107 research outputs found

    Quantitative study of hyperthermia in human tumours

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    The Perceptions and Rehabilitation Experience of Older People After Falling in the Hospital

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    Purpose: Falls are a major cause of disability and mortality due to injury. To reduce fall rates and improve health outcomes, it is important to design services based on patient experience and engagement. This study aimed to explore the experiences of older patients who fell during their hospital stay. Design: Five patients from two rehabilitation wards in the United Kingdom participated in this qualitative study. Methods: Semistructured interviews, incident reports, and medical records provided information about each fall. Thematic, discourse, and descriptive analysis were used to analyze data. Findings: The data demonstrated how a fall impacted patientsā€™ experience of rehabilitation and resulted in changes to mobility, self-confidence, management of falls risk, avoidance of daily activities, and increased assistance from others. Conclusions: Falling in hospital can influence patientsā€™ ability to reach their potential of an optimal level of functioning. Clinical Relevance: There is a need to place an equal and mutual understanding on the physical, psychological, and social impact of falling to reduce falls and improve functional outcomes

    Impact of Targeted Agents on Survival of Chronic Lymphocytic Leukemia Patients Fit for Fludarabine, Cyclophosphamide, and Rituximab (FCR) Relative to Age- and Sex-Matched Population

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    To assess the impact of first-line treatment with targeted agents (TAs) or fludarabine, cyclophosphamide, and rituximab (FCR)-based chemo-immunotherapy (CIT) on overall survival (OS) compared to age- and sex-matched individuals in the general population, we conducted an aggregated analysis of phase 3 clinical trials, including the two FLAIR sub-studies, ECOG1912, and CLL13 trials. The restricted mean survival time (RMST), an alternative measure in outcome analyses capturing OS changes over the entire history of the disease, was used to minimize biases associated with the short follow-up time of trials. Patients treated with TAs demonstrated a higher 5-year RMST (58.1 months; 95% CI: 57.4 to 58.8) compared to those treated with CIT (5-year RMST, 56.9 months; 95% CI: 56.7ā€“58.2). Furthermore, the OS comparison of treatment groups with the AGMGP suggests that TAs may mitigate the impact of CLL on OS during the first five years post-treatment initiation. In summary, the 5-year RMST difference was āˆ’0.4 months (95% CI: āˆ’0.8 to 0.2; p = 0.10) when comparing CLL patients treated with TAs to the Italian age- and gender-matched general population (AGMGP). A similar trend was observed when CLL patients treated with TAs were compared to the US AGMGP (5-year RMST difference, 0.3 months; 95% CI: āˆ’0.1 to 0.9; p = 0.12). In contrast, CLL patients treated with FCR exhibited sustained OS differences when compared to both the Italian cohort (5-year RMST difference: āˆ’1.6 months; 95% CI: āˆ’2.4 to āˆ’0.9; p < 0.0001) and the US AGMGP cohort (5-year RMST difference: āˆ’0.9 months; 95% CI: āˆ’1.7 to āˆ’0.2; p = 0.015). Although these results support TAs as the preferred first-line treatment for younger CLL patients, it is crucial to acknowledge that variations in patient selection criteria and clinical profiles across clinical trials necessitate a cautious interpretation of these findings that should be viewed as directional and hypothesis-generating. A longer follow-up is needed to assess the survival improvement of younger CLL patients treated with TAs relative to the AGMGP

    Successful Downstaging of High Rectal and Recto-Sigmoid Cancer by Neo-Adjuvant Chemo-Radiotherapy

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    Ā© 2008 Libertas Academica Ltd. All rights reserved.Purpose: The benefit of neoadjuvant therapy for tumours above the peritoneal reflection is not clear. The purpose of this study is to demonstrate the feasibility and downstaging of treating locally advanced tumours from high rectum to distal sigmoid with preoperative chemoradiotherapy (CRT).Methods and Materials: Seventeen patients with high rectal, rectosigmoid or distal sigmoid tumours above the peritoneal reflection received neoadjuvant CRT, selected on MRI findings indicating T4 disease or threatened circumferential resection margin. All patients were administered neoadjuvant chemotherapy, with Oxaliplatin or Mitomycin C and a Fluoropyrimidine. The pelvis received long-course CT-planned conformal RT, 45 Gy in 25 fractions, with a boost of 5.4ā€“9 Gy in 3ā€“5 fractions. Thirteen patients were treated with concomitant oral or intravenous Fluoropyrimidine chemotherapy.Results: Median follow-up was 37 months. Overall survival was 82.35% (95% Confidence Interval (CI) 54.7ā€“93.9) and disease free survival 81.25% (95% CI 52.5ā€“93.5). Only 1 patient suffered loco-regional relapse. Chemotherapy regimens were well tolerated, though some patients required dose reductions. Nine patients (52.9%) lowered pathologic disease AJCC stage, i.e. ā€˜downstagedā€™. Six patients (35.3%) achieved complete pathological response. Clear margins were attained in all but 1 patient. Three patients were converted from cT4 to ypT3. No patient required a gap during CRT. One patient suffered a grade III acute toxicity, but no grade IV (RTOG). There were 3 grade III and 3 grade IV late toxicities (LENT-SOMA).Conclusions: Locally advanced high rectal and recto-sigmoid tumours may be treated with pre-operative CRT with acceptable toxicity, impressive down-staging, and clear surgical margins

