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1.
BMC Cancer ; 24(1): 823, 2024 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-38987693

RESUMO

BACKGROUND: Approximately 40% of treated head and neck cancer (HNC) patients develop recurrence. The risk of recurrence declines with time from treatment. Current guidelines recommend clinical follow-up every two months for the first two years after treatment, with reducing intensity over the next three years. However, evidence for the effectiveness of these regimes in detecting recurrence is lacking, with calls for more flexible, patient-centred follow-up strategies. METHODS: PETNECK2 is a UK-based multi-centre programme examining a new paradigm of follow-up, using positron emission tomography-computed tomography (PET-CT)-guided, symptom-based, patient-initiated surveillance. This paradigm is being tested in a unblinded, non-inferiority, phase III, randomised controlled trial (RCT). Patients with HNC, one year after completing curative intent treatment, with no clinical symptoms or signs of loco-regional or distant metastasis will be randomised using a 1:1 allocation ratio to either regular scheduled follow-up, or to PET-CT guided, patient-initiated follow-up. Patients at a low risk of recurrence (negative PET-CT) will receive a face-to-face education session along with an Information and Support (I&S) resource package to monitor symptoms and be in control of initiating an urgent appointment when required. The primary outcome of the RCT is overall survival. The RCT also has an in-built pilot, a nested QuinteT Recruitment Intervention (QRI), and a nested mixed-methods study on patient experience and fear of cancer recurrence (FCR). An initial, single-arm feasibility study has been completed which determined the acceptability of the patient-initiated surveillance intervention, the completion rates of baseline questionnaires, and optimised the I&S resource prior to implementation in the RCT. DISCUSSION: We hypothesise that combining an additional 12-month post-treatment PET-CT scan and I&S resource will both identify patients with asymptomatic recurrence and identify those at low risk of future recurrence who will be empowered to monitor their symptoms and seek early clinical follow-up when recurrence is suspected. This change to a patient-centred model of care may have effects on both quality of life and fear of cancer recurrence. TRIAL REGISTRATION: ISRCTN: 13,709,798; 15-Oct-2021.


Assuntos
Estudos de Viabilidade , Neoplasias de Cabeça e Pescoço , Recidiva Local de Neoplasia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Humanos , Neoplasias de Cabeça e Pescoço/diagnóstico por imagem , Neoplasias de Cabeça e Pescoço/terapia , Neoplasias de Cabeça e Pescoço/psicologia , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Recidiva Local de Neoplasia/diagnóstico por imagem , Seguimentos , Estudos Multicêntricos como Assunto , Masculino , Feminino , Estudos de Equivalência como Asunto , Reino Unido
2.
Acta Anaesthesiol Scand ; 68(1): 130-136, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37691474

RESUMO

BACKGROUND: Fluid overload is associated with increased mortality in intensive care unit (ICU) patients. The GODIF trial aims to assess the benefits and harms of fluid removal with furosemide versus placebo in stable adult patients with moderate to severe fluid overload in the ICU. This article describes the detailed statistical analysis plan for the primary results of the second version of the GODIF trial. METHODS: The GODIF trial is an international, multi-centre, randomised, stratified, blinded, parallel-group, pragmatic clinical trial, allocating 1000 adult ICU patients with moderate to severe fluid overload 1:1 to furosemide versus placebo. The primary outcome is days alive and out of hospital within 90 days post-randomisation. With a power of 90% and an alpha level of 5%, we may reject or detect an improvement of 8%. The primary analyses of all outcomes will be performed in the intention-to-treat population. For the primary outcome, the Kryger Jensen and Lange method will be used to compare the two treatment groups adjusted for stratification variables supplemented with sensitivity analyses in the per-protocol population and with further adjustments for prognostic variables. Secondary outcomes will be analysed with multiple linear regressions, logistic regressions or the Kryger Jensen and Lange method as suitable with adjustment for stratification variables. CONCLUSION: The GODIF trial data will increase the certainty about the effects of fluid removal using furosemide in adult ICU patients with fluid overload. TRIAL REGISTRATIONS: EudraCT identifier: 2019-004292-40 and ClinicalTrials.org: NCT04180397.


Assuntos
Furosemida , Desequilíbrio Hidroeletrolítico , Adulto , Humanos , Furosemida/uso terapêutico , Cuidados Críticos/métodos , Unidades de Terapia Intensiva , Resultado do Tratamento
3.
Artigo em Inglês | MEDLINE | ID: mdl-38769040

RESUMO

BACKGROUND: Piperacillin/tazobactam may be associated with less favourable outcomes than carbapenems in patients with severe bacterial infections, but the certainty of evidence is low. METHODS: The Empirical Meropenem versus Piperacillin/Tazobactam for Adult Patients with Sepsis (EMPRESS) trial is an investigator-initiated, international, parallel-group, randomised, open-label, adaptive clinical trial with an integrated feasibility phase. We will randomise adult, critically ill patients with sepsis to empirical treatment with meropenem or piperacillin/tazobactam for up to 30 days. The primary outcome is 30-day all-cause mortality. The secondary outcomes are serious adverse reactions within 30 days; isolation precautions due to resistant bacteria within 30 days; days alive without life support and days alive and out of hospital within 30 and 90 days; 90- and 180-day all-cause mortality and 180-day health-related quality of life. EMPRESS will use Bayesian statistical models with weak to somewhat sceptical neutral priors. Adaptive analyses will be conducted after follow-up of the primary outcome for the first 400 participants concludes and after every 300 subsequent participants, with adaptive stopping for superiority/inferiority and practical equivalence (absolute risk difference <2.5%-points) and response-adaptive randomisation. The expected sample sizes in scenarios with no, small or large differences are 5189, 5859 and 2570 participants, with maximum 14,000 participants and ≥99% probability of conclusiveness across all scenarios. CONCLUSIONS: EMPRESS will compare the effects of empirical meropenem against piperacillin/tazobactam in adult, critically ill patients with sepsis. Due to the pragmatic, adaptive design with high probability of conclusiveness, the trial results are expected to directly inform clinical practice.

