Current Issue : January - March Volume : 2016 Issue Number : 1 Articles : 6 Articles
Background: About 90 % of patients with intra-thoracic malignancy experience breathlessness. Breathing training is\nhelpful, but it is unknown whether repeated sessions are needed. The present study aims to test whether three\nsessions are better than one for breathlessness in this population.\nMethods: This is a multi-centre randomised controlled non-blinded parallel arm trial. Participants were allocated to\nthree sessions or single (1:2 ratio) using central computer-generated block randomisation by an independent Trials\nUnit and stratified for centre. The setting was respiratory, oncology or palliative care clinics at eight UK centres.\nInclusion criteria were people with intrathoracic cancer and refractory breathlessness, expected prognosis ââ?°Â¥3\nmonths, and no prior experience of breathing training. The trial intervention was a complex breathlessness\nintervention (breathing training, anxiety management, relaxation, pacing, and prioritisation) delivered over three\nhour-long sessions at weekly intervals, or during a single hour-long session. The main primary outcome was worst\nbreathlessness over the previous 24 hours (ââ?¬Ë?worstââ?¬â?¢), by numerical rating scale (0 = none; 10 = worst imaginable).\nOur primary analysis was area under the curve (AUC) ââ?¬Ë?worstââ?¬â?¢ from baseline to 4 weeks. All analyses were by\nintention to treat.\nResults: Between April 2011 and October 2013, 156 consenting participants were randomised (52 three; 104 single).\nOverall, the ââ?¬Ë?worstââ?¬â?¢ score reduced from 6.81 (SD, 1.89) to 5.84 (2.39). Primary analysis [n = 124 (79 %)], showed no\nbetween-arm difference in the AUC: three sessions 22.86 (7.12) vs single session 22.58 (7.10); P value = 0.83); mean\ndifference 0.2, 95 % CIs (ââ?¬â??2.31 to 2.97). Complete case analysis showed a non-significant reduction in QALYs with\nthree sessions (mean difference ââ?¬â??0.006, 95 % CIs ââ?¬â??0.018 to 0.006). Sensitivity analyses found similar results. The\nprobability of the single session being cost-effective (threshold value of Ã?£20,000 per QALY) was over 80 %.\nConclusions: There was no evidence that three sessions conferred additional benefits, including cost-effectiveness,\nover one. A single session of breathing training seems appropriate and minimises patient burden....
Background: PARP inhibitors have shown promising clinical results in cancer patients carrying BRCA1/2 mutations.\nTheir clinical efficacy could logically be influenced by PARP1 protein levels in patient tumors.\nMethods: We screened three cohorts of patients with ovarian cancer, totaling 313 samples, and evaluated PARP1\nprotein expression by immunohistochemistry with further validation by western blotting.\nResults: We observed that up to 60 % of tumors showed little PARP1 protein expression. In serous ovarian tumors,\ncomparing intratumoral PARP1 expression between chemo-na�¯ve and post-chemotherapy patients revealed a decrease\nin intratumoral PARP1 following chemotherapy in all three cohorts (immunohistochemistry: p < 0.001, n = 239; western\nblot: p = 0.012, n = 74). The findings were further confirmed in a selection of matched samples from the same patients\nbefore and after chemotherapy.\nConclusion: Our data suggest that patients should be screened for PARP1 expression prior to therapy with PARP\ninhibitors. Further, the observed reduction of intratumoral PARP1 post-chemotherapy suggests that treating\nchemo-na�¯ve patients with PARP inhibitors prior to the administration of chemotherapy, or concurrently, might\nincrease the responsiveness to PARP1 inhibition. Thus, a change in the timing of PARP inhibitor administration may be\nwarranted for future clinical trials....
