ACTivity as medicine In Oncology for Head and Neck (ACTIOHN): Protocol for a feasibility study investigating a patient-centred approach to exercise for people with head and neck cancer.

BACKGROUND AND AIM: Attempts at personalisation of exercise programmes in head and neck cancer (HaNC) have been limited. The main aim of the present study is to investigate the feasibility and acceptability of introducing a remotely delivered, fully personalised, collaborative, and flexible approach to prescribing and delivering exercise programmes into the HaNC usual care pathway. METHODS: This is a single arm, feasibility study. Seventy patients diagnosed with HaNC will be recruited from two regional HaNC centres in the United Kingdom. Patients will undertake an 8-week exercise programme designed and delivered by cancer exercise specialists. The exercise programme will start any time between the time of diagnosis and up to 8 weeks after completing treatment, depending on patient preference. The content of the exercise programme will be primarily based on patient needs, preferences, and goals, but guided by current physical activity guidelines for people with cancer. The primary outcome measure is retention to the study. Secondary quantitative outcomes are uptake to the exercise programme, different measures of exercise adherence, pre- and post-intervention assessments of fatigue (Multidimensional Fatigue Symptom Inventory-Short Form), quality of life (SF-36), physical activity levels (International Physical Activity Questionnaire-Short Form), and various components of physical fitness. The outcomes of the nested qualitative study are acceptability and feasibility of the intervention evaluated via interviews with patients, health care professionals, and the cancer exercise specialists. Intervention and participant fidelity will be determined using checklists and scrutiny of each patient's logbook and the cancer exercise specialists' meeting notes. Analysis of quantitative data will be via standard summary statistics. Qualitative data will be analysed using thematic analysis. EXPECTED RESULTS: This feasibility study will inform the design and conduct of a future randomised controlled trial. Success will be defined according to a traffic light system for identifying the appropriateness of progression to a randomised controlled trial. TRIAL REGISTRATION: International Standard Randomised Controlled Trial Number registry (ISRCTN82505455).

Photobiomodulation in the management of oral mucositis for adult head and neck cancer patients receiving irradiation: the LiTEFORM RCT.

BACKGROUND: Oral mucositis is a debilitating and painful complication of head and neck cancer irradiation that is characterised by inflammation of the mucous membranes, erythema and ulceration. Oral mucositis affects 6000 head and neck cancer patients per year in England and Wales. Current treatments have not proven to be effective. International studies suggest that low-level laser therapy may be an effective treatment. OBJECTIVES: To assess the clinical effectiveness and cost-effectiveness of low-level laser therapy in the management of oral mucositis in head and neck cancer irradiation. To identify barriers to and facilitators of implementing low-level laser therapy in routine care. DESIGN: Placebo-controlled, individually randomised, multicentre Phase III superiority trial, with an internal pilot and health economic and qualitative process evaluations. The participants, outcome assessors and therapists were blinded. SETTING: Nine NHS head and neck cancer sites in England and Wales. PARTICIPANTS: A total of 87 out of 380 participants were recruited who were aged ≥ 18 years and were undergoing head and neck cancer irradiation with ≥ 60 Gy. INTERVENTION: Random allocation (1 : 1 ratio) to either low-level laser therapy or sham low-level laser therapy three times per week for the duration of irradiation. The diode laser had the following specifications: wavelength 660 nm, power output 75 mW, beam area 1.5 cm2, irradiance 50 mW/cm2, exposure time 60 seconds and fluence 3 J/cm2. There were 20-30 spots per session. Sham low-level laser therapy was delivered in an identical manner. MAIN OUTCOME MEASURE: The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks following the start of irradiation. Higher scores indicate a worse outcome. RESULTS: A total of 231 patients were screened and, of these, 87 were randomised (low-level laser therapy arm, n = 44; sham arm, n = 43). The mean age was 59.4 years (standard deviation 8.8 years) and 69 participants (79%) were male. The mean Oral Mucositis Weekly Questionnaire-Head and Neck Cancer score at 6 weeks was 33.2 (standard deviation 10) in the low-level laser therapy arm and 27.4 (standard deviation 13.8) in the sham arm. LIMITATIONS: The trial lacked statistical power because it did not meet the recruitment target. Staff and patients willingly participated in the trial and worked hard to make the LiTEFORM trial succeed. However, the task of introducing, embedding and sustaining new low-level laser therapy services into a complex care pathway proved challenging. Sites could deliver low-level laser therapy to only a small number of patients at a time. The administration of low-level laser therapy was viewed as straightforward, but also time-consuming and sometimes uncomfortable for both patients and staff, particularly those staff who were not used to working in a patient's mouth. CONCLUSIONS: This trial had a robust design but lacked power to be definitive. Low-level laser therapy is relatively inexpensive. In contrast with previous trials, some patients found low-level laser therapy sessions to be difficult. The duration of low-level laser therapy sessions is, therefore, an important consideration. Clinicians experienced in oral cavity work most readily adapt to delivering low-level laser therapy, although other allied health professionals can be trained. Blinding the clinicians delivering low-level laser therapy is feasible. There are important human resource, real estate and logistical considerations for those setting up low-level laser therapy services. FUTURE WORK: Further well-designed randomised controlled trials investigating low-level laser therapy in head and neck cancer irradiation are needed, with similar powered recruitment targets but addressing the recruitment challenges and logistical findings from this research. TRIAL REGISTRATION: This trial is registered as ISRCTN14224600. FUNDING: This project was funded by the National Institute for Health and Care Research ( NIHR ) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 26, No. 46. See the NIHR Journals Library website for further project information.