4.
Anaesthesia ; 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-39083657

RESUMO

BACKGROUND: Opioid analgesic use before total hip or knee arthroplasty has been associated with worse postoperative outcomes. This pilot study aimed to examine the feasibility of a telehealth-based pharmacist-partnered opioid tapering intervention before elective primary hip or knee arthroplasty and its potential effectiveness compared with usual care. METHODS: This study was conducted at seven hospitals in New South Wales, Australia. Eligible patients were those aged ≥ 18 years, scheduled to undergo primary hip or knee arthroplasty for osteoarthritis and taking opioid analgesics pre-operatively. The intervention group participated in an opioid tapering telehealth service, a partnership between a pharmacist and general practitioner, for 3 months pre-operatively up to the day of surgery, while the control group received usual care. The primary outcomes of the study were to investigate the feasibility of the intervention (i.e. adherence to treatment) and potential effectiveness in decreasing baseline daily opioid dose by > 50% before surgery. RESULTS: Between December 2021 and June 2023, 70 patients were recruited and assigned randomly to the intervention group (n = 35) or control group (n = 35). Baseline characteristics were similar between groups. Thirty patients in each group completed their allocated treatment. All patients allocated to the intervention group completed at least one appointment with a pharmacist, with the median (IQR [range]) being 2 (1-4 [1-6]) appointments. The number of patients who successfully decreased their baseline daily opioid dose by ≥ 50% before surgery was 27/30 in the intervention group compared with 5/30 in the usual care group (p < 0.001). CONCLUSIONS: The findings of this pilot study support the feasibility of a telehealth-delivered, pharmacist-partnered opioid tapering service for patients scheduled for primary hip or knee arthroplasty. A broader multicentre study to examine the effectiveness of this intervention on clinical outcomes is warranted.

5.
Clin Rehabil ; 38(3): 347-360, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-37700695

RESUMO

OBJECTIVE: To compare the effects of electrical dry needling with a non-invasive multi-component intervention in patients with chronic low back pain. DESIGN: A randomised single-blind clinical trial. SETTING: Outpatient Physiotherapy Clinic; home. PARTICIPANTS: Sixty-four patients with chronic low back pain aged 30-65 years. INTERVENTIONS: Six-week electrical dry needling on myofascial trigger points, and a non-invasive multicomponent intervention (home exercise programme, stretching and ischemic compression). MAIN MEASURES: Pain (Visual Analogue Scale), disability (Roland-Morris Disability Questionnaire and Oswestry Disability Index), kinesiophobia (Tampa Scale of Kinesiophobia), quality of life and sleep (Short Form 36-item Health Survey and Pittsburgh Sleep Quality Index), isometric endurance of trunk flexor muscles (McQuade test), lumbar mobility in flexion (finger-to-floor distance), and pressure pain threshold (algometer) were assessed at baseline, after 6 weeks, and after 2 months. RESULTS: ANOVA showed statistically significant differences in group-by-time interaction for most pain pressure thresholds of myofascial trigger points (P < 0.05), for disability (Roland-Morris Disability Questionnaire: F = 6.14, P = 0.016; and Oswestry Disability Index: F = 7.36, P = 0.009), for trunk anteflexion (F = 10.03, P = 0.002) and for habitual sleep efficacy (F = 6.65, P = 0.012), use of hypnotics (F = 4.77, P = 0.033) and total score of quality of sleep (F = 8.23, P = 0.006). CONCLUSIONS: In comparison to a non-invasive multicomponent intervention, electrical dry needling has more positive effects on disability, pain intensity, kinesiophobia, and reducing patients' sensitivity to myofascial trigger points pressure, at post-treatment and at 2 months. CLINICAL TRIAL REGISTRATION NUMBER: NCT04804228. Registered on May 28th, 2021. Available at https://clinicaltrials.gov/ct2/show/NCT04804228.