Background: Artemisinin-resistant Plasmodium falciparum has emerged in the Greater Mekong sub-region and poses\na major global public health threat. Slow parasite clearance is a key clinical manifestation of reduced susceptibility to\nartemisinin. This study was designed to establish the baseline values for clearance in patients from Sub-Saharan African\ncountries with uncomplicated malaria treated with artemisinin-based combination therapies (ACTs).\nMethods: A literature review in PubMed was conducted in March 2013 to identify all prospective clinical trials\n(uncontrolled trials, controlled trials and randomized controlled trials), including ACTs conducted in Sub-Saharan Africa,\nbetween 1960 and 2012. Individual patient data from these studies were shared with the WorldWide Antimalarial\nResistance Network (WWARN) and pooled using an a priori statistical analytical plan. Factors affecting early parasitological\nresponse were investigated using logistic regression with study sites fitted as a random effect. The risk of bias in\nincluded studies was evaluated based on study design, methodology and missing data.\nResults: In total, 29,493 patients from 84 clinical trials were included in the analysis, treated with artemether-lumefantrine\n(n = 13,664), artesunate-amodiaquine (n = 11,337) and dihydroartemisinin-piperaquine (n = 4,492). The overall parasite\nclearance rate was rapid. The parasite positivity rate (PPR) decreased from 59.7 % (95 % CI: 54.5ââ?¬â??64.9) on day 1 to 6.7 %\n(95 % CI: 4.8ââ?¬â??8.7) on day 2 and 0.9 % (95 % CI: 0.5ââ?¬â??1.2) on day 3. The 95th percentile of observed day 3 PPR was 5.3 %.\nIndependent risk factors predictive of day 3 positivity were: high baseline parasitaemia (adjusted odds ratio (AOR) = 1.16\n(95 % CI: 1.08ââ?¬â??1.25); per 2-fold increase in parasite density, P <0.001); fever (>37.5 Ã?°C) (AOR = 1.50 (95 % CI: 1.06ââ?¬â??2.13),\nP = 0.022); severe anaemia (AOR = 2.04 (95 % CI: 1.21ââ?¬â??3.44), P = 0.008); areas of low/moderate transmission setting\n(AOR = 2.71 (95 % CI: 1.38ââ?¬â??5.36), P = 0.004); and treatment with the loose formulation of artesunate-amodiaquine\n(AOR = 2.27 (95 % CI: 1.14ââ?¬â??4.51), P = 0.020, compared to dihydroartemisinin-piperaquine).\nConclusions: The three ACTs assessed in this analysis continue to achieve rapid early parasitological clearance across\nthe sites assessed in Sub-Saharan Africa. A threshold of 5 % day 3 parasite positivity from a minimum sample size of 50\npatients provides a more sensitive benchmark in Sub-Saharan Africa compared to the current recommended threshold\nof 10 % to trigger further investigation of artemisinin susceptibility....
Background: Targeting CTLA-4 is a recent strategic approach in cancer control: blocking CTLA-4 enhances an\nantitumor immunity by promoting T-cell activation and cytotoxic T-lymphocyte proliferation. This induction of a\ntolerance break against the tumor may be responsible for immune-related adverse events (irAEs). Our objective was\nto assess the incidence and nature of irAEs in oncologic patients receiving anti-CTLA-4 antibodies (ipilimumab and\ntremelimumab).\nMethods: A systematic search of literature up to February 2014 was performed in MEDLINE, EMBASE, and Cochrane\ndatabases to identify relevant articles. Paired reviewers independently selected articles for inclusion and extracted\ndata. Pooled incidence was calculated using RÃ?©, package meta.\nResults: Overall, 81 articles were included in the study, with a total of 1265 patients from 22 clinical trials included\nin the meta-analysis. Described irAEs consisted of skin lesions (rash, pruritus, and vitiligo), colitis, and less frequently\nhepatitis, hypophysitis, thyroiditis, and some rare events such as sarcoidosis, uveitis, Guillain-BarrÃ?© syndrome,\nimmune-mediated cytopenia and polymyalgia rheumatic/Horton. The overall incidence of all-grade irAEs was 72 %\n(95 % CI, 65ââ?¬â??79 %). The overall incidence of high-grade irAEs was 24 % (95 % CI, 18ââ?¬â??30 %). The risk of developing\nirAEs was dependent of dosage, with incidence of all-grade irAEs being evaluated to 61 % (95 % CI, 56ââ?¬â??66 %) for\nipilimumab 3 mg/kg and 79 % (95 % CI, 69ââ?¬â??89 %) for ipilimumab 10 mg/kg. Death due to irAEs occurred in 0.86 %\nof patients.\nThe median time of onset of irAEs was about 10 weeks (IQR, 6ââ?¬â??12) after the onset of treatment, corresponding with\nthe first three cycles but varied according to the organ system involved. Such immune activation could also be\nindicative for tumor-specific T-cell activation and irAE occurrence was associated with clinical response to CTLA-4\nblocking in 60 % of patients.\nConclusion: The price of potential long-term survival to metastatic tumors is an atypical immune toxicity, reflecting\nthe mechanism of action of anti-CTLA-4 antibodies. A better knowledge of these irAEs and its management in a\nmultidisciplinary approach will help to reduce morbidity and therapy interruptions....
