Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 133
Filtrar
1.
Haemophilia ; 2022 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-35020243

RESUMO

INTRODUCTION: Recurrent bleeds into joints causes arthropathy leading to pain and reduced joint movement. This may cause a reduction in postural balance and increase the falls risk in patients with haemophilia (PWH). With an ageing PWH population the need to assess functional balance in clinic will be essential to monitor function and implement interventions to help maintain balance and prevent falls. AIM: To assess the utility of the Four-Square Step Test (FSST) in PWH. METHODS: 80 PWH of all severity types were recruited and underwent a battery of outcome measures: FSST, Timed up & go (TUG), Short performance physical battery (SPPB), Haemophilia Activity List (HAL), ABC confidence questionnaire, and Haemophilia Joint Health score (HJHS). Demographics were collected, together with self-reported falls/trips history. RESULTS: All 80 participants were able to complete all test measures. Median age 44.5 years. Number of participants reporting falls ranged from 23% in severe to 3% in mild. Recent trips 53% severe to 17% mild. Excellent Inter and intra-reliability, ICC of .981 (CI .953-.992), P < .001 and ICC .989 (.983-.993) P < .001, respectively. Strong correlations between FSST and TUG/ SPPB .753 and -.728, moderate correlation between FSST and ABC/HAL -.484, -.464 P < .01. CONCLUSION: FSST is a valid and safe measure to use in PWH. It correlates strongly with other functional measures, has excellent inter and intra rater reliability. FSST correlates with age rather than severity type and provides information to the clinician on the speed/ability to change direction and clear an obstacle. ABC questionnaire was able to differentiate between severities and offers insight into patient confidence to move. SPPB had a ceiling effect with 52/80 scoring 12 and may not be suitable for PWH.

2.
Knee ; 34: 89-97, 2021 Dec 06.
Artigo em Inglês | MEDLINE | ID: mdl-34883332

RESUMO

AIM: To compare the outcomes of cemented and cementless Unicompartmental Knee Replacements (UKR) at 5 years after surgery. METHODS: 262 cemented and 262 cementless medial mobile-bearing UKR, implanted by four high-volume surgeons using identical indications and surgical techniques, were reviewed by independent physiotherapists at 5 years. Survival, Oxford Knee Score (OKS), American Knee Society Score (AKSS), and EQ-5D-5L were assessed. The cementless cohort was mainly implanted after the cemented. Each cohort was divided into early and late sub-groups and compared, to assess if any differences were due to progressive improvement in surgical practice over time. RESULTS: There were no significant differences between the cohorts for demographics, pre-operative scores, and 5-year revision (0.8%), re-operation (1.5%), and complication rates (5%). The cementless cohort had significantly better 5-year OKS (43v41, p = 0.008), AKSS-Objective (94v90, p = 0.049) and EQ-5D-5L (0.81v0.87, p = 0.0001). Pain sub-scores within OKS, AKSS, and EQ-5D-5L were also significantly better in the cementless cohort, and the differences were proportionally much greater and more significant than differences in their respective overall scores. There was no significant improvement in scores between the early and late subgroups of the cohorts, whereas the 'early-cementless' cohort had significantly better scores than the contemporaneously implanted 'late-cemented' cohort. This suggests that differences found were due to implant type, instead of improved surgical practice over time. CONCLUSION: Cementless UKR is associated with better clinical outcomes than cemented UKR, which is primarily due to improved pain relief. Both cemented and cementless UKR are safe with low reoperation and complication rates, and a 5-year survival of 99%.

3.
Mil Med ; 2021 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-34910163

RESUMO

Trimethoprim-sulfamethoxazole-induced aseptic meningitis (TSIAM) is a rare adverse reaction to a commonly prescribed antibiotic. We describe a case of severe TSIAM which resembled septic shock. A 30-year-old male with relapsed Hodgkin's lymphoma 25 days status post autologous stem cell transplant presented to our clinic for evaluation of trimethoprim-sulfamethoxazole (TMP-SMX) hypersensitivity. After review of patient's history and records, we had a low suspicion for a TMP-SMX adverse reaction and conducted an oral challenge to one 160 mg/800 mg tab of TMP-SMX. Four hours later, the patient developed vomiting, lightheadedness, and disorientation with progression to rigors, fever, tachycardia, and hypotension. He was admitted for fluid resuscitation and broad-spectrum antibiotic coverage for neutropenic fever and possible septic shock. A lumbar puncture performed due to complaints of headache, photophobia, and neck pain showed 375 white blood cells/µL with 73% neutrophil predominance, normal glucose (75 mg/dL), and elevated protein (101 mg/dL); additional cerebrospinal fluid (CSF) studies were negative for infectious etiologies. Fever and headache resolved by hospital day 4, at which time patient was discharged home. We believe this case represents TSIAM given the characteristic timing of symptom onset, CSF findings, and timing of symptom resolution without other clear etiology found on extensive infectious evaluation. It is important for allergists to recognize TSIAM, including its potential presentation as shock, in order to appropriately diagnose and counsel patients who seek evaluation for TMP-SMX adverse reactions.