Assuntos
Dor Lombar , Pontos-Gatilho , Humanos , Dor Lombar/diagnóstico , Dor Lombar/terapia , Indução Percutânea de Colágeno , Qualidade de Vida , Método Simples-Cego , Adulto , Pessoa de Meia-Idade , Idoso
6.
Ophthalmic Physiol Opt ; 44(5): 876-883, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38712751

RESUMO

OBJECTIVE: This randomised clinical trial assessed the impact on symptoms, tear film dynamics and ocular surface integrity of daily disposable silicone-hydrogel contact lenses (CLs) over a month, paying special attention to lid wiper epitheliopathy (LWE) and its implications for CL discomfort. METHODS: Neophyte CL wearers (n = 44, 21.09 ± 5.00 years old) were randomly assigned to either the experimental (n = 24) or control group (n = 20). Participants assigned to the experimental group were required to wear daily disposable CLs for 1 month for at least 8 h/day and 6 days/week. All participants were healthy subjects (no history of ocular surgery or active ocular disease) with spherical refractive errors between -8.00 and +5.00 D and cylindrical power <0.75 D. At the baseline and 1-month sessions, the Dry Eye Questionnaire 5 (DEQ-5) was completed, together with the measurement of tear film osmolarity with the TearLab osmometer, tear meniscus height (TMH) and lipid layer pattern (LLP) using a slit-lamp with Tearscope Plus attached, fluorescein break-up time (FBUT), maximum blink interval (MBI), corneal staining with fluorescein under cobalt blue light and LWE with lissamine green under slit lamp and halogen white light. RESULTS: At the baseline session, LWE showed a negative correlation with DEQ-5 (r = -0.37, p = 0.02). Significant differences in FBUT and LWE (p = 0.04) and a positive correlation between LWE and DEQ-5 (r = 0.49, p = 0.007) were observed at 1 month. Intrasession analysis at 1 month showed significant differences between the experimental and control groups in DEQ-5, FBUT and LWE (all p ≤ 0.02). Intersession analysis in the experimental group showed variations in DEQ-5, FBUT and LWE (all p ≤ 0.02) but no significant variation in the control group (all p ≥ 0.11). CONCLUSION: The presence of LWE was significantly correlated with higher symptom values in the DEQ-5. Also, participants in the experimental group presented higher values of LWE after 1 month of CL wear, in comparison with the control group.


Assuntos
Lentes de Contato Hidrofílicas , Equipamentos Descartáveis , Síndromes do Olho Seco , Lágrimas , Humanos , Masculino , Feminino , Lágrimas/fisiologia , Lágrimas/metabolismo , Adulto Jovem , Síndromes do Olho Seco/fisiopatologia , Síndromes do Olho Seco/diagnóstico , Adulto , Erros de Refração/terapia , Erros de Refração/fisiopatologia , Silicones , Adolescente , Inquéritos e Questionários , Doenças Palpebrais/fisiopatologia , Doenças Palpebrais/terapia , Concentração Osmolar
7.
Neth Heart J ; 32(6): 254-261, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38776038

RESUMO

BACKGROUND: Several ethnic minorities have an increased risk of cardiovascular events, but previous European trials that investigated clinical outcome after coronary stenting did not assess the patients' ethnic background. AIMS: To compare ethnic minority and Western European trial participants in terms of both cardiovascular risk profile and 1­year clinical outcome after percutaneous coronary intervention. METHODS: In the BIO-RESORT and BIONYX randomised trials, which assessed new-generation drug-eluting stents, information on patients' self-reported ethnic background was prospectively collected. Pooled patient-level data of 5803 patients, enrolled in the Netherlands and Belgium, were analysed in this prespecified analysis. The main endpoint was target vessel failure after 1 year. RESULTS: Patients were classified as belonging to an ethnic minority (n = 293, 5%) or of Western European origin (n = 5510, 95%). Follow-up data were available in 5772 of 5803 (99.5%) patients. Ethnic minority patients were younger, less often female, more often current smokers, more often medically treated for diabetes, and more often had a positive family history of coronary artery disease. The main endpoint target vessel failure did not differ between ethnic minority and Western European patients (3.5% vs 4.9%, hazard ratio 0.71, 95% confidence interval 0.38-1.33; p = 0.28). There was also no difference in mortality, myocardial infarction, and repeat revascularisation rates. CONCLUSIONS: Despite the unfavourable cardiovascular risk profile of ethnic minority patients, short-term clinical outcome after treatment with contemporary drug-eluting stents was highly similar to that in Western European patients. Further efforts should be made to ensure the enrolment of more ethnic minority patients in future coronary stent trials.