The 1994 genocide against the Tutsi destroyed the health system in Rwanda. It is impressive that a small country\nlike Rwanda has advanced its health system to the point of now offering near universal health insurance coverage.\nThrough a series of strategic structural changes to its health system, catalyzed through international assistance,\nRwanda has demonstrated a commitment towards improving patient and population health indicators. In\nparticular, the rapid scale up of antiretroviral therapy (ART) has become a great success story for Rwanda. The\ncountry achieved universal coverage of ART at a CD4 cell count of 200 cells/mm3 in 2007 and increased the\nthreshold for initiation of ART to �350 cells/mm3 in 2008. Further, 2013 guidelines raised the threshold for initiation\nto �500 cells/mm3 and suggest immediate therapy for key affected populations. In 2015, guidelines recommend\noffering immediate treatment to all patients. By reviewing the history of HIV and the scale-up of treatment delivery\nin Rwanda since the genocide, this paper highlights some of the key innovations of the Government of Rwanda\nand demonstrates the ways in which the national response to the HIV epidemic has catalyzed the implementation\nof interventions that have helped strengthen the overall health system....
Background: Recent meta-analyses confirm a relationship between diet quality and both depression and cognitive\nhealth in adults. While the biological pathways that underpin these relationships are likely multitudinous, extensive\nevidence from animal studies points to the involvement of the hippocampus. The aim of this study was to examine\nthe association between dietary patterns and hippocampal volume in humans, and to assess whether diet was\nassociated with differential rates of hippocampal atrophy over time.\nMethods: Data were drawn from the Personality and Total Health Through Life Study and focused on a subsample\nof the cohort (n = 255) who were aged 60ââ?¬â??64 years at baseline in 2001, completed a food frequency questionnaire,\nand underwent two magnetic resonance imaging scans approximately 4 years apart. Longitudinal generalized\nestimating equation linear regression models were used to assess the association between dietary factors and left\nand right hippocampal volumes over time.\nResults: Every one standard deviation increase in healthy ââ?¬Å?prudentââ?¬Â dietary pattern was associated with a 45.7 mm3\n(standard error 22.9 mm3) larger left hippocampal volume, while higher consumption of an unhealthy ââ?¬Å?Westernââ?¬Â\ndietary pattern was (independently) associated with a 52.6 mm3 (SE 26.6 mm3) smaller left hippocampal volume.\nThese relationships were independent of covariates including age, gender, education, labour-force status,\ndepressive symptoms and medication, physical activity, smoking, hypertension and diabetes. While hippocampal\nvolume declined over time, there was no evidence that dietary patterns influenced this decline. No relationships were\nobserved between dietary patterns and right hippocampal volume.\nConclusions: Lower intakes of nutrient-dense foods and higher intakes of unhealthy foods are each independently\nassociated with smaller left hippocampal volume. To our knowledge, this is the first human study to demonstrate\nassociations between diet and hippocampal volume concordant with data previously observed in animal models....
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