Lynch syndrome: barriers to and facilitators of screening and disease management

Background Lynch syndrome is a hereditary cancer with confirmed carriers at high risk for colorectal (CRC) and extracolonic cancers. The purpose of the current study was to develop a greater understanding of the factors influencing decisions about disease management post-genetic testing. Methods The study used a grounded theory approach to data collection and analysis as part of a multiphase project examining the psychosocial and behavioral impact of predictive DNA testing for Lynch syndrome. Individual and small group interviews were conducted with individuals from 10 families with the MSH2 intron 5 splice site mutation or exon 8 deletion. The data from confirmed carriers (n = 23) were subjected to re-analysis to identify key barriers to and/or facilitators of screening and disease management. Results Thematic analysis identified personal, health care provider and health care system factors as dominant barriers to and/or facilitators of managing Lynch syndrome. Person-centered factors reflect risk perceptions and decision-making, and enduring screening/disease management. The perceived knowledge and clinical management skills of health care providers also influenced participation in recommended protocols. The health care system barriers/facilitators are defined in terms of continuity of care and coordination of services among providers. Conclusions Individuals with Lynch syndrome often encounter multiple barriers to and facilitators of disease management that go beyond the individual to the provider and health care system levels. The current organization and implementation of health care services are inadequate. A coordinated system of local services capable of providing integrated, efficient health care and follow-up, populated by providers with knowledge of hereditary cancer, is necessary to maintain optimal health

Comparative effectiveness of manipulation, mobilisation and the Activator instrument in treatment of non-specific neck pain: a systematic review

BACKGROUND: Neck pain is a common problem and different forms of manual therapy are used in its treatment. The purpose of this systematic review was to critically appraise the literature that directly compared manipulation, mobilisation and the Activator instrument for non-specific neck pain. METHODS: Electronic databases (MEDLINE, MANTIS and CINAHL) were searched from their inception to October 2005 for all English language randomised clinical trials that directly compared manipulation, mobilisation and the Activator instrument. Inclusion and exclusion criteria were applied to select the studies and these studies were then evaluated using validated criteria. RESULTS: Five such studies were identified. The methodological quality was mostly poor. Findings from the studies were mixed and no one therapy was shown to be more effective than the others. CONCLUSION: Further high quality research has to be done before a recommendation can be made as to the most effective manual method for non-specific neck pain

Persistence of immune responses after heterologous and homologous third COVID-19 vaccine dose schedules in the UK: eight-month analyses of the COV-BOOST trial

Background: COV-BOOST is a multicentre, randomised, controlled, phase 2 trial of seven COVID-19 vaccines used as a third booster dose in June 2021. Monovalent messenger RNA (mRNA) COVID-19 vaccines were subsequently widely used for the third and fourth-dose vaccination campaigns in high-income countries. Real-world vaccine effectiveness against symptomatic infections following third doses declined during the Omicron wave. This report compares the immunogenicity and kinetics of responses to third doses of vaccines from day (D) 28 to D242 following third doses in seven study arms. Methods: The trial initially included ten experimental vaccine arms (seven full-dose, three half-dose) delivered at three groups of six sites. Participants in each site group were randomised to three or four experimental vaccines, or MenACWY control. The trial was stratified such that half of participants had previously received two primary doses of ChAdOx1 nCov-19 (Oxford–AstraZeneca; hereafter referred to as ChAd) and half had received two doses of BNT162b2 (Pfizer–BioNtech, hereafter referred to as BNT). The D242 follow-up was done in seven arms (five full-dose, two half-dose). The BNT vaccine was used as the reference as it was the most commonly deployed third-dose vaccine in clinical practice in high-income countries. The primary analysis was conducted using all randomised and baseline seronegative participants who were SARS-CoV-2 naïve during the study and who had not received a further COVID-19 vaccine for any reason since third dose randomisation. Results: Among the 817 participants included in this report, the median age was 72 years (IQR: 55–78) with 50.7% being female. The decay rates of anti-spike IgG between vaccines are different among both populations who received initial doses of ChAd/ChAd and BNT/BNT. In the population that previously received ChAd/ChAd, mRNA vaccines had the highest titre at D242 following their vaccine dose although Ad26. COV2. S (Janssen; hereafter referred to as Ad26) showed slower decay. For people who received BNT/BNT as their initial doses, a slower decay was also seen in the Ad26 and ChAd arms. The anti-spike IgG became significantly higher in the Ad26 arm compared to the BNT arm as early as 3 months following vaccination. Similar decay rates were seen between BNT and half-BNT; the geometric mean ratios ranged from 0.76 to 0.94 at different time points. The difference in decay rates between vaccines was similar for wild-type live virus-neutralising antibodies and that seen for anti-spike IgG. For cellular responses, the persistence was similar between study arms. Conclusions: Heterologous third doses with viral vector vaccines following two doses of mRNA achieve more durable humoral responses compared with three doses of mRNA vaccines. Lower doses of mRNA vaccines could be considered for future booster campaigns

