Combination Therapy for Neuropathic Pain: A Review of Recent Evidence

Pharmacological treatment is not very effective for neuropathic pain (NP). A progressive decrease in the estimated effect of NP drugs has been reported, giving rise to an increase in the use of the multimodal analgesic approach. We performed a new independent review to assess whether more and better-quality evidence has become available since the last systematic review. We evaluated the efficacy, tolerability, and safety of double-blinded randomized controlled trials involving only adult participants and comparing combination therapy (CT: ≥2 drugs) with a placebo and/or at least one other comparator with an NP indication. The primary outcome assessed was the proportion of participants reporting ≥50% pain reductions from baseline. The secondary outcome assessed was the proportion of drop-outs due to treatment-emergent adverse events. After removing duplicates, 2323 citations were screened, with 164 articles assessed for eligibility, from which 16 were included for qualitative analysis. From the latter, only five lasted for at least 12 weeks and only six complied with the required data for complete analysis. CT has been adopted for years without robust evidence. Efforts have been made to achieve better-quality evidence, but the quality has not improved over the years. In this regard, guidelines for NP should attempt to make recommendations about CT research, prioritizing which combinations to analyze

Neoplasia intraepitelial anal en pacientes de riesgo: ¿cómo y a quién realizar un programa de cribado?

Sr. Editor, en referencia al interesante artículo publicado por Silva y cols., creemos importante comentar algunos aspectos relativos a la citología anal como herramienta de cribado de neoplasia intraepitelial anal (AIN) en pacientes de riesgo

Ocular pain and discomfort after advanced surface ablation (ASA): an ignored complaint

Purpose: Laser vision correction is one of the most commonly performed elective surgical procedures in ophthalmology. Generally, discomfort besides pain (photophobia, burning sensation, tearing, and foreign body sensation) after these procedures is not taken into consideration in the clinical practice. The objective is to provide data on these symptoms and their relevance after advanced surface ablation (ASA). Methods: Single-center survey study based on a structured questionnaire relative to the patients' perceived symptoms after ASA. Inclusion criteria were: ≥18 years old, no ocular disease, with myopia (0.75 to 9 D) or hyperopia (0.25 to 5 D) with or without astigmatism, receiving ASA on at least one eye. All procedures were performed by the same surgeon. A descriptive analysis was performed. Results: Seventy-three consecutive patients (34 men and 39 women) were included in the study. The median (range) of age was 33 (19-64) years. Sixty-nine patients had surgery done on both eyes. Postoperative pain was the most frequent comorbidity (97% [95% confidence interval {CI}: 90-100]) with a median (range) of intensity (verbal numerical rating scale) score of 7 (2-10). Photophobia: 85% (95% CI: 75-92); burning sensation: 62% (95% CI: 50-73); tearing: 59% (95% CI: 47-70); and foreign body sensation: 48% (95% CI: 36-60) were also prevalent postoperative symptoms. Pain during ASA was reported for 44% (95% CI: 32-56) of patients. Conclusion: Comorbidities such as pain, photophobia, burning sensation, tearing, and foreign body sensation are prevalent after ASA procedure. Postoperative pain should be taken into consideration due to its prevalence and intensity. A new and more efficient postoperative analgesic protocol should be established

Pain perception description after advanced surface ablation

Purpose: The objective of this study was to characterize the evolution of ocular pain after advanced surface ablation (ASA) to improve strategies in postoperative pain management. Methods: This was a multicenter, prospective, descriptive, cohort study. The inclusion criteria were healthy individuals ≥18 years old receiving bilateral alcohol-assisted surface ablation with epithelial removal. Pain intensity was evaluated with the visual analog scale (VAS) and the numeric pain rating scale before and after surgery. Comorbidities (photophobia, burning, tearing, and foreign body sensation) and Hospital Anxiety and Depression (HAD) questionnaire were evaluated before and at 6 hours after surgery. Postoperative treatments included cold patch, topical cold antibiotics, topical steroids, and benzodiazepines. Results: Thirty-two consecutive patients having similar profiles of postoperative pain evolution were included. At 0.5 hour after ASA, the pain score by VAS was 37±20 mm, and the maximum pain, 61±31 mm, occurred at 24 hours. Afterward, it decreased progressively until 72 hours after surgery (19±20 mm). Most patients (81%) scored >60 mm, and 44% required rescue medication. Among the comorbidities, all patients had photophobia and 84% had burning sensation. At 6 hours, the HAD score was 5.4±3.9, within the range of values considered as normal. Conclusion: Postoperative acute ocular pain after ASA showed a characteristic evolution over time. Recognition of the pattern could be important for improving the acceptance of ASA and for improving strategies in pain management in the postoperative period

