Therapeutics and Clinical Risk Management最新文献

Objectives: We evaluated the 6-week mortality of SARS-CoV-2 hospitalized patients treated using a standardized protocol in 2020 in Marseille, France.

Methods: A retrospective monocentric cohort study was conducted in the standard hospital wards at the Institut Hospitalo-Universitaire Méditerranée Infection, between March and December 2020 in adults with SARS-CoV-2 PCR-proven infection.

Results: Of the 2111 hospitalized patients (median age, 67 [IQR 55-79] years; 1154 [54.7%] men), 271 were transferred to the intensive care unit (12.8%) and 239 died (11.3%; the mean age of patients who died was 81.2 (±9.9)). Treatment with hydroxychloroquine plus azithromycin (HCQ-AZ), used in 1270 patients, was an independent protective factor against death (0.68 [0.52 - 0.88]). This effect was consistent for all subgroups of age, comorbidities, severity of the disease and comedications with zinc or corticosteroids. Zinc was independently protective against death (0.39 [0.23 - 0.67]), in a subgroup analysis of patients treated with HCQ-AZ without dexamethasone. The use of high-flow oxygen therapy in elderly patients who were not eligible for intensive care unit transfer saved 19 patients (33.9%).

Conclusions: In our 2020 cohort, treating COVID-19 with HCQ-AZ was associated with lower mortality. These results need to be analyzed in the context of academic discussions about observational studies versus randomized clinical trials. More data will deserve to be analyzed in the SARS-Cov 2 variants, vaccination and post-vaccination era.

Background: Adverse drug events (ADEs) are regarded as the most essential therapeutic issue during management of drug-resistant tuberculosis (DR-TB) due to the long duration of therapy and concurrent use of many second-line medications. This study aimed to determine the incidence and factors associated with ADEs among patients receiving DR-TB treatment at Mulago hospital in Uganda.

Methods: A retrospective cohort study was conducted among 417 DR-TB patient records at Mulago National Referral Hospital from January 2013 to December 2020. Using the data abstraction form, data were collected on socio-demographic and clinical factors, adverse drug events and treatment follow-up time. Data were double entered in Epi data version 3.2 and later exported to Stata version 14.0 for analysis. The incidence rate of adverse drug events was computed using number of cases of ADE divided by overall patient follow-up time. Poisson regression model was used to determine the factors associated with ADEs. The predictors were considered significant at if p< 0.05.

Results: The overall incidence was 5.56 ADEs per 100 person months (95% confidence interval (CI) 5.01, 6.15). Treatment regimens containing an aminoglycoside (incident rate ratio (IRR) 1.106, 95% CI 1.005-1.216 p=0.0391), linezolid (IRR 1.145, 95% CI 1.008-1.229 p = 0.037) or pyrazinamide (IRR 1.226, 95% CI 1.072-1.401 p = 0.003) and the treatment duration (in months) (IRR 1.005, 95% CI 1.001-1.010 p = 0.042) were associated with ADEs.

Conclusion: Regimens containing aminoglycosides, linezolid, or pyrazinamide and increase in treatment duration (months) were associated with an increased risk of ADEs. Clinicians should quickly adopt all oral shorter treatment regimens to obviate the need for aminoglycosides and reduce exposure duration.

Paroxysmal nocturnal hemoglobinuria (PNH) is a rare disorder of hematopoietic stem cells genetically defined by the acquisition of somatic mutations in the X-linked phosphatidylinositol glycan anchor biosynthesis, class A (PIGA) gene. PIGA is essential for the synthesis of glycosyl phosphatidylinositol (GPI) anchor proteins and its mutations result in a deficiency of such molecules on the membrane of blood cells derived from the mutant clone. In particular, the lack of the GPI-linked complement regulatory proteins CD55 and CD59 is responsible for the increased sensitivity of PNH erythrocytes to complement-mediated destruction. Indeed, the classical clinical picture of PNH includes signs and symptoms of intravascular hemolysis along with variable degrees of cytopenia and a strong tendency to thrombosis, hallmarks of the disease. Before the introduction of anti-complement inhibitors, PNH was characterized by a high mortality primarily due to thrombotic events. The approval of the terminal anti-complement inhibitor eculizumab in 2007 introduced a paradigm shift in the treatment of the disease with improvement of the chronic hemolytic process and dramatic reduction of the thrombotic rate. However, eculizumab has a relatively short half-life when considering a life-long treatment, with obvious consequences as to the quality of life of treated patients necessitating relatively frequent drug administrations. Moreover, up to 30% of PNH patients undergoing eculizumab therapy show a suboptimal response, continuing to require red cell transfusions because of extravascular hemolysis or breakthrough hemolytic episodes. In 2019, the FDA approved the second-generation C5 inhibitor ravulizumab, a long-lasting agent with a better control of disease manifestations. Herein, we discuss the use of ravulizumab in PNH, its differences with first-generation C5 inhibitors, the research evidence supporting the safety and efficacy of this drug and its impact on costs for health systems and quality of life of PNH patients.

