Episodes Of Serious Adverse Events Research Articles

Efficacy and Safety of Modafinil for Treatment of Amphetamine-Type Stimulant Use Disorder: A Systematic Review and Meta-Analysis of Randomized Placebo-Controlled Trials: Efficacité et innocuité du modafinil pour le traitement des troubles liés à l'usage de stimulants de type amphétamine : revue systématique et méta-analyse d'essais randomisés contrôlés par placebo.

Amphetamine-type stimulants (ATSs) are related to significant harm worldwide, with limited effective pharmacological treatments for ATS use disorder (ATSUD). Modafinil has been explored as a potential treatment for ATSUD. This systematic review and meta-analysis (PROSPERO ID: CRD42023388487) aimed to evaluate the efficacy and safety of modafinil for the treatment of ATSUD. A comprehensive search of major indexing sources and trial registries, from inception to search date, was conducted on February 15, 2023, and updated on October 31, 2023. Eligible studies were randomized placebo-controlled trials (RCTs) of modafinil in individuals meeting the criteria for the Diagnostic and Statistical Manual of Mental Disorders, fourth and fifth editions, diagnoses of ATSUD. Eligible studies were assessed for risk of bias, using the Cochrane Risk of Bias tool. The primary outcome included the effect of modafinil on ATS use. Secondary outcomes included retention in treatment, ATS craving, treatment discontinuation due to adverse events (AEs), and serious AEs. Subgroup analysis by modafinil dose was conducted where appropriate. Risk ratio (RR) or Peto's odds ratio (OR) was calculated for the meta-analysis of dichotomous variables and standardized mean difference (SMD) was calculated for the random-effect meta-analysis of continuous variables. Five RCTs (N = 451 participants) were included. Modafinil did not significantly impact ATS use (RR = 0.99; 95% CI, 0.97 to 1.02; p = 0.655), retention in treatment (RR = 1.02; 95% CI, 0.91 to 1.14; p = 0.799), ATS craving (SMD = -0.36; 95% CI, -1.19 to 0.47; p = 0.398), or treatment discontinuation due to AEs (Peto's OR = 0.48; 95% CI, 0.20 to 1.14; p = 0.100). These results were consistent across subgroup analyses. More episodes of serious AEs were reported in the modafinil group than in the placebo group, at higher doses (Peto's OR = 4.80; 95% CI, 1.18 to 19.56, p = 0.029). There is currently no evidence suggesting that modafinil has a statistically significant effect on efficacy outcomes in populations with ATSUD. Continued research into effective treatments and harm reduction strategies for ATSUD is essential.

Drug-Drug Interactions With Cyclosporine in the Anti-Hepatitis C Viral PrOD Combination Regimen of Paritaprevir/Ritonavir-Ombitasvir and Dasabuvir in Organ Transplant Recipients With Severe Hepatic Fibrosis or Cirrhosis.

The clinical guidelines suggest that the dosing of cyclosporine (CsA), during combination therapy with paritaprevir/ritonavir-ombitasvir and dasabuvir (PrOD), would be only one-fifth of the pre-PrOD total daily dose to be administered once daily. However, this dosing may not be applicable to all patients depending on their clinical condition. This study focuses on the pharmacokinetic dynamics of PrOD with CsA in Asian organ transplant recipients with severe liver fibrosis or cirrhosis who undergo concurrent treatment with PrOD treatment and CsA. The efficacy and safety of PrOD treatment was also evaluated. Data from 7 patients obtained between January 2017 and September 2017 were retrospectively analyzed. Determinations of the blood concentrations of CsA were made, whether used as a single treatment or in combination therapy with PrOD. The combination regimen compared with CsA administered alone resulted in a 4.53-fold and 5.52-fold increase in the area under the concentration-time curve from time 0-12 hours (AUC0-12 h) of CsA on days 1 and 15, respectively. In addition, the maximal concentration, time to maximum concentration, and terminal phase elimination half-life (t1/2) of CsA were increased during the combined treatment of PrOD and CsA. The authors proposed reducing the CsA dosage during PrOD treatment to one-seventh of that of the pre-PrOD treatment of the total daily dose to maintain target CsA levels. All patients achieved sustained virologic responses at week 12. There were no episodes of serious adverse events or graft rejections observed. Although the combination with PrOD significantly affects the pharmacokinetics of CsA, it is effective and safe with regular monitoring of the CsA blood concentrations and appropriate CsA dose adjustment.

