Background Iron supplementation is crucial for the treatment of anemia of chronic kidney disease (CKD). Although intravenous (IV) iron is preferred for patients with CKD receiving dialysis (CKD stage ...5D), the method of iron replacement for patients with CKD stages 3 to 5 is controversial. Study Design Systematic review and meta-analysis. A search was performed until October 2015 of MEDLINE, Cochrane Library, conference proceedings in nephrology, and reference lists of included trials. Setting & Population Patients with CKD stages 3 to 5 or 5D. Selection Criteria for Studies All randomized controlled trials, regardless of publication status or language. Intervention IV versus oral iron supplementation. Outcomes The primary outcome was defined as percentage of patients reaching an elevation in hemoglobin (Hb) concentration > 1 g/dL. Secondary end points included percentage of patients who reached Hb levels > 11 g/dL, absolute Hb concentration, change in Hb concentration, transferrin saturation, ferritin levels, erythropoiesis-stimulating agents and blood transfusion requirement, and quality of life. Safety analysis included all-cause mortality and serious and all adverse events. Results 24 trials were identified, 13 including 2,369 patients with CKD stages 3 to 5 and 11 including 818 patients with CKD stage 5D. Patients treated with IV iron were more likely to reach an Hb response > 1 g/dL (risk ratios RRs of 1.61 95% CI, 1.39-1.87 for CKD stages 3-5 and 2.14 95% CI, 1.68-2.72 for CKD stage 5D). Safety analysis showed similar rates of mortality and serious and any adverse effects. IV iron replacement was associated with higher risk for hypotension (RR, 3.71; 95% CI, 1.74-7.94) and fewer gastrointestinal adverse events (RR, 0.43; 95% CI, 0.28-0.67). Limitations Significant heterogeneity between trials; follow-up was usually limited to 3 months. Conclusions Our results agree with current recommendations for IV iron replacement for patients with CKD stage 5D and support increased use of IV iron for patients with CKD stages 3 to 5.
Purpose
There is uncertainty about outcomes differences between partial breast irradiation (PBI) and whole breast irradiation (WBI) for early-stage breast cancer.
Methods
Prospective randomized ...trials comparing adjuvant PBI to WBI in early-stage invasive breast cancer were identified using PubMed. Odds ratios (OR), 95% confidence intervals and absolute risks were computed for pre-specified efficacy and toxicity outcomes including cosmesis. Subgroup analysis evaluated the effect of PBI modality (external beam radiation treatment EBRT, intraoperative radiation treatment IORT or brachytherapy) on efficacy. Meta-regression analysis explored the influence of median follow-up, patient and tumor characteristics on results.
Results
Nine trials comprising 14514 patients were included. While PBI was associated with increased odds of local recurrence compared to WBI (OR 1.69,
P
< 0.001), it was associated with reduced odds of death without breast cancer recurrence (OR 0.55,
P
< 0.001) and with improvement in overall survival (OS) that approached, but did not meet statistical significance (OR 0.84,
P
= 0.06). Subgroup analysis for PBI modality showed significant differences in the odds of local recurrence, based on method of PBI with EBRT showing the lowest magnitude of inferiority. Nodal involvement was associated with higher local recurrence risk, while larger tumors were associated with lesser improvement in death without breast cancer recurrence and OS. PBI was associated with higher odds of fat necrosis (OR 1.72,
P
= 0.002). Worse cosmetic outcome with PBI approached statistical significance (OR 1.23,
P
= 0.06).
Conclusions
Compared to WBI, PBI is associated with higher odds for local recurrence and toxicity, but less death without breast cancer recurrence. The balance between benefit and risk of PBI appears optimal for women with smaller hormone receptor positive tumors, without nodal involvement and treated with EBRT.
Tick-borne encephalitis (TBE) is a viral infection of the central nervous system that occurs in many parts of Europe and Asia. Humans mainly acquire TBE through tick bites, but TBE occasionally is ...contracted through consuming unpasteurized milk products from viremic livestock. We describe cases of TBE acquired through alimentary transmission in Europe during the past 4 decades. We conducted a systematic review and meta-analysis of 410 foodborne TBE cases, mostly from a region in central and eastern Europe. Most cases were reported during the warmer months (April–August) and were associated with ingesting unpasteurized dairy products from goats. The median incubation period was short, 3.5 days, and neuroinvasive disease was common (38.9%). The clinical attack rate was 14% (95% CI 12%–16%), and we noted major heterogeneity. Vaccination programs and public awareness campaigns could reduce the number of persons affected by this potentially severe disease.