4.
Age Ageing ; 50(6): 2238-2245, 2021 11 10.
Artigo em Inglês | MEDLINE | ID: mdl-34673923

RESUMO

BACKGROUND: Increase in life-expectancy is not necessarily matched by an increase in quality of life. OBJECTIVE: (1) To explore the quality of life of patients over the age of 85 in the second decade following unicompartmental knee replacement surgery (2) To understand the usefulness of a priori themes from an evidence synthesis as a framework for primary qualitative analysis. DESIGN: Qualitative Research. A hermeneutic phenomenological approach, using a priori themes as sensitising concepts. PARTICIPANTS: Adults over the age of 85 who were part of an outcomes study in the second decade following unicompartmental knee joint replacement. METHODS: Semi-structured interviews in people's homes. Transcripts were coded and data sorted using a priori themes as sensitising concepts. Data that did not fit these themes, or that added nuance, were analysed thematically through constant comparison. RESULTS: We interviewed seven white women and five white men, aged 85-100. Data resonated with a priori themes and supported additional themes that help us to understand older peoples' experience: (1) losing our autonomy can be challenging, so be kind; (2) we must take care of our own bodies and the NHS; (3) I am more afraid of not dying. CONCLUSIONS: Findings indicate that health outcomes for older people should incorporate measures of participation and well-being; they highlight the importance of kindness in healthcare; they indicate that older people do not want to place additional burden on the NHS, and this can act as a barrier to care; they support the need for open conversations about dying well.


Assuntos
Artroplastia do Joelho , Qualidade de Vida , Idoso , Idoso de 80 Anos ou mais , Antropologia Cultural , Comunicação , Feminino , Humanos , Masculino , Pesquisa Qualitativa
5.
Disabil Rehabil ; : 1-9, 2021 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-34651530

RESUMO

PURPOSE: The life expectancy of people with haemophilia is increasing due to improved medical care. This improvement is accompanied by the co-morbidities of ageing, which include musculoskeletal degeneration and the associated effect on proprioception and balance. This study aims to explore the views and everyday experiences of those living with haemophilia regarding this. MATERIALS AND METHODS: Nine people with moderate or severe haemophilia aged 43-58 years participated in semi-structured interviews and thematic analysis was used to examine the data. RESULTS: Participants described pain and reduced movement in joints as a result of repeated bleeds, which caused problems with mobility and balance. Constant vigilance of their surroundings together with the potential consequences of bleeds caused continual worry. Participants were resourceful in their strategies to cope with the effects of haemophilia, to reduce pain and to minimise the risk of falling. However, participants felt stigmatised because of their condition. CONCLUSION: People with haemophilia have difficulties with their mobility and balance that can increase their risk of falling. Healthcare professionals need to understand and address the physical and psycho-social factors that contribute to the risk of falls. A multi-disciplinary approach to devise effective strategies to counteract and monitor the risk of falls would be useful.Implications for RehabilitationHealthcare professionals should identify movements that are fearful and work on ways to increase confidence and ability to perform these.Healthcare professionals need to identify the recovery strategies used to maintain balance and build these movements into home exercise programmes.Effective pain reduction strategies, both pharmacological and non-pharmacological, need to be investigated and optimised.Footwear choice has implications for both pain reduction and balance and should be discussed in routine reviews.Optimising vision would maximise visual input to aid balance.

6.
Cancer Gene Ther ; 2021 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-34522028

RESUMO

Deregulated polyamine biosynthesis is emerging as a common feature of neuroblastoma and drugs targeting this metabolic pathway such as DFMO are in clinical and preclinical development. The polyamine analog verlindamycin inhibits the polyamine biosynthesis pathway enzymes SMOX and PAOX, as well as the histone demethylase LSD1. Based on our previous research in acute myeloid leukemia (AML), we reasoned verlindamycin may also unblock neuroblastoma differentiation when combined with all-trans-retinoic acid (ATRA). Indeed, co-treatment with verlindamycin and ATRA strongly induced differentiation regardless of MYCN status, but in MYCN-expressing cells, protein levels were strongly diminished. This process was not transcriptionally regulated but was due to increased degradation of MYCN protein, at least in part via ubiquitin-independent, proteasome-dependent destruction. Here we report that verlindamycin effectively induces the expression of functional tumor suppressor-antizyme via ribosomal frameshifting. Consistent with previous results describing the function of antizyme, we found that verlindamycin treatment led to the selective targeting of ornithine decarboxylase (the rate-limiting enzyme for polyamine biosynthesis) as well as key oncoproteins, such as cyclin D and Aurora A kinase. Retinoid-based multimodal differentiation therapy is one of the few interventions that extends relapse-free survival in MYCN-associated high-risk neuroblastoma and these results point toward the potential use of verlindamycin in this regimen.

7.
Physiotherapy ; 113: 107-115, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34571284

RESUMO

OBJECTIVES: The aim of this study was to explore physiotherapists' perceptions of how patients' adherence and non-adherence to recommended exercise affects their practice. DESIGN: A qualitative study with a focus group and semi-structured interviews. The focus group and interviews were audio recorded and transcribed verbatim. Transcripts were analysed using thematic analysis. SETTING: MSK physiotherapy services in the United Kingdom. PARTICIPANTS: Focus group: 8 UK registered physiotherapists (age range=24-48; seven female, one male). Semi-structured interviews: 10 UK registered physiotherapists (age range=28-52; eight female, two male). RESULTS: Participants described how exercise adherence could be a challenging aspect of clinical practice and how they tried to improve it. Four main themes were identified: 1) A challenge but worth it; 2) It's frustrating but you can't win them all; 3) Striving to see the individual; and 4) Striving to help the patient. The importance of establishing a good working relationship with patients was emphasised. This included working collaboratively with the patient, avoiding blaming them for non-adherence and thinking about the language they used in discussing exercises. CONCLUSION: Patient non-adherence to recommended exercise is a challenging aspect of clinical practice. Physiotherapists can acknowledge this difficulty, and the frustrations it may potentially bring, yet remain resilient in the face of it. Clinicians should consider potential approaches and strategies to optimise the potential for behaviour change, and to improve exercise adherence. Robust interventions to help clinicians facilitate better exercise adherence are also needed.