8.
J Hepatol ; 78(3): 479-492, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36334688

RESUMO

BACKGROUND & AIMS: The LIVIFY trial investigated the safety, tolerability, and efficacy of vonafexor, a second-generation, non-bile acid farnesoid X receptor agonist in patients with suspected fibrotic non-alcoholic steatohepatitis (NASH). METHODS: This double-blind phase IIa study was conducted in two parts. Patients were randomised (1:1:1:1) to receive placebo, vonafexor 100 mg twice daily (VONA-100BID), vonafexor 200 mg once daily (VONA-200QD), or 400 mg vonafexor QD (VONA-400QD) in Part A (safety run-in, pharmacokinetics/pharmacodynamics) or placebo, vonafexor 100 mg QD (VONA-100QD), or VONA-200QD (1:1:1) in Part B. The primary efficacy endpoint was a reduction in liver fat content (LFC) by MRI-proton density fat fraction, while secondary endpoints included reduced corrected T1 values and liver enzymes, from baseline to Week 12. RESULTS: One hundred and twenty patients were randomised (Part A, n = 24; Part B, n = 96). In Part B, there was a significant reduction in least-square mean (SE) absolute change in LFC from baseline to Week 12 for VONA-100QD (-6.3% [0.9]) and VONA-200QD (-5.4% [0.9]), vs. placebo (-2.3% [0.9], p = 0.002 and 0.012, respectively). A >30% relative LFC reduction was achieved by 50.0% and 39.3% of patients in the VONA-100QD and VONA-200QD arms, respectively, but only in 12.5% in the placebo arm. Reductions in body weight, liver enzymes, and corrected T1 were also observed with vonafexor. Creatinine-based glomerular filtration rate improved in the active arms but not the placebo arm. Mild to moderate generalised pruritus was reported in 6.3%, 9.7%, and 18.2% of participants in the placebo, VONA-100QD, and VONA-200QD arms, respectively. CONCLUSIONS: In patients with suspected fibrotic NASH, vonafexor was safe and induced potent liver fat reduction, improvement in liver enzymes, weight loss, and a possible renal benefit. CLINICAL TRIAL NUMBER (EUDRACT): 2018-003119-22. GOV IDENTIFIER: NCT03812029. IMPACT AND IMPLICATIONS: Non-alcoholic steatohepatitis (NASH) has become a leading cause of chronic liver disease worldwide. Affected patients are also at higher risk of developing chronic kidney disease. There are no approved therapies and only few options to treat this population. The phase IIa LIVIFY trial results show that single daily administration of oral vonafexor, an FXR agonist, leads in the short term to a reduction in liver fat, liver enzymes, fibrosis biomarkers, body weight and abdominal circumference, and a possible improvement in kidney function, while possible mild moderate pruritus (a peripheral FXR class effect) and an LDL-cholesterol increase are manageable with lower doses and statins. These results support exploration in longer and larger trials, with the aim of addressing the unmet medical need in NASH.


Assuntos
Hepatopatia Gordurosa não Alcoólica , Humanos , Hepatopatia Gordurosa não Alcoólica/complicações , Fígado/patologia , Cirrose Hepática/complicações , Peso Corporal , Rim , Método Duplo-Cego , Resultado do Tratamento
9.
BMC Med Res Methodol ; 23(1): 274, 2023 11 21.
Artigo em Inglês | MEDLINE | ID: mdl-37990159

RESUMO

BACKGROUND: For certain conditions, treatments aim to lessen deterioration over time. A trial outcome could be change in a continuous measure, analysed using a random slopes model with a different slope in each treatment group. A sample size for a trial with a particular schedule of visits (e.g. annually for three years) can be obtained using a two-stage process. First, relevant (co-) variances are estimated from a pre-existing dataset e.g. an observational study conducted in a similar setting. Second, standard formulae are used to calculate sample size. However, the random slopes model assumes linear trajectories with any difference in group means increasing proportionally to follow-up time. The impact of these assumptions failing is unclear. METHODS: We used simulation to assess the impact of a non-linear trajectory and/or non-proportional treatment effect on the proposed trial's power. We used four trajectories, both linear and non-linear, and simulated observational studies to calculate sample sizes. Trials of this size were then simulated, with treatment effects proportional or non-proportional to time. RESULTS: For a proportional treatment effect and a trial visit schedule matching the observational study, powers are close to nominal even for non-linear trajectories. However, if the schedule does not match the observational study, powers can be above or below nominal levels, with the extent of this depending on parameters such as the residual error variance. For a non-proportional treatment effect, using a random slopes model can lead to powers far from nominal levels. CONCLUSIONS: If trajectories are suspected to be non-linear, observational data used to inform power calculations should have the same visit schedule as the proposed trial where possible. Additionally, if the treatment effect is expected to be non-proportional, the random slopes model should not be used. A model allowing trajectories to vary freely over time could be used instead, either as a second line analysis method (bearing in mind that power will be lost) or when powering the trial.


Assuntos
Tamanho da Amostra , Humanos , Simulação por Computador
10.
Rev Med Virol ; 32(1): e2239, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-33882179

RESUMO

In this article, we express our opinion about tocilizumab as an effective treatment in coronavirus disease 2019, based on a narrative review and a deep analysis of tocilizumab randomised trial results. Eight trials were included. No one was in favour for controlled arm about main endpoint of death or mechanical ventilation incidence at day 28-30. Five trials on heterogenous populations seem to not demonstrate tocilizumab efficacy, but showed encouraging results in subgroup analysis on severe/critical patients (in favour for tocilizumab). Trials on severe/critical COVID-19 pneumonia as REMAP-CAP and RECOVERY showed mortality benefit of tocilizumab administration; CORIMUNO, REMAP-CAP and RECOVERY showed that tocilizumab decreased the incidence of mechanical ventilation. No safety signal about tocilizumab used was noticed in all trials. We concluded that tocilizumab reduces mortality and mechanical ventilation requirement if administered with the right timing in COVID-19 pneumonia. The challenge now is to define the optimal group and timing for tocilizumab benefit and we suggest that: (i) tocilizumab has a place in treatment of severe/critical COVID-19 pneumonia, with a high level of O2 flow or noninvasive ventilation or high flow nasal cannula; (ii) possibly early after intubation in patients on mechanical ventilation. Initiating tocilizumab in critically ill patients early before irreversible respiratory failure, especially in patients at an inflammatory stage could be the key to successful outcome.


