Are clinical practice guidelines for low back pain interventions of high quality and updated? A systematic review using the AGREE II instrument.

BACKGROUND: Clinical practice guidelines (CPGs) provide recommendations for practice, but the proliferation of CPGs issued by multiple organisations in recent years has raised concern about their quality. The aim of this study was to systematically appraise CPGs quality for low back pain (LBP) interventions and to explore inter-rater reliability (IRR) between quality appraisers. The time between systematic review search and publication of CPGs was recorded. METHODS: Electronic databases (PubMed, Embase, PEDro, TRIP), guideline organisation databases, websites, and grey literature were searched from January 2016 to January 2020 to identify GPCs on rehabilitative, pharmacological or surgical intervention for LBP management. Four independent reviewers used the Appraisal of Guidelines for Research and Evaluation II (AGREE II) tool to evaluate CPGs quality and record the year the CPGs were published and the year the search strategies were conducted. RESULTS: A total of 21 CPGs met the inclusion criteria and were appraised. Seven (33%) were broad in scope and involved surgery, rehabilitation or pharmacological intervention. The score for each AGREE II item was: Editorial Independence (median 67%, interquartile range [IQR] 31-84%), Scope and Purpose (median 64%, IQR 22-83%), Rigour of Development (median 50%, IQR 21-72%), Clarity and Presentation (median 50%, IQR 28-79%), Stakeholder Involvement (median 36%, IQR 10-74%), and Applicability (median 11%, IQR 0-46%). The IRR between the assessors was nearly perfect (interclass correlation 0.90; 95% confidence interval 0.88-0.91). The median time span was 2 years (range, 1-4), however, 38% of the CPGs did not report the coverage dates for systematic searches. CONCLUSIONS: We found methodological limitations that affect CPGs quality. In our opinion, a universal database is needed in which guidelines can be registered and recommendations dynamically developed through a living systematic reviews approach to ensure that guidelines are based on updated evidence. LEVEL OF EVIDENCE: 1 TRIAL REGISTRATION: REGISTRATION PROSPERO DETAILS: CRD42019127619 .

Evidence-Based Medicine (EBM) is properly perceived but its application is still limited in the orthopedic clinical practice: an online survey among the European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) members.

PURPOSE: To evaluate the knowledge and awareness of Evidence-Based Medicine (EBM) among members of the European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA). METHODS: A questionnaire was developed that explored the following areas: (i) respondents' attitudes to EBM; (ii) their motivation to implement EBM in daily practice; (iii) their educational background, knowledge and skills related to accessing and interpreting information; (iv) their level of attention to, and use of, scientific literature; (v) access to and availability of evidence; (vi) perceived barriers in using EBM in clinical practice. The resulting data were analyzed using descriptive statistics, and the correlation between age, educational background and country was further investigated. RESULTS: Two-hundred and eighty-eight ESSKA members (11% of the total population) compiled the questionnaire. The participants covered all the five continents and an expected prevalence of European professionals (77%) was observed. The vast majority of participants were medical doctors (91%), mainly specialized in knee surgery with minimal involvement in research. 97% of the participants declared having some knowledge of EBM, acquired mainly during their professional education, with some geographical differences. The youngest clinicians and those from Eastern Europe reported the greatest difficulty in using EBM in daily practice. The application of EBM in clinical practice is positively affected by the time dedicated to research and negatively correlates with the time dedicated to patient care. CONCLUSIONS: The results of this survey highlight the need for further investigation into the main reasons behind the limited diffusion of the EBM approach, despite the medical community's knowledge and interest in the concept. A wider application of EMB would upgrade clinical practice, linking medical knowledge and scientific evidence to patients' needs which would result of benefit to patients, but also more in general to the health system.

Does cemented or cementless single-stage exchange arthroplasty of chronic periprosthetic hip infections provide similar infection rates to a two-stage? A systematic review.

BACKGROUND: The best surgical modality for treating chronic periprosthetic hip infections remains controversial, with a lack of randomised controlled studies. The aim of this systematic review is to compare the infection recurrence rate after a single-stage versus a two-stage exchange arthroplasty, and the rate of cemented versus cementless single-stage exchange arthroplasty for chronic periprosthetic hip infections. METHODS: We searched for eligible studies published up to December 2015. Full text or abstract in English were reviewed. We included studies reporting the infection recurrence rate as the outcome of interest following single- or two-stage exchange arthroplasty, or both, with a minimum follow-up of 12 months. Two reviewers independently abstracted data and appraised quality assessment. RESULTS: After study selection, 90 observational studies were included. The majority of studies were focused on a two-stage hip exchange arthroplasty (65 %), 18 % on a single-stage exchange, and only a 17 % were comparative studies. There was no statistically significant difference between a single-stage versus a two-stage exchange in terms of recurrence of infection in controlled studies (pooled odds ratio of 1.37 [95 % CI = 0.68-2.74, I2 = 45.5 %]). Similarly, the recurrence infection rate in cementless versus cemented single-stage hip exchanges failed to demonstrate a significant difference, due to the substantial heterogeneity among the studies. CONCLUSION: Despite the methodological limitations and the heterogeneity between single cohorts studies, if we considered only the available controlled studies no superiority was demonstrated between a single- and two-stage exchange at a minimum of 12 months follow-up. The overalapping of confidence intervals related to single-stage cementless and cemented hip exchanges, showed no superiority of either technique.

Anosmin-1 stimulates outgrowth and branching of developing Purkinje axons.