Safety and efficacy of cognitive training plus epigallocatechin-3-gallate in young adults with Down's syndrome (TESDAD): a double-blind, randomised, placebo-controlled, phase 2 trial

Background Early cognitive intervention is the only routine therapeutic approach used for amelioration of intellectual deficits in individuals with Down's syndrome, but its effects are limited. We hypothesised that administration of a green tea extract containing epigallocatechin-3-gallate (EGCG) would improve the effects of non-pharmacological cognitive rehabilitation in young adults with Down's syndrome.; Methods We enrolled adults (aged 16-34 years) with Down's syndrome from outpatient settings in Catalonia, Spain, with any of the Down's syndrome genetic variations (trisomy 21, partial trisomy, mosaic, or translocation) in a double-blind, placebo-controlled, phase 2, single centre trial (TESDAD). Participants were randomly assigned at the IMIM-Hospital del Mar Medical Research Institute to receive EGCG (9 mg/kg per day) or placebo and cognitive training for 12 months. We followed up participants for 6 months after treatment discontinuation. We randomly assigned participants using random-number tables and balanced allocation by sex and intellectual quotient. Participants, families, and researchers assessing the participants were masked to treatment allocation. The primary endpoint was cognitive improvement assessed by neuropsychologists with a battery of cognitive tests for episodic memory, executive function, and functional measurements. Analysis was on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT01699711.; Findings The study was done between June 5, 2012, and June 6, 2014. 84 of 87 participants with Down's syndrome were included in the intention-to-treat analysis at 12 months (43 in the EGCG and cognitive training group and 41 in the placebo and cognitive training group). Differences between the groups were not significant on 13 of 15 tests in the TESDAD battery and eight of nine adaptive skills in the Adaptive Behavior Assessment System II (ABAS-II). At 12 months, participants treated with EGCG and cognitive training had significantly higher scores in visual recognition memory (Pattern Recognition Memory test immediate recall, adjusted mean difference: 6.23 percentage points [95% CI 0.31 to 12.14], p=0.039; d 0.4 [0.05 to 0.84]), inhibitory control (Cats and Dogs total score, adjusted mean difference: 0.48 [0.02 to 0.93], p=0.041; d 0.28 [0.19 to 0.74]; Cats and Dogs total response time, adjusted mean difference: -4.58 s [-8.54 to -0.62], p=0.024; d -0.27 [-0.72 to -0.20]), and adaptive behaviour (ABAS-II functional academics score, adjusted mean difference: 5.49 [2.13 to 8.86], p=0.002; d 0.39 [-0.06 to 0.84]). No differences were noted in adverse effects between the two treatment groups.; Interpretation EGCG and cognitive training for 12 months was significantly more effective than placebo and cognitive training at improving visual recognition memory, inhibitory control, and adaptive behaviour. Phase 3 trials with a larger population of individuals with Down's syndrome will be needed to assess and confirm the long-term efficacy of EGCG and cognitive training.; Funding Jerome Lejeune Foundation, Instituto de Salud Carlos III FEDER, MINECO, Generalitat de Catalunya.Peer ReviewedPostprint (author's final draft

Indocyanine green angiography-guided thyroidectomy versus conventional thyroidectomy for preserving parathyroid function: study protocol for a randomized single-blind controlled trial

Introduction: Angiography with indocyanine green (ICG) fluorescence performed before thyroidectomy would allow identification of the vascularization of parathyroid glands, maximizing efforts for preserving functioning glands intraoperatively. The rationale of the study was based on the hypothesis that showing the vascular pattern of the parathyroid glands by means of ICG angiography before performing the thyroidectomy could prevent permanent hypoparathyroidism. Methods and analysis: We propose a randomized single-blind controlled and multicenter clinical trial to assess the efficacy and safety of ICG angiography-guided thyroidectomy to identify the vascular pattern of the parathyroid glands versus conventional thyroidectomy in patients scheduled for elective total thyroidectomy. Patients will be randomized 1:1 to ICG angiography-guided thyroidectomy (experimental group) or conventional thyroidectomy (control group). Patients in the experimental group will undergo ICG angiography before thyroidectomy to identify the feeding vessels of the parathyroid glands and then, post-thyroidectomy ICG angiography to predict immediate parathyroid gland function by scoring the degree of fluorescence of the glands. Patients in the control group will undergo post-thyroidectomy ICG angiography only. The primary outcome measure will be the rate of patients with permanent hypoparathyroidism. Secondary outcome measures will be rate of postoperative hypoparathyroidism, the percentage of well vascularized parathyroid glands remaining in situ, the levels of iPTH and serum calcium after surgery and the influence of the type of vascular pattern of the parathyroid glands over these outcomes, as well as the safety profile of ICG angiography. Discussion: The results will contribute to adopt a new surgical strategy based on intraoperative ICG angiography before performing total thyroidectomy, according to which the rate of permanent hypoparathyroidism could be substantially reduced