Assuntos
Anticorpos Monoclonais Humanizados/uso terapêutico , Tratamento Farmacológico da COVID-19 , COVID-19/diagnóstico , COVID-19/mortalidade , Mortalidade Hospitalar , Humanos , Interleucina-6 , Ensaios Clínicos Controlados Aleatórios como Assunto , Respiração Artificial , SARS-CoV-2 , Resultado do Tratamento
11.
BJOG ; 130(13): 1579-1588, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37334772

RESUMO

OBJECTIVE: To investigate the effect of treatment with neoadjuvant chemotherapy (NACT) followed by interval debulking surgery (IDS), versus primary debulking surgery (PDS), on quality of life (QoL) in patients with advanced epithelial ovarian cancer (EOC). DESIGN: Randomised trial conducted in a single institution. SETTING: Division of Gynaecologic Oncology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy. SAMPLE: Patients with stage-IIIC/IV EOC and high tumour load. METHODS: Patients were randomised (1:1) to undergo either PDS (PDS group) or NACT followed by IDS (NACT/IDS group). MAIN OUTCOME MEASURES: Quality-of-life (QoL) data, assessed using the European Organization for Research and Treatment of Cancer core QoL questionnaire (QLQ-C30) and ovarian cancer module (OV28); co-primary outcomes were the QLQ-C30 global health score at 12 months (cross-sectional analysis) and the difference in mean QLQ-C30 global health score over time between treatment groups (longitudinal analysis). RESULTS: From October 2011 to May 2016, 171 patients were enrolled (PDS = 84; NACT/IDS = 87). We observed no clinical or statistically significant difference between treatment groups in any of the QoL functioning scales at 12 months, including QLQ-C30 global health score (NACT/IDS group vs PDS group, mean difference 4.7, 95% CI -4.99 to 14.4, p = 0.340). Over time, we found lower global health scores for those undergoing PDS than for those receiving NACT (difference in mean score 6.27, 95% CI 0.440-12.11, p = 0.035), albeit this was not clinically relevant. CONCLUSIONS: We found no difference in global QoL related to treatment approach at 12 months, even though patients in the NACT/IDS group reported better global health scores across the 12-month period compared with the PDS group; these findings further confirm that NACT/IDS might be a feasible option for patients unsuitable for PDS.


Assuntos
Terapia Neoadjuvante , Neoplasias Ovarianas , Humanos , Feminino , Animais , Carcinoma Epitelial do Ovário/tratamento farmacológico , Carcinoma Epitelial do Ovário/cirurgia , Terapia Neoadjuvante/métodos , Qualidade de Vida , Escorpiões , Procedimentos Cirúrgicos de Citorredução , Estudos Transversais , Quimioterapia Adjuvante/métodos , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/cirurgia , Estadiamento de Neoplasias , Estudos Retrospectivos
12.
Acta Anaesthesiol Scand ; 67(8): 1121-1127, 2023 09.
Artigo em Inglês | MEDLINE | ID: mdl-37165711

RESUMO

BACKGROUND: Aneurysmal subarachnoid haemorrhage (aSAH) is a life-threatening disease caused by rupture of an intracranial aneurysm. A common complication following aSAH is hydrocephalus, for which placement of an external ventricular drain (EVD) is an important first-line treatment. Once the patient is clinically stable, the EVD is either removed or replaced by a ventriculoperitoneal shunt. The optimal strategy for cessation of EVD treatment is, however, unknown. Gradual weaning may increase the risk of EVD-related infection, whereas prompt closure carries a risk of acute hydrocephalus and redundant shunt implantations. We designed a randomised clinical trial comparing the two commonly used strategies for cessation of EVD treatment in patients with aSAH. METHODS: DRAIN is an international multi-centre randomised clinical trial with a parallel group design comparing gradual weaning versus prompt closure of EVD treatment in patients with aSAH. Participants are randomised to either gradual weaning which comprises a multi-step increase of resistance over days, or prompt closure of the EVD. The primary outcome is a composite outcome of VP-shunt implantation, all-cause mortality, or ventriculostomy-related infection. Secondary outcomes are serious adverse events excluding mortality, functional outcome (modified Rankin scale), health-related quality of life (EQ-5D) and Fatigue Severity Scale (FSS). Outcome assessment will be performed 6 months after ictus. Based on the sample size calculation (event proportion 80% in the gradual weaning group, relative risk reduction 20%, type I error 5%, power 80%), 122 patients are needed in each intervention group. Outcome assessment for the primary outcome, statistical analyses and conclusion drawing will be blinded. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03948256.


Assuntos
Hidrocefalia , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/complicações , Hemorragia Subaracnóidea/terapia , Qualidade de Vida , Desmame , Hidrocefalia/etiologia , Hidrocefalia/cirurgia , Drenagem/efeitos adversos , Drenagem/métodos , Estudos Retrospectivos , Ensaios Clínicos Controlados Aleatórios como Assunto , Estudos Multicêntricos como Assunto
13.
Anaesthesia ; 78(12): 1465-1471, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37864459

RESUMO

The effects of oral dexamethasone on peripheral nerve blocks have not been investigated. We randomly allocated adults scheduled for forearm or hand surgery to oral placebo (n = 61), dexamethasone 12 mg (n = 61) or dexamethasone 24 mg (n = 57) about 45 min before lateral infraclavicular block. Mean (SD) time until first pain after block were: 841 (327) min; 1171 (318) min; and 1256 (395) min, respectively. Mean (98.3%CI) differences in time until first postoperative pain for dexamethasone 24 mg vs. placebo and vs. dexamethasone 12 mg were: 412 (248-577) min, p < 0.001; and 85 (-78 to 249) min, p = 0.21, respectively. Mean (98.3%CI) difference in time until first postoperative pain for dexamethasone 12 mg vs. placebo was 330 (186-474) min, p < 0.001. Both 24 mg and 12 mg of oral dexamethasone increased the time until first postoperative pain compared with placebo in patients having upper limb surgery under infraclavicular brachial plexus block.


