The impact of endogenous annexin A1 on glucocorticoid control of in ammatory arthritis

This work was supported by a Wellcome Trust (UK) project grant 083551. SMO is funded by Fundação de Amparo à Pesquisa do Estado de São Paulo – FAPESP (Grant 2011/00128-1) and Conselho Nacional de Desenvolvimento Científico e Tecnológico – CNPq (Grant 302768/2010-6)

Successful ACL reconstruction with a variant of the pes anserinus

An anatomical variant of the pes anserinus encountered during anterior cruciate ligament reconstructive surgery which has not been previously described is discussed. During routine harvesting, the sartorius fascia was incised and the semitendinosus and gracilis tendons were identified. At the distal portion, it was noted that each tendon gave off an additional tendinous slip. The slip from the semitendinosus tendon had attached to the gracilis tendon and vice versa, thereby creating a double pes anserinus. This variant was used to construct the graft, and at 1 year review the patient had returned to full sporting activities with no complications encountered

Can early warning scores identify deteriorating patients in pre-hospital settings? A systematic review

OBJECTIVE: To evaluate the effectiveness and predictive accuracy of early warning scores (EWS) to predict deteriorating patients in pre-hospital settings. METHODS: Systematic review. Seven databases searched to August 2017. Study quality was assessed using QUADAS-2. A narrative synthesis is presented. ELIGIBILITY: Studies that evaluated EWS predictive accuracy or that compared outcomes in populations that did or did not use EWS, in any pre-hospital setting were eligible for inclusion. EWS were included if they aggregated three or more physiological parameters. RESULTS: Seventeen studies (157,878 participants) of predictive accuracy were included (16 in ambulance service and 1 in nursing home). AUCs ranged from 0.50 (CI not reported) to 0.89 (95%CI 0.82, 0.96). AUCs were generally higher (>0.80) for prediction of mortality within short time frames or for combination outcomes that included mortality and ICU admission. Few patients with low scores died at any time point. Patients with high scores were at risk of deterioration. Results were less clear for intermediate thresholds (≥4 or 5). Five studies were judged at low or unclear risk of bias, all others were judged at high risk of bias. CONCLUSIONS: Very low and high EWS are able to discriminate between patients who are not likely and those who are likely to deteriorate in the pre-hospital setting. No study compared outcomes pre- and post-implementation of EWS so there is no evidence on whether patient outcomes differ between pre-hospital settings that do and do not use EWS. Further studies are required to address this question and to evaluate EWS in pre-hospital settings

Approaches in topical ocular drug delivery and developments in the use of contact lenses as drug-delivery devices

The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link.Drug-delivery approaches have diversified over the last two decades with the emergence of nanotechnologies, smart polymeric systems and multimodal functionalities. The intended target for specific treatment of disease is the key defining developing parameter. One such area which has undergone significant advancements relates to ocular delivery. This has been expedited by the development of material advancement, mechanistic concepts and through the deployment of advanced process technologies. This review will focus on the developments within lens-based drug delivery while touching on conventional and current methods of topical ocular drug delivery. A summary table will provide quick reference to note the key findings in this area. In addition, the review also elucidates current theranostic and diagnostic approaches based on ocular lenses

Strontium potently inhibits mineralisation in bone-forming primary rat osteoblast cultures and reduces numbers of osteoclasts in mouse marrow cultures

The basic mechanisms by which strontium ranelate acts on bone are still unclear. We show that an important action of strontium salts is to block calcification in cultures of osteoblasts, the bone-forming cells. These results suggest that strontium treatment could have previously overlooked effects on bone

Pyoderma gangrenosum after totally implanted central venous access device insertion

<p>Abstract</p> <p>Background</p> <p>Pyoderma gangrenosum is an aseptic skin disease. The ulcerative form of pyoderma gangrenosum is characterized by a rapidly progressing painful irregular and undermined bordered necrotic ulcer. The aetiology of pyoderma gangrenosum remains unclear. In about 70% of cases, it is associated with a systemic disorder, most often inflammatory bowel disease, haematological disease or arthritis. In 25–50% of cases, a triggering factor such as recent surgery or trauma is identified. Treatment consists of local and systemic approaches. Systemic steroids are generally used first. If the lesions are refractory, steroids are combined with other immunosuppressive therapy or to antimicrobial agents.</p> <p>Case presentation</p> <p>A 90 years old patient with myelodysplastic syndrome, seeking regular transfusions required totally implanted central venous access device (Port-a-Cath^®) insertion. Fever and inflammatory skin reaction at the site of insertion developed on the seventh post-operative day, requiring the device's explanation. A rapid progression of the skin lesions evolved into a circular skin necrosis. Intravenous steroid treatment stopped the necrosis' progression.</p> <p>Conclusion</p> <p>Early diagnosis remains the most important step to the successful treatment of pyoderma gangrenosum.</p

