Expert United Kingdom consensus on the preservation of joint health in people with moderate and severe haemophilia A: A modified Delphi panel

Aim: For people with haemophilia A (PwHA), bleeding in the joints leads to joint damage and haemophilia-related arthropathy, impacting range of motion and life expectancy. Existing guidelines for managing haemophilia A support healthcare professionals (HCPs) and PwHA in their efforts to preserve joint health. However, such guidance should be reviewed, considering emerging evidence and consensus as presented in this manuscript. Methods: Fifteen HCPs experienced in the management of PwHA in the UK participated in a three-round Delphi panel. Consensus was defined at ≥70% of panellists agreeing or disagreeing for Likert-scale questions, and ≥70% selecting the same option for multiple- or single-choice questions. Questions not reaching consensus were revised for the next round. Results: 26.8% (11/41), 44.8% (13/29) and 93.3% (14/15) of statements reached consensus in Rounds 1, 2 and 3, respectively. HCPs agreed that prophylaxis should be offered to patients with a baseline factor VIII (FVIII) level of ≤5 IU/dL and that, where there is no treatment burden, the aim of prophylaxis should be to achieve a trough FVIII level ≥15 IU/dL and maintain a longer period with FVIII levels of ≥20-30 IU/dL to provide better bleed protection. The aspirational goal for PwHA is to prevent all joint bleeds, which may be achieved by maintaining normalised (50-150 IU/dL) FVIII levels. Conclusion: The panel of experts were largely aligned on approaches to preserving joint health in PwHA, and this consensus may help guide HCPs

Clinical effects of Garcinia kola in knee osteoarthritis

<p>Abstract</p> <p>Objectives</p> <p>Over the past years, there has been a growing number of knee osteoarthritis (KOA) patients who are not willing to comply with long-term non-steroidal anti-inflammatory drugs (NSAID) treatment and wish to use herbal anti- rheumatic medicine. This study assessed the clinical effects of <it>Garcinia kola </it>(GK) in KOA patients.</p> <p>Patients and methods</p> <p>Prospective randomized, placebo controlled, double blind, clinical trial approved by the institutional medical ethics review board and written informed consent obtained from each patient. All KOA patients presenting at the Obafemi Awolowo University Teaching Hospital complex were recruited into the study. The patients were grouped into four (A = Placebo, B = Naproxen, C = <it>Garcinia kola</it>, D = Celebrex). The drugs and placebo were given twice a day per oral route. Each dose consisted of 200 mg of <it>G. kola</it>, Naproxen (500 mg), Celebrex (200 mg) and Ascorbic acid (100 mg). The primary outcome measure over six weeks study period was the change in mean WOMAC pain visual analogue scales (VAS). Secondary outcome measures included the mean change in joint stiffness and physical function (mobility/walking).</p> <p>Results</p> <p>143 patients were recruited, 84 (58.7%, males – 24, females – 60) satisfied the selection criteria and completed the study. The effect of knee osteoarthritis bilateralism among the subjects was not significant on their outcome (p > 0.05). The change in the mean WOMAC pain VAS after six weeks of <it>G. kola </it>was significantly reduced compared to the placebo (p < 0.001). Multiple comparisons of the mean VAS pain change of <it>G. kola </it>group was not lowered significantly against the naproxen and celebrex groups (p > 0.05). The onset of <it>G. kola </it>symptomatic pain relief was faster than the placebo (p < 0.001). However, it was slower than the active comparators (p > 0.05). The duration of therapeutic effect of <it>Garcinia kola </it>was longer than the placebo (p > 0.001). <it>G. kola </it>period of effect was less than naproxen and celebrex (p < 0.001). <it>G. kola </it>subjects had improved mean change mobility/walking after six weeks better than the control group(p < 0.001). The mean change in mobility of the <it>G. kola </it>group when compared to the active comparators was not significantly better (p < 0.05). The mean change of knee joint stiffness (p < 0.001) and the change of mean WOMAC score (p < 0.001) were improved on <it>Garcinia kola </it>as compared to the placebo. The mid term outcome of eleven <it>Garcinia kola </it>subjects after cessation of use had a mean pain relief period of 17.27 +/- 5.15 days (range: 9–26 days). There was no significant cardiovascular, renal or drug induced adverse reaction to <it>Garcinia kola</it>.</p> <p>Conclusion</p> <p><it>Garcinia kola </it>appeared to have clinically significant analgesic/anti-inflammatory effects in knee osteoarthritis patients. <it>Garcinia kola </it>is a potential osteoarthritis disease activity modifier with good mid term outcome. Further studies are required for standardization of dosages and to determine long-term effects.</p

Mimicking the Neurotrophic Factor Profile of Embryonic Spinal Cord Controls the Differentiation Potential of Spinal Progenitors into Neuronal Cells

Recent studies have indicated that the choice of lineage of neural progenitor cells is determined, at least in part, by environmental factors, such as neurotrophic factors. Despite extensive studies using exogenous neurotrophic factors, the effect of endogenous neurotrophic factors on the differentiation of progenitor cells remains obscure. Here we show that embryonic spinal cord derived-progenitor cells express both ciliary neurotrophic factor (CNTF) and brain-derived neurotrophic factor (BDNF) mRNA before differentiation. BDNF gene expression significantly decreases with their differentiation into the specific lineage, whereas CNTF gene expression significantly increases. The temporal pattern of neurotrophic factor gene expression in progenitor cells is similar to that of the spinal cord during postnatal development. Approximately 50% of spinal progenitor cells differentiated into astrocytes. To determine the effect of endogenous CNTF on their differentiation, we neutralized endogenous CNTF by administration of its polyclonal antibody. Neutralization of endogenous CNTF inhibited the differentiation of progenitor cells into astrocytes, but did not affect the numbers of neurons or oligodendrocytes. Furthermore, to mimic the profile of neurotrophic factors in the spinal cord during embryonic development, we applied BDNF or neurotrophin (NT)-3 exogenously in combination with the anti-CNTF antibody. The exogenous application of BDNF or NT-3 promoted the differentiation of these cells into neurons or oligodendrocytes, respectively. These findings suggest that endogenous CNTF and exogenous BDNF and NT-3 play roles in the differentiation of embryonic spinal cord derived progenitor cells into astrocytes, neurons and oligodendrocytes, respectively

