What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian consensus conference on pain in neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Association of kidney disease measures with risk of renal function worsening in patients with type 1 diabetes

Background: Albuminuria has been classically considered a marker of kidney damage progression in diabetic patients and it is routinely assessed to monitor kidney function. However, the role of a mild GFR reduction on the development of stage 653 CKD has been less explored in type 1 diabetes mellitus (T1DM) patients. Aim of the present study was to evaluate the prognostic role of kidney disease measures, namely albuminuria and reduced GFR, on the development of stage 653 CKD in a large cohort of patients affected by T1DM. Methods: A total of 4284 patients affected by T1DM followed-up at 76 diabetes centers participating to the Italian Association of Clinical Diabetologists (Associazione Medici Diabetologi, AMD) initiative constitutes the study population. Urinary albumin excretion (ACR) and estimated GFR (eGFR) were retrieved and analyzed. The incidence of stage 653 CKD (eGFR < 60 mL/min/1.73 m2) or eGFR reduction > 30% from baseline was evaluated. Results: The mean estimated GFR was 98 \ub1 17 mL/min/1.73m2 and the proportion of patients with albuminuria was 15.3% (n = 654) at baseline. About 8% (n = 337) of patients developed one of the two renal endpoints during the 4-year follow-up period. Age, albuminuria (micro or macro) and baseline eGFR < 90 ml/min/m2 were independent risk factors for stage 653 CKD and renal function worsening. When compared to patients with eGFR > 90 ml/min/1.73m2 and normoalbuminuria, those with albuminuria at baseline had a 1.69 greater risk of reaching stage 3 CKD, while patients with mild eGFR reduction (i.e. eGFR between 90 and 60 mL/min/1.73 m2) show a 3.81 greater risk that rose to 8.24 for those patients with albuminuria and mild eGFR reduction at baseline. Conclusions: Albuminuria and eGFR reduction represent independent risk factors for incident stage 653 CKD in T1DM patients. The simultaneous occurrence of reduced eGFR and albuminuria have a synergistic effect on renal function worsening

What is the role of the placebo effect for pain relief in neurorehabilitation? Clinical implications from the Italian Consensus Conference on Pain in Neurorehabilitation

Background: It is increasingly acknowledged that the outcomes of medical treatments are influenced by the context of the clinical encounter through the mechanisms of the placebo effect. The phenomenon of placebo analgesia might be exploited to maximize the efficacy of neurorehabilitation treatments. Since its intensity varies across neurological disorders, the Italian Consensus Conference on Pain in Neurorehabilitation (ICCP) summarized the studies on this field to provide guidance on its use. Methods: A review of the existing reviews and meta-analyses was performed to assess the magnitude of the placebo effect in disorders that may undergo neurorehabilitation treatment. The search was performed on Pubmed using placebo, pain, and the names of neurological disorders as keywords. Methodological quality was assessed using a pre-existing checklist. Data about the magnitude of the placebo effect were extracted from the included reviews and were commented in a narrative form. Results: 11 articles were included in this review. Placebo treatments showed weak effects in central neuropathic pain (pain reduction from 0.44 to 0.66 on a 0-10 scale) and moderate effects in postherpetic neuralgia (1.16), in diabetic peripheral neuropathy (1.45), and in pain associated to HIV (1.82). Moderate effects were also found on pain due to fibromyalgia and migraine; only weak short-term effects were found in complex regional pain syndrome. Confounding variables might have influenced these results. Clinical implications: These estimates should be interpreted with caution, but underscore that the placebo effect can be exploited in neurorehabilitation programs. It is not necessary to conceal its use from the patient. Knowledge of placebo mechanisms can be used to shape the doctor-patient relationship, to reduce the use of analgesic drugs and to train the patient to become an active agent of the therapy

Can Coronaviruses Steal Genes from the Host as Evidenced in Western European Hedgehogs by EriCoV Genetic Characterization?

