Analysis of N1‐acetyl‐N2‐formyl‐5‐methoxykynuramine/N1‐acetyl‐5‐methoxy‐kynuramine formation from melatonin in mice

Abstract: The interactions of melatonin, a potent endogenous antioxidant, with reactive oxygen species generate several products that include N¹‐acetyl‐N²‐formyl‐5‐methoxykynuramine (AFMK) and N¹‐acetyl‐5‐methoxy‐kynuramine (AMK). The physiological or pathological significance of AFMK/AMK formation during the process of melatonin metabolism in mammals has not been clarified. Using a metabolomic approach in the current study, the AFMK/AMK pathway was thoroughly investigated both in mice and humans. Unexpectedly, AFMK and AMK were not identified in the urine of humans nor in the urine, feces or tissues (including liver, brain, and eyes) in mice under the current experimental conditions. Metabolomic analysis did identify novel metabolites of AMK, i.e. hydroxy‐AMK and glucuronide‐conjugated hydroxy‐AMK. These two newly identified metabolites were, however, not found in the urine of humans. In addition, oxidative stress induced by acetaminophen in the mouse model did not boost AFMK/AMK formation. These data suggest that AFMK/AMK formation is not a significant pathway of melatonin disposition in mice, even under conditions of oxidative stress.     

Hub‐and‐spoke model for a 5‐day structured patient education programme for people with Type 1 diabetes

Aims Structured education programmes for people with Type 1 diabetes can deliver improved diabetes control (including reduced severe hypoglycaemia) and quality of life. They can be cost‐effective but are resource intensive. We tested the ability to deliver an evidence‐based 5‐day programme in diabetes centres too small to deliver the courses. Methods Specialist medical and nursing staff from three district general hospital diabetes services (the ‘spokes’) were trained in all aspects of the education programme, except those directly related to course delivery, by a larger centre (the ‘hub’). The hub staff delivered the 5‐day patient education courses, but all other patient education and management was managed locally. Diabetes control and quality of life were assessed at 1 year post‐course. Results In 63 patients with follow‐up data, glycated haemoglobin (HbA_1c) fell by 0.42 ± 1.0% (P = 0.001), with a greater fall in those with high HbA_1c at baseline, and no mean weight gain. Emergency call‐out for severe hypoglycaemia fell from 10 episodes in seven patients the year before to one episode in one patient (P = 0.03). Quality‐of‐life measures improved, with reduced negative impact of diabetes on diabetes‐related quality of life (P < 0.00004) and ‘present quality of life’ improving (P < 0.001). Conclusions The benefits of a 5‐day structured education programme can be provided to patients with Type 1 diabetes attending centres without the resources to provide the teaching course itself, by a ‘hub‐and‐spoke’ methodology.     

Comparison of the efficacy of 1‐day high‐dose quadruple therapy versus 7‐day triple therapy for treatment of Helicobacter pylori infection

BACKGROUND: The proton pump inhibitor (PPI)‐based 7‐day triple therapy is the regimen with the highest cure rates for eradication of Helicobacter pylori infection and has been recommended as the first‐line regimen in the world. It had been reported that a 1‐day quadruple therapy could also successfully cure 95% of the H. pylori infected patients. OBJECTIVES: To observe the efficacy of 1‐day high‐dose quadruple therapy versus 7‐day triple therapy for treatment of H. pylori infection, and to observe side‐effects of the two different regimens. METHODS: This randomized, open, parallel‐controlled study was conducted at Renji Hospital between November 2004 to March 2005. A total of 80 consecutive patients with non‐ulcer dyspepsia, who were H. pylori positive proven by both rapid urease test and histology were included and randomly assigned to 1‐day quadruple therapy or 7‐day triple therapy. Thirty‐nine patients were administered with 1‐day high‐dose quadruple therapy including esomeprazole 40 mg b.i.d., colloidal bismuth subcitrate 440 mg q.i.d., amoxicillin 2 g q.i.d. and metronidazole (400 mg q.i.d.) for 1 day. Forty‐one patients received a standard 7‐day triple therapy consisting of esomeprazole 20 mg b.i.d., clarithromycin 500 mg b.i.d. and amoxicillin 1 g b.i.d. for 7 days. The eradication rates were evaluated by the ¹³C‐urea breath test at least 4 weeks after completion of a course treatment. RESULTS: Seventy‐seven patients completed the trial and three patients dropped out. The eradication rates in the 1‐day therapeutic group and the 7‐day therapeutic group were 39.5% (15/38) and 84.6% (33/39), respectively. There was a statistically significant difference between the two groups (P < 0.0001). Short‐lasting and self‐limiting side effects including thirst, a metallic taste, diarrhea and abdominal pain were reported in three patients (7.9%) in the 1‐day group and seven patients (18%) in the 7‐day group (P = 0.31). CONCLUSIONS: A 1‐day high‐dose quadruple therapy with amoxicillin, metronidazole, bismuth salt, and esomeprazole is not effective for eradication of H. pylori compared with the standard 7‐day triple therapy.     