Aims
The aims of the current study were to determine the distribution of aetiologies for the drug‐induced syndrome of inappropriate antidiuretic hormone secretion (SIADH) in hospitalized patients, ...and to characterize them according to the different drug groups.
Methods
A single‐centre retrospective study was carried out, including all patients diagnosed with SIADH in a large community hospital and tertiary centre between 1 January 2007 and 1 January 2013 who were treated with drugs known to be associated with SIADH. Two physicians reviewed every patient's medical file for predetermined relevant clinical data.
Results
The study cohort included 198 patients who had SIADH and received drugs associated with SIADH. Most patients 146 (73.7%) were diagnosed with drug‐associated SIADH, while 52 (26.3%) were diagnosed with SIADH due to other aetiologies. The Naranjo algorithm differentiated well between the two groups (P < 0.001). Five drug classes (antidepressants, anticonvulsants, antipsychotic agents, cytotoxic agents and pain medications) were implicated in 82.3% of patients diagnosed with drug‐associated SIADH. Specific serotonin reuptake inhibitors and carbamazepine were commonly implicated. There were no clinically significant differences in the characteristics or severity of SIADH according to drug class.
Conclusions
The clinical characteristics of SIADH caused by different drugs are comparable. Patients with SIADH treated with drugs from five common medication classes will probably be diagnosed with drug‐induced SIADH. Physicians should be aware of the significance of these medication classes as SIADH aetiologies.
Abstract
Background
Clinician reporting of symptomatic adverse events (AEs) in phase I trials uses the Common Terminology Criteria for Adverse Events (CTCAE). The utility of the patient-reported ...outcomes (PROs) version of the CTCAE (PRO-CTCAE) in this setting is unknown. This prospective, observational study compared patient- and clinician-reported symptomatic AEs in phase I patients.
Methods
Phase I study–eligible patients at Princess Margaret were surveyed with the PRO-CTCAE full-item library (78 symptomatic AEs) at baseline (BL), mid-cycle 1, and mid-cycle 2 (C2). Patient and trial characteristics, best response, and survival data were collected. Presence or absence of patient- (PRO-CTCAE) or clinician-reported symptomatic AEs were compared (kappa) at defined timepoints and overall (BL+ mid-cycle 1 + C2).
Results
Of 292 patients approached from May 2017 to January 2019, a total of 265 (90.8%) were consented, with 243 (91.7%) evaluable and 552 PRO-CTCAE surveys (completion rate = 98.7%) included in analyses. Evaluation of overall patient-reported symptomatic AEs identified 50 PRO-CTCAE and 11 CTCAE items with 10% or greater reporting frequency. Nineteen CTCAE items were reported as 1% or less despite matched PRO-CTCAE items reporting as 10% or greater. Underreported categories included sexual health, bodily emissions, and cognition. Clinician- relative to patient-reporting frequency (ratio) demonstrated 9 symptomatic AEs with a 50-fold or more lower clinician reporting rate. Overall patient–clinician agreement for individual symptomatic AEs ranged from poor (κ = 0.00-0.19) to moderate (κ = 0.40-0.59), with discordance driven by lack of clinician reporting. Dyspnea (κ = 0.54) and peripheral neuropathy (κ = 0.63) at BL and limb edema (κ = 0.55) at C2 demonstrated the highest patient–clinician agreement.
Conclusions
Poor to moderate patient–clinician agreement for symptomatic AEs suggests clinician underreporting in phase I trials. Analyses of severity and interference PRO categories are ongoing.
Vaccines have changed modern medicine, and are a mainstay in reducing morbidity and mortality from infections. Our research group recently published a study in which we found that vaccines approved ...by the US Food and Drugs Administration were safe with few clinically important post-approval adverse effects. The current COVID-19 pandemic presents regulators with the unprecedented challenge of balancing a public demand for the rapid development and approval of a safe and effective SARS-CoV-2 vaccine without compromising the strict pre-marketing requirements used for previous vaccines. Here, we review the approval process and safety profiles of FDA approved vaccines and discuss some of the challenges currently facing the FDA regarding the SARS-CoV-2 vaccine approval.