Assuntos
Analgesia , Bloqueio do Plexo Braquial , Adulto , Humanos , Dexametasona , Dor Pós-Operatória , Extremidade Superior/cirurgia , Anestésicos Locais
14.
BMC Musculoskelet Disord ; 24(1): 149, 2023 Feb 27.
Artigo em Inglês | MEDLINE | ID: mdl-36849935

RESUMO

BACKGROUND: Volar plate injuries are a common hand injury and complications associated with this injury such as a fixed flexion deformity, persistent pain and oedema can have a significant impact on a person's function. The literature reports these injuries are treated using various splinting materials such as thermoplastic, in varying degrees of proximal interphalangeal joint flexion or buddy loops. Despite volar plate injuries being reported as common, optimal non-surgical treatment of these injuries remains unclear. This study aims to investigate whether a dorsal blocking orthosis in a neutral position (00) is more effective than buddy loops for a volar plate injury to the proximal interphalangeal joint in preventing a fixed flexion deformity, reducing pain, managing oedema, and promoting function. METHODS: This study is a single-centre, prospective parallel-group, single blinded (assessor), randomised clinical trial. Patients between 18-65 years, who have sustained a volar plate injury to a single digit, have adequate cognitive functioning and give written informed consent will be invited to participate in this study. Patients will be randomised to either the control group where they will be fitted with buddy loops and commence early active motion exercises or the experimental group where they will receive a dorsal thermoplastic orthosis in a neutral position and commence early active motion exercises. The primary outcome measure is passive proximal interphalangeal joint extension and secondary outcome measures include passive range of motion, total passive motion, active range of motion, total active motion, grip strength, oedema, pain, function and adherence to treatment. Assessments will be completed until 8 weeks following commencement of treatment. The sample size calculation indicates that 23 patients is required in each group. With an expected dropout rate of 25% a total of 32 patients will be enrolled in each group. DISCUSSION: This study will assist in trying to improve treatment of volar plate injuries and assist in reducing complications associated with volar plate injuries, potentially reducing the need for prolonged hand therapy. TRIAL REGISTRATION: This trial has been registered with the Australian New Zealand Clinical Trials Registry (ACTRN12622001425785p). Ethical approval has been granted by the South Eastern Sydney Local Health District ethical committee (2022/ETH01697).


Assuntos
Braquetes , Contratura , Humanos , Estudos Prospectivos , Austrália , Aparelhos Ortopédicos , Extremidades , Ensaios Clínicos Controlados Aleatórios como Assunto
15.
J Intellect Disabil Res ; 67(10): 986-1002, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37344986

RESUMO

BACKGROUND: No previous studies have reported predictors and moderators of outcome of psychological therapies for depression experienced by adults with intellectual disabilities (IDs). We investigated baseline variables as outcome predictors and moderators based on a randomised controlled trial where behavioural activation was compared with guided self-help. METHODS: This study was an exploratory secondary data analysis of data collected during a randomised clinical trial. Participants (n = 161) were randomised to behavioural activation or guided self-help and followed up for 12 months. Pre-treatment variables were included if they have previously been shown to be associated with an increased risk of having depression in adults with IDs or have been reported as a potential predictor or moderator of outcome of treatment for depression with psychological therapies. The primary outcome measure, the Glasgow Depression Scale for Adults with Learning Disabilities (GDS-LD), was used as the dependant variable in mixed effects regression analyses testing for predictors and moderators of outcome, with baseline GDS-LD, treatment group, study centre and antidepressant use as fixed effects, and therapist as a random effect. RESULTS: Higher baseline anxiety (mean difference in outcome associated with a 1 point increase in anxiety 0.164, 95% confidence interval [CI] 0.031, 0.297; P = 0.016), lower performance intelligence quotient (IQ) (mean difference in outcome associated with a 1 point increase in IQ 0.145, 95% CI 0.009, 0.280; P = 0.037) and hearing impairment (mean difference 3.449, 95% CI 0.466, 6.432; P = 0.024) were predictors of poorer outcomes, whilst greater severity of depressive symptoms at baseline (mean difference in outcome associated with 1 point increase in depression -0.160, 95% CI -0.806, -0.414; P < 0.001), higher expectation of change (mean difference in outcome associated with a 1 point increase in expectation of change -1.013, 95% CI -1.711, -0.314; p 0.005) and greater percentage of therapy sessions attended (mean difference in outcome with 1 point increase in percentage of sessions attended -0.058, 95% CI -0.099, -0.016; P = 0.007) were predictors of more positive outcomes for treatment after adjusting for randomised group allocation. The final model included severity of depressive and anxiety symptoms, lower WASI performance IQ subscale, hearing impairment, higher expectation of change and percentage of therapy sessions attended and explained 35.3% of the variance in the total GDS-LD score at 12 months (R2  = 0.353, F4, 128  = 17.24, P < 0.001). There is no evidence that baseline variables had a moderating effect on outcome for treatment with behavioural activation or guided self-help. CONCLUSIONS: Our results suggest that baseline variables may be useful predictors of outcomes of psychological therapies for adults with IDs. Further research is required to examine the value of these potential predictors. However, our findings suggest that therapists consider how baseline variables may enable them to tailor their therapeutic approach when using psychological therapies to treat depression experienced by adults with IDs.


