for further pharmacovigilance studies on IILI when used for COVID-19 treatment. [ABSTRACT FROM AUTHOR]

Introduction. The need for comprehensive geriatric assessment (CGA) in older adults with cancer is increasing, which makes it necessary to have a screening instrument to identify those who would benefit from this evaluation. This study aimed to investigate diagnostic performance of the Timed Up and Go test (TUG) for identifying vulnerable or frail older adults with cancer who might benefit from CGA. Material and methods. This observational and retrospective study took place at the geriatric center of Almenara Hospital in Lima, Peru We extracted CGA reports from electronic medical records of outpatients and inpatients aged 60 years and older with cancer, who were evaluated between November 2022 and July 2023. Patients were classified based on SIOG-2 (International Society of Geriatric Oncology) criteria as fit, vulnerable, or frail, based on scales including Activities of Daily Living (ADL), Instrumental ADL, Mini-Nutritional Assessment (MNA), Mini-Mental State Exam (MMSE), Geriatric Depression Scale, and Cumulative Illness Rating Scale-Geriatrics (CIRS-G). For the study, two groups were formed: fit patients and non-fit patients (vulnerable plus frail). We estimated sensitivity, specificity, and positive predictive values of the TUG test. The accuracy of the TUG test was analyzed using the area under the receiver operating characteristic curve (AUC). Results. Among the 283 included patients, 154 were men (54.4%) and 129 women (45.6%), and the mean age was 76.8 ± 15.8 years. The most common neoplasms were colorectal (19.4%), stomach (15.2%), prostate (9.9%), and bile duct cancers (8.1%). The percentage of fit and non-fit patients was 21.9% and 78.1%, respectively. When the TUG test was equal to or greater than 15.5 seconds, sensitivity, specificity, positive predictive value, and AUC were 68.5% (95% CI 61.9-74.5), 88.5% (77.8-95.3), 95.6% (91.1-98.2), and 84.8% (0.80-0.90), respectively. Conclusions. A TUG test result equal to or greater than 15.5 seconds demonstrated good screening properties for identifying older cancer patients who were vulnerable or frail and could benefit from CGA. [ABSTRACT FROM AUTHOR]

Introduction: Diffuse large B-cell lymphoma (DLBCL) is a common neoplasm in older people; in this group, personalized therapies are important because while some patients are frailer, others are fitter. However, knowledge is lacking as to which frailty identification tools are most commonly used in older patients living with DLBCL. The aim of this systematic review was to address this knowledge gap. Material and methods: We searched the PubMed, EMBASE, and Cochrane databases and Google Scholar for studies published before December 2022. We included studies conducted with DLBCL patients aged 60 years or older, where a frailty classification (i.e. fit, unfit, or frail) had been reported in the context of prognostication and/or personalization of treatment. Results: Sixteen studies were included in our review, with a total of 8,705 DLBCL patients (mean age 76 years, 54% men). Overall, 42% were classified as 'frail', and 40% as 'fit'. The most frequent frailty identification method was the Comprehensive Geriatric Assessment (CGA) (simplified: 75%, full: 13%), followed by the physical phenotype (6%) and the cumulative deficits index (6%) tools. The most common CGA domains utilized in the classification of frailty were the evaluation of basic activities of daily living (86%), instrumental activities of daily living (63%), comorbidities (81%), and geriatric syndromes (19%). Conclusion: Two in five DLBCL patients aged 60 years or older were classified as frail, and an almost equal proportion as fit, most commonly post-application of simplified CGA. More studies are required to validate specific frailty identification instruments in this population. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to conduct a meta-analysis of the frequency of isoniazid-induced liver injury (INH-ILI) in patients receiving isoniazid (INH) preventative therapy (IPT). Background: The frequency of hepatotoxicity (drug-induced liver injury: DILI) of antituberculosis drugs has been studied, especially when INH, rifampin, and pyrazinamide are co-administered. However, little is known about the frequency of DILI in patients with latent tuberculosis infection (LTBI), where IPT is indicated. Methods: We searched PubMed, Google Scholar, and the Cochrane Database of Systematic Reviews for studies reporting the frequency of INH-ILI in patients with IPT using one or more diagnostic indicators included in the criteria of the DILI Expert Working Group. Results: Thirty-five studies comprising a total of 22,193 participants were included. The overall average frequency of INH-ILI was 2.6% (95% CI, 1.7-3.7%). The mortality associated with INH-DILI was 0.02% (4/22193). Subgroup analysis revealed no significant differences in the frequency of INH-ILI in patients older or younger than 50 years, children, patients with HIV, candidates for liver, kidney, or lung transplant, or according to the type of study design. Conclusion: The frequency of INH-ILI in patients receiving IPT is low. Studies on INH-ILI are needed where the current DILI criteria are used. [ABSTRACT FROM AUTHOR]