IRWIS (IDegLira Real world Indian Study): A Real-World Observational Study For Use of IDegLira In Indian Patients

IntroductionNovel therapies, like the fixed dose coformulation of insulin degludec (100 U/ml) and liraglutide (3.6 mg/ml) (IDegLira), are key to achieving glycemic targets in some patients with difficult to control diabetes. Our objective was to evaluate the efficacy and safety of IDegLira in Indian patients with type 2 diabetes mellitus that was inadequately controlled on multiple oral anti-diabetic agents with or without insulin therapy. MethodsThis was a multicenter, retrospective, real-world observational study. Clinical case records were analyzed for 61 patients with poorly controlled type 2 diabetes mellitus (HbA1c >8.5%) who were treated with IDegLira over a 26-week period. ResultsThere were significant reductions in mean fasting (112.51± 24.80 vs. 188.48 ± 52.19 mg/dl; P <0.001) and postprandial plasma glucose levels (166.21 ± 29.12 vs. 289.19 ± 98.75 mg/dl; P <0.001) and HbA1c (7.61 ± 0.92 vs. 9.81 ± 1.78%; P <0.001) after 26 weeks of treatment with IDegLira. There were significant changes in mean weight (79.82 ± 10.75 vs. 86.58 ± 10.79 kg) and BMI (30.92 ± 3.86 vs. 33.17 ± 4.01kg/m2). While there was no significant decrease in diastolic blood pressure, there was a drop of around 4 mm in systolic blood pressure. Eleven episodes of hypoglycaemia were reported in 6 patients. No patients reported any episodes of serious adverse events. ConclusionsIDegLira had significant beneficial effects on glycaemic control and body weight over a 6-month period in Indian patients with type 2 diabetes that was poorly controlled on multiple oral anti-diabetic agents with or without insulin therapy. IDegLira was also found to be safe in this patient population.

Predictors of toxicity-related hospitalization in four randomized studies of 5-fluorouracil-based chemotherapy in metastatic colorectal cancer.

To evaluate the predictors of toxicity-related hospitalization associated with various chemotherapy regimens among metastatic colorectal cancer patients METHODS: This pooled analysis includes patient-level datasets from four randomized clinical studies (NCT00272051; NCT00305188; NCT00115765; NCT00364013). Through univariate and multivariate logistic regression analyses, factors predicting the development of serious adverse events, fatal adverse events, and toxicity-related hospitalizations were determined. A total of 2533 patients were included in the current study. A total of 1010 patients (39.9%) experienced one or more episodes of serious adverse events. These include 914 patients (36.1%) who were hospitalized at least once and 148 patients (5.8%) who suffered from a fatal adverse event. Within multivariate logistic regression analysis, older age (P < 0.001), higher ECOG score (P < 0.001), bevacizumab-containing chemotherapy (P < 0.001), and panitumumab-containing chemotherapy (P < 0.001) were predictive of hospitalization. Similarly, older age (P < 0.001), higher ECOG score (P < 0.001), and panitumumab-containing chemotherapy (P = 0.003) were predictive of fatal adverse events in multivariate logistic regression analysis. Moreover, in a multivariate Cox regression analysis, hospitalization was predictive of worse overall survival (P < 0.001) and progression-free survival (P < 0.001). Older age, poorer performance status, and bevacizumab- and panitumumab-containing regimens are associated with a higher risk of hospitalization. Moreover, hospitalization is predictive of worse overall and progression-free survival.