8.
Health Technol Assess ; 25(48): 1-158, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34382931

RESUMO

BACKGROUND: Rotator cuff-related shoulder pain is very common, but there is uncertainty regarding which modes of exercise delivery are optimal and the long-term benefits of corticosteroid injections. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of progressive exercise compared with best-practice physiotherapy advice, with or without corticosteroid injection, in adults with a rotator cuff disorder. DESIGN: This was a pragmatic multicentre superiority randomised controlled trial (with a 2 × 2 factorial design). SETTING: Twenty NHS primary care-based musculoskeletal and related physiotherapy services. PARTICIPANTS: Adults aged ≥ 18 years with a new episode of rotator cuff-related shoulder pain in the previous 6 months. INTERVENTIONS: A total of 708 participants were randomised (March 2017-May 2019) by a centralised computer-generated 1 : 1 : 1 : 1 allocation ratio to one of four interventions: (1) progressive exercise (n = 174) (six or fewer physiotherapy sessions), (2) best-practice advice (n = 174) (one physiotherapy session), (3) corticosteroid injection then progressive exercise (n = 182) (six or fewer physiotherapy sessions) or (4) corticosteroid injection then best-practice advice (n = 178) (one physiotherapy session). MAIN OUTCOME MEASURES: The primary outcome was Shoulder Pain and Disability Index (SPADI) score over 12 months. Secondary outcomes included SPADI subdomains, the EuroQol 5 Dimensions, five-level version, sleep disturbance, fear avoidance, pain self-efficacy, return to activity, Global Impression of Treatment and health resource use. Outcomes were collected by postal questionnaires at 8 weeks and at 6 and 12 months. A within-trial economic evaluation was also conducted. The primary analysis was intention to treat. RESULTS: Participants had a mean age of 55.5 (standard deviation 13.1) years and 49.3% were female. The mean baseline SPADI score was 54.1 (standard deviation 18.5). Follow-up rates were 91% at 8 weeks and 87% at 6 and 12 months. There was an overall improvement in SPADI score from baseline in each group over time. Over 12 months, there was no evidence of a difference in the SPADI scores between the progressive exercise intervention and the best-practice advice intervention in shoulder pain and function (adjusted mean difference between groups over 12 months -0.66, 99% confidence interval -4.52 to 3.20). There was also no difference in SPADI scores between the progressive exercise intervention and best-practice advice intervention when analysed at the 8-week and 6- and 12-month time points. Injection resulted in improvement in shoulder pain and function at 8 weeks compared with no injection (adjusted mean difference -5.64, 99% confidence interval -9.93 to -1.35), but not when analysed over 12 months (adjusted mean difference -1.11, 99% confidence interval -4.47 to 2.26), or at 6 and 12 months. There were no serious adverse events. In the base-case analysis, adding injection to best-practice advice gained 0.021 quality-adjusted life-years (p = 0.184) and increased the cost by £10 per participant (p = 0.747). Progressive exercise alone was £52 (p = 0.247) more expensive per participant than best-practice advice, and gained 0.019 QALYs (p = 0.220). At a ceiling ratio of £20,000 per quality-adjusted life-year, injection plus best-practice advice had a 54.93% probability of being the most cost-effective treatment. LIMITATIONS: Participants and physiotherapists were not blinded to group allocation. Twelve-month follow-up may be insufficient for identifying all safety concerns. CONCLUSIONS: Progressive exercise was not superior to a best-practice advice session with a physiotherapist. Subacromial corticosteroid injection improved shoulder pain and function, but provided only modest short-term benefit. Best-practice advice in combination with corticosteroid injection was expected to be most cost-effective, although there was substantial uncertainty. FUTURE WORK: Longer-term follow-up, including any serious adverse effects of corticosteroid injection. TRIAL REGISTRATION: Current Controlled Trials ISRCTN16539266 and EudraCT 2016-002991-28. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 48. See the NIHR Journals Library website for further project information.


