Rectal perforations caused by cleansing enemas in chronically constipated patients: Two case reports

Constipation is a common disease that is frequently treated with cleansing enemas. Enemas are considered as effective and in some cases may cause serious adverse events. Iatrogenic perforations due to enemas lead to adverse outcomes in elderly patients with a poor general condition. Perforation remains an infrequent and rarely reported complication. In this work, we describe the cases of two patients with rectal perforation caused by a cleansing enema. The first patient had rectal perforation that led to a para-rectal abscess and the second patient had generalized peritonitis caused by rectal perforation.

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Pharmacology and Adverse Events of Emergency-Use Authorized Medication in Moderate to Severe COVID-19

Pharmaceuticals ◽

10.3390/ph14100955 ◽

2021 ◽

Vol 14 (10) ◽

pp. 955

Author(s):

Jen-Yu Hsu ◽

Yan-Chiao Mao ◽

Po-Yu Liu ◽

Kuo-Lung Lai

Keyword(s):

Adverse Events ◽

Metabolic Pathways ◽

Case Reports ◽

Secondary Infection ◽

Treatment Strategies ◽

Serious Adverse Events ◽

Small Molecule Drugs ◽

Post Market ◽

Inflammatory Processes ◽

Effective Drugs

Some effective drugs have been approved or issued an Emergency Use Authorization for the treatment of COVID-19 in hospitalized patients, but post-market surveillance is warranted to monitor adverse events. We reviewed clinical trials and case reports in patients with moderate-to-severe COVID-19 infection who received remdesivir, baricitinib, tocilizumab, or sarilumab. The drug-specific pharmacokinetics, toxicity, and drug interactions are summarized in this study. Remdesivir and baricitinib are small-molecule drugs that are mainly metabolized by the kidneys, while tocilizumab and sarilumab are monoclonal antibody drugs with metabolic pathways that are currently not fully understood. The most common adverse events of these drugs are alterations in liver function, but serious adverse events have rarely been attributed to them. Only a few studies have reported that remdesivir might be cardiotoxic and that baricitinib might cause thromboembolism. Biological agents such as baricitinib, tocilizumab, and sarilumab could inhibit the pathway of inflammatory processes, leading to immune dysregulation, so the risk of secondary infection should be assessed before prescribing. Further recognition of the pathogenic mechanism and risk factors of adverse events is essential for optimizing treatment strategies.

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Invasive Fungal Infections in Infants—Focus on Anidulafungin

Clinical Medicine Insights Pediatrics ◽

10.4137/cmped.s8028 ◽

2013 ◽

Vol 7 ◽

pp. CMPed.S8028 ◽

Cited By ~ 4

Author(s):

Michael H. Wilke

Keyword(s):

Risk Factors ◽

Adverse Events ◽

Safety Profile ◽

Fungal Infections ◽

Case Reports ◽

Small Body ◽

Pediatric Intensive Care ◽

Invasive Fungal Infections ◽

Serious Adverse Events ◽

Good Safety Profile

Introduction Invasive fungal infection in pediatric intensive care units (PICU) is a rising challenge. Candida species are the most common microorganisms in these infections. Due to growing resistance against fluconazole, echinocandins are being used for the appropriate therapy. However, the recent IDSA guidelines recommend them only in cases where fluconazole or Amphotericin B cause treatment failure or are contraindicated. In a literature review, the importance of invasive fungal infections in PICU settings and the role of anidulafungin shall be examined. Materials and Methods Articles were retrieved form PubMed covering the years 2000–2012. Various search terms were used. Then the articles were clustered in different types like ‘review,’ ‘pharmacokinetics,’ ‘case reports’ and others. Results From 67 search results, 14 articles were selected. Of these, 7 were related to anidulafungin, while 7 were related to echinocandins or fungal infections in the PICU. Anidulafungin was examined in 4 PK/PD studies where a good safety profile was found. No serious adverse events occurred. The articles reporting risk factors show that central venous catheters, receipt of antibiotics, receipt of parenteral nutrition, and neutropenia are the most important independent risk factors for invasive fungal infections in PICU. Three reviews of antifungal agents show that echinocandins may be useful due to their safety profile; micafungin is the best examined one and further trials are needed. Discussion The published literature on invasive fungal infections in PICU settings has grown over the years. There are only a few articles, however, which are directly related to the use of anidulafungin in this setting. A most recent publication showed good PK/PD dynamics and a good safety profile for anidulafungin. So far, no RCT in the area of invasive candidiasis in infants and neonates has been published. A review of currently registered trials at ClinicalTrials.gov has shown one more trial related to PK/PD and two trials that investigate the use of anidulafungin or anidulafungin in combination with Voriconazole in pediatrics. Conclusion The small body of existing literature on anidulafungin in infants shows success in treatment, no drug-related adverse events, and good pharmacodynamics. A dosing of 0.75 mg/kg/day or 1.5 mg/kg/day is as effective as 50 mg/day or 100 mg/day in adults. More trials on the use in clinical reality of PICU or NICU should follow.