Aim: The aim of the present study was to review in VigiBase the reports of serious hepatic disorders associated with the use of ivermectin for COVID-19 in adults. Background: In the face of the global health emergency caused by SARS-CoV-2, ivermectin, among other drugs, has been repurposed in some Latin American countries to treat COVID-19. Studies are needed on the safety of ivermectin for this new indication. VigiBase is the WHO pharmacovigilance database that registers all individual case safety reports (ICSRs) from more than 130 countries. Methods: We extracted the ICSRs of men or women aged ≥ 18 years and dated between 1 January 2020 and 7 March 2021 which included an association with the use of ivermectin. Results: Of 1393 ICSRs associated with ivermectin, 60 (4.3%) were registered as "serious." Ivermectin had been used for COVID-19 in 25 of those cases. Among the latter, 6 experienced hepatic disorders (hepatitis, hepatocellular injury, cholestasis, increased alanine aminotransferase and/or aspartate aminotransferase levels, abnormal liver function tests). Conclusion: The safety of the use of ivermectin should be studied more exhaustively, especially as regards the possibility of hepatic disorders developing when the drug is used for COVID-19. [ABSTRACT FROM AUTHOR]

Background: There is caurrently great interest in establishing the relationship between the severity of SARS-COV-2 infection in hypertensive patients who use angiotensin II antagonists (AIIRAs). Objective: To study the relationship between the previous use of angiotensin II antagonists (ARB) in hypertensive patients and mortality from COVID-19. Materials and methods: A retrospective observational study was carried out in a tertiary care hospital in Lima, Peru, in hypertensive patients hospitalized in March 2021 for severe COVID-19. Results: A total of 101 patients entered the study, with a mean age of 70.1 + 12.0 and 48% male. ARB users and non-users were 45 (45.6%) and 56 (54.4%), respectively. The Charlson Comorbidity Index was higher in the ARB group (3.6 + 1.56 vs 3.04 + 1.24) (p<0.05). Total and male vs women mortality, among those using ARBs or not, were 57.8% vs 62% (p = 0.633) and 36.36% vs 63.64% (p <0.05), respectively. Mean lactate dehydrogenase concentration was lower in those taking ARBs compared to non-users, 394.18 + 152.3 vs 503.5 + 252.7 (p<0.05); No significant difference was observed in the leukocyte count and serum levels of C-Reactive Protein, Ferritin, D-dimer and fibrinogen. Conclusion: Among hospitalized COVID-19 patients with hypertension, prior use of ARBSs was not associated with mortality risk. [ABSTRACT FROM AUTHOR]

Objective: To describe the clinical characteristics of drug-induced liver injury (DILI) in multidrug-resistant tuberculosis (MDR-TB) patients. Materials and methods: A retrospective study conducted in hospitalized patients with MDR-TB and DILI. The criteria of the DILI Expert Working Group were used for the diagnosis of DILI, and the RUCAM (Roussel Uclaf Causality Assessment Method) for the causality analysis. The specific association between DILI and antitubercular drugs was established by drug rechallenge or discontinuation and recovery. Results: Seven cases of MDR-TB and DILI are described in this research. The mean age (standard deviation) was 39.10 (3.30) years. Mean DILI occurred 30.40 (27.70) days after starting the treatment. Three (43.00 %) patients presented jaundice. Regarding the type of injury, four (57.00 %) had hepatocellular injury and three (43.00 %) cholestatic injury. Four patients showed mild DILI and three moderate DILI. All the patients had taken pyrazinamide (pyrazinamide alone: four patients; pyrazinamide and ethionamide: one patient; pyrazinamide, rifampin and isoniazid: one patient; pyrazinamide and rifampicin: one patient). The mean hospital stay was 48.10 (48.70) days. The mean serum alkaline phosphatase (AP), alanine aminotransferase (ALT) and gamma-glutamyl-transpeptidase (GGT) were 2.40 (1.10), 7.90 (7.10) and 5.60 (3.70) times the upper limit of normal (ULN), respectively. The mean total bilirubin was 2.30 (2.00), with a range of 0.50 to 6.40 mg/dl. As part of the discharge plan, quinolones were given to seven patients (levofloxacin: six patients; ofloxacin: one patient) and amoxicillin/clavulanic acid was added to one patient. Conclusions: MDR-TB patients may develop DILI after the first month of treatment. Hepatocellular injury was the most common type of liver injury, and pyrazinamide was the most frequently used antimycobacterial. [ABSTRACT FROM AUTHOR]