Due to their need for living cells, viruses have developed adaptive evolutionary strategies to survive and perpetuate in reservoir hosts that play a crucial role in the ecology of emerging pathogens. Pathogenic and potentially pandemic betacoronaviruses arose in humans in 2002 (SARS-CoV, disappeared in July 2003), 2012 (MERS-CoV, still circulating in Middle East areas), and 2019 (SARS-CoV-2, causing the current global pandemic). As universally recognized, bats host ancestors of the above-mentioned zoonotic viruses. However, hedgehogs have been recently identified in Europe and Asia as possible reservoirs of MERS-CoV-like strains classified as Erinaceus coronavirus (EriCoV). To elucidate the evolution and genetics of EriCoVs, NGS (next generation sequencing) and Sanger sequencing were used to examine fecal samples collected in Northern Italy in 2018/2019 from 12 hedgehogs previously found EriCoV-positive by RT-PCR. By sequence analysis, eight complete EriCoV genomes, obtained by NGS, showed a high phylogenetic correlation with EriCoV strains previously reported in Eurasia. Interestingly, eight viral strains presented an additional ORF encoding for the CD200 ortholog located between the genes encoding for the Spike and the ORF3a proteins. The CD200 ortholog sequences were closely similar to the host CD200 protein but varying among EriCoVs. The result, confirmed by Sanger sequencing, demonstrates for the first time that CoVs can acquire host genes potentially involved in the immune-modulatory cascade and possibly enabling the virus to escape the host defence

Multicenter real-life study on access-related outcomes after EVAR: percutaneous is the way

BACKGROUND: Endovascular aortic repair (EVAR) is the first-line treatment for abdominal aortic aneurysms (AAA) in fit patients. Percutaneous vascular access (pEVAR) allows to ulteriorly decrease the invasivity of EVAR in comparison to surgical femoral cutdown (sEVAR). The aim of this multicentric study was to compare the two access techniques and their impact on operative time, hospitalization, short and long-term complications, and mortality. METHODS: Baseline and peripoperative data of consecutive patients undergoing standard EVAR in four Italian vascular academic centers collected in the Italian Collaborators for EVAR (ICE) registry have been retrospectively analyzed. The mortality and complication risk have been calculated with dedicated scores (SVS/AAVS score system, ACS risk calculator). Primary outcomes were technical success of percutaneous access, 30-days mortality and access-related perioperative complications. Operative time, length of hospital stay (LOS), 90-day readmission and type of anesthesia were considered as Secondary outcomes. RESULTS: From January 2018 to February 2021, 608 consecutive patients underwent EVAR: 373 (61.3%) pEVAR and 202 (33.2%) sEVAR; 33 (5.4%) patients who underwent a hybrid approach (one surgical, one percutaneous) were excluded. Operative time (median 80.00 m [IQR 60.00-110.00] vs. 112.50 m [IQR 90.00-144.00], P<0.001), 90-days readmission rate (1.4% vs. 6.9%, P=0.001) and LOS (4.00 days [IQR 3.00-7.00] in pEVAR vs. 5.00 days [IQR 3.25-8.00] in sEVAR, P=0.012) were lower in the pEVAR group. Type of anesthesia (local 71.7%% vs. general 22.8%; P<0.001) was significantly different between the groups. Technical success rate of pEVAR was 97.3% with lower rates of mortality (1.4% pEVAR vs. 6% sEVAR, P=0.004). Early access-related complications had higher rate in sEVAR group, and the difference was significant (5.4% in sEVAR vs. 1.6% in pEVAR, P=0.02). CONCLUSIONS: Percutaneous access for EVAR is safe and feasible when compared with surgical access with high technical success rate and low complication. The results of our analysis demonstrate that percutaneous access was associated with decreasing operative time, length of hospital stay, the use of general anesthesia and in hospital readmission

Optimizing insulin glargine plus one injection of insulin glulisine in type 2 diabetes in the ELEONOR study: similar effects of telecare and conventional self-monitoring of blood glucose on patient functional health status and treatment satisfaction.

OBJECTIVE: To determine the functional health status and treatment satisfaction in patients with type 2 diabetes from the Evaluation of Lantus Effect ON Optimization of use of single dose Rapid insulin (ELEONOR) study that investigated whether a telecare program helps optimization of basal insulin glargine with one bolus injection of insulin glulisine. RESEARCH DESIGN AND METHODS: Functional health status and treatment satisfaction were investigated using the 36-Item Short-Form (SF-36) Health Survey, the World Health Organization Well-Being Questionnaire (WBQ), and the Diabetes Treatment Satisfaction Questionnaire. RESULTS: Of 291 randomized patients, 238 completed the study (telecare: 114; self-monitoring blood glucose: 124). Significant improvements were detected in most SF-36 domains, in WBQ depression and anxiety scores, and in treatment satisfaction, without differences between study groups. CONCLUSIONS: An insulin regimen that substantially improves metabolic control, while minimizing the risk of hypoglycemia, can positively affect physical and psychologic well-being and treatment satisfaction irrespective of the educational support system used

Telecare Provides comparable efficacy to conventional self-monitored blood glucose in patients with type 2 diabetes titrating one injection of insulin glulisine-the ELEONOR study.