    Aspirin and ibuprofen, in bulk and nanoforms: Effects on DNA damage in peripheral lymphocytes from breast cancer patients and healthy individuals

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    YesRegular use of non-steroidal anti-inflammatory drugs (NSAIDs) may be protective against tumours, including breast cancer. We have studied the effects of ibuprofen and aspirin on DNA damage in lymphocytes obtained from breast cancer patients and healthy female controls. Both nanoparticle (NPs) and bulk formulations were used in the comet and micronucleus (MN) assays. Non-toxic doses (250 ng/ml ibuprofen; 500 ng/ml aspirin) were tested. Aspirin, both bulk and nano formulations, significantly reduced DNA damage measured with the comet and micronucleus assays; the nano formulation was more effective. Ibuprofen was not effective in the comet assay but showed a significant reduction in MN frequency, with the nano formulation being more effective. NPs may have better penetration through the nuclear membrane relative to the bulk formulation. NSAIDs such as aspirin and ibuprofen may have a promising role in cancer prevention and treatment.LIBYAN GOVERNMEN

    Effects of neuromuscular gait modification strategies on indicators of knee joint load in people with medial knee osteoarthritis:A systematic review and meta-analysis

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    OBJECTIVES: This systematic review aimed to determine the effects of neuromuscular gait modification strategies on indicators of medial knee joint load in people with medial knee osteoarthritis. METHODS: Databases (Embase, MEDLINE, Cochrane Central, CINAHL and PubMed) were searched for studies of gait interventions aimed at reducing medial knee joint load indicators for adults with medial knee osteoarthritis. Studies evaluating gait aids or orthoses were excluded. Hedgesā€™ g effect sizes (ES) before and after gait retraining were estimated for inclusion in quality-adjusted meta-analysis models. Certainty of evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. RESULTS: Seventeen studies (k = 17; n = 362) included two randomised placebo-controlled trials (RCT), four randomised cross-over trials, two case studies and nine cohort studies. The studies consisted of gait strategies of ipsilateral trunk lean (k = 4, n = 73), toe-out (k = 6, n = 104), toe-in (k = 5, n = 89), medial knee thrust (k = 3, n = 61), medial weight transfer at the foot (k = 1, n = 10), wider steps (k = 1, n = 15) and external knee adduction moment (KAM) biofeedback (k = 3, n = 84). Meta-analyses found that ipsilateral trunk lean reduced early stance peak KAM (KAM1, ES and 95%CI: -0.67, -1.01 to -0.33) with a dose-response effect and reduced KAM impulse (-0.37, -0.70 to -0.04) immediately after single-session training. Toe-out had no effect on KAM1 but reduced late stance peak KAM (KAM2; -0.42, -0.73 to -0.11) immediately post-training for single-session, 10 or 16-week interventions. Toe-in reduced KAM1 (-0.51, -0.81 to -0.20) and increased KAM2 (0.44, 0.04 to 0.85) immediately post-training for single-session to 6-week interventions. Visual, verbal and haptic feedback was used to train gait strategies. Certainty of evidence was very-low to low according to the GRADE approach. CONCLUSION: Very-low to low certainty of evidence suggests that there is a potential that ipsilateral trunk lean, toe-out, and toe-in to be clinically helpful to reduce indicators of medial knee joint load. There is yet little evidence for interventions over several weeks

    Use of newly isolated phages for the control of Pseudomonas aeruginosa PAO1 and ATCC 10145 biofilms

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    Pseudomonas aeruginosa is a relevant opportunistic pathogen involved in nosocomial infections. that frequently shows low antibiotic susceptibility. One of its virulence factors is associated with the ability to adhere to surfaces and form virulent biofilms. This work describes the isolation and characterization of lytic phages capable of infecting antibiotic-resistant P. aeruginosa strains. In addition, characterization of P. aeruginosa biofilms and the potential of newly isolated phages for planktonic and biofilm control was accessed. According to the results, the isolated phages showed different spectra of activity and efficiency of lysis. Four broad lytic phages were selected for infection of planktonic cells; however, despite their broad range of activity, two of the selected phages failed to efficiently control planktonic cultures. Therefore, only two phages (phiIBB-PAA2 and phiIBB-PAP21), highly capable of causing strong biomass reduction of planktonic cells, were tested against 24 h biofilms using a m.o.i. of 1. Both phages reduced approximately 1-2 log the biofilm population after 2 h of infection and reduction was further enhanced after 6 h of biofilm infection. However, biofilm cells of P. aeruginosa PAO1 acquired resistance to phiIBB-PAP21; consequently, an increase in the number of cells after 24 h of treatment was observed. Conversely, phage phiIB-PAA2 for P. aeruginosa ATCC10145 continued to destroy biofilm cells, even after 24 h of infection. In these biofilms, phages caused a 3 log reduction in the number of viable counts of biofilm cells