Assuntos
Terapia por Exercício , Manguito Rotador , Adolescente , Corticosteroides , Adulto , Análise Custo-Benefício , Feminino , Humanos , Modalidades de Fisioterapia , Dor de Ombro/tratamento farmacológico
9.
BMJ Open ; 11(8): e052598, 2021 08 27.
Artigo em Inglês | MEDLINE | ID: mdl-34452970

RESUMO

OBJECTIVES: To evaluate whether a home-based rehabilitation programme for people assessed as being at risk of a poor outcome after knee arthroplasty offers superior outcomes to traditional outpatient physiotherapy. DESIGN: A prospective, single-blind, two-arm randomised controlled superiority trial. SETTING: 14 National Health Service physiotherapy departments in the UK. PARTICIPANTS: 621 participants identified at high risk of a poor outcome after knee arthroplasty using a bespoke screening tool. INTERVENTIONS: A multicomponent home-based rehabilitation programme delivered by rehabilitation assistants with supervision from qualified therapists versus usual care outpatient physiotherapy. MAIN OUTCOME MEASURES: The primary outcome was the Late-Life Function and Disability Instrument (LLFDI) at 12 months. Secondary outcomes were the Oxford Knee Score (a disease-specific measure of function), Knee injury and Osteoarthritis Outcome Score Quality of Life subscale, Physical Activity Scale for the Elderly, 5 dimension, 5 level version of Euroqol (EQ-5D-5L) and physical function assessed using the Figure of 8 Walk test, 30 s Chair Stand Test and Single Leg Stance. RESULTS: 621 participants were randomised between March 2015 and January 2018. 309 were assigned to CORKA (Community Rehabilitation after Knee Arthroplasty) home-based rehabilitation, receiving a median five treatment sessions (IQR 4-7). 312 were assigned to usual care, receiving a median 4 sessions (IQR 2-6). The primary outcome, LLFDI function total score at 12 months, was collected for 279 participants (89%) in the home-based CORKA group and 287 participants (92%) in the usual care group. No clinically or statistically significant difference was found between the groups (intention-to-treat adjusted difference=0.49 points; 95% CI -0.89 to 1.88; p=0.48). There were no statistically significant differences between the groups on any of the patient-reported or physical secondary outcome measures at 6 or 12 months.There were 18 participants in the intervention group reporting a serious adverse event (5.8%), only one directly related to the intervention, all other adverse events recorded throughout the trial related to underlying chronic medical conditions. CONCLUSIONS: The CORKA intervention was not superior to usual care. The trial detected no significant differences, clinical or statistical, between the two groups on either primary or secondary outcomes. CORKA offers an evaluation of an intervention utilising a different service delivery model for this patient group. TRIAL REGISTRATION NUMBER: ISRCTN13517704.


Assuntos
Artroplastia do Joelho , Idoso , Análise Custo-Benefício , Humanos , Modalidades de Fisioterapia , Estudos Prospectivos , Qualidade de Vida , Método Simples-Cego , Medicina Estatal
10.
Lancet ; 398(10298): 416-428, 2021 07 31.
Artigo em Inglês | MEDLINE | ID: mdl-34265255

RESUMO

BACKGROUND: Corticosteroid injections and physiotherapy exercise programmes are commonly used to treat rotator cuff disorders but the treatments' effectiveness is uncertain. We aimed to compare the clinical effectiveness and cost-effectiveness of a progressive exercise programme with a single session of best practice physiotherapy advice, with or without corticosteroid injection, in adults with a rotator cuff disorder. METHODS: In this pragmatic, multicentre, superiority, randomised controlled trial (2 × 2 factorial), we recruited patients from 20 UK National Health Service trusts. We included patients aged 18 years or older with a rotator cuff disorder (new episode within the past 6 months). Patients were excluded if they had a history of significant shoulder trauma (eg, dislocation, fracture, or full-thickness tear requiring surgery), neurological disease affecting the shoulder, other shoulder conditions (eg, inflammatory arthritis, frozen shoulder, or glenohumeral joint instability), received corticosteroid injection or physiotherapy for shoulder pain in the past 6 months, or were being considered for surgery. Patients were randomly assigned (centralised computer-generated system, 1:1:1:1) to progressive exercise (≤6 sessions), best practice advice (one session), corticosteroid injection then progressive exercise, or corticosteroid injection then best practice advice. The primary outcome was the Shoulder Pain and Disability Index (SPADI) score over 12 months, analysed on an intention-to-treat basis (statistical significance set at 1%). The trial was registered with the International Standard Randomised Controlled Trial Register, ISRCTN16539266, and EuDRACT, 2016-002991-28. FINDINGS: Between March 10, 2017, and May 2, 2019, we screened 2287 patients. 708 patients were randomly assigned to progressive exercise (n=174), best practice advice (n=174), corticosteroid injection then progressive exercise (n=182), or corticosteroid injection then best practice advice (n=178). Over 12 months, SPADI data were available for 166 (95%) patients in the progressive exercise group, 164 (94%) in the best practice advice group, 177 (97%) in the corticosteroid injection then progressive exercise group, and 175 (98%) in the corticosteroid injection then best practice advice group. We found no evidence of a difference in SPADI score between progressive exercise and best practice advice when analysed over 12 months (adjusted mean difference -0·66 [99% CI -4·52 to 3·20]). We also found no evidence of a difference between corticosteroid injection compared with no injection when analysed over 12 months (-1·11 [-4·47 to 2·26]). No serious adverse events were reported. INTERPRETATION: Progressive exercise was not superior to a best practice advice session with a physiotherapist in improving shoulder pain and function. Subacromial corticosteroid injection provided no long-term benefit in patients with rotator cuff disorders. FUNDING: UK National Institute for Health Research Technology Assessment Programme.


