Microevolution and patterns of dissemination of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans

The natural history, microevolution, and patterns of interindividual transmission and global dissemination of the JP2 clone of Aggregatibacter (Actinobacillus) actinomycetemcomitans were studied by population genetic analysis. The JP2 clone is strongly associated with aggressive periodontitis in adolescents of African descent and differs from other clones of the species by several genetic peculiarities, including a 530-bp deletion in the promoter region of the leukotoxin gene operon, which results in increased leukotoxic activity. Multilocus sequence analysis of 82 A. actinomycetemcomitans strains, 66 of which were JP2 clone strains collected over a period of more than 20 years, confirmed that there is a clonal population structure with evolutionary lineages corresponding to serotypes. Although genetically highly conserved, as shown by alignment of sequences of eight housekeeping genes, strains belonging to the JP2 clone had a number of point mutations, particularly in the pseudogenes hbpA and tbpA. Characteristic mutations allowed isolates from individuals from the Mediterranean area and from West Africa, including the Cape Verde Islands, to be distinguished. The patterns of mutations indicate that the JP2 clone initially emerged as a distinct genotype in the Mediterranean part of Africa approximately 2,400 years ago and subsequently spread to West Africa, from which it was transferred to the American continents during the transatlantic slave trade. The sustained exclusive colonization of individuals of African descent despite geographical separation for centuries suggests that the JP2 clone has a distinct host tropism. The colonization of family members by JP2 clone strains with unique point mutations provides strong evidence that there is intrafamilial transmission and suggests that dissemination of the JP2 clone is restricted to close contacts.     

In vitro selection of Plasmodium falciparum 3D7 for expression of variant surface antigens associated with severe malaria in African children

P. falciparum-infected red blood cells (IRBC) can adhere to endothelial host receptors through parasite-encoded, clonally variant surface antigens (VSA). The VSA-mediated IRBC adhesion and the acquired VSA-specific antibody response have both been linked to IRBC organ tropism and disease severity. Parasites isolated from young children with severe malaria (SM) tend to express a limited and conserved set of VSA (VSASM) that are both stronger and more commonly recognized by IgG in the plasma of malaria-exposed individuals than VSA (VSAUM) expressed by parasites causing uncomplicated malaria (UM) in older semi-immune children. Establishment of the genetic mechanism underlying changes in VSA expression in response to in vitro selective pressure is now possible because of the availability of the entire genomic sequence of the P. falciparum clone 3D7. As a first step towards direct molecular identification of VSASM-encoding genes in 3D7, we report here a method of enforcing expression of VSASM-like antigens in this parasite clone by a novel selection method using plasma from semi-immune children with low VSAUM-specific, but high VSASM-specific, IgG reactivity. In addition to the resulting increase in VSA-specific IgG recognition, VSASM-expressing 3D7(3D7-Dodowa1) showed reduced adhesion to CD36. Finally, levels of IgG specific for the VSA expressed by 3D7-Dodowa1 were uniformly higher than those of IgG with specificity for VSA expressed by the unselected 3D7 in plasma samples from geographically and epidemiologically diverse areas of endemic parasite transmission. The described selection method appears a useful tool in the identification of genes encoding VSA involved in severe and life-threatening P. falciparum malaria.     

Tele‐Health Followup Strategy for Tight Control of Disease Activity in Rheumatoid Arthritis: Results of a Randomized Controlled Trial

Objective

To test the effect of patient‐reported outcome (PRO)–based tele‐health followup for tight control of disease activity in patients with rheumatoid arthritis (RA), and the differences between tele‐health followup performed by rheumatologists or rheumatology nurses.

Methods

A total of 294 patients were randomized (1:1:1) to either PRO‐based tele‐health followup carried out by a nurse (PRO‐TN) or a rheumatologist (PRO‐TR), or conventional outpatient followup by physicians. The primary outcome was a change in the Disease Activity Score in 28 joints (DAS28) after week 52. Secondary outcomes were physical function, quality of life, and self‐efficacy. The noninferiority margin was a DAS28 score change of 0.6. Mean differences were estimated following per protocol, intent‐to‐treat (ITT), and multivariate imputation analysis.