Objective: To evaluate the associations between different types of diabetes distress and health-related quality of life (HRQOL) among patients with type 2 diabetes (T2DM) using antihypertensive and/or antihyperlipidemic medications in Indonesia and to explore the differences between those using only antihypertensive, only antihyperlipidemic, or both medications.

Methods: A multicenter cross-sectional study was conducted in Community Health Centers in three cities in Indonesia among patients with T2DM aged at least 18 years who were using antihypertensive and/or antihyperlipidemic medications. Diabetes distress subscales (emotional, regimen-related, interpersonal, and physician-related distress) and HRQOL were assessed using a validated diabetes distress scale-17 and EQ-5D-5L scale, respectively. Multiple linear regression models were used to evaluate the associations between different types of diabetes distress and HRQOL adjusting for confounders.

Results: Most of the 503 participants were females (67.6%) and aged 60-69 years (40.8%). Emotional distress was negatively associated with HRQOL among the whole group of patients (β: -0.08; 95% confidence interval (CI): -0.10, -0.05; p < 0.001). This association was similar across all therapeutic subgroups. Regimen-related distress (β: -0.06; 95% CI: -0.09, -0.03; p < 0.001) and interpersonal distress (β: -0.02; 95% CI: -0.05, -0.01; p = 0.022) were negatively associated, whereas physician-related distress (β: 0.04; 95% CI: 0.01, 0.07; p = 0.037) was positively associated with HRQOL among the whole group. These associations were also observed among those using only antihypertensive medication.

Conclusion: Emotional distress affects HRQOL in T2DM patients treated for cardiovascular comorbidities, independent of antihypertensive and/or antihyperlipidemic medication use.

Objective: The current work aimed to examine the rates of and risk factors for mortality and readmission after heart failure (HF).

Setting: A systematic search was carried out in PubMed, the Cochrane Library, and EMBASE to identify eligible reports. The random-effects model was utilized to evaluate the pooled results.

Participants: A total of 27 studies with 515,238 participants were finally meta-analysed. The HF patients had an average age of 76.3 years, with 51% of the sample being male, in the pooled analysis.

Primary and secondary outcome measures: The outcome measures were 30-day and 1-year readmission rates, mortality, and risk factors for readmission and mortality.

Results: The effect sizes for readmission and mortality were estimated as the mean and 95% confidence interval (CI). The estimated 30-day and 1-year all-cause readmission rates were 0.19 (95% CI 0.14-0.23) and 0.53 (95% CI 0.46-0.59), respectively, while the all-cause mortality rates were 0.14 (95% CI 0.10-0.18) and 0.29 (95% CI 0.25-0.33), respectively. Comorbidities were highly prevalent in individuals with HF.

Conclusion: Heart failure hospitalization is followed by high readmission and mortality rates.

Objective: Oral sodium bicarbonate is often used to correct acid-base disturbance in patients with chronic kidney disease (CKD). However, there is little evidence on patient-level benign outcomes to support the practice.

Methods: We conducted a systematic review and meta-analysis to examine the efficacy and safety of oral sodium bicarbonate in CKD patients. A total of 1853 patients with chronic metabolic acidosis or those with low-normal serum bicarbonate (22-24 mEq/L) were performed to compare the efficacy and safety of oral sodium bicarbonate in patients with CKD.