Background. It has been postulated that metformin could have anti-SARS-CoV-2 action. This raises the hypothesis that people who take metformin may have lower SARS-CoV-2 severity and/or mortality. Objectives. To conduct a meta-analysis of the association between the use of Metformin and risk of severity and mortality in SARS-CoV-2 infection. Methods. We searched PubMed, EMBASE, Google scholar, the Cochrane Database of Systematic Reviews and preprint servers (medRxiv and Research Square) for studies published between December 2019 and January 2021. Data was extracted on study location, year of publication, design, number of participants, sex, age at baseline, body mass index, and exposure and outcome definition. Effect statistics were pooled using random effects models with 95% confidence intervals (CI). The quality of included studies was assessed with the Newcastle-Ottawa Scale (NOS). Results. Thirty-two observational studies were included, combining to a total sample of 44306 participants. The mean NOS score of included studies was 7.9. Results suggested that metformin use was associated with a reduced risk of SARS-CoV-2 mortality (OR = 0.56, 95% CI: 0.46-0.68, P < 0.001; 22 studies) but not with disease severity (OR = 0.85, 95% CI: 0.71-1.02, P = 0.077; 15 studies). In the subgroup analysis, metformin reduces the risk of mortality (OR = 0.69, 95% CI: 0.55-0.88; P = 0.002) and severity (OR = 0.83, 95% CI: 0.70-0.97, P = 0.023) in patients aged 70 and above. Conclusions. The use of metformin was associated to lower risk of mortality from SARS-CoV-2 infection. This association does not imply causation and further research is required to clarify potential mechanisms. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the nutritional status as a predictor of mortality in elderly people with gastric cancer. Materials and methods: An observational, prospective and analytical study which included 47 patients over 60 years of age with a diagnosis of gastric cancer, referred to the geriatric department of the Hospital Nacional Guillermo Almenara from March 2014 to October 2015. The Body Mass Index (BMI) and the Mini Nutritional Assessment Short-Form (MNA-SF) were used to evaluate the patients. Results: Forty-seven (47) patients with a diagnosis of gastric cancer were included: 33 (70.2 %) were males, and the mean age was 75.52 (SD +/- 6.88) years for males and 77 (SD + / - 7.66) years for women. When performing the survival analysis, it was found that the nutritional assessment using the MNA-SF obtained statistical significance (p <0.05). Conclusions: In conclusion, A poor nutritional status is a prognostic factor of gastric cancer mortality in elderly people. [ABSTRACT FROM AUTHOR]

Context: In the last decades, patients with chronic terminal diseases have had more frequent visits to emergency services. Aims: This study aims to determine the proportion of terminal illness in patients readmitted to emergency room, to evaluate the use of this service and rate of death. Settings and Design: A cross-sectional study in a tertiary hospital with 120 stretchers which annually reports 160 thousand attentions and 22 thousand admissions. Subjects and Methods: Included 18-year-old patients or older who were readmitted to emergency room. Patient and/or caregiver were interviewed; medical record was reviewed and made 1-year follow-up. Terminal cancer was determined by histologically confirmation in Stage IV and nononcologic terminal disease by total functional dependence (Katz index) or severe cognitive impairment (Pfeiffer questionnaire) in addition of advanced organ failure. Statistical Analysis Used: Fisher's exact and U of Mann--Whitney tests for two independent samples. Results: Ninety-two (26%) of 349 were readmissions; 29 (36.7%) of 79 evaluated patients were identifying with terminal disease. Eleven (38%) of them had cancer (genitourinary in 64%). Nononcologic terminal disease was identified in 18 cases (62%) (Neurodegenerative involvement in 50%). More frequent symptoms were dyspnea 41%, mental confusion 24%, and pain 21%. Terminal patients had 6.2 (standard deviation 8.2) emergency visits at last year, being admitted 48,6% of these visits. Six-month mortality rate was 73 and 61% in oncologic and nononcolgic patients, respectively (P < 0.05). Conclusions: End-stage disease is frequent in readmitted patients to emergency, more of nononcologic kind. These patients use frequently emergency service, with high mortality (more elevated in oncologic). [ABSTRACT FROM AUTHOR]

Objective: To investigate the use and accessibility to drugs in patients covered by the National Social Security Argentina (SNSSA). Material and Methods: We studied the accessibility to drugs that were consumed the last 15 days before hospitalizaron, in 500 patients in 5 hospitals in the area of Buenos Aires. Results: Of the 500 patients surveyed, 292 patients had medical prescription 15 days before being hospitalized, 171 (58.6%) patients had no access to medicines. The mean age was 47.4 + 18.8 and range of 0.1 to 89 years; 173 (34.6%) were male and 327 (65.4%) female. The distribution of coverage of patients studied was predominantly belonging to the Public System with 280 (56.0 %), Social Work 175 (35.0 %) and Prepay 45 (9.0%). The reasons for non- accessibility were mainly: the errors in processes ranging from issuing prescriptions, improper filling of forms to non-availability of medicines in pharmacies. Conclusions: The lack of access to medicines for patients covered by SNSSA is a common phenomenon. [ABSTRACT FROM AUTHOR]