Assuntos
Corticosteroides/administração & dosagem , Terapia por Exercício/métodos , Guias de Prática Clínica como Assunto , Lesões do Manguito Rotador/terapia , Síndrome de Colisão do Ombro/terapia , Adulto , Idoso , Feminino , Humanos , Injeções Intra-Articulares , Masculino , Pessoa de Meia-Idade , Resultado do Tratamento
11.
Pain Med ; 22(6): 1333-1344, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-33751119

RESUMO

OBJECTIVE: There is a large body of research exploring what it means for a person to live with chronic pain. However, existing research does not help us understand what it means to recover. We aimed to identify qualitative research that explored the experience of living with chronic pain published since 2012 and to understand the process of recovery. DESIGN: A synthesis of qualitative research using meta-ethnography. METHODS: We used the seven stages of meta-ethnography. We systematically searched for qualitative research, published since 2012, that explored adults' experiences of living with, and being treated for, chronic pain. We used constant comparison to distill the essence of ideas into themes and developed a conceptual model. RESULTS: We screened 1,328 titles and included 195 studies. Our conceptual model indicates that validation and reconnection can empower a person with chronic pain to embark on a journey of healing. To embark on this journey requires commitment, energy, and support. CONCLUSIONS: The innovation of our study is to conceptualize healing as an ongoing and iterating journey rather than a destination. Health interventions for chronic pain would usefully focus on validating pain through meaningful and acceptable explanations; validating patients by listening to and valuing their stories; encouraging patients to connect with a meaningful sense of self, to be kind to themselves, and to explore new possibilities for the future; and facilitating safe reconnection with the social world. This could make a real difference to people living with chronic pain who are on their own healing journeys.


Assuntos
Dor Crônica , Adulto , Antropologia Cultural , Dor Crônica/terapia , Atenção à Saúde , Humanos , Pesquisa Qualitativa
12.
Disabil Rehabil ; 43(2): 284-296, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-31180732

RESUMO

Introduction: Sarcomas are rare cancers of bone and soft tissue, and limb salvage surgery is the standard treatment followed by multidisciplinary rehabilitation. The scoping review aimed to summarize the evidence for occupational therapy intervention for adult sarcoma patients following limb salvage surgery.Methods: A review of the literature using a scoping framework was undertaken starting with a systematic database search, followed by an analysis of the literature. The literature was described using a numerical analysis, and the following headings; (a) rehabilitation, (b) activity limitations and participation restrictions, (c) functional outcomes.Findings: Seventeen articles met the review criteria, papers were diverse in study location, type, population, methods and outcomes used. Following limb salvage surgery patients experience functional deficits, activity limitations and participation restrictions in life roles and loss of previous identity. Prehabilitation can influence functional outcomes. Functional activity was found to plateau at 4-12 months following limb salvage surgery, with some patients identifying a need for further rehabilitation.Conclusion: The review identified limited evidence guiding occupational therapy practice for sarcoma patients following limb salvage surgery. Further research is needed to demonstrate the effectiveness of occupational therapy intervention in the early and late stages of rehabilitation and develop evidence based guidelines.Implications for rehabilitationSarcoma patients experience activity limitations and participation restrictions in activities of daily living, work and leisure following limb salvage surgery.Prehabilitation and early intervention can influence functional outcomes.Functional ability may plateau at 4-12 months following limb salvage surgery.Some groups of patients will benefit from late rehabilitation to maximize their rehabilitation potential.


Assuntos
Terapia Ocupacional , Sarcoma , Neoplasias de Tecidos Moles , Atividades Cotidianas , Adulto , Humanos , Salvamento de Membro , Sarcoma/cirurgia , Neoplasias de Tecidos Moles/cirurgia , Resultado do Tratamento
13.
Health Technol Assess ; 24(65): 1-116, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33250068

RESUMO

BACKGROUND: Over 100,000 primary knee arthroplasty operations are undertaken annually in the UK. Around 15-30% of patients do not report a good outcome. Better rehabilitation strategies may improve patient-reported outcomes. OBJECTIVES: To compare the outcomes from a traditional outpatient physiotherapy model with those from a home-based rehabilitation programme for people assessed as being at risk of a poor outcome after knee arthroplasty. DESIGN: An individually randomised, two-arm controlled trial with a blinded outcome assessment, a parallel health economic evaluation and a nested qualitative study. SETTING: The trial took place in 14 NHS physiotherapy departments. PARTICIPANTS: People identified as being at high risk of a poor outcome after knee arthroplasty. INTERVENTIONS: A multicomponent home-based rehabilitation package delivered by rehabilitation assistants with supervision from qualified therapists compared with usual-care outpatient physiotherapy. MAIN OUTCOME MEASURES: The primary outcome was the Late Life Function and Disability Instrument at 12 months. Secondary outcomes were the Oxford Knee Score (a disease-specific measure of function); Knee injury and Osteoarthritis Outcome Score; Quality of Life subscale; Physical Activity Scale for the Elderly; EuroQol-5 Dimensions, five-level version; and physical function assessed using the Figure-of-8 Walk Test, 30-Second Chair Stand Test and Single Leg Stance. Data on the use of health-care services, time off work and informal care were collected using participant diaries. RESULTS: In total, 621 participants were randomised. A total of 309 participants were assigned to the COmmunity based Rehabilitation after Knee Arthroplasty (CORKA) home-based rehabilitation programme, receiving a median of five treatment sessions (interquartile range 4-7 sessions). A total of 312 participants were assigned to usual care, receiving a median of four sessions (interquartile range 2-6 sessions). The primary outcome, Late Life Function and Disability Instrument function total score at 12 months, was collected for 279 participants (89%) in the home-based CORKA group and 287 participants (92%) in the usual-care group. No clinically or statistically significant difference was found between the groups (intention-to-treat adjusted difference 0.49 points, 95% confidence interval -0.89 to 1.88 points; p = 0.48). There were no statistically significant differences between the groups in any of the patient-reported or physical secondary outcome measures at 6 or 12 months post randomisation. The health economic analysis found that the CORKA intervention was cheaper to provide than usual care (£66 less per participant). Total societal costs (combining health-care costs and other costs) were lower for the CORKA intervention than usual care (£316 less per participant). Adopting a societal perspective, CORKA had a 75% probability of being cost-effective at a threshold of £30,000 per quality-adjusted life-year. Adopting the narrower health and social care perspective, CORKA had a 43% probability of being cost-effective at the same threshold. LIMITATIONS: The interventions were of short duration and were set within current commissioning guidance for UK physiotherapy. Participants and treating therapists could not be blinded. CONCLUSIONS: This randomised controlled trial found no important differences in outcomes when post-arthroplasty rehabilitation was delivered using a home-based, rehabilitation assistant-delivered rehabilitation package or a traditional outpatient model. However, the health economic evaluation found that when adopting a societal perspective, the CORKA home-based intervention was cost-saving and more effective than, and thus dominant over, usual care, owing to reduced time away from paid employment for this group. Further research could look at identifying the risk of poor outcome and further evaluation of a cost-effective treatment, including the workforce model to deliver it. TRIAL REGISTRATION: Current Controlled Trials ISRCTN13517704. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 24, No. 65. See the NIHR Journals Library website for further project information.