Applying refinement to the use of mice and rats in rheumatoid arthritis research

Rheumatoid arthritis (RA) is a painful, chronic disorder and there is currently an unmet need for effective therapies that will benefit a wide range of patients. The research and development process for therapies and treatments currently involves in vivo studies, which have the potential to cause discomfort, pain or distress. This Working Group report focuses on identifying causes of suffering within commonly used mouse and rat ‘models’ of RA, describing practical refinements to help reduce suffering and improve welfare without compromising the scientific objectives. The report also discusses other, relevant topics including identifying and minimising sources of variation within in vivo RA studies, the potential to provide pain relief including analgesia, welfare assessment, humane endpoints, reporting standards and the potential to replace animals in RA research

Asthma self-assessment in a Medicaid population

<p>Abstract</p> <p>Background</p> <p>Self-assessment of symptoms by patients with chronic conditions is an important element of disease management. A recent study in a commercially-insured population found that patients who received automated telephone calls for asthma self-assessment felt they benefitted from the calls. Few studies have evaluated the effectiveness of disease self-assessment in Medicaid populations. The goals of this study were to: (1) assess the feasibility of asthma self-assessment in a population predominantly insured by Medicaid, (2) study whether adding a gift card incentive increased completion of the self-assessment survey, and (3) evaluate how the self-assessment affected processes and outcomes of care.</p> <p>Methods</p> <p>We studied adults and children aged 4 years and older who were insured by a Medicaid-focused managed care organization (MCO) in a pre- and post-intervention study. During the pre-incentive period, patients with computerized utilization data that met specific criteria for problematic asthma control were mailed the Asthma Control Test (ACT), a self-assessment survey, and asked to return it to the MCO. During the intervention period, patients were offered a $20 gift card for returning the completed ACT to the MCO. To evaluate clinical outcomes, we used computerized claims data to assess the number of hospitalization visits and emergency department visits experienced in the 3 months after receiving the ACT. To evaluate whether the self-management intervention improved processes of care, we conducted telephone interviews with patients who returned or did not return the ACT by mail.</p> <p>Results</p> <p>During the pre-incentive period, 1183 patients were identified as having problems with asthma control; 25 (2.0%) of these returned the ACT to the MCO. In contrast, during the incentive period, 1612 patients were identified as having problems with asthma control and 87 (5.4%) of these returned the ACT to the MCO (p < 0.0001). Of all 95 ACTs that were returned, 87% had a score of 19 or less, which suggested poor asthma control.</p> <p>During the 3 months after they received the ACT, patients who completed it had similar numbers of outpatient visits, emergency department visits, and hospitalizations for asthma as patients who did not complete the ACT. We completed interviews with 95 patients, including 28 who had completed the ACT and 67 who had not. Based on an ACT administered at the time of the interview, patients who had previously returned the ACT to the MCO had asthma control similar to those who had not (mean scores of 14.2 vs. 14.6, p = 0.70). Patients had similar rates of contacting their providers within the past 2 months whether they had completed the mailed ACT or not (71% vs. 76%, p = 0.57).</p> <p>Conclusion</p> <p>Mailing asthma self-assessment surveys to patients with poorly controlled asthma was not associated with better asthma-associated outcomes or processes of care in the Medicaid population studied. Adding a gift card incentive did not meaningfully increase response rates. Asthma disease management programs for Medicaid populations will most likely need to involve alternative strategies for engaging patients and their providers in managing their conditions.</p

Atomic structures of TDP-43 LCD segments and insights into reversible or pathogenic aggregation.

The normally soluble TAR DNA-binding protein 43 (TDP-43) is found aggregated both in reversible stress granules and in irreversible pathogenic amyloid. In TDP-43, the low-complexity domain (LCD) is believed to be involved in both types of aggregation. To uncover the structural origins of these two modes of β-sheet-rich aggregation, we have determined ten structures of segments of the LCD of human TDP-43. Six of these segments form steric zippers characteristic of the spines of pathogenic amyloid fibrils; four others form LARKS, the labile amyloid-like interactions characteristic of protein hydrogels and proteins found in membraneless organelles, including stress granules. Supporting a hypothetical pathway from reversible to irreversible amyloid aggregation, we found that familial ALS variants of TDP-43 convert LARKS to irreversible aggregates. Our structures suggest how TDP-43 adopts both reversible and irreversible β-sheet aggregates and the role of mutation in the possible transition of reversible to irreversible pathogenic aggregation