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1.
Bone Jt Open ; 3(10): 815-825, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36263725

RESUMO

AIMS: There remains a lack of consensus regarding the management of chronic anterior sternoclavicular joint (SCJ) instability. This study aimed to assess whether a standardized treatment algorithm (incorporating physiotherapy and surgery and based on the presence of trauma) could successfully guide management and reduce the number needing surgery. METHODS: Patients with chronic anterior SCJ instability managed between April 2007 and April 2019 with a standardized treatment algorithm were divided into non-traumatic (offered physiotherapy) and traumatic (offered surgery) groups and evaluated at discharge. Subsequently, midterm outcomes were assessed via a postal questionnaire with a subjective SCJ stability score, Oxford Shoulder Instability Score (OSIS, adapted for the SCJ), and pain visual analogue scale (VAS), with analysis on an intention-to-treat basis. RESULTS: A total of 47 patients (50 SCJs, three bilateral) responded for 75% return rate. Of these, 31 SCJs were treated with physiotherapy and 19 with surgery. Overall, 96% (48/50) achieved a stable SCJ, with 60% (30/50) achieving unrestricted function. In terms of outcomes, 82% (41/50) recorded good-to-excellent OSIS scores (84% (26/31) physiotherapy, 79% (15/19) surgery), and 76% (38/50) reported low pain VAS scores at final follow-up. Complications of the total surgical cohort included a 19% (5/27) revision rate, 11% (3/27) frozen shoulder, and 4% (1/27) scar sensitivity. CONCLUSION: This is the largest midterm series reporting chronic anterior SCJ instability outcomes when managed according to a standardized treatment algorithm that emphasizes the importance of appropriate patient selection for either physiotherapy or surgery, based on a history of trauma. All but two patients achieved a stable SCJ, with stability maintained at a median of 70 months (11 to 116) for the physiotherapy group and 87 months (6 to 144) for the surgery group.Cite this article: Bone Jt Open 2022;3(10):815-825.

2.
J Med Chem ; 63(9): 4762-4775, 2020 05 14.
Artigo em Inglês | MEDLINE | ID: mdl-32297742

RESUMO

The exchange protein activated by cAMP (EPAC) is a promising drug target for a wide disease range, from neurodegeneration and infections to cancer and cardiovascular conditions. A novel partial agonist of the EPAC isoform 1 (EPAC1), I942, was recently discovered, but its mechanism of action remains poorly understood. Here, we utilize NMR spectroscopy to map the I942-EPAC1 interactions at atomic resolution and propose a mechanism for I942 partial agonism. We found that I942 interacts with the phosphate binding cassette (PBC) and base binding region (BBR) of EPAC1, similar to cyclic adenosine monophosphate (cAMP). These results not only reveal the molecular basis for the I942 vs cAMP mimicry and competition, but also suggest that the partial agonism of I942 arises from its ability to stabilize an inhibition-incompetent activation intermediate distinct from both active and inactive EPAC1 states. The mechanism of action of I942 may facilitate drug design for EPAC-related diseases.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/metabolismo , Sulfonamidas/metabolismo , Sítio Alostérico , Arginina/química , AMP Cíclico/metabolismo , Fatores de Troca do Nucleotídeo Guanina/agonistas , Fatores de Troca do Nucleotídeo Guanina/química , Humanos , Conformação Molecular , Simulação de Acoplamento Molecular , Ressonância Magnética Nuclear Biomolecular , Ligação Proteica , Eletricidade Estática , Sulfonamidas/química
3.
Trials ; 18(1): 614, 2017 Dec 22.
Artigo em Inglês | MEDLINE | ID: mdl-29273079

RESUMO

BACKGROUND: Frozen shoulder (also known as adhesive capsulitis) occurs when the capsule, or the soft tissue envelope around the ball and socket shoulder joint, becomes scarred and contracted, making the shoulder tight, painful and stiff. It affects around 1 in 12 men and 1 in 10 women of working age. Although this condition can settle with time (typically taking 1 to 3 years), for some people it causes severe symptoms and needs referral to hospital. Our aim is to evaluate the clinical and cost-effectiveness of two invasive and costly surgical interventions that are commonly used in secondary care in the National Health Service (NHS) compared with a non-surgical comparator of Early Structured Physiotherapy. METHODS: We will conduct a randomised controlled trial (RCT) of 500 adult patients with a clinical diagnosis of frozen shoulder, and who have radiographs that exclude other pathology. Early Structured Physiotherapy with an intra-articular steroid injection will be compared with manipulation under anaesthesia with a steroid injection or arthroscopic (keyhole) capsular release followed by manipulation. Both surgical interventions will be followed with a programme of post-procedural physiotherapy. These treatments will be undertaken in NHS hospitals across the United Kingdom. The primary outcome and endpoint will be the Oxford Shoulder Score (a patient self-reported assessment of shoulder function) at 12 months. This will also be measured at baseline, 3 and 6 months after randomisation; and on the day that treatment starts and 6 months later. Secondary outcomes include the Disabilities of Arm Shoulder and Hand (QuickDASH) score, the EQ-5D-5 L score, pain, extent of recovery and complications. We will explore the acceptability of the different treatments to patients and health care professionals using qualitative methods. DISCUSSION: The three treatments being compared are the most frequently used in secondary care in the NHS, but there is uncertainty about which one works best and at what cost. UK FROST is a rigorously designed and adequately powered study to inform clinical decisions for the treatment of this common condition in adults. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Register, ID: ISRCTN48804508 . Registered on 25 July 2014.


Assuntos
Artroscopia/métodos , Bursite/terapia , Manipulações Musculoesqueléticas/métodos , Modalidades de Fisioterapia , Adulto , Anestesia , Artroscopia/economia , Análise Custo-Benefício , Coleta de Dados , Estudos de Avaliação como Assunto , Feminino , Humanos , Masculino , Estudos Multicêntricos como Assunto , Manipulações Musculoesqueléticas/economia , Avaliação de Resultados em Cuidados de Saúde , Modalidades de Fisioterapia/economia , Ensaios Clínicos Controlados Aleatórios como Assunto , Tamanho da Amostra
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