Antibody-functionalized polymer nanoparticle leading to memory recovery in Alzheimer's disease-like transgenic mouse model

Alzheimer's disease (AD) is a neurodegenerative disorder related, in part, to the accumulation of amyloid-β peptide (Aβ) and especially the Aβ peptide 1-42 (Aβ_1-42). The aim of this study was to design nanocarriers able to: (i) interact with the Aβ_1-42 in the blood and promote its elimination through the “sink effect” and (ii) correct the memory defect observed in AD-like transgenic mice. To do so, biodegradable, PEGylated nanoparticles were surface-functionalized with an antibody directed against Aβ_1-42. Treatment of AD-like transgenic mice with anti-Aβ_1-42-functionalized nanoparticles led to: (i) complete correction of the memory defect; (ii) significant reduction of the Aβ soluble peptide and its oligomer level in the brain and (iii) significant increase of the Aβ levels in plasma. This study represents the first example of Aβ_1-42 monoclonal antibody-decorated nanoparticle-based therapy against AD leading to complete correction of the memory defect in an experimental model of AD.     

Evaluating Twitter as a complementary data source for pharmacovigilance

Background: Social media are currently considered as a potential complementary source of knowledge for drug safety surveillance. Our primary objective was to estimate the frequency of adverse drug reactions (ADRs) experienced by Twitter users. Our secondary objective was to determine whether tweets constitute a valuable and informative source of data for pharmacovigilance purposes, despite limitations on character number per tweet.

Research design and methods: We selected a list of 33 drugs subject to careful monitoring due to safety concern in France and Europe, and extracted tweets using the streaming API from 30 September 2014 to 5 April 2015. Two pharmacovigilance centers classified these tweets manually as potential ADR case reports.

Results: Among 10,534 tweets, 848 (8.05%) implied or mentioned an ADR without meeting the four FDA criteria required for reporting an ADR, and 289 (2.74%) tweets were classified as ‘case reports.’ Among them 20 (7.27%) tweets mentioned an unexpected ADR and 33 (11.42%) tweets mentioned a serious ADR.

Conclusions: With the use of dedicated tools, Twitter could become a complementary source of information for pharmacovigilance, despite a major limitation regarding causality assessment of ADRs in individual tweets, which may improve with the new limitation to 280 characters per tweet.     

The impact of long‐term care on quality of life

Long‐term care services are provided to help people manage the consequences of impairment, but their impact goes beyond the meeting of basic needs. Accordingly, the main aim was to explore the marginal effectiveness of care when measured in terms of people's overall care‐related quality of life (CRQoL) and assess changes in marginal effect for increasing intensity. The associated aim was to refine and apply an observational method to estimate marginal effectiveness. A “production function” approach was used with survey data, including Adult Social Care Outcomes Toolkit‐measured CRQoL, whereby we statistically modelled the expected relationship between service utilisation rates and CRQoL. This method seeks to limit endogeneity issues by controlling on observables and using instrumental variable. Using a survey of publicly funded long‐term care service users in England, we found that community‐based long‐term care significantly improved people's CRQoL but with diminishing marginal effects and effects differentiated by baseline impairment levels. There are implications for how the care system should respond to changes in global public budgets. For example, where there is unmet need, a system aimed to maximise (unadjusted) CRQoL would put more emphasis on access (more recipients) than intensity of support compared to a system operating on a needs basis.     

Predictors of a positive response to biventricular pacing in patients with severe heart failure and ventricular conduction delay

BACKGROUND: Cardiac resynchronization therapy (CRT) is recommended in patients with ejection fraction <35%, QRS width> 120 ms, and New York Heart Association (NYHA) functional class III or IV despite optimal medical therapy. We aimed to define demographic, clinical, and electrocardiographic predictors of positive clinical response to CRT. METHODS AND RESULTS: Hundred consecutive patients fulfilling the recommended criteria were implanted with a CRT device. Demographic, clinical, two-dimensional echocardiographic and electrographic parameters were measured at baseline and after 6 months of simultaneous biventricular pacing. A positive response to CRT included an improvement of at least one NYHA functional class associated with an absence of hospitalization for worsening heart failure. At the end of follow-up, 12 patients were dead and 71% of the patients were classified as responders. After 6 months of CRT, the ejection fraction was significantly higher (P = 0.035) in responders versus nonresponders. Multivariate analysis identified three independent predictors of positive response to CRT: an idiopathic origin of the cardiomyopathy (P = 0.043), a wider QRS before implantation (P = 0.017), and a narrowing of the QRS after implantation (P = 0.037). CONCLUSION: An idiopathic origin of the cardiomyopathy, a wider QRS before implantation, and a narrowing of the QRS width after implantation were identified as independent predictors of clinical positive response to CRT.     

Evaluation of a predictive model of end-stage kidney disease in a French-based cohort

Background

The risk of ESKD is highly heterogeneous among renal diseases, and risk scores were developed to account for multiple progression factors. Kidney failure risk equation (KFRE) is the most widely accepted, although external validation is scarce. The objective of this study was to evaluate the usefulness of this score in a French case–control cohort and test the pertinence of the proposed thresholds.

Methods

A retrospective case–control study comparing a group of patients starting renal replacement therapy (RRT) to a group of patients with CKD stages 3–5. Multivariate analysis to assess the predictors of ESKD risk. Discrimination of 4-, 6- and 8-variable scores using ROC curves and compared with eGFR alone and albumin/creatinine ratio (ACR) alone.