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Effects of Dapagliflozin in Stage 4 Chronic Kidney Disease

Journal of the American Society of Nephrology ◽

10.1681/asn.2021020167 ◽

2021 ◽

pp. ASN.2021020167

Author(s):

Glenn Chertow ◽

Priya Vart ◽

Niels Jongs ◽

Robert Toto ◽

Jose Luis Gorriz ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Adverse Events ◽

Controlled Trial ◽

Composite Endpoint ◽

Cardiovascular Death ◽

Adverse Outcomes ◽

Serious Adverse Events ◽

Stage 4 ◽

Cardiovascular Endpoint

Background In the Dapagliflozin And Prevention of Adverse Outcomes in Chronic Kidney Disease (DAPA-CKD) randomized placebo-controlled trial, the sodium-glucose cotransporter 2 inhibitor dapagliflozin significantly reduced risk of kidney failure and prolonged survival in CKD patients with or without type 2 diabetes. Methods In this prespecified analysis of dapagliflozin's effects in patients with stage 4 CKD (eGFR<30 mL/min per 1.73m2) at baseline, we randomized adults with eGFR of 25-75 mL/min per 1.73m2 and urinary albumin-to-creatinine ratio of 200-5000 mg/g to receive dapagliflozin 10 mg/day or placebo. The primary outcome was a composite of time to ≥50% sustained decline in eGFR, end-stage kidney disease, or kidney or cardiovascular death. Secondary outcomes were a kidney composite (same as the primary endpoint but without cardiovascular death), a composite of cardiovascular death or heart failure hospitalization, and all-cause death. Results A total of 293 participants received dapagliflozin and 331 received placebo. Relative to placebo, dapagliflozin was associated with reductions in the primary composite endpoint (hazard ratio [HR], 0.73; 95% confidence interval [95% CI], 0.53 to 1.0), the kidney endpoint (HR, 0.71; 95% CI, 0.49 to 1.02), the cardiovascular endpoint (HR, 0.83; 95% CI, 0.45 to 1.53), and the mortality endpoint (HR, 0.68; 95% CI, 0.39 to 1.21). The eGFR slope declined by 2.15 and 3.38 mL/min per 1.73m2 per year in the dapagliflozin and placebo groups, respectively (P=0.005). Patients treated with dapagliflozin or placebo had similar rates of serious adverse events and adverse events of interest. Conclusions Among patients with stage 4 CKD and albuminuria, dapagliflozin's benefits were consistent with those observed in the DAPA-CKD trial overall, with no evidence of increased risks.

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Efficacy of tumor treating fields (TTFields) in elderly patients with newly diagnosed glioblastoma (GBM): Sub-group analysis of the phase III EF-14 trial.

Journal of Clinical Oncology ◽

10.1200/jco.2020.38.15_suppl.e24019 ◽

2020 ◽

Vol 38 (15_suppl) ◽

pp. e24019-e24019

Author(s):

Zvi Ram ◽

Chae-Yong Kim ◽

Jay-Jiguang Zhu

Keyword(s):