Results: There was a significant increase in serum bicarbonate level (MD 2.37 mEq/L; 95% CI, 1.03 to 3.72) and slowed the decline in estimated glomerular filtration rate (eGFR) (MD -4.44 mL/min per 1.73 m², 95% CI, -4.92 to -3.96) compared with the control groups. The sodium bicarbonate lowered T50-time, an indicator of vascular calcification (MD -20.74 min; 95% CI, -49.55 to 8.08); however, there was no significant difference between the two groups. In addition, oral sodium bicarbonate dramatically reduced systolic blood pressure (MD -2.97 mmHg; 95% CI, -5.04 to -0.90) and diastolic blood pressure (MD -1.26 mmHg; 95% CI, -2.33 to -0.19). There were no statistically significant body weight, urine pH and mean mid-arm muscle circumference.

Conclusion: Treatment of metabolic acidosis with sodium bicarbonate may slow the decline rate of kidney function and potentially significantly improve vascular endothelial function in patients with CKD.

Prospero registration number: CRD42020207185.

Purpose: Currently, there is no uniform standard to guide postoperative adjuvant chemotherapy for patients with multifocal non-small cell lung cancers (NSCLCs) ≤3 cm. Therefore, there is an urgent need to explore prognostic molecular markers to identify high-risk patients with multifocal NSCLCs ≤3 cm. We aimed to explore the potential value of metastasis-associated protein 1(MTA1) expression in risk stratification of patients with multifocal NSCLCs ≤3 cm.

Methods: We retrospectively analyzed the clinical data and postoperative survival data of patients with multifocal NSCLCs ≤3 cm. Paraffin-embedded tissue sections were used for immunohistochemistry. Semiquantitative immunoreactivity scoring (IRS) system was used to evaluate the nuclear expression of MTA1. SPSS software (version 23.0) was used to analyze the data.

Results: The IRS of MTA1 nuclear expression in 259 lesions of 119 patients ranged from 2.2 to 11.7 (median: 5.6). Our results showed that MTA1 expression was highest in high-risk pathological subtypes of lung adenocarcinoma. MTA1 expression in multiple primary lung cancers (MPLCs) was lower than that in intrapulmonary metastases (IPMs). The median follow-up duration was 25.97 months. The disease-free survival (DFS) of patients with MPLCs was significantly better than that of patients with IPMs, and the DFS of patients with high MTA1 expression was significantly worse than that of patients with low MTA1 expression. Multivariate Cox analysis showed that high MTA1 expression (hazard ratio: 7.937, 95% confidence interval: 2.433-25.64, p =0.001) was a statistically significant predictor of worse DFS in patients with multifocal NSCLCs ≤3 cm.

Conclusion: MTA1 expression can stratify the risk in patients with multifocal NSCLCs ≤3 cm. Patients with MTA1 immunohistochemical score >5.6 are at a high risk of postoperative recurrence, and these patients may benefit from postoperative adjuvant chemotherapy.

Purpose: Several randomized clinical trials (RCTs) investigated the effects of the manual placental removal on hemorrhage or other hemorrhage-related complications compared with the spontaneous placental removal during cesarean section (CS), while the results remained controversial and were inconsistent. The purpose of this meta-analysis was to quantify the pooled effects of the methods of placental removal on hemorrhage during CS.

Patients and methods: A systematic literature search was conducted using PubMed, EMBASE, Web of Science, and Google Scholar. Heterogeneity was tested by I ² statistics and Q-statistic. The random-effects model or fixed-effects model were used to calculate the pooled effect for the included studies according to heterogeneity. And the term of standardized mean difference (SMD) with 95% confidence intervals (CI) was pooled and estimated the effects across all studies.

Results: A total of nine RCTs were included in this meta-analysis. Compared with spontaneous group, manual placental removal increased the amount of hemorrhage (SMD = 0.53, 95% CI [0.12, 0.94]; Z = 2.54, P = 0.011) and increased the risk of endometritis (OR = 1.84, 95% CI [1.31, 2.58]; Z = 3.52, P < 0.0001). In contrast, there was no significant difference concerning the operating time (SMD = -0.30, 95% CI [-0.85, 0.24]; Z = 1.09, P = 0.276), the length of hospital stays (SMD = 0.11, 95% CI [-0.08, 0.30]; Z = 1.11, P = 0.265), and blood transfusion requirement (OR = 1.36, 95% CI [0.91, 2.04]; Z = 1.52, P = 0.129), respectively.

Conclusion: Comparing with spontaneous placental removal, manual placental removal appeared to be less positive effect during CS. Because of the limitations of this meta-analysis, more high-quality RCTs are needed to confirm our findings.