Relative effectiveness and adverse effects of cervical manipulation, mobilisation and the activator instrument in patients with sub-acute non-specific neck pain: results from a stopped randomised trial

<p>Abstract</p> <p>Background</p> <p>Neck pain of a mechanical nature is a common complaint seen by practitioners of manual medicine, who use a multitude of methods to treat the condition. It is not known, however, if any of these methods are superior in treatment effectiveness. This trial was stopped due to poor recruitment. The purposes of this report are (1) to describe the trial protocol, (2) to report on the data obtained from subjects who completed the study, (3) to discuss the problems we encountered in conducting this study.</p> <p>Methods</p> <p>A pragmatic randomised clinical trial was undertaken. Patients who met eligibility criteria were randomised into three groups. One group was treated using specific segmental high velocity low amplitude manipulation (diversified), another by specific segmental mobilisation, and a third group by the Activator instrument. All three groups were also treated for any myofascial distortions and given appropriate exercises and advice. Participants were treated six times over a three-week period or until they reported being pain free. The primary outcome measure for the study was Patient Global Impression of Change (PGIC); secondary outcome measures included the Short-Form Health Survey (SF-36v₂), the neck Bournemouth Questionnaire, and the numerical rating scale for pain intensity. Participants also kept a diary of any pain medication taken and noted any perceived adverse effects of treatment. Outcomes were measured at four points: end of treatment, and 3, 6, and 12 months thereafter.</p> <p>Results</p> <p>Between January 2007 and March 2008, 123 patients were assessed for eligibility, of these 47 were considered eligible, of which 16 were allocated to manipulation, 16 to the Activator instrument and 15 to the mobilisation group. Comparison between the groups on the PGIC adjusted for baseline covariants did not show a significant difference for any of the endpoints. Within group analyses for change from baseline to the 12-month follow up for secondary outcomes were significant for all groups on the Bournemouth Questionnaire and for pain, while the mobilisation group had a significant improvement on the PCS and MCS subscales of the SF-36_v2. Finally, there were no moderate, severe, or long-lasting adverse effects reported by any participant in any group.</p> <p>Conclusions</p> <p>Although the small sample size must be taken into consideration, it appears that all three methods of treating mechanical neck pain had a long-term benefit for subacute neck pain, without moderate or serious adverse events associated with any of the treatment methods. There were difficulties in recruiting subjects to this trial. This pragmatic trial should be repeated with a larger sample size.</p

Meat Intake and the Dose of Vitamin B3 - Nicotinamide:Cause of the Causes of Disease Transitions, Health Divides, and Health Futures?

Meat and vitamin B 3 – nicotinamide – intake was high during hunter-gatherer times. Intake then fell and variances increased during and after the Neolithic agricultural revolution. Health, height, and IQ deteriorated. Low dietary doses are buffered by ‘welcoming’ gut symbionts and tuberculosis that can supply nicotinamide, but this co-evolved homeostatic metagenomic strategy risks dysbioses and impaired resistance to pathogens. Vitamin B 3 deficiency may now be common among the poor billions on a low-meat diet. Disease transitions to non-communicable inflammatory disorders (but longer lives) may be driven by positive ‘meat transitions’. High doses of nicotinamide lead to reduced regulatory T cells and immune intolerance. Loss of no longer needed symbiotic ‘old friends’ compounds immunological over-reactivity to cause allergic and auto-immune diseases. Inhibition of nicotinamide adenine dinucleotide consumers and loss of methyl groups or production of toxins may cause cancers, metabolic toxicity, or neurodegeneration. An optimal dosage of vitamin B 3 could lead to better health, but such a preventive approach needs more equitable meat distribution. Some people may require personalised doses depending on genetic make-up or, temporarily, when under stress