Feasibility of a multidisciplinary group videoconferencing approach for chronic low back pain: a randomized, open- label, controlled, pilot clinical trial (EN-FORMA).

Background: Low back pain is a common condition that becomes even more prevalent with aging. A non-pharmacological multidisciplinary approach for chronic non-specific low back pain (CNSLBP) has been recommended, but integrating different healthcare professionals is challenging. A multidisciplinary group videoconferencing approach (MGVA) can be helpful. Our aim was to provide evidence on MGVA's feasibility in managing CNSLBP and its impact on clinical practice. Methods: We conducted an open-label, randomized, controlled, parallel-group pilot clinical trial with CNSLBP patients irresponsive to conservative treatment. Patients between 18 and 67 years of age were randomly assigned (1:1) to either Standard-of-Care + MGVA (experimental group) or Standard-of-Care alone (control group). MGVA consisted of integrated sessions for physical rehabilitation/physiotherapy, psychology, and social work treatments. The control group received standard clinical practice treatment. The feasibility was assessed by the number of study procedures completed to at least 80% as planned. The impact on clinical practice was evaluated by the number of patients who changed their status from "candidate" to "non-candidate" to low back surgery as the treatment of choice for CNSLBP. The SF-36, Oswestry Disability Index, and TMMS-24 questionnaires were used. We performed a whole population-based descriptive analysis. Results: We included 20 patients, but only 18 were randomized (2 withdrew consent before randomization). The mean (SD) age was 53.1 (5.9) years, and mostly women (13/18); 7 were actively employed. In the experimental group, 6/9 (67%, 95%CI:35-88%) patients attended at least 80% of the scheduled procedures, while in the control group, 8/9 (89%, 95%CI:57-98%) did. Additionally, 1 out of 4 (25%) patients in the experimental group changed their status from "candidate" for low back surgery to "non-candidate". None of the 2 patients in the control group did so. We found differences between groups in the SF-36 mental health component (p-value:0.061), Oswestry Disability Index (p-value:0.032), and TMMS-24 Repair component (p-value:0.014) at the end of the trial favoring MGVA. Conclusions: The multidisciplinary group videoconferencing approach to managing chronic non-specific low back pain was feasible, suggesting overall beneficial effects on patients' health and could play a role in changing a patient's status from "candidate" to "non-candidate" for surgery

Incidence of Recurrent High-Grade Anal Dysplasia in HIV-1-Infected Men and Women Following Infrared Coagulation Ablation: A Retrospective Cohort Study

This single-center, retrospective cohort study sought to estimate the cumulative incidence in HIV-1-infected patients of biopsy-proven high-grade anal intraepithelial neoplasia (HGAIN) recurrence after infrared coagulation (IRC) treatment. The study was based on data from a prospectively compiled database of 665 HIV-1-infected outpatients who attended a hospital Clinical Proctology/HIV Unit between January 2012 and December 2015. Patient records were checked to see which ones had received IRC treatment but later experienced a recurrence of HGAIN. Cytology samples were also checked for the presence of human papilloma virus (HPV). A total of 81 of the 665 patients (12%, 95%CI: 10-15%), of whom 65 were men and 16 women, were diagnosed with HGAIN and again treated with IRC. Of these 81, 20 (25%) experienced recurrent HGAIN, this incidence being true of both men (16/65, 95%CI: 19-57%) and women (4/16, 95%CI: 10-50%). The median time to recurrence was 6 (2-19) months overall, 6 (2-19) months in men, and 4 (2-6) months in women. HPV infection was detected in all patients except two, with HPV-16 being the most common genotype. This rate of incidence of recurrent HGAIN following IRC treatment is consistent with other reports and highlights the importance of continued post-treatment surveillance, particularly in the first year