Adverse Events ◽

Elderly Patients ◽

Electric Fields ◽

Group Analysis ◽

Progression Free Survival ◽

Underlying Disease ◽

Phase Iii ◽

Newly Diagnosed ◽

Serious Adverse Events ◽

Tumor Treating Fields

e24019 Background: Tumor Treating Fields (TTFields) are an anti-mitotic, regional treatment modality, utilizing low intensity alternating electric fields delivered non-invasively to the tumor using a portable medical device. TTFields are FDA-approved for glioblastoma and malignant pleural mesothelioma. In the EF-14 [NCT00916409] phase 3 GBM study, TTFields significantly extended survival in newly diagnosed GBM when added to maintenance temozolomide (TMZ). Elderly GBM patients usually have worse prognosis and often receive only partial treatment for the disease. The aim of the following post-hoc analysis was to examine the effects of TTFields in the elderly population (≥65 years of age) enrolled in the EF-14 study. Methods: All 134 elderly patients (≥65 years of age) from the EF-14’s intent-to-treat population were included in the analysis, Overall survival (OS) and progression-free survival (PFS), as well as adverse events were compared between the TMZ + TTFields arm and the TMZ alone arm. Results: The median age was 69 (range: 65-83), 69% were male. Median PFS from randomization was 6.5 months versus 3.9 months in the TTFields + TMZ versus TMZ alone arms, respectively (hazard ratio [HR], 0.47 [95%CI 0.30, 0.74] P < 0.0236). Median OS was 17.4 months versus 13.7 months in the TTFields + TMZ versus TMZ alone arm, respectively (HR 0.51 [CI 0.33, 0.77] P < 0.020). Serious adverse events (SAEs) were reported in 39% of patients treated with TTFields + TMZ and in 33% of patients treated with TMZ alone. None of the SAEs were considered related to TTFields. SAEs were considered related to TMZ or to the underlying disease. Grades 1-2 skin AEs were observed in 51% of patients. Conclusions: Consistent with the overall outcome of the EF-14 study, elderly patients treated with TMZ + TTFields showed significantly better OS compared to patients on TMZ alone, and without increase in grade 3-4 toxicity. Clinical trial information: NCT00916409 .

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Abstract 14733: Influence of High Risk Adrenergic Receptor Genotypes on Outcome in Infants With Single Ventricle

Circulation ◽

10.1161/circ.132.suppl_3.14733 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Ronand Ramroop ◽

Dorin Manase ◽

George Manase ◽

Cory Simmons ◽

Jane W Newburger ◽

...

Keyword(s):

Adverse Events ◽

Clinical Outcomes ◽

Confidence Intervals ◽

Adrenergic Receptor ◽

Single Ventricle ◽

Adverse Outcomes ◽

Hospital Length Of Stay ◽

Serious Adverse Events ◽

Free Survival

Introduction: Variants in adrenergic receptor (ADR) genes are associated with adverse clinical outcomes in patients with heart failure. We evaluated the association of variants in ADR receptor genes with outcomes in infants with single ventricle lesions. Methods: Infants with single ventricle lesions participating in the Pediatric Heart Network Single Ventricle Reconstruction Trial (randomized to Norwood with modified Blalock-Taussig shunt versus right ventricle-pulmonary artery shunt) underwent genotyping for 4 single nucleotide polymorphisms (SNPs) in 3 ADR genes: ADRB1-A/G (rs1801252), ADRB1-C/G (rs1801253), ADRB2-C/G (rs1042714) and ADRA2A-C/T (rs553668). Linear and logistic regression, deviance tests, t-tests and F-tests were used to analyze association of genotype with clinical outcomes including hospital length of stay (LOS) at Norwood, occurrence of serious adverse events (SAE), and transplant-free survival during 14 months follow-up using a dominant model. Results: The study included 347 eligible patients (62% male; 83% white). The mean age at Norwood procedure was 6±3.6 days and median Norwood LOS was 8 days. During 14 months follow-up, 147 patients had SAEs, 94 patients died and 14 were transplanted. ADRB1 AA (rs1801252) genotype was associated with longer Norwood LOS. The difference in LOS between AA vs AG/GG was 7.99 days (confidence intervals, 0.27, 15.71; p=0.043). ADRA2A CC (rs553668) genotype was associated with higher odds of SAEs i.e. 103/216 (47.6%) in CC compared to 36/106 (34%) in CT/TT [Odds ratio 1.77 (confidence intervals, 1.09, 2.87), p=0.018]. Transplant-free survival was not different between genotype groups. Combined analysis of risk genotypes did not confer an additive risk of adverse outcomes. Conclusions: ADR genotypes known to cause adrenergic upregulation were associated with prolonged Norwood hospitalization and/or serious adverse events in infant single ventricles. This may be secondary to adverse effects of adrenergic overexpression on cardiac function and systemic hemodynamics. Analysis is ongoing to replicate these findings for utility as predictive markers for outcomes in infant single ventricles.

