Extended dual antiplatelet therapy with ticagrelor 60 mg in patients with prior myocardial infarction: The design of ALETHEIA,a multi‐country observational study

IntroductionClinical guidelines recommend extended treatment with dual antiplatelet therapy (DAPT) with ticagrelor 60 mg (twice daily) beyond 12 months in high‐risk patients with a history of myocardial infarction (MI) who have previously tolerated DAPT and are not at heightened bleeding risk. However, evidence on patterns of use and associated clinical outcomes in routine clinical practice is limited.MethodsALETHEIA is an observational, multi‐country study, designed to describe characteristics, treatment persistence, and bleeding and cardiovascular (CV) outcomes in post‐MI patients who initiate ticagrelor 60 mg in routine clinical practice ({"type":"clinical-trial","attrs":{"text":"NCT04568083","term_id":"NCT04568083"}}NCT04568083). The study will include electronic health data in the United States (US; Medicare, commercial claims) and Europe (Sweden, Italy, United Kingdom, Germany). Characteristics will be described among patients with and without ticagrelor 60 mg ≥1 year post‐MI. Assuming an a priori threshold of 5000 person‐years on‐treatment is met, to ensure sufficient precision, clinical outcomes (bleeding and CV events) among patients treated with ticagrelor 60 mg will be assessed. Risk factors for clinical outcomes and treatment discontinuation will be assessed in patients with ticagrelor 60 mg and meta‐analysis used to combine estimates across databases. Cohort selection will initiate from the ticagrelor 60 mg US and European approval dates and end February 2020. An estimated total of 7250 patients prescribed ticagrelor 60 mg are expected to be included.DiscussionAn increased understanding of patterns of ticagrelor 60 mg use and associated clinical outcomes among high‐risk patients with a prior MI is needed. The a priori specified stepwise approach adapted in this observational study is expected to generate useful evidence for clinical decision‐making and treatment optimization.     

Epidemiologic profiling: evaluating foodborne outbreaks for which no pathogen was isolated by routine laboratory testing: United States, 1982-9.

The objective was to evaluate foodborne outbreaks of undetermined aetiology by comparing them to pathogen-specific epidemiologic profiles of laboratory-confirmed foodborne outbreaks. National foodborne outbreak data reported to CDC during 1982-9 were categorized by clinico-epidemiologic profiles based on incubation, duration, percent vomiting, fever and vomiting to fever ratio. From the pathogen-specific profiles, five syndromes were developed: a vomiting-toxin syndrome resembling Bacillus cereus and Staphylococcus aureus; a diarrhoea-toxin syndrome characteristic of Clostridium perfringens, a diarrhaeogenic Escherichia coli syndrome, a Norwalk-like virus syndrome, and a salmonella like syndrome. Of 712 outbreaks, 624 (87.6%) matched one of five syndromes; 340 (47.8%) matched the Norwalk-like syndrome and 83 (11.7%) matched the salmonella-like syndrome. After combining information on known pathogens and epidemiologic profiles, only 88 (12.4%) outbreaks remained unclassified. Norwalk-like virus outbreaks appear as common as salmonella-like outbreaks. We conclude that profiling can help classify outbreaks, guide investigations and direct laboratory testing to help detect new and emerging pathogens.     

CTG-repeat length in distal and proximal leg muscles of symptomatic and non-symptomatic patients with myotonic dystrophy: relation to muscle strength and degree of histopathological abnormalities

Myotonic dystrophy (DM) is an autosomal dominant, multisystemic disorder with a variable phenotypic expression including muscle weakness and myotonia. The muscle wasting is most marked in distal limbs and in facial and neck muscles, although proximal limb muscles become affected as the disease progresses. The CTG-trinucleotide-repeat expansion associated with myotonic dystrophy is usually larger in muscle tissue than in leukocytes. It is unclear whether the repeat length itself bears any relation to the differences in the degree of weakness and atrophy between different muscles. We therefore analysed CTG-repeat lengths in blood and in proximal (m. vastus lateralis) and distal (m. tibialis anterior) muscles of patients with DM (n = 4) and non-symptomatic carriers of the mutant DM allele (n = 2) using conventional Southern blot hybridization. Muscle strength and histopathological abnormalities were evaluated for each muscle. In patients with clinical symptoms, the degree of paresis and morphological abnormalities was markedly more pronounced in m. tibialis anterior than in m. vastus lateralis. In these individuals, the CTG-repeat length was larger in muscles than in leukocytes, whereas in the two non-symptomatic carriers no difference could be detected. Furthermore, there was no clear difference in the repeat length between the two muscles in any of the patients. In conclusion, the selective muscular weakness and atrophy in DM do not seem to be related to differences in CTG-repeat length between different muscles.     