Results

Overall, patients had low disease activity at baseline and end followup. Demographics and baseline characteristics were similar between groups. Noninferiority was established for the DAS28. In the ITT analysis, mean differences in the DAS28 score between PRO‐TR versus control were ?0.10 (90% confidence interval [90% CI] ?0.30, 0.13) and ?0.19 (90% CI ?0.41, 0.02) between PRO‐TN versus control. When including 1 yearly visit to the outpatient clinic, patients in PRO‐TN had mean ± SD 1.72 ± 1.03 visits/year, PRO‐TR had 1.75 ± 1.03 visits/year, and controls had 4.15 ± 1.0 visits/year. This included extra visits due to inflammatory flare.

Conclusion

Among RA patients with low disease activity or remission, a PRO‐based tele‐health followup for tight control of disease activity in RA can achieve similar disease control as conventional outpatient followup. The degree of disease control did not differ between patients seen by rheumatologists or rheumatology nurses.

     

Hypersensitivity pneumonitis in a cluster of sawmill workers: a 10-year follow-up of exposure,symptoms, and lung function

Background:

The long-term prognosis of repeated acute episodes of hypersensitivity pneumonitis (HP) is not well described. We report on a 10-year follow-up of a 10-person cluster from a Norwegian sawmill who had all experienced relapsing episodes of HP.

Objectives:

To evaluate the health symptoms, work-related sick-leave, and lung function of 10 workers exposed to mold in a Norwegian sawmill.

Methods:

Participants were evaluated at baseline and 10 years later at follow-up. A structured interview, measurement of serum IgG antibodies to Rhizopus microsporus (R. microsporus) antigens, lung function tests, high resolution computed tomography (HRCT) of the chest, and personal measurements of exposure to mold spores and dust were completed for each participant.

Results:

At baseline, nearly all workers reported acute episodes of HP more than twice a month. At follow-up, both the frequency and intensity of symptoms had declined. Sick-leave was reduced and gas diffusing capacity improved – paralleling the gradually reduced air levels of mold spores.

Conclusions:

In spite of an initially high occurrence of symptoms, long-term clinical and physiological outcome was good. With reduced exposure to mold spores, symptoms declined and lung function was restored.     

Remote ischemic preconditioning with – but not without – metabolic support protects the neonatal porcine heart against ischemia-reperfusion injury

Background

While remote ischemic preconditioning (rIPC) protects the mature heart against ischemia-reperfusion (IR) injury, the effect on the neonatal heart is not known. The neonatal heart relies almost solely on carbohydrate metabolism, which is modified by rIPC in the mature heart. We hypothesized that rIPC combined with metabolic support with glucose-insulin (GI) infusion improves cardiac function and reduces infarct size after IR injury in neonatal piglets in-vivo.

Methods and results

32 newborn piglets were randomized into 4 groups: control, GI, GI + rIPC and rIPC. GI and GI + rIPC groups received GI infusion continuously from 40 min prior to ischemia. rIPC and GI + rIPC groups underwent four cycles of 5 min limb ischemia. Myocardial IR injury was induced by 40 min occlusion of the left anterior descending artery followed by 2 h reperfusion. Myocardial lactate concentrations were assessed in microdialysis samples analyzed by mass spectrometry. Infarct size was measured using triphenyltetrazolium chloride staining. Systolic recovery (dP/dt_max as % of baseline) after 2 h reperfusion was 68.5 ± 13.8% in control, 53.7 ± 11.2% in rIPC (p < 0.05), and improved in GI (83.6 ± 18.8%, p < 0.05) and GI + rIPC (87.0 ± 15.7%, p < 0.01).

Conclusion

rIPC + GI protects the neonatal porcine heart against IR injury in-vivo. rIPC alone has detrimental metabolic and functional effects that are abrogated by simultaneous GI infusion.     