Oral 5-aminolevulinic acid mediated photodynamic diagnosis using fluorescence cystoscopy for non-muscle-invasive bladder cancer: A randomized, double-blind, multicentre phase II/III study

Photodynamic diagnosis (PDD) of non-muscle-invasive bladder cancer (NMIBC) following transurethral administration of a hexalated form of 5-aminolevulinic acid (5-ALA), 5-ALA hexyl ester, is widely performed in Western countries. In this study, effectiveness and safety of the oral administration of 5-ALA is assessed in a phase II/III study of PDD for NMIBC in comparison to those of conventional white-light endoscopic diagnosis. Patients with NMIBC were allocated to two groups that were orally administered 10 and 20 mg/kg of 5-ALA under the double-blind condition. Effectiveness was evaluated by setting the primary endpoint to sensitivity. Safety was also analyzed. Moreover, clinically recommended doses of 5-ALA was also investigated as an investigator-initiated multicenter cooperative clinical trial in which five medical institutions participated. All 62 enrolled patients completed the clinical trial. The sensitivities of PDD were higher (84.4 and 75.8% in the 10 and 20 m g/kg-groups, respectively) than those of conventional endoscopic diagnosis (67.5 and 47.6%, respectively) (p = 0.014 and p < 0.001, respectively). Five episodes of serious adverse events developed in four patients; whereas a causal relationship with the investigational agent was ruled out in all episodes. This investigator-initiated clinical trial confirmed the effectiveness and safety of PDD for NMIBC following oral administration of 5-ALA. Both doses of 5-ALA may be clinically applicable; however, the rate of detecting tumors only by PDD was higher in the 20 mg/kg-group suggesting that this dose would be more useful.

Treatment outcome of late steroid-resistant nephrotic syndrome: a study by the Midwest Pediatric Nephrology Consortium.

Idiopathic nephrotic syndrome (NS) in children is classified as steroid sensitive or steroid resistant. Steroid sensitivity typically portends a low risk of permanent renal failure. However, some initially steroid-sensitive patients later develop steroid resistance. These patients with late steroid resistance (LSR) are often treated with immunosuppressant medications, but the effect of these additional drugs on the long-term prognosis of LSR is still unknown. A retrospective chart review was performed on patients diagnosed with idiopathic NS and subsequent LSR during the 8-year study period from 2002 up to and including 2009, with a minimum of 2 years of follow-up. Primary outcome measures were proteinuria and renal function. A total of 29 patients were classified as having LSRNS. The majority of patients received treatment with calcineurin inhibitors and/or mycophenolate mofetil. Seven patients received three or more non-steroid immunosuppressant medications. Sustained complete or partial remission was achieved in 69 % of patients. Three developed end-stage renal disease, and all others maintained normal renal function. There were 13 episodes of serious adverse events, none of which were fatal or irreversible. Most patients with LSRNS responded to immunosuppressive therapy by reduction or resolution of proteinuria and preservation of renal function. The results suggest that immunosuppressive treatment is a viable option in NS patients who develop LSR.

Phase II trial of neoadjuvant 5-fluorouracil, epirubicin and cyclophosphamide (FEC100) followed by weekly paclitaxel and trastuzumab (PH) for HER2 positive breast cancer (Kinki Multidisciplinary Breast Oncology Group; KMBOG-0402).