Assuntos
Artroplastia do Joelho/reabilitação , Análise Custo-Benefício/economia , Serviços de Assistência Domiciliar/economia , Pacientes Ambulatoriais/estatística & dados numéricos , Medidas de Resultados Relatados pelo Paciente , Idoso , Artroplastia do Joelho/economia , Feminino , Humanos , Masculino , Modalidades de Fisioterapia , Inquéritos e Questionários , Reino Unido
14.
BMJ ; 371: m3576, 2020 10 13.
Artigo em Inglês | MEDLINE | ID: mdl-33051212

RESUMO

OBJECTIVE: To evaluate whether a progressive course of outpatient physiotherapy offers superior outcomes to a single physiotherapy review and home exercise based intervention when targeted at patients with a predicted poor outcome after total knee arthroplasty. DESIGN: Parallel group randomised controlled trial. SETTING: 13 secondary and tertiary care centres in the UK providing postoperative physiotherapy. PARTICIPANTS: 334 participants with knee osteoarthritis who were defined as at risk of a poor outcome after total knee arthroplasty, based on the Oxford knee score, at six weeks postoperatively. 163 were allocated to therapist led outpatient rehabilitation and 171 to a home exercise based protocol. INTERVENTIONS: All participants were reviewed by a physiotherapist and commenced 18 sessions of rehabilitation over six weeks, either as therapist led outpatient rehabilitation (progressive goal oriented functional rehabilitation protocol, modified weekly in one-one contact sessions) or as physiotherapy review followed by a home exercise based regimen (without progressive input from a physiotherapist). MAIN OUTCOME MEASURES: Primary outcome was Oxford knee score at 52 weeks, with a 4 point difference between groups considered to be clinically meaningful. Secondary outcomes included additional patient reported outcome measures of pain and function at 14, 26, and 52 weeks post-surgery. RESULTS: 334 patients were randomised. Eight were lost to follow-up. Intervention compliance was more than 85%. The between group difference in Oxford knee score at 52 weeks was 1.91 (95% confidence interval -0.18 to 3.99) points, favouring the outpatient rehabilitation arm (P=0.07). When all time point data were analysed, the between group difference in Oxford knee score was a non-clinically meaningful 2.25 points (0.61 to 3.90, P=0.01). No between group differences were found for secondary outcomes of average pain (0.25 points, -0.78 to 0.28, P=0.36) or worst pain (0.22 points, -0.71 to 0.41, P=0.50) at 52 weeks or earlier time points, or of satisfaction with outcome (odds ratio 1.07, 95% confidence interval 0.71 to 1.62, P=0.75) or post-intervention function (4.64 seconds, 95% confidence interval -14.25 to 4.96, P=0.34). CONCLUSIONS: Outpatient therapist led rehabilitation was not superior to a single physiotherapist review and home exercise based regimen in patients at risk of poor outcomes after total knee arthroplasty. No clinically relevant differences were observed across primary or secondary outcome measures. TRIALS REGISTRATION: Current Controlled Trials ISRCTN23357609 and ClinicalTrials.gov NCT01849445.