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Risk of Adverse Outcomes in Females Taking Oral Creatine Monohydrate: A Systematic Review and Meta-Analysis

Nutrients ◽

10.3390/nu12061780 ◽

2020 ◽

Vol 12 (6) ◽

pp. 1780

Author(s):

Deborah L. de Guingand ◽

Kirsten R. Palmer ◽

Rodney J. Snow ◽

Miranda L. Davies-Tuck ◽

Stacey J. Ellery

Keyword(s):

Weight Gain ◽

Adverse Events ◽

Meta Analysis ◽

Creatine Supplementation ◽

Hepatic Function ◽

Creatine Monohydrate ◽

Adverse Outcomes ◽

Post Intervention ◽

Serious Adverse Events ◽

Significant Difference

Creatine Monohydrate (CrM) is a dietary supplement routinely used as an ergogenic aid for sport and training, and as a potential therapeutic aid to augment different disease processes. Despite its increased use in recent years, studies reporting potential adverse outcomes of CrM have been mostly derived from male or mixed sex populations. A systematic search was conducted, which included female participants on CrM, where adverse outcomes were reported, with meta-analysis performed where appropriate. Six hundred and fifty-six studies were identified where creatine supplementation was the primary intervention; fifty-eight were female only studies (9%). Twenty-nine studies monitored for adverse outcomes, with 951 participants. There were no deaths or serious adverse outcomes reported. There were no significant differences in total adverse events, (risk ratio (RR) 1.24 (95% CI 0.51, 2.98)), gastrointestinal events, (RR 1.09 (95% CI 0.53, 2.24)), or weight gain, (mean difference (MD) 1.24 kg pre-intervention, (95% CI −0.34, 2.82)) to 1.37 kg post-intervention (95% CI −0.50, 3.23)), in CrM supplemented females, when stratified by dosing regimen and subject to meta-analysis. No statistically significant difference was reported in measures of renal or hepatic function. In conclusion, mortality and serious adverse events are not associated with CrM supplementation in females. Nor does the use of creatine supplementation increase the risk of total adverse outcomes, weight gain or renal and hepatic complications in females. However, all future studies of creatine supplementation in females should consider surveillance and comprehensive reporting of adverse outcomes to better inform participants and health professionals involved in future trials.

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United States Pharmacopeia (USP) Safety Review of Gamma-Aminobutyric Acid (GABA)

Nutrients ◽

10.3390/nu13082742 ◽

2021 ◽

Vol 13 (8) ◽

pp. 2742

Author(s):

Hellen A. Oketch-Rabah ◽

Emily F. Madden ◽

Amy L. Roe ◽

Joseph M. Betz

Keyword(s):

Blood Pressure ◽

Adverse Events ◽

Dietary Supplement ◽

Clinical Studies ◽

Case Reports ◽

Endocrine System ◽

Chronic Administration ◽

Fermented Milk ◽

Gamma Aminobutyric Acid ◽

Serious Adverse Events

Gamma-amino butyric acid (GABA) is marketed in the U.S. as a dietary supplement. USP conducted a comprehensive safety evaluation of GABA by assessing clinical studies, adverse event information, and toxicology data. Clinical studies investigated the effect of pure GABA as a dietary supplement or as a natural constituent of fermented milk or soy matrices. Data showed no serious adverse events associated with GABA at intakes up to 18 g/d for 4 days and in longer studies at intakes of 120 mg/d for 12 weeks. Some studies showed that GABA was associated with a transient and moderate drop in blood pressure (<10% change). No studies were available on effects of GABA during pregnancy and lactation, and no case reports or spontaneous adverse events associated with GABA were found. Chronic administration of GABA to rats and dogs at doses up to 1 g/kg/day showed no signs of toxicity. Because some studies showed that GABA was associated with decreases in blood pressure, it is conceivable that concurrent use of GABA with anti-hypertensive medications could increase risk of hypotension. Caution is advised for pregnant and lactating women since GABA can affect neurotransmitters and the endocrine system, i.e., increases in growth hormone and prolactin levels.