Efficacy and safety of a 5‐day regimen of azacitidine for patients with high‐risk myelodysplastic syndromes

Although a 7‐day (d) regimen of azacitidine (AZA) is the standard treatment of high‐risk myelodysplastic syndromes (MDS), AZA is difficult to administer during weekends in an outpatient setting. We retrospectively investigated the outcome of a 5‐d regimen of AZA in patients with high‐risk MDS. High‐risk MDS was defined as MDS with intermediate‐2‐ or high‐risk MDS according to the International Prognostic Scoring System. Every months AZA was given at 75 mg/m² per day for 5–7 d in hospital for first cycle and 5 d in outpatient for second cycle and later. Between April 2011 and December 2013, AZA treatment was initiated in 25 patients (men, 22; women, 3; median age, 75 yr; age range, 59–86 yr). The median number of AZA cycles was 10 (range, 1–24). Twenty patients received more than three cycles of AZA and 13 (52%) achieved any hematological improvement (HI). The median time to first response was two cycles (1–3). The most common non‐hematological adverse events were neutropenia in 21 patients and thrombocytopenia in 17 patients. Nineteen patients died. The main cause of death was disease progression (five patients) and infectious complications (11 patients). The median overall survival was 13.2 months. The 5‐d AZA regimen showed a good continuation rate of more than three cycles and an equivalent HI with the 7‐d regimen.     

A phase II study of 5‐day intravenous azacitidine in patients with myelodysplastic syndromes

The approved 7‐day schedule of subcutaneous azacitidine for myelodysplastic syndrome is associated with injection site reactions and bruising and may be inconvenient because of the need for weekend doses. Although pharmacokinetic data with IV azacitidine suggests equivalence, there are no efficacy data published. Patients with all myelodysplastic syndromes (MDS) FAB subtypes were enrolled and received 75 mg/m²/d of azacitidine by 20‐min intravenous infusion for 5 days in every 28 days. Global methylation studies were performed at baseline and prior to Cycle 3. Twenty‐five patients were enrolled and 22 were evaluable. Median age was 69.5 years; 9 (41%) patients had lower‐risk disease (IPSS Low or Int‐1) and 13 (59%) had higher‐risk disease (IPSS Int‐2 or High). Twenty‐seven percent of patients responded (5 CRs and 1 PR). The median time to response was 108 days. The median PFS was 339 days (11.3 months), the median OS was 444 days (14.8 months) and the median duration of response (DOR) was 450 days (15.0 months). Global methylation studies suggest a greater degree of demethylation in responders. This regimen appeared to offer a PR + CR rate and median DOR somewhat similar to what has been reported with the 7‐day subcutaneous regimen; however, OS was shorter. Am. J. Hematol. 2009. © 2009 Wiley‐Liss, Inc.     

Mail‐delivered arthritis self‐management tool kit: A randomized trial and longitudinal followup

Objective

To determine the effectiveness of an intervention Tool Kit of arthritis self‐management materials to be sent once through the mail, and to describe the populations reached.

Methods

Spanish speakers (n = 335), non‐Hispanic English‐speaking African Americans (n = 156), and other non‐Hispanic English speakers (n = 404) were recruited separately and randomized within each of the 3 ethnic/racial categories to immediately receive the intervention Tool Kit (n = 458) or to a 4‐month wait‐list control status (n = 463). At the end of 4 months, controls were sent the Tool Kit. All subjects were followed in a longitudinal study for 9 months. Self‐administered measures included health status, health behavior, arthritis self‐efficacy, medical care utilization, and demographic variables. Using analyses of covariance and t‐tests, analyses were conducted for all participants and for Spanish‐ and English‐language groups.

Results

At 4 months, comparing all intervention subjects with randomized wait‐list controls, there were significant (P < 0.01) benefits in all outcomes except medical care utilization and self‐rated health. The results were maintained at 9 months compared with baseline. On average, the Tool Kit reached persons ages 50–56 years with 12–15 years of schooling. There were few differences between English‐ and Spanish‐language participants in either the effectiveness or reach variables.

Conclusion

A mailed Arthritis Self‐Management Tool Kit proved effective in improving health status, health behavior, and self‐efficacy variables for up to 9 months. It also reached younger persons in both English‐ and Spanish‐language groups and Spanish speakers with higher education levels than previous studies of the small‐group Arthritis Self‐Management Program.     

COVID‐19 cardiac involvement in a 38‐day old infant

The spectrum of clinical manifestations of coronavirus disease 2019 in children is yet to be fully elucidated. We report the case of an infant who tested positive for severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) and developed mild cardiovascular inflammation, a novelty for patients of very young age, that contributes to defining the puzzling nature of this disease in pediatric patients. The potential cardiovascular involvement of SARS‐CoV‐2 in children should always be taken into account.     

An alternative 1‐day smear microscopy protocol for the diagnosis of pulmonary tuberculosis

Background and objective: This study was undertaken to assess the feasibility of diagnosing pulmonary tuberculosis (PTB) by collecting two sputum samples on a single day (1‐day protocol), and to compare this protocol with the national policy of collecting two samples on consecutive days (2‐day protocol). Methods: A total of 513 individuals with cough that had persisted for more than 2 weeks were screened for PTB by collection of three sputum samples: a spot sample on the first day, a sample collected 1 h after the first sample and a sample collected the following morning. For the 2‐day protocol, the diagnostic performance of the first and third samples was considered, while the 1‐day protocol was evaluated using the two samples collected on the first day. Staining and microscopy were performed in a blinded manner by two different technicians. Results: Of the 513 patients, 40 defaulted on the second day. Of the total number of patients recruited, 124 (24.2%) were smear‐positive. Using the 2‐day protocol, 121 patients (97.6%) were identified as smear‐positive, whereas with the 1‐day protocol 118 patients (95.2%) were identified as smear‐positive (P = 0.3). Of the patients who defaulted, seven (17.5%) were smear‐positive. Comparison of the variation in results indicated that collection of a morning sample on the second day provided no significant benefit over collection of a second spot sample on the first day. Conclusions: As the 2‐day protocol did not show a statistically significant difference in diagnostic performance compared with the 1‐day protocol, the latter may be adopted as an alternative protocol, particularly for patients who are more likely to default.