Assuntos
Depressão , Deficiência Intelectual , Adulto , Humanos , Depressão/terapia , Deficiência Intelectual/terapia , Deficiência Intelectual/psicologia , Terapia Comportamental/métodos , Ansiedade , Comportamentos Relacionados com a Saúde
16.
Int J Audiol ; 62(5): 400-409, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-35436167

RESUMO

OBJECTIVE: To assess the benefits of the Ida Institute's Why improve my hearing? Telecare Tool used before the initial hearing assessment appointment. DESIGN: A prospective, single-blind randomised clinical trial with two arms: (i) Why improve my hearing? Telecare Tool intervention, and (ii) standard care control. STUDY SAMPLE: Adults with hearing loss were recruited from two Audiology Services within the United Kingdom's publicly-funded National Health Service. Of 461 individuals assessed for eligibility, 57 were eligible to participate. RESULTS: Measure of Audiologic Rehabilitation Self-efficacy for Hearing Aids (primary outcome) scores did not differ between groups from baseline to post-assessment (Mean change [Δ]= -2.28; 95% confidence interval [CI]= -6.70, 2.15, p= .307) and 10-weeks follow-up (Mean Δ= -2.69; 95% CI= -9.52, 4.15, p = .434). However, Short Form Patient Activation Measure scores significantly improved in the intervention group compared to the control group from baseline to post-assessment (Mean Δ= -6.06, 95% CI= -11.31, -0.82, p = .024, ES= .61) and 10-weeks follow-up (Mean Δ= -9.87, 95% CI= -15.34, -4.40, p = .001, ES= -.97). CONCLUSIONS: This study demonstrates that while a patient-centred telecare intervention completed before management decisions may not improve an individual's self-efficacy to manage their hearing loss, it can lead to improvements in readiness.


Assuntos
Surdez , Perda Auditiva , Adulto , Humanos , Estudos Prospectivos , Método Simples-Cego , Medicina Estatal , Perda Auditiva/reabilitação , Audição , Qualidade de Vida , Análise Custo-Benefício
17.
J Oral Rehabil ; 50(6): 460-467, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36794621

RESUMO

BACKGROUND: Previous study showed that in individuals with obstructive sleep apnea (OSA), the contractions of masseter muscles after respiratory events can be nonspecific motor phenomena, dependent on the duration of respiratory arousals rather than the occurrence of the respiratory events. However, the role of intermittent hypoxia in the occurrence of jaw-closing muscle activities (JCMAs) was not taken into consideration. An exposure to intermittent hypoxia has been shown to initiate a series of activities, including muscular sympathetic activity in patients with OSA. OBJECTIVE: To determine the effects of mandibular advancement appliance (MAA) therapy on JCMA time-related to oxygen desaturation with and without arousal in individuals with OSA. METHODS: Eighteen individuals with OSA (age: 49.4 ± 9.8 years, apnea-hypopnea index (AHI): 10.0|18.4|30.3, JCMA index: 1.7|4.3|5.6), participated in a randomised controlled crossover clinical trial, in which two ambulatory polysomnographic recordings were performed: one with MAA in situ and the other without MAA in situ. JCMAs were recorded bilaterally from both masseter and temporalis muscles. RESULTS: There was no significant effect of the MAA on the overall JCMA index (Z = -1.372, p = .170). With the MAA in situ, JCMA index time-related to oxygen desaturation with arousal significantly decreased (Z = -2.657, p = .008), while there was no significant effect of the MAA on the JCMA index time-related to oxygen desaturation without arousal (Z = -0.680, p = .496). CONCLUSION: Effective mandibular advancement appliance therapy significantly reduces jaw-closing muscle activities time-related to oxygen desaturation with arousal in individuals with OSA.


Assuntos
Avanço Mandibular , Apneia Obstrutiva do Sono , Humanos , Adulto , Pessoa de Meia-Idade , Polissonografia , Apneia Obstrutiva do Sono/terapia , Hipóxia , Músculos , Oxigênio
18.
Ann Oncol ; 33(1): 67-79, 2022 01.
Artigo em Inglês | MEDLINE | ID: mdl-34562610