During development, Purkinje axons elongate along precise trajectories and acquire stereotypic branching patterns to innervate targets in the deep nuclei and cerebellar cortex. These processes are accomplished through cell-intrinsic mechanisms, whose operation is regulated by environmental signaling cues. Here, we show that Anosmin-1, the protein defective in the X-linked form of Kallmann syndrome, is one among such cues. Anosmin-1, that stimulates axon elongation and branching in the olfactory system, is expressed by Purkinje cells and deep nuclear neurons of the rat cerebellum during the ontogenetic period when Purkinje axons acquire their mature pattern. These neurons also express the putative Anosmin-1 receptor, fibroblast growth factor receptor 1. Application of Anosmin-1 to dissociated cultures of embryonic (embryonic day 17, E17) or postnatal (postnatal day 0, P0) rat cerebellar cells enhances neuritic elongation and exerts a strong promoting action on the budding of collateral branches and on the extension of terminal arbors. Opposite effects are observed when neutralizing anti-Anosmin-1 antibodies are applied to the same cultures. Comparable results are obtained by administering the protein or the blocking antibodies to organotypic cultures of postnatal (P0) rat cerebellum. In P10 cerebellar slices, Anosmin-1 does not enhance the spontaneous regenerative capabilities of severed Purkinje axons, but promotes the terminal outgrowth of injured neurites into embryonic neocortical explants apposed to the axotomy site. Although Anosmin-1 is unable to change the overall intrinsic growth competence of Purkinje cells, it exerts a powerful stimulatory action on the budding and extension of collateral branches and terminal plexus, contributing to the patterning of Purkinje axons.

Evolution of the Purkinje cell response to injury and regenerative potential during postnatal development of the rat cerebellum.

To understand the mechanisms leading to the progressive loss of intrinsic neuronal growth properties during central nervous system development, we have investigated the evolution of the response to injury and regenerative potential of immature Purkinje cells, axotomized at different postnatal ages from postnatal day (P)3 to P12. In adult rodents, these neurons are characterised by a weak cell body response to axotomy, which is associated with a remarkable resistance to injury and a poor regenerative capability. During the first postnatal week, Purkinje cells are strongly sensitive to injury and massively degenerate within a few days. Immature Purkinje cells react to neurite transection by a strong upregulation of c-Jun, accompanied by a moderate, but consistent, expression of the growth-associated protein (GAP)-43. In contrast, nicotinamide adenine dinucleotide monophosphate (NADPH)-diaphorase reactivity, which can be activated by adult Purkinje neurons, is not modified in their juvenile counterparts. The severed Purkinje axons show a vigorous regenerative sprouting both into the lesioned cerebellar environment and into embryonic neocortical tissue transplanted into the injury site. The typical adult features of the response to injury progressively develop during the second postnatal week, when the injured neurons acquire resistance, cell body changes become milder, the regenerative potential declines, and the severed axons undergo characteristic morphological modifications, including torpedoes and the hypertrophy of recurrent collateral branches. This complete reversal of the features and the outcome of the Purkinje cell reaction to axotomy likely results from the profound changes that occur in the maturing Purkinje cells and/or in their microenvironment during this phase of cerebellar development.

Relationships between neuronal cell adhesion molecule and LHRH neurons in the urodele brain: a developmental immunohistochemical study.

Polysialic acid (PSA), a homopolymer attached to neural cell adhesion molecule (NCAM) is considered a major hallmark of vertebrate cell migration. We studied the distribution of PSA-NCAM by immunohistochemistry, during brain development, in two urodele amphibians, Pleurodeles waltl and the neotenic newt Ambystoma mexicanum. In both species a gradual increase of immunolabelling was observed throughout the brain from developmental stage 30 to stage 52. At the onset of metamorphosis, some differences became evident: in Pleurodeles immunostaining was gradually restricted to the olfactory system while in Ambystoma, PSA-NCAM maintained a more extended distribution (for example throughout the telencephalic walls) suggesting, for the brain of this latter species, a rather preserved neuronal plasticity. The aim of the present work was to correlate the above described PSA-NCAM-immunoreactivity (IR) with the distribution of luteinizing hormone-releasing hormone (LH-RH) containing neurons, which represent a well known example of neural elements migrating from the olfactory placode. LHRH-IR, undetectable till stage 30, was later found together with PSA-NCAM-IR in both the olfactory system and septo-hypothalamic areas. Such observations further support a role of PSA in providing a migration route toward the establishment of a part, at least, of the urodele LHRH system. The possible functional meaning of the LHRH-containing neurons localized between dorsal and ventral thalamus of Ambystoma, never reported before in this area, almost devoid of PSA-NCAM-IR, is discussed.

Effect of centrally administered atropine and pirenzepine on radial arm maze performance in the rat.

The effect of two anticholinergic drugs administered intracerebroventricularly on acquisition of an 8-arm radial maze task was examined in the rat. Increasing doses of atropine (1, 4.5, 22.5, 45 micrograms/rat) and pirenzepine (4.5, 15, 60, 90 micrograms/rat) significantly impaired performance in the working-memory components of the task. For both drugs this impairment was linearly related to the log of the administered doses and log-dose-response relationship were parallel. The regression lines calculated for each parameter for both drugs were parallel to each other, thus allowing us to calculate the potency of atropine versus pirenzepine: atropine was 5.4 times more potent than pirenzepine for correct arm entries, 10 times more potent for the number of errors and 4 times more potent for the total time taken to complete the task. The relevance of M1 and M2 subtype central acetylcholine receptors in cognitive processes is discussed.