Abstract Abstract #3160 Background: Achievement of pathological complete response (pCR) by primary systemic chemotherapy (PST) correlates with improved disease-free survival in operable breast cancer patients. Based on data of the higher pCR rate with concomitant chemotherapy and trastuzumab (H) presented by the randomized prospective trial (Buzdar AU, et al: JCO 23:3676-85; 2005), we performed a multi-center, prospective phase II study to assess the addition of H to primary systemic chemotherapy in HER2+ pts in Japan.&amp;#x2028; Methods: Generally, the concomitant combination therapy with anthracycline-containing regimens and H is not recommended because of the increasing rate of cardiac toxicity. This study was designed to evaluate the efficacy and safety of PST for the operable breast cancer with HER2+ phenotype. PST is the sequential chemotherapy with 4 cycles of FEC100 followed by 12 times in combination with weekly paclitaxel (P) 80mg/m2 and H 2mg/kg (PH x 12).. The inclusion criteria is pts with histopathologically confirmed invasive breast carcinoma, T1-3N+M0/T2-3N0M0, HER2 positive by FISH or immunohistochemistry (IHC) 3+, PS=0-1, adequate hematologic, renal, hepatic and cardiac function and a written informed consent. The study was designed to detect a pCR rate of &amp;gt;43% in at least 42 pts. The evaluation of pathological response was carried out on all the surgical specimens sliced every 5 mm interval.&amp;#x2028; Results: From Dec 2004 to Dec 2007, 43 pts were enrolled. Pre-reviewed data is now available for all pts: median age 56 [26-75 years]; 15 (35%) pre-menopausal; median clinical tumor size 40 mm [15-80]; 14 (33%) were ER-positive phenotype. All pts had a normal cardiac function before entry and after FEC→PH. No episodes of serious adverse events were reported. Febrile neutropenia was observed on 5 pts (12%). Grade 2 or 3 neuropathy was limited to 4 pts (9%). Other grade 3 non-hematological toxicities were not observed. Two pts requested to stop the treatment with P after 6 times of infusion because of neuropathy, edema and hyperpigmentation on the face, however, they had completed 12 times of H infusion. After PST, breast conservative surgery was done in 38 patients (88%) and mastectomy in 5 (12%). The overall pCR rate was 60% (26/43), and 6 of 26 pts had only component of DICS.&amp;#x2028; Conclusions: In HER2+ pts, PST with FEC100x4 followed by PHx12 was active and promising, achieving high pathological complete response without significant toxicity. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 3160.

THE SAFETY AND EFFICACY OF AUTOMATED-WEANING FROM MECHANICAL VENTILATION FOLLOWING CARDIAC SURGERY

Introduction: To determine the safety and efficacy of automatic weaning (AW), we compared adverse events associated with weaning by AW with conventional intermittent mandatory ventilation (IMV) in adult patients after cardiac surgery. Previously, in order to standardize weaning by eliminating clinician bias, we used an advanced algorithm for AW with volume-targeted variable pressure support and demonstrated significant reduction in time to extubation in patients undergoing coronary bypass. [1,2] Methods: Ninety eight patients undergoing elective surgical myocardial revascularization entered an IRB approved, randomized, prospective study comparing weaning from mechanical ventilation by an AW or by conventional IMV mode. Weaning for Group 1 was performed on a newly available mechanical ventilator, the Venturi (Cardiopulmonary Corporation, Milford, CT), employing an advanced algorithm for AW by volume-targeted variable pressure support. During apneic periods, the Venturi delivered the set tidal volume and rate by a volume control mode, whereas during spontaneous breathing, the ventilator automatically delivered 15 +/- 8 cm H2 O of pressure support to achieve a targeted tidal volume of 6-8cc/kg. Clinically stable patients with acceptable blood gases were eligible for extubation at pressure support levels < 7 cm H2 O. For Group 2, weaning was managed by the ICU team based on standard practice. Demographic and hemodynamic data, and ventilatory parameters were recorded. Adverse events were defined as serious (cardiopulmonary arrest and reintubation) and non-serious (PO2 < 60 mm Hg, PCO2 >55 mm Hg, and PH > 7.55). The incidence of non-serious events were derived from the total blood gas values obtained in each group. Continuous data are presented as mean +/- SD. Further analysis was performed using a Student's t-text and a p value <or=to0.05 was considered significant. Results: Consistent with our previous findings, the mean time to extubation was significantly reduced in the AW group (p<or=to0.05). The AW (N=48) and the IMV (N=50) groups had similar demographic and hemodynamic data and ventilatory parameters. There were no episodes of serious adverse events in either group. Non-serious adverse events are reported in Table 1 and were also clinically insignificant in both groups.Table 1Conclusion: Our results demonstrate that employing an automated weaning protocol is both safe and efficacious in patients following cardiac surgery.