RESUMO

BACKGROUND: Concurrent chemotherapy and thoracic radiotherapy followed by prophylactic cranial irradiation (PCI) is the standard treatment in limited-disease small-cell lung cancer (LD-SCLC), with 5-year overall survival (OS) of only 25% to 33%. PATIENTS AND METHODS: STIMULI is a 1:1 randomised phase II trial aiming to demonstrate superiority of consolidation combination immunotherapy versus observation after chemo-radiotherapy plus PCI (protocol amendment-1). Consolidation immunotherapy consisted of four cycles of nivolumab [1 mg/kg, every three weeks (Q3W)] plus ipilimumab (3 mg/kg, Q3W), followed by nivolumab monotherapy (240 mg, Q2W) for up to 12 months. Patient recruitment closed prematurely due to slow accrual and the statistical analyses plan was updated to address progression-free survival (PFS) as the only primary endpoint. RESULTS: Of the 222 patients enrolled, 153 were randomised (78: experimental; 75: observation). Among the randomised patients, median age was 62 years, 60% males, 34%/65% current/former smokers, 31%/66% performance status (PS) 0/1. Up to 25 May 2020 (median follow-up 22.4 months), 40 PFS events were observed in the experimental arm, with median PFS 10.7 months [95% confidence interval (CI) 7.0-not estimable (NE)] versus 42 events and median 14.5 months (8.2-NE) in the observation, hazard ratio (HR) = 1.02 (0.66-1.58), two-sided P = 0.93. With updated follow-up (03 June 2021; median: 35 months), median OS was not reached in the experimental arm, while it was 32.1 months (26.1-NE) in observation, with HR = 0.95 (0.59-1.52), P = 0.82. In the experimental arm, median time-to-treatment-discontinuation was only 1.7 months. CTCAE v4 grade ≥3 adverse events were experienced by 62% of patients in the experimental and 25% in the observation arm, with 4 and 1 fatal, respectively. CONCLUSIONS: The STIMULI trial did not meet its primary endpoint of improving PFS with nivolumab-ipilimumab consolidation after chemo-radiotherapy in LD-SCLC. A short period on active treatment related to toxicity and treatment discontinuation likely affected the efficacy results.


Assuntos
Neoplasias Pulmonares , Nivolumabe , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Quimiorradioterapia/efeitos adversos , Feminino , Humanos , Ipilimumab/efeitos adversos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/radioterapia , Masculino , Pessoa de Meia-Idade
19.
Psychol Med ; 52(13): 2751-2759, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-33402230

RESUMO

BACKGROUND: Agitated patients constitute 10% of all emergency psychiatric treatment. Management guidelines, the preferred treatment of clinicians differ in opinion and practice. In Lebanon, the use of the triple therapy haloperidol plus promethazine plus chlorpromazine (HPC) is frequently used but no studies involving this combination exists. METHOD: A pragmatic randomised open trial (September 2018-July 2019) in the Lebanese Psychiatric Hospital of the Cross in Beirut Lebanon involving 100 people requiring urgent intramuscular sedation due to aggressive behaviour were given intramuscular chlorpromazine 100 mg plus haloperidol 5 mg plus promethazine 25 mg (HPC) or intramuscular haloperidol 5 mg plus promethazine 25 mg. RESULTS: Primary outcome data were available for 94 (94%) people. People allocated to the haloperidol plus promethazine (HP) group showed no clear difference at 20 min compared with patients allocated to the HPC group [relative risk (RR) 0.84, 95% confidence interval (CI) 0.47-1.50]. CONCLUSIONS: Neither intervention consistently impacted the outcome of 'calm', or 'asleep' and had no discernible effect on the use of restraints, use of additional drugs or recurrence. If clinicians are faced with uncertainty on which of the two intervention combinations to use, the simpler HP is much more widely tested and the addition of chlorpromazine adds no clear benefit with a risk of additional adverse effects.


Assuntos
Antipsicóticos , Haloperidol , Humanos , Haloperidol/efeitos adversos , Clorpromazina/uso terapêutico , Prometazina/uso terapêutico , Líbano , Hospitais Psiquiátricos , Agitação Psicomotora , Antipsicóticos/uso terapêutico
20.
Cephalalgia ; 42(4-5): 302-311, 2022 04.
Artigo em Inglês | MEDLINE | ID: mdl-34541914

RESUMO

BACKGROUND: Several studies propose that brain energy deficit might be partially involved in the pathophysiology of migraine. Previously, studies demonstrated that ketogenic diet causes a substantial reduction in migraine frequency. Since the ketogenic diet is restricting and its adherence is difficult, we proposed to supplement ketone bodies exogenously to provide a prophylactic effect in migraineurs. AIM: To evaluate the prophylactic effect of exogenous DL-beta-hydroxybutyrate supplementation in episodic migraineurs. METHODS: A double-blind, placebo-controlled, randomised crossover trial was conducted, involving 41 patients with episodic migraine. Patients were randomised 1:1 into placebo or beta-hydroxybutyrate group before entering the first treatment period. Each treatment period was 12 weeks long, followed by four weeks of washout phase and four weeks of run-in phase before entering into the corresponding second treatment period. The primary endpoint was the number of migraine days in the last four weeks of treatment, adjusted for baseline. RESULTS: We observed no clinically significant amelioration of migraine frequency or intensity under DL-beta-hydroxybutyrate treatment as compared to placebo regarding number of migraine days (mean difference [95% CI]: -1.1[-5.07, 2.85]), migraine intensity (0-10 VAS: 1.5[-0.8, 3.7]). CONCLUSION: The selected dose of supplemented exogenous DL-beta-hydroxybutyrate did not demonstrate efficacy in episodic migraineurs.ClinicalTrials.gov Identifier: NCT03132233.


Assuntos
Transtornos de Enxaqueca , Ácido 3-Hidroxibutírico/uso terapêutico , Estudos Cross-Over , Método Duplo-Cego , Humanos , Transtornos de Enxaqueca/tratamento farmacológico , Transtornos de Enxaqueca/prevenção & controle , Resultado do Tratamento
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