Reporting and dealing with missing quality of life data in RCTs : has the picture changed in the last decade?

Peer reviewedPublisher PD

Storage stability of whole and nibbed, conventional and high oleic peanuts (<i>Arachis hypogeae </i>L.)

Peanuts are increasingly being used as nibbed ingredients in cereal bars, confectionery and breakfast cereals. However, studies on their oxidative stability in this format are limited. Storage trials to determine the stability to oxidation were carried out on whole and nibbed kernels of conventional (CP) and high oleic (HOP) peanuts, with respect to temperature and modified atmosphere packaging. HOP exhibited the highest oxidative stability, with a lag phase in whole kernels of 12–15 weeks before significant oxidation occurred. HOP also showed higher levels of intrinsic antioxidants, a trolox equivalent antioxidant capacity (TEAC) of 70 mMol equivalence and radical scavenging percentage (RSP) of 99.8 % at the beginning of storage trials, whereas CP showed values of 40 mMol and 81.2 %, respectively. The intrinsic antioxidants at the beginning of these storage trials were shown to affect the peroxide value (PV), where RSP and TEAC decreased, and PV increased. Therefore, in peanuts the processing format (nibbed or whole) had the highest influence on susceptibility of lipid oxidation, highest to lowest importance: processing format &gt; temperature &gt; atmospheric conditions

Second-line antiretroviral therapy in a workplace and community-based treatment programme in South Africa: determinants of virological outcome.

: Background: As antiretroviral treatment (ART) programmes in resource-limited settings mature, more patients are experiencing virological failure. Without resistance testing, deciding who should switch to second-line ART can be difficult. The consequences for second-line outcomes are unclear. In a workplace- and community-based multi-site programme, with 6-monthly virological monitoring, we describe outcomes and predictors of viral suppression on second-line, protease inhibitor-based ART.Methods: We used prospectively collected clinic data from patients commencing first-line ART between 1/1/03 and 31/12/08 to construct a study cohort of patients switched to second-line ART in the presence of a viral load (VL) ?400 copies/ml. Predictors of VL&lt;400 copies/ml within 15 months of switch were assessed using modified Poisson regression to estimate risk ratios.Results: 205 workplace patients (91.7% male; median age 43 yrs) and 212 community patients (38.7% male; median age 36 yrs) switched regimens. At switch compared to community patients, workplace patients had a longer duration of viraemia, higher VL, lower CD4 count, and higher reported non-adherence on first-line ART. Non-adherence was the reported reason for switching in a higher proportion of workplace patients. Following switch, 48.3% (workplace) and 72.0% (community) achieved VL&lt;400, with non-adherence (17.9% vs. 1.4%) and virological rebound (35.6% vs. 13.2% with available measures) reported more commonly in the workplace programme. In adjusted analysis of the workplace programme, lower switch VL and younger age were associated with VL&lt;400. In the community programme, shorter duration of viraemia, higher CD4 count and transfers into programme on ART were associated with VL&lt;400.Conclusion: High levels of viral suppression on second-line ART can be, but are not always, achieved in multi-site treatment programmes with both individual- and programme-level factors influencing outcomes. Strategies to support both healthcare workers and patients during this switch period need to be evaluated; sub-optimal adherence, particularly in the workplace programme must be addressed

Integration of Tobacco Treatment Services into Cancer Care at Stanford.

As part of a National Cancer Institute Moonshot P30 Supplement, the Stanford Cancer Center piloted and integrated tobacco treatment into cancer care. This quality improvement (QI) project reports on the process from initial pilot to adoption within 14 clinics. The Head and Neck Oncology Clinic was engaged first in January 2019 as a pilot site given staff receptivity, elevated smoking prevalence, and a high tobacco screening rate (95%) yet low levels of tobacco cessation treatment referrals (&lt;10%) and patient engagement (&lt;1% of smokers treated). To improve referrals and engagement, system changes included an automated "opt-out" referral process and provision of tobacco cessation treatment as a covered benefit with flexible delivery options that included phone and telemedicine. Screening rates increased to 99%, referrals to 100%, 74% of patients were reached by counselors, and 33% of those reached engaged in treatment. Patient-reported abstinence from all tobacco products at 6-month follow-up is 20%. In July 2019, two additional oncology clinics were added. In December 2019, less than one year from initiating the QI pilot, with demonstrated feasibility, acceptability, and efficacy, the tobacco treatment services were integrated into 14 clinics at Stanford Cancer Center

Modulation of NKG2D expression in human CD8(+) T cells corresponding with tuberculosis drug cure.

BACKGROUND: Biomarkers predicting tuberculosis treatment response and cure would facilitate drug development. This study investigated expression patterns of the co-stimulation molecule NKG2D in human tuberculosis and treatment to determine its potential usefulness as a host biomarker of tuberculosis drug efficacy. METHODS: Tuberculosis patients (n = 26) were recruited in Lahore, Pakistan, at diagnosis and followed up during treatment. Household contacts (n = 24) were also recruited. NKG2D expression was measured by qRT-PCR in RNA samples both ex vivo and following overnight mycobacterial stimulation in vitro. Protein expression of NKG2D and granzyme B was measured by flow cytometry. RESULTS: NKG2D expression in newly diagnosed tuberculosis patients was similar to household contacts in ex vivo RNA, but was higher following in vitro stimulation. The NKG2D expression was dramatically reduced by intensive phase chemotherapy, in both ex vivo blood RNA and CD8(+) T cell protein expression, but then reverted to higher levels after the continuation phase in successfully treated patients. CONCLUSION: The changes in NKG2D expression through successful treatment reflect modulation of the peripheral cytotoxic T cell response. This likely reflects firstly in vivo stimulation by live Mycobacterium tuberculosis, followed by the response to dead bacilli, antigen-release and finally immunopathology resolution. Such changes in host peripheral gene expression, alongside clinical and microbiological indices, could be developed into a biosignature of tuberculosis drug-induced cure to be used in future clinical trials

How do anticipated worry and regret predict seasonal influenza vaccination uptake among Chinese adults?