    Sequence variation in mature microRNA-608 and benefit from neo-adjuvant treatment in locally advanced rectal cancer patients

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    Single nucleotide polymorphisms (SNPs) in microRNA genes have been associated with colorectal cancer (CRC) risk, survival and response to treatment. Conflicting results are available on the association between rs4919510, a SNP in mature miR-608 and clinical outcome in CRC. Here, we analyzed the association between rs4919510 and benefit from perioperative treatment in a randomised phase II trial of neoadjuvant Capecitabine and Oxaliplatin (CAPOX) followed by chemo-radiotherapy, surgery and adjuvant CAPOX Ā± Cetuximab in high-risk locally advanced rectal cancer (LARC). A total of 155/164 (94.5%) patients were assessable. 95 (61.3%) were homozygous for CC, 55 (35.5%) heterozygous (CG) and 5 (3.2%) homozygous for GG. Median follow-up was 64.9 months. In the CAPOX arm the 5-year progression-free survival (PFS) and overall survival (OS) rates were 54.6% and 60.7% for CC and 82.0% and 82.1% for CG/GG, respectively (HR PFS 0.13, 95% CI: 0.12-0.83, P = 0.02; HR OS 0.38, 95% CI: 0.14-1.01, P = 0.05). In the CAPOX-C arm PFS and OS were 73.2 and 82.2%, respectively for CC carriers and 64.6 and 73.1% for CG/GG carriers (HR PFS 1.38, 95% CI: 0.61-3.13, P = 0.44; HR OS 1.34, 95% CI: 0.52-3.48, P = 0.55). An interaction was found between study treatment and rs4919510 genotype for both PFS (P = 0.02) and OS (P = 0.07). This is the first study investigating rs4919510 in LARC. The CC genotype appeared to be associated with worse prognosis compared to the CG/GG genotype in patients treated with chemotherapy and chemo-radiotherapy alone. Addition of Cetuximab to chemotherapy and chemo-radiotherapy in CC carriers appeared to improve clinical outcome

    CRIMSON [CRisis plan IMpact: Subjective and Objective coercion and eNgagement] Protocol: A randomised controlled trial of joint crisis plans to reduce compulsory treatment of people with psychosis

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    Background: The use of compulsory treatment under the Mental Health Act (MHA) has continued to rise in the UK and in other countries. The Joint Crisis Plan (JCP) is a statement of service users' wishes for treatment in the event of a future mental health crisis. It is developed with the clinical team and an independent facilitator. A recent pilot RCT showed a reduction in the use of the MHA amongst service users with a JCP. The JCP is the only intervention that has been shown to reduce compulsory treatment in this way. The CRIMSON trial aims to determine if JCPs, compared with treatment as usual, are effective in reducing the use of the MHA in a range of treatment settings across the UK. Methods/Design: This is a 3 centre, individual-level, single-blind, randomised controlled trial of the JCP compared with treatment as usual for people with a history of relapsing psychotic illness in Birmingham, London and Lancashire/Manchester. 540 service users will be recruited across the three sites. Eligible service users will be adults with a diagnosis of a psychotic disorder (including bipolar disorder), treated in the community under the Care Programme Approach with at least one admission to a psychiatric inpatient ward in the previous two years. Current inpatients and those subject to a community treatment order will be excluded to avoid any potential perceived pressure to participate. Research assessments will be conducted at baseline and 18 months. Following the baseline assessment, eligible service users will be randomly allocated to either develop a Joint Crisis Plan or continue with treatment as usual. Outcome will be assessed at 18 months with assessors blind to treatment allocation. The primary outcome is the proportion of service users treated or otherwise detained under an order of the Mental Health Act (MHA) during the follow-up period, compared across randomisation groups. Secondary outcomes include overall costs, service user engagement, perceived coercion and therapeutic relationships. Sub-analyses will explore the effectiveness of the JCP in reducing use of the MHA specifically for Black Caribbean and Black African service users (combined). Qualitative investigations with staff and service users will explore the acceptability of the JCPs. Discussion: JCPs offer a potential solution to the rise of compulsory treatment for individuals with psychotic disorders and, if shown to be effective in this trial, they are likely to be of interest to mental health service providers worldwide
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