Results

314 patients with a ratio of 1 case for 1 control. In multivariate analysis, increasing age and higher eGFR were associated with a lower risk of ESKD (OR 0.62, 95% CI 0.48–0.79; and OR 0.72, 95% CI 0.59–0.86, respectively). The log-transformed ACR was associated with a higher risk of ESKD (OR 1.25 per log unit, 95% CI 1.02–1.55). The 4-variable score was significantly higher in the RRT group than in the CKD-ND group, and was more efficient than the eGFR (AUROC 0.66, 95% CI 0.60–0.72, p?=?0.018) and the log-transformed ACR (AUROC 0.63 95% CI 0.60–0.72, p?=?0.0087) to predict ESKD. The 6-variable score including BP metrics and diabetes was not more discriminant as the 4-variable score. The 8-variable score had similar performance compared with the 4-score (AUROC 8-variable score: 0.70, 95% CI 0.64–0.76, p?=?0.526). A 40% and 20% score thresholds were not superior to eGFR?<?15 and 20 mL/min/1.73 m², respectively. A 10% threshold was more specific than an eGFR?<?30 mL/min/1.73 m².

Conclusion

KFRE was highly discriminant between patients progressing to ESKD vs those non-progressing. The 4-variable score may help stratify renal risk and referral in the numerous patients with stage 3 CKD. Conversely, the proposed thresholds for creating vascular access or preemptive transplantation were not superior to eGFR alone.

     

Gastric Bypass But Not Sleeve Gastrectomy Increases Risk of Major Osteoporotic Fracture: French Population-Based Cohort Study

The objective of this work was to investigate the risk of major osteoporotic fracture (MOF; hip, proximal humerus, wrist and distal forearm, and clinical spine) in bariatric surgery patients versus matched controls. Bariatric surgery is associated with an increase in fracture risk. However, it remains unclear whether the same degree of fracture risk is associated with sleeve gastrectomy, which has recently surpassed gastric bypass. Records from the French National Inpatient database were used from 2008 to 2018. Bariatric surgery patients, aged 40 to 65 years, with BMI ≥40 kg/m², hospitalized between January 1, 2010 and December 31, 2014, were matched to one control (1:1) by age, sex, Charlson comorbidity index, year of inclusion, and class of obesity (40 to 49.9 kg/m² versus ≥50 kg/m²). We performed a Cox regression analysis to assess the association between the risk of any MOF and, respectively, (i) bariatric surgery (yes/no) and (ii) type of surgical procedure (gastric bypass, gastric banding, vertical banded gastroplasty, and sleeve gastrectomy) versus no surgery. A total of 81,984 patients were included in the study (40,992 in the bariatric surgery group, and 40,992 matched controls). There were 585 MOFs in the surgical group (2.30 cases per 1000 patient-year [PY]) and 416 MOFs in the matched controls (1.93 cases per 1000 PY). The risk of MOF was significantly higher in the surgical group (hazard ratio [HR] 1.22; 95% CI, 1.08–1.39). We observed an increase in risk of MOF for gastric bypass only (HR 1.70; 95% CI, 1.46–1.98) compared with the matched controls. In patients aged 40 to 65 years, gastric bypass but not sleeve gastrectomy or the other procedures increased risk of major osteoporotic fractures. © 2020 American Society for Bone and Mineral Research.     

Correlation between groin pain and cup design of hip-resurfacing implants: a prospective study

Purpose

Cup design has been incriminated as the source of groin pain after hip resurfacing but has not been well described; thus, it was assessed in a prospective study looking at three implant types.

Methods

A group-match was done between three groups of hip resurfacing devices according to age, sex, body mass index, activity level, osteoarthritis aetiology and pre-operative scores.

Results

The global groin pain rate was 5.7 % at six months and 2.7 % at last follow-up. Groin pain rate was significantly different between the three groups (p = 0.004) and had a strong influence on the subjective results (p = 0.04). No groin pain emerged between six months and last follow-up. No clinical differences were noted in Harris hip score and Merle d’Aubigné-Postel score at last follow-up. However, the Oxford hip score and Devane activity score were significantly lower for cups with macrostructures.

Conclusion

The low groin pain rate in this prospective cohort was probably secondary to the specific surgical technique used and seems to be correlated with cup design. Macrostructures on the external part of the cup could be significantly harmful.     

Perineal burn care: French working group recommendations

Objectives

Burns to the perineum are frequently exposed to faeces. Diverting colostomy is often described to prevent faecal soiling. Because this technique is invasive with frequent complications, use of non-surgical devices including specifically designed faecal management systems has been reported in perineal burns.

Methods

In order to standardise the faecal management strategy in patients with perineal burns, a group of French experts was assembled. This group first evaluated the ongoing practice in France by analysing a questionnaire sent to every French burn centre. Based on the results of this study and on literature data, the experts proposed recommendations on the management of perineal burns in adults.

Results

Specifically designed faecal management systems are the first-line method to divert faeces in perineal burns. The working group proposed recommendations and an algorithm to assist in decisions in the management of perineal burns in four categories of patients, depending on total burn skin area, depth and extent of the perineal burn.

Conclusion

In France, non-surgical devices are the leading means of faecal diversion in perineal burns. The proposed algorithm may assist in decisions in the management of perineal burns. The expert group emphasises that large clinical studies are needed to better evaluate these devices.