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Efficacy and Tolerability of Lacosamide in Lennox–Gastaut Syndrome: A Systematic Review and Meta-analysis

Journal of Neurosciences in Rural Practice ◽

10.1055/s-0041-1740580 ◽

2022 ◽

Author(s):

Prateek Kumar Panda ◽

Indar Kumar Sharawat ◽

Lesa Dawman ◽

Pragnya Panda ◽

Ananthanarayanan Kasinathan ◽

...

Keyword(s):

Systematic Review ◽

Adverse Events ◽

Seizure Frequency ◽

Retrospective Studies ◽

Case Reports ◽

Random Effect ◽

Random Effect Model ◽

Case Series ◽

Eligibility Criteria ◽

Serious Adverse Events

Abstract Purpose Lennox–Gastaut syndrome (LGS) is one of the most difficult to treat childhood-onset epileptic encephalopathies. There is growing evidence that lacosamide is safe and efficacious in patients and adults with refractory epilepsy. However, the evidence regarding the efficacy of lacosamide in LGS is controversial so far. We aimed to evaluate the efficacy and tolerability of lacosamide in patients with LGS. Methods We conducted a systematic review on MEDLINE, EMBASE, COCHRANE CENTRAL, Google Scholar, and Web of Science, collating all available literature till July 31, 2020. The qualitative review included case reports, case series, and both controlled/uncontrolled trials as well as retrospective studies, but for determining pooled estimates, we only included studies with a sample size of 5 or more. The primary outcome was the efficacy of lacosamide in patients with LGS. Clinical variables related to efficacy and adverse events attributed to lacosamide were extracted from each publication. The pooled estimate of variables related to these parameters was performed using a random-effect model. Results Of the 68 items identified by the search, 14 were reviewed as full-text. Eleven articles including two prospective and six retrospective studies fulfilled eligibility criteria and described outcomes in 81 patients (42 adults, 39 children, 60% male, range—1.4–61 years). On average, 35.2%, 27.9%, 7.3%, and 29.4% patients had > 50% reduction, < 50% reduction, no change, and worsening of seizure frequency, respectively. Although 36% of patients had adverse events like somnolence, behavioral abnormalities including irritability, aggressiveness, nausea, tremor, memory problems, dizziness, gastrointestinal discomfort, vomiting, and weight loss, no serious adverse events were noted. Conclusion The evidence available in the current literature is not sufficient to support or refute the use of lacosamide in patients with LGS. Although it is one of the possible therapeutic options worth exploring in patients with LGS, caution is still necessary, as there are reports of worsening of seizure frequency in some patients.

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A Cumulative Review of the Range and Incidence of Significant Adverse Events Associated with Acupuncture

Acupuncture in Medicine ◽

10.1136/aim.22.3.122 ◽

2004 ◽

Vol 22 (3) ◽

pp. 122-133 ◽

Cited By ~ 251

Author(s):

Adrian White

Keyword(s):

Adverse Events ◽

Case Reports ◽

Central Nervous System Infection ◽

Auricular Acupuncture ◽

External Ear ◽

Serious Adverse Events ◽

Medical Treatments ◽

Serious Adverse Event ◽

The Central Nervous System ◽

Common Infection

Objective To summarise the range and frequency of significant adverse events associated with acupuncture in order to provide evidence on which to base continuing efforts to improve the safety of acupuncture practice. Methods Searches were conducted of computerised databases, previous reviews of case reports, population surveys, prospective surveys of acupuncture practice and relevant sections of textbooks for primary and secondary reports to indicate the range of significant adverse events associated with acupuncture. Data from prospective surveys of acupuncture were combined to estimate the incidence of serious adverse events. Results A total of 715 adverse events was included. There were 90 primary reports of trauma, and 186 secondary reports; the most common were pneumothorax and injury to the central nervous system. Infection accounted for 204 primary reports and 91 secondary reports. Over 60% of these cases were hepatitis B. The next most common infection was of the external ear, as a complication of auricular acupuncture. The 144 miscellaneous events mainly comprised seizures and drowsiness judged severe enough to cause a traffic hazard. There were 12 primary reports of deaths. According to the evidence from 12 prospective studies which surveyed more than a million treatments, the risk of a serious adverse event with acupuncture is estimated to be 0.05 per 10 000 treatments, and 0.55 per 10 000 individual patients. Conclusions The risk of serious events occurring in association with acupuncture is very low, below that of many common medical treatments. The range of adverse events reported is wide and some events, specifically trauma and some episodes of infection, are likely to be avoidable.

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