To amass all available evidence from randomized controlled trials regarding the safety of pulse corticosteroids therapy, in order to establish its safety.
All electronic databases from 1/1966 up to ...02/2019 were reviewed to find all randomized controlled trials comparing pulse corticosteroids to oral corticosteroids or to placebo/no treatment. Two reviewers independently extracted and recorded data regarding type of corticosteroid treatment, dosages, length of treatment and follow-up. Risk ratios (RR) with 95% (CI) for differences between pulse corticosteroids and comparator were pooled using a fixed effect meta-analysis. The primary outcome was occurrence of severe adverse events (SAEs). Secondary outcomes included any adverse events (AEs), AEs requiring discontinuation, AEs per system involved and all-cause mortality.
A total of 64 trials were included: 18 trials which compared pulse corticosteroids to oral corticosteroids and 46 trials which compared pulse corticosteroids to placebo/no intervention. Pulse corticosteroids was not associated with increased risk for SAEs for both comparators: RR 0.77 (95% CI 0.52-1.14), and RR 0.99 (95% CI 0.93-1.06), respectively. Sensitivity analysis based on adequate allocation concealment and use of a valid AE grading did not alter the results. Subgroup analysis revealed no increased risk of specific SAEs or AEs with pulse corticosteroids compared to oral corticosteroids.
Pulse corticosteroids was not associated with an increase risk of SAEs and should be regarded as safe.
The patient‐reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO‐CTCAE) complements capture of symptomatic adverse events (AEs) by clinicians. Previous trials have ...typically used a limited subset of relevant symptomatic AEs to reduce patient burden. We aimed to determine the feasibility of administering all 80 AEs included in the PRO‐CTCAE library by approaching consecutive patients enrolled in a large academic phase I program at three points in time. Here, we report a preplanned analysis after enrolling the first 20 patients. All items were answered on 51 of 56 potential visits (adherence 91%). Three (5%) additional PRO‐CTCAE assessments were partially completed, and two (4%) were missed because of conflicting appointments. No patient withdrew consent or chose not to complete the assessments once enrolled on study. Future trials of experimental drugs that incorporate the PRO‐CTCAE should consider using this unselected approach to identify adverse events more completely.
Evidence shows that subjective toxicities are underreported in patients with cancer and that collection of this information directly from patients can improve the reliability and precision of symptomatic adverse events detection. This study reported the feasibility of using the complete set of subjective symptoms from PRO‐CTCAE library developed by the National Cancer Institute in patients on phase I clinical trials.
Current guidelines recommend maintaining vancomycin trough concentrations between 15-20 mg/L for serious methicillin resistant staphylococcus aureus (MRSA) infections. This recommendation is based on ...limited evidence.
A retrospective study including patients with vancomycin susceptible MRSA infections (MIC< = 2 mg/L), treated with vancomycin. We compared outcomes among patients attaining high (> = 15mg/L) vs low (<15mg/L) trough vancomycin levels. We used a propensity score to matching patients achieving low and high levels and conducted an adjusted analysis in the propensity score (PS)-matched cohort using regression analysis. Primary outcome was 30-day all-cause mortality.
Among 285 patients included, there were no significant differences between patients achieving high and low vancomycin levels in mortality (46/131, 35.1% vs 41/154, 26.6%), clinical success, microbiological success, or nephrotoxicity. Similarly, in the PS-matched cohort (n = 162), there was no significant difference in mortality between patients with high and low vancomycin levels (24/53, 45.3% vs 57/109, 52.3%, respectively), adjusted odds ratio for mortality with high levels 0.63 (95% confidence interval 0.28-1.43). In both cohorts, patients with pneumonia achieving high levels had significantly higher clinical and microbiological success (PS-matched cohort: clinical success: 16/32, 50.0% vs 5/27, 18.5%, p = 0.012; microbiological success: 19/32, 59.4% vs 7/27, 25.9%, p = 0.010), without significant differences in mortality.
We found no association between vancomycin levels > = 15 mg/L and clinical outcomes in patients with MRSA infections. In patients with MRSA pneumonia, vancomycin levels > = 15 mg/L were associated with higher clinical success rates. Further larger cohort studies are needed to define optimal vancomycin levels according to the site of infection.
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