Characterization of drug-related problems identified by clinical pharmacy staff at Danish hospitals

Background In 2010, a database of drug related problems (DRPs) was implemented to assist clinical pharmacy staff in documenting clinical pharmacy activities locally. A study of quality, reliability and generalisability showed that national analyses of the data could be conducted. Analyses at the national level may help identify and prevent DRPs by performing national interventions. Objective The aim of the study was to explore the DRP characteristics as documented by clinical pharmacy staff at hospital pharmacies in the Danish DRP-database during a 3-year period. Setting Danish hospital pharmacies. Method Data documented in the DRP-database during the initial 3 years after implementation were analyzed retrospectively. The DRP-database contains DRPs reported at hospitals by clinical pharmacy staff. The analyses focused on DRP categories, implementation rates and drugs associated with the DRPs. Main outcome measure Characteristics of DRPs. Results In total, 72,044 DRPs were documented in the DRP-database during the first 3 years of implementation, and the number of documented DRPs increased every year. An overall stable implementation rate of approximately 58 % was identified. The DRPs identified were multi-facetted, however evenly distributed for each of the 3 years. The most frequently identified DRP categories were: “Dose”, followed by “Nonadherence to guidelines” and “Supplement to treatment”. The highest implementation rates were found for the following DRP categories: “Non-adherence to guidelines” (79 %) followed by “Therapeutic duplication” (73 %) and “Dosing time and interval” (70 %). Even though the top 25 drugs were involved in 58 % of all DRPs, multiple drugs were associated with DRPs. The drugs most frequently involved in DRPs were paracetamol (4.6 % of all DRPs), simvastatin (3.0 %), lansoprazole (2.7 %), morphine (2.6 %) and alendronic acid (2.4 %). Conclusions The study found that a national database on DRPs contained multi-facetted DRPs, however evenly distributed for each of the 3 years. Even though the top 25 drugs were involved in 58 % of all DRPs, multiple drugs were associated with DRPs. The study emphasizes the importance of detecting and intervening for DRPs.     

A late sharp increase in influenza detections and low interim vaccine effectiveness against the circulating A(H3N2) strain,Denmark, 2021/22 influenza season up to 25 March 2022

We estimated interim influenza A vaccine effectiveness (VE) following a late sharp rise in cases during an influenza A(H3N2)-dominated 2021/22 season, after lifting COVID-19 restrictions. In children aged 2–6 years offered a live attenuated influenza vaccine, adjusted VE was 62.7% (95% CI: 10.9–84.4) in hospitalised and 64.2% (95% CI: 50.5–74.1) in non-hospitalised children. In non-hospitalised patients aged 7–44 years, VE was 24.8% (95% CI: 12.8–35.2); VE was non-significant in remaining age groups and hospital/non-hospital settings.     

Use of Personal Continuous Glucose Monitoring Device Is Associated With Reduced Risk of Hypoglycemia in a 16-Week Clinical Trial of People With Type 1 Diabetes Using Continuous Subcutaneous Insulin Infusion

Aims:Continuous glucose monitoring (CGM) has the potential to promote diabetes self-management at home with a better glycemic control as outcome. Investigation of the effect of CGM has typically been carried out based on randomized controlled trials with prespecified CGM devices on CGM-naïve participants. The aim of this study was to investigate the effect on glycemic control in people using their personal CGM before and during the trial.Materials and Methods:Data from the Onset 5 trial of 472 people with type 1 diabetes using either their personal CGM (n = 117) or no CGM (n = 355) and continuous subcutaneous insulin infusion in a 16-week treatment period were extracted. Change from baseline in glycated hemoglobin A1c (HbA_1c), number of hypoglycemic episodes, and CGM metrics at the end of treatment were analyzed with analysis of variance repeated-measures models.Results:Use of personal CGM compared with no CGM was associated with a reduction in risk of documented symptomatic hypoglycemia (event rate ratio: 0.82; 95% CI: 0.69-0.97) and asymptomatic hypoglycemia (event rate ratio: 0.72; 95% CI: 0.53-0.97), reduced time spent in hypoglycemia (P = .0070), and less glycemic variability (P = .0043) without a statistically significant increase in HbA_1c (P = .2028).Conclusions:Results indicate that use of personal CGM compared with no CGM in a population of type 1 diabetes is associated with a safer glycemic control without a statistically significantly deteriorated effect on HbA_1c, which adds to the evidence about the real-world use of CGM, where device type is not prespecified, and users are not CGM naïve.