BACKGROUND: We compared telecare and conventional self-monitored blood glucose (SMBG) programs for titrating the addition of one bolus injection of insulin glulisine in patients with type 2 diabetes uncontrolled on oral hypoglycemic agents for ≥3 months who were first titrated with basal insulin glargine. METHODS: This randomized, multicenter, parallel-group study included 241 patients (mean screening glycosylated hemoglobin [HbA(1c)], 8.8% [73 mmol/mol]). In the run-in phase, any antidiabetes medication, except for metformin, was discontinued. Metformin was then up-titrated to 2 g/day (1 g twice daily) until study completion. Following run-in, all patients started glargine for 8-16 weeks, targeting fasting plasma glucose (FPG) ≤5.6 mmol/L using conventional SMBG. Patients with FPG ≤7 mmol/L added a glulisine dose at the meal with the highest postprandial plasma glucose excursion, titrated to target 2-h postprandial plasma glucose level <7.8 mmol/L using telecare or SMBG for 24 weeks. Patients with FPG >7 mmol/L at week 16 were withdrawn from the study. RESULTS: After glargine titration, 224 patients achieved FPG ≤7 mmol/L, without any difference between telecare and SBMG groups (mean±SD, 6.2±0.8 vs. 6.0±0. 9 mmol/L, respectively). HbA(1c) levels were lower following titration and were similar for telecare and SMBG (7.9±0.9% vs. 7.8±0.9% [63 vs. 62 mmol/mol], respectively). Adding glulisine further reduced HbA(1c) in both groups (-0.7% vs. -0.7%); 45.2% and 54.8% (P=0.14), respectively, of patients achieved HbA(1c) ≤7.0% (≤53 mmol/mol). Weight change and hypoglycemia were similar between groups. CONCLUSIONS: Patients adding one dose of glulisine at the meal with the highest postprandial plasma glucose excursion to titrated basal glargine achieved comparable improvements in glycemic control irrespective of traditional or telecare blood glucose monitoring

Telecare Provides comparable efficacy to conventional self-monitored blood glucose in patients with type 2 diabetes titrating one injection of insulin glulisine-the ELEONOR study.

BACKGROUND: We compared telecare and conventional self-monitored blood glucose (SMBG) programs for titrating the addition of one bolus injection of insulin glulisine in patients with type 2 diabetes uncontrolled on oral hypoglycemic agents for ≥3 months who were first titrated with basal insulin glargine. METHODS: This randomized, multicenter, parallel-group study included 241 patients (mean screening glycosylated hemoglobin [HbA(1c)], 8.8% [73 mmol/mol]). In the run-in phase, any antidiabetes medication, except for metformin, was discontinued. Metformin was then up-titrated to 2 g/day (1 g twice daily) until study completion. Following run-in, all patients started glargine for 8-16 weeks, targeting fasting plasma glucose (FPG) ≤5.6 mmol/L using conventional SMBG. Patients with FPG ≤7 mmol/L added a glulisine dose at the meal with the highest postprandial plasma glucose excursion, titrated to target 2-h postprandial plasma glucose level <7.8 mmol/L using telecare or SMBG for 24 weeks. Patients with FPG >7 mmol/L at week 16 were withdrawn from the study. RESULTS: After glargine titration, 224 patients achieved FPG ≤7 mmol/L, without any difference between telecare and SBMG groups (mean±SD, 6.2±0.8 vs. 6.0±0. 9 mmol/L, respectively). HbA(1c) levels were lower following titration and were similar for telecare and SMBG (7.9±0.9% vs. 7.8±0.9% [63 vs. 62 mmol/mol], respectively). Adding glulisine further reduced HbA(1c) in both groups (-0.7% vs. -0.7%); 45.2% and 54.8% (P=0.14), respectively, of patients achieved HbA(1c) ≤7.0% (≤53 mmol/mol). Weight change and hypoglycemia were similar between groups. CONCLUSIONS: Patients adding one dose of glulisine at the meal with the highest postprandial plasma glucose excursion to titrated basal glargine achieved comparable improvements in glycemic control irrespective of traditional or telecare blood glucose monitoring