Objectives: To test two hypothesized models of how anticipated affect, cognitive risk estimate and vaccination intention might influence vaccination uptake against seasonal influenza. Methods: The study collected baseline and follow-up data during the main influenza seasons (January-March) of 2009 and 2010, respectively, among 507 university students and staff of a university in Hong Kong. Following logistic regression to determine eligible variables, two mediation models of cognitive risk estimate, anticipated affect, vaccination intention and vaccination uptake against seasonal influenza were tested using structural equation modeling. Results: Mediation analyses found that anticipated worry if not vaccinated influenced seasonal influenza vaccination uptake through its effects on either perceived probability of influenza infection (β= 0.45) or intention (.β= 0.45) while anticipated regret if not vaccinated influenced vaccination uptake through its effect on intention (β= 0.45) only; anticipated regret if vaccinated impeded vaccination uptake indirectly through its effect on vaccination intention (β= -0.26) or directly (β= -0.20); perceived probability of influenza infection influenced vaccination uptake through its effect on intention (β= 0.20) or directly (β= 0.22); and finally, intention influenced vaccination uptake directly (β= 0.58). Conclusion: The results suggest that anticipated affect seems to drive risk estimates related to seasonal influenza vaccination rather than vice versa and intention remains an important mediator of the associations of anticipated affect and cognitive risk estimate with vaccination uptake against seasonal influenza. © 2013 Elsevier Ltd.postprin

Non-inferiority trials: are they inferior? A systematic review of reporting in major medical journals

OBJECTIVE: To assess the adequacy of reporting of non-inferiority trials alongside the consistency and utility of current recommended analyses and guidelines. DESIGN: Review of randomised clinical trials that used a non-inferiority design published between January 2010 and May 2015 in medical journals that had an impact factor >10 (JAMA Internal Medicine, Archives Internal Medicine, PLOS Medicine, Annals of Internal Medicine, BMJ, JAMA, Lancet and New England Journal of Medicine). DATA SOURCES: Ovid (MEDLINE). METHODS: We searched for non-inferiority trials and assessed the following: choice of non-inferiority margin and justification of margin; power and significance level for sample size; patient population used and how this was defined; any missing data methods used and assumptions declared and any sensitivity analyses used. RESULTS: A total of 168 trial publications were included. Most trials concluded non-inferiority (132; 79%). The non-inferiority margin was reported for 98% (164), but less than half reported any justification for the margin (77; 46%). While most chose two different analyses (91; 54%) the most common being intention-to-treat (ITT) or modified ITT and per-protocol, a large number of articles only chose to conduct and report one analysis (65; 39%), most commonly the ITT analysis. There was lack of clarity or inconsistency between the type I error rate and corresponding CIs for 73 (43%) articles. Missing data were rarely considered with (99; 59%) not declaring whether imputation techniques were used. CONCLUSIONS: Reporting and conduct of non-inferiority trials is inconsistent and does not follow the recommendations in available statistical guidelines, which are not wholly consistent themselves. Authors should clearly describe the methods used and provide clear descriptions of and justifications for their design and primary analysis. Failure to do this risks misleading conclusions being drawn, with consequent effects on clinical practice

Measles to the Rescue: A Review of Oncolytic Measles Virus

Oncolytic virotherapeutic agents are likely to become serious contenders in cancer treatment. The vaccine strain of measles virus is an agent with an impressive range of oncolytic activity in pre-clinical trials with increasing evidence of safety and efficacy in early clinical trials. This paramyxovirus vaccine has a proven safety record and is amenable to careful genetic modification in the laboratory. Overexpression of the measles virus (MV) receptor CD46 in many tumour cells may direct the virus to preferentially enter transformed cells and there is increasing awareness of the importance of nectin-4 and signaling lymphocytic activation molecule (SLAM) in oncolysis. Successful attempts to retarget MV by inserting genes for tumour-specific ligands to antigens such as carcinoembryonic antigen (CEA), CD20, CD38, and by engineering the virus to express synthetic microRNA targeting sequences, and "blinding" the virus to the natural viral receptors are exciting measures to increase viral specificity and enhance the oncolytic effect. Sodium iodine symporter (NIS) can also be expressed by MV, which enables in vivo tracking of MV infection. Radiovirotherapy using MV-NIS, chemo-virotherapy to convert prodrugs to their toxic metabolites, and immune-virotherapy including incorporating antibodies against immune checkpoint inhibitors can also increase the oncolytic potential. Anti-viral host immune responses are a recognized barrier to the success of MV, and approaches such as transporting MV to the tumour sites by carrier cells, are showing promise. MV Clinical trials are producing encouraging preliminary results in ovarian cancer, myeloma and cutaneous non-Hodgkin lymphoma, and the outcome of currently open trials in glioblastoma multiforme, mesothelioma and squamous cell carcinoma are eagerly anticipated

A cohort study of influences, health outcomes and costs of patients' health-seeking behaviour for minor ailments from primary and emergency care settings

To compare health-related and cost-related outcomes of consultations for symptoms suggestive of minor ailments in emergency departments (EDs), general practices and community pharmacies