Assuntos
Artroplastia do Joelho/reabilitação , Terapia por Exercício/métodos , Osteoartrite do Joelho/reabilitação , Dor Pós-Operatória/reabilitação , Modalidades de Fisioterapia , Idoso , Artroplastia do Joelho/efeitos adversos , Protocolos Clínicos , Feminino , Humanos , Articulação do Joelho/patologia , Articulação do Joelho/cirurgia , Masculino , Pessoa de Meia-Idade , Osteoartrite do Joelho/cirurgia , Medição da Dor , Dor Pós-Operatória/etiologia , Cooperação do Paciente , Medidas de Resultados Relatados pelo Paciente , Resultado do Tratamento
15.
J Clin Invest ; 130(11): 5875-5892, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33016930

RESUMO

The undruggable nature of oncogenic Myc transcription factors poses a therapeutic challenge in neuroblastoma, a pediatric cancer in which MYCN amplification is strongly associated with unfavorable outcome. Here, we show that CYC065 (fadraciclib), a clinical inhibitor of CDK9 and CDK2, selectively targeted MYCN-amplified neuroblastoma via multiple mechanisms. CDK9 - a component of the transcription elongation complex P-TEFb - bound to the MYCN-amplicon superenhancer, and its inhibition resulted in selective loss of nascent MYCN transcription. MYCN loss led to growth arrest, sensitizing cells for apoptosis following CDK2 inhibition. In MYCN-amplified neuroblastoma, MYCN invaded active enhancers, driving a transcriptionally encoded adrenergic gene expression program that was selectively reversed by CYC065. MYCN overexpression in mesenchymal neuroblastoma was sufficient to induce adrenergic identity and sensitize cells to CYC065. CYC065, used together with temozolomide, a reference therapy for relapsed neuroblastoma, caused long-term suppression of neuroblastoma growth in vivo, highlighting the clinical potential of CDK9/2 inhibition in the treatment of MYCN-amplified neuroblastoma.


Assuntos
Adenosina/análogos & derivados , Quinase 2 Dependente de Ciclina/antagonistas & inibidores , Quinase 9 Dependente de Ciclina/antagonistas & inibidores , Proteína Proto-Oncogênica N-Myc/biossíntese , Neuroblastoma/tratamento farmacológico , Temozolomida/farmacologia , Adenosina/farmacologia , Linhagem Celular Tumoral , Quinase 2 Dependente de Ciclina/metabolismo , Quinase 9 Dependente de Ciclina/metabolismo , Elementos Facilitadores Genéticos , Humanos , Proteína Proto-Oncogênica N-Myc/genética , Neuroblastoma/genética , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Fator B de Elongação Transcricional Positiva/genética , Fator B de Elongação Transcricional Positiva/metabolismo , Transcrição Genética/efeitos dos fármacos
16.
Int Urogynecol J ; 31(12): 2631-2644, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32870341

RESUMO

INTRODUCTION AND HYPOTHESIS: Pelvic organ prolapse (POP) affects the lives of many people. We aimed to systematically search for, identify and synthesize qualitative research that explores what it is like to live with POP and make this knowledge available for healthcare improvement. METHODS: We systematically searched Medline, PsychInfo, Embase and CINAHL, from inception to March 2020, for qualitative research exploring the experience of living with POP. We used meta-ethnography to synthesize findings. This is a conceptual approach to qualitative evidence synthesis. We used the recent guidelines for reporting meta-ethnography. RESULTS: We screened 3103 titles and 255 abstracts and included 37 primary studies. These incorporated the experience of 777 women, (aged 18 to 95 years) from a range of countries. We organized 162 ideas into 27 conceptual categories and 10 themes. We developed a conceptual model that helps us to understand the experience of pelvic organ prolapse. This model indicates that (1) the physical losses of POP are intricately linked to loss of identity; (2) women conceptualized POP as part of womanhood, yet also its thief; (3) there is a vicious cycle of taboo, silence and misunderstanding about POP and its treatment; (4) this silence is exacerbated by a feeling that POP is not taken seriously in healthcare. CONCLUSIONS: This meta-ethnography helps us to understand the experience of living with a POP. Our model illustrates the complex process of healthcare decision making. Further studies to explore the complexity of decision making from the perspective of patient and health professional are timely.


Assuntos
Antropologia Cultural , Prolapso de Órgão Pélvico , Atenção à Saúde , Feminino , Humanos , Pesquisa Qualitativa
18.
EBioMedicine ; 59: 102971, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32846370

RESUMO

BACKGROUND: In neuroblastoma, genetic alterations in ATRX, define a distinct poor outcome patient subgroup. Despite the need for new therapies, there is a lack of available models and a dearth of pre-clinical research. METHODS: To evaluate the impact of ATRX loss of function (LoF) in neuroblastoma, we utilized CRISPR-Cas9 gene editing to generate neuroblastoma cell lines isogenic for ATRX. We used these and other models to identify therapeutically exploitable synthetic lethal vulnerabilities associated with ATRX LoF. FINDINGS: In isogenic cell lines, we found that ATRX inactivation results in increased DNA damage, homologous recombination repair (HRR) defects and impaired replication fork processivity. In keeping with this, high-throughput compound screening showed selective sensitivity in ATRX mutant cells to multiple PARP inhibitors and the ATM inhibitor KU60019. ATRX mutant cells also showed selective sensitivity to the DNA damaging agents, sapacitabine and irinotecan. HRR deficiency was also seen in the ATRX deleted CHLA-90 cell line, and significant sensitivity demonstrated to olaparib/irinotecan combination therapy in all ATRX LoF models. In-vivo sensitivity to olaparib/irinotecan was seen in ATRX mutant but not wild-type xenografts. Finally, sustained responses to olaparib/irinotecan therapy were seen in an ATRX deleted neuroblastoma patient derived xenograft. INTERPRETATION: ATRX LoF results in specific DNA damage repair defects that can be therapeutically exploited. In ATRX LoF models, preclinical sensitivity is demonstrated to olaparib and irinotecan, a combination that can be rapidly translated into the clinic. FUNDING: This work was supported by Christopher's Smile, Neuroblastoma UK, Cancer Research UK, and the Royal Marsden Hospital NIHR BRC.