Criteria for the definition of Pituitary Tumor Centers of Excellence (PTCOE): A Pituitary Society Statement

Introduction With the goal of generate uniform criteria among centers dealing with pituitary tumors and to enhance patient care, the Pituitary Society decided to generate criteria for developing Pituitary Tumors Centers of Excellence (PTCOE). Methods To develop that task, a group of ten experts served as a Task Force and through two years of iterative work an initial draft was elaborated. This draft was discussed, modified and finally approved by the Board of Directors of the Pituitary Society. Such document was presented and debated at a specific session of the Congress of the Pituitary Society, Orlando 2017, and suggestions were incorporated. Finally the document was distributed to a large group of global experts that introduced further modifications with final endorsement. Results After five years of iterative work a document with the ideal criteria for a PTCOE is presented. Conclusions Acknowledging that very few centers in the world, if any, likely fulfill the requirements here presented, the document may be a tool to guide improvements of care delivery to patients with pituitary disorders. All these criteria must be accommodated to the regulations and organization of Health of a given country

Pituitary society expert Delphi consensus: operative workflow in endoscopic transsphenoidal pituitary adenoma resection

Abstract: Purpose: Surgical workflow analysis seeks to systematically break down operations into hierarchal components. It facilitates education, training, and understanding of surgical variations. There are known educational demands and variations in surgical practice in endoscopic transsphenoidal approaches to pituitary adenomas. Through an iterative consensus process, we generated a surgical workflow reflective of contemporary surgical practice. Methods: A mixed-methods consensus process composed of a literature review and iterative Delphi surveys was carried out within the Pituitary Society. Each round of the survey was repeated until data saturation and > 90% consensus was reached. Results: There was a 100% response rate and no attrition across both Delphi rounds. Eighteen international expert panel members participated. An extensive workflow of 4 phases (nasal, sphenoid, sellar and closure) and 40 steps, with associated technical errors and adverse events, were agreed upon by 100% of panel members across rounds. Both core and case-specific or surgeon-specific variations in operative steps were captured. Conclusions: Through an international expert panel consensus, a workflow for the performance of endoscopic transsphenoidal pituitary adenoma resection has been generated. This workflow captures a wide range of contemporary operative practice. The agreed “core” steps will serve as a foundation for education, training, assessment and technological development (e.g. models and simulators). The “optional” steps highlight areas of heterogeneity of practice that will benefit from further research (e.g. methods of skull base repair). Further adjustments could be made to increase applicability around the world

Highland Guatemalan women are extremely short of stature, and no lactation duration effects on body composition are observed in a cross-sectional survey.

Early linear growth in Guatemala has historically been compromised, resulting in adults of short stature. We hypothesized that the rate of short stature among mothers in the Western Highlands would have tracked from their own childhood when younger than 5 years, and that maternal weight declines progressively from delivery through lactation. Maternal weight and height were collected in 542 lactating mothers of infant and toddlers, ranging in age from 15 to 48 years, with subsequent classification of mothers for short stature (relative to the 1977 World Health Organization/National Center for Health Statistics growth curves) and for underweight (body mass index [BMI], <18.5 kg/

Gender differences and temporal trends over two decades in acromegaly: a single center study in 112 patients

Purpose: To evaluate the impact of gender and year at surgery on clinical presentation and postoperative outcomes in acromegaly. Methods: Retrospective review of patients operated between 1994 and 2016 to compare presentation and outcomes in groups defined by gender and year of surgery. Kaplan–Meier survival analyses with a composite endpoint (recurrence, reoperation, and radiation) were used for gender comparison and Youden indices for biochemical remission rates changes during study period. Results: Primary indications for evaluation were phenotype, neurological symptoms, incidentaloma, hypogonadism, and galactorrhea. At surgery, men (N = 54) were younger (43.6 ± 12.7 years) than women (N = 58, 48.7 ± 12.3, P = 0.04). Male:female ratios before and after age 50 were 1.4 and 0.6 respectively. Men had higher mean IGF-1 levels (874 ± 328 vs 716 ± 296, P \u3c 0.01) and smaller tumors (1.8 ± 1.3 cm vs 2.3 ± 1.5, P = 0.04). Postoperative remission rates were comparable (51% men, 56% women) and inversely associated with cavernous sinus invasion and GH levels. Women had longer mean follow-up (5.2 ± 3.4 years vs 3.6 ± 3.6 men, P = 0.02) and longer endpoint-free survival (P \u3c 0.01). At last follow-up, 89.6% women and 70% men had normal IGF-1 levels (P = 0.03). Postoperative remission rates were higher in patients operated after February 15, 2011 (67.35 vs 43.5% previously, P = 0.01). In late vs early surgery group, physical changes as main indication for screening decreased (54 vs 30%, P \u3c 0.01), while incidentaloma and hypogonadism increased. Median GH levels were lower in late vs early surgery group (P = 0.03). Conclusion: We demonstrate gender-specific characteristics and an evolving spectrum of clinical presentation with implications for earlier diagnosis and personalized management of acromegaly