Longitudinal Clinical and Cognitive Changes Along the Alzheimer Disease Continuum in Down Syndrome

IMPORTANCE Alzheimer disease (AD) is the main medical problem in adults with Down syndrome (DS). However, the associations of age, intellectual disability (ID), and clinical status with progression and longitudinal cognitive decline have not been established. OBJECTIVE To examine clinical progression along the AD continuum and its related cognitive decline and to explore the presence of practice effects and floor effects with repeated assessments. DESIGN, SETTING, AND PARTICIPANTS This is a single-center cohort study of adults (aged >18 years) with DS with different ID levels and at least 6 months of follow-up between November 2012 and December 2021. The data are from a population-based health plan designed to screen for AD in adults with DS in Catalonia. Spain. Individuals were classified as being asymptomatic, having prodromal AD, or having AD dementia. EXPOSURES Neurological and neuropsychological assessments. MAIN OUTCOMES AND MEASURES The main outcome was clinical change along the AD continuum. Cognitive decline was measured by the Cambridge Cognitive Examination for Older Adults With Down Syndrome and the modified Cued Recall Test. RESULTS A total of 632 adults with DS (mean [SD] age, 42.6 [11.4] years; 292 women [46.2%]) with 2847 evaluations (mean [SD] follow-up, 28.8 [18.7] months) were assessed. At baseline, there were 436 asymptomatic individuals, 69 patients with prodromal AD, and 127 with AD dementia. After 5 years of follow-up, 17.1% (95% CI, 12.5%-21.5%) of asymptomatic individuals progressed to symptomatic AD in an age-dependent manner (0.6% [95% CI, 0%-1.8%] for age = 50 years; P < .001), and 94.1% (95% CI. 84.6%-98.0%) of patients with prodromal AD progressed to dementia with no age dependency. Cognitive decline in the older individuals was most common among those who progressed to symptomatic AD and symptomatic individuals themselves. Importantly, individuals with mild and moderate ID had no differences in longitudinal cognitive decline despite having different performance at baseline. This study also found practice and floor effects, which obscured the assessment of longitudinal cognitive decline. CONCLUSIONS AND RELEVANCE This study found an association between the development of symptomatic AD and a high risk of progressive cognitive decline among patients with DS. These results support the need for population health plans to screen for AD-related cognitive decline from the fourth decade of life and provide important longitudinal data to inform clinical trials in adults with DS to prevent AD

Periodontal disease's contribution to Alzheimer's disease progression in Down syndrome

Altres ajuts: This study was supported by National institutes of Health (NIH)/National Institute on Aging grants AG035137, AG032554, AG12101, AG022374, and AG13616, NIH DE023139-02, Alzheimer's Association NIRG-12-173937, and NIH/NCATS UL1 TR000038. Conflict of interest: No conflict of interest is reported for A.R.K., M.J., P.C., R.G.C., D.S., K.R.C.A., M.R., A.M., J.O.F., S.V., M.C.-I., and B.B. M.J. de Leon has a patent on an image analysis technology that was licensed to Abiant Imaging, Inc., by NYU, and has a financial interest in this license agreement, and NYU holds stock options on the company. M. de Leon has received compensation for consulting services from Abiant Imaging. Dr L. Glodzic was a principal investigator on an Investigator-Initiated project funded by Forest Laboratories and received an honorarium for serving as a consultant to Roche Pharma. Contributors: A.R.K., M.J.de.L., and J.F. wrote the manuscript. All the other authors reviewed the manuscript and contributed with the scientific literature, concepts, and modeling. All authors reviewed the manuscript for intellectual content and approved the final draft.People with Down syndrome (DS) are at an increased risk for Alzheimer's disease (AD). After 60 years of age, >50% of DS subjects acquire dementia. Nevertheless, the age of onset is highly variable possibly because of both genetic and environmental factors. Genetics cannot be modified, but environmental risk factors present a potentially relevant intervention for DS persons at risk for AD. Among them, inflammation, important in AD of DS type, is potential target. Consistent with this hypothesis, chronic peripheral inflammation and infections may contribute to AD pathogenesis in DS. People with DS have an aggressive form of periodontitis characterized by rapid progression, significant bacterial and inflammatory burden, and an onset as early as 6 years of age. This review offers a hypothetical mechanistic link between periodontitis and AD in the DS population. Because periodontitis is a treatable condition, it may be a readily modifiable risk factor for AD