Assuntos
Antineoplásicos/farmacologia , Dano ao DNA/efeitos dos fármacos , Reparo do DNA/efeitos dos fármacos , Neuroblastoma/genética , Proteína Nuclear Ligada ao X/genética , Animais , Antineoplásicos/uso terapêutico , Sistemas CRISPR-Cas , Linhagem Celular Tumoral , Modelos Animais de Doenças , Edição de Genes , Técnicas de Inativação de Genes , Humanos , Imuno-Histoquímica , Camundongos , Neuroblastoma/tratamento farmacológico , Neuroblastoma/mortalidade , Neuroblastoma/patologia , Inibidores de Poli(ADP-Ribose) Polimerases/farmacologia , Inibidores de Poli(ADP-Ribose) Polimerases/uso terapêutico , Prognóstico , Ensaios Antitumorais Modelo de Xenoenxerto
19.
BMJ Open ; 10(7): e028915, 2020 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-32620710

RESUMO

OBJECTIVES: To estimate the relationship between patient characteristics and referral decisions made by musculoskeletal hubs, and to assess the possible impact of an evidence-based referral tool. DESIGN: Retrospective analysis of medical records and decision tree model evaluating policy changes using local and national data. SETTING: One musculoskeletal interface clinic (hub) in England. PARTICIPANTS: 922 adults aged ≥50 years referred by general practitioners with symptoms of knee or hip osteoarthritis. INTERVENTIONS: We assessed the current frequency and determinants of referrals from one hub and the change in referrals that would occur at this centre and nationally if evidence-based thresholds for referral (Oxford Knee and Hip Scores, OKS/OHS) were introduced. MAIN OUTCOME MEASURE: OKS/OHS, referrals for surgical assessment, referrals for arthroplasty, costs and quality-adjusted life years. RESULTS: Of 110 patients with knee symptoms attending face-to-face hub consultations, 49 (45%) were referred for surgical assessment; the mean OKS for these 49 patients was 18 (range: 1-41). Of 101 hip patients, 36 (36%) were referred for surgical assessment (mean OHS: 21, range: 5-44). No patients referred for surgical assessment were above previously reported economic thresholds for OKS (43) or OHS (45). Setting thresholds of OKS ≤31 and OHS ≤35 might have resulted in an additional 22 knee referrals and 26 hip referrals in our cohort. Extrapolating hub results across England suggests a possible increase in referrals nationally, of around 13 000 additional knee replacements and 4500 additional hip replacements each year. CONCLUSIONS: Musculoskeletal hubs currently consider OKS/OHS and other factors when making decisions about referral to secondary care for joint replacement. Those referred typically have low OHS/OKS, and introducing evidence-based OKS/OHS thresholds would prevent few inappropriate (high-functioning, low-pain) referrals. However, our findings suggest that some patients not currently referred could benefit from arthroplasty based on OKS/OHS. More research is required to explore other important patient characteristics currently influencing hub decisions.


Assuntos
Artroplastia de Quadril , Adulto , Inglaterra , Humanos , Pessoa de Meia-Idade , Modelos Teóricos , Encaminhamento e Consulta , Estudos Retrospectivos
20.
Haemophilia ; 26(4): 718-725, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32364278

RESUMO

INTRODUCTION: Historically persons with haemophilia (PWH) were not encouraged to participate in exercise due to the risk of bleeding and the lack of factor products available. This has now changed, and the availability of safe products allows PWH to be active and participate in sports. Studies have found that exercise has a positive effect on pain, joint health and movement with PWH. AIM: To record the amount and types of physical activity undertaken by a haemophilia population at a single treatment centre. METHODS: An observational cross-sectional study to assess physical activity and quality of life of all registered patients over the age of 18 at the Oxford Haemophilia and Thrombosis Centre. Participants were posted questionnaires including the International Physical activity Questionnaire (IPAQ), Haemophilia Activity List (HAL), EQ-5D-5L and asked to list their physical activities. RESULTS: A total of 256 questionnaires were sent, with a 40% response rate for severe and 28% for mild patients. 85% met the UK physical activity guidelines. Sedentary behaviour for an average weekday was 6.4 hours, and weekends were 5.3 hours. Joint disease and severity type influenced the amount of activity undertaken, together with values for HAL and EQ-5D-5L. Twenty two types of activities were listed. CONCLUSION: It is encouraging to see the amount of physical activity PWH participate in, however, time spent in a sedentary state needs monitoring. PWH want to be active and the challenge for caregivers is to find activities they can do and strategies to maintain participation.


Assuntos
Exercício Físico/fisiologia , Exercício Físico/psicologia , Hemofilia A/terapia , Hemorragia/prevenção & controle , Adulto , Idoso , Estudos Transversais , Hemofilia A/complicações , Hemofilia A/fisiopatologia , Hemorragia/etiologia , Humanos , Artropatias/complicações , Artropatias/diagnóstico , Artropatias/prevenção & controle , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Qualidade de Vida , Comportamento Sedentário , Índice de Gravidade de Doença , Inquéritos e Questionários/estatística & dados numéricos , Reino Unido/epidemiologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...