Detection of imipenem-resistant and metronidazole-resistant Bacteroides fragilis group strains in fecal samples

Objective: To investigate the imipenem and metronidazole resistance profiles of Bacteroides fragilis group strains in fecal samples and to detect the resistance genes ( ccrA and nim ) coding for imipenem and metronidazole resistance in B. fragilis group strains.
Methods: In total, 925 fecal samples, 729 from consecutive diarrhea patients and 196 from healthy controls, were collected at Huddinge University Hospital in 1997. A modified disk diffusion method was employed to screen for imipenem-resistant and metronidazole-resistant B. fragilis group strains. In strains considered resistant by the modified disk diffusion method, the minimum inhibitory concentrations (MICs) were further determined by the agar dilution method. PCR assays were used to detect the carbapenem-hydrolyzing metallo-β-lactamase gene ( ccrA ) and the 5-nitroimidazole resistance genes ( nim ) in pure cultures (purePCR), directly from fecal samples through direct broth enrichment (dirPCR) and by immunomagnetic separation (imsPCR).
Results: Two imipenem-resistant B. fragilis strains, one of which was simultaneously resistant to metronidazole, and two B. fragilis group strains with MICs near the breakpoint for metronidazole resistance, were isolated from the fecal samples of diarrhea patients. The ccrA gene was identified in all the imipenem-resistant B. fragilis strains by purePCR, dirPCR and imsPCR. The nim genes were also detectable by these PCR assays.
Conclusions: The incidences of imipenem-resistant and metronidazole-resistant B. fragilis group strains were low in the investigated diarrhea patients. Simultaneous resistance to imipenem and metronidazole is of great concern in clinical medicine, and the proposed PCR assays may be useful in epidemiologic studies of distribution of resistance genes in the fecal microflora.     

Improved survival after laparoscopic compared to open gastrectomy for advanced gastric cancer: a Swedish population-based cohort study

Background

Laparoscopic gastrectomy is increasingly used for the treatment of locally advanced gastric cancer but concerns remain whether similar results can be obtained compared to open gastrectomy, especially in Western populations. This study compared the short-term postoperative, oncological and survival outcomes following laparoscopic versus open gastrectomy based on data from the Swedish National Register for Esophageal and Gastric Cancer.

Methods

Patients who underwent surgery with curative intent for adenocarcinoma of the stomach or gastroesophageal junction Siewert type III from 2015 to 2020 were identified, and 622 patients with cT2-4aN0-3M0 tumors were included. The impact of surgical approach on short-term outcomes was assessed using multivariable logistic regression. Long-term survival was compared using multivariable Cox regression.

Results

In total, 350 patients underwent open and 272 laparoscopic gastrectomy, of which 12.9% were converted to open surgery. The groups were similar regarding distribution of clinical disease stage (27.6% stage I, 46.0% stage II, and 26.4% stage III). Neoadjuvant chemotherapy was administered to 52.7% of the patients. There was no difference in the rate of postoperative complications, but laparoscopic approach was associated with lower 90 day mortality (1.8 vs 4.9%, p = 0.043). The median number of resected lymph nodes was higher after laparoscopic surgery (32 vs 26, p < 0.001), while no difference was found in the rate of tumor-free resection margins. Better overall survival was observed after laparoscopic gastrectomy (HR 0.63, p < 0.001).

Conclusions

Laparoscopic gastrectomy can be safely preformed for advanced gastric cancer and is associated with improved overall survival compared to open surgery.