Around 9 out of 10 head and neck cancer patients undergoing treatment experience pain, swelling and sores in their mouth (oral mucositis). This can lead to weight loss, painful ulcers, difficulty talking, eating and drinking, and even hospitalisation. Current care includes helping patients to keep their mouth and teeth clean, encouraging them to have a healthy diet and prescribing mouthwashes, painkillers and mouth-coating gels. However, these treatments give limited help in preventing or treating this condition. The LiTEFORM trial looked at whether or not low-level laser therapy could be used to prevent and treat oral mucositis. Patients were allocated to one of two arms at random: active laser or fake (sham) laser. Neither the patients nor the hospital staff knew which laser was being used. Eighty-seven people joined the study during the time allowed (44 received low-level laser therapy and 43 received sham treatment); however, this was a smaller number than the planned target of 380 people. As a result, no meaningful conclusion can be drawn from the results about whether the therapy is beneficial or cost-effective. People receiving the low-level laser therapy reported slightly more soreness in their mouth than those receiving the sham laser, but this could be down to chance. The number of participants is too small to draw conclusions about whether or not the low-level laser is helpful. Some patients found the laser treatment sessions to be difficult. Setting up a new service delivering laser therapy at the same time as cancer treatments was more complicated than originally anticipated. Problems included the scheduling of appointments, finding suitable rooms and having enough trained staff with time to deliver laser therapy. However, this study has provided us with knowledge on how best to set up a laser therapy service in the NHS as part of the cancer treatment pathway and the costs involved. These findings could help future studies looking into low-level laser therapy for those with head and neck cancer.

Screening for biomarkers predictive of gestational diabetes mellitus.

Screening for glucose intolerance during pregnancy provides an opportunity to offer management to those women diagnosed with gestational diabetes mellitus. However, there is a need to diagnose gestational diabetes early to minimize exposure of the developing fetus to suboptimal conditions and prevent perinatal complications and their sequelae. The purpose of this study was to identify potential biomarkers for impending gestational diabetes that appear in the plasma before impaired glucose tolerance. Pregnant women were prospectively recruited to the study and blood was collected at the first antenatal visit and at the time of routine oral glucose tolerance test. Women diagnosed with gestational diabetes were matched with an equal number of normal pregnant (control) women. Biomarkers under investigation included endocrine and metabolic hormones, cytokines and chemokines, and surrogate markers of oxidative stress. Compared to controls, women with gestational diabetes exhibited elevated plasma insulin and reduced plasma adiponectin concentrations at 28 weeks gestation. Significant differences in insulin and adiponectin concentrations were also observed in plasma at 11 weeks gestation. Bivariate logistic regression analysis showed that both insulin and adiponectin are associated with subsequent development of gestational diabetes. Plasma insulin and adiponectin concentrations, when measured at 11 weeks, may be predictive of impending gestational diabetes. Further studies are warranted to determine the reliability of these biomarkers.

Miscarriage risk for asymptomatic women after a normal first-trimester prenatal visit.

OBJECTIVE: To estimate the risk of miscarriage among asymptomatic women after a prenatal visit between 6 and 11 weeks of gestation where proof of fetal viability of a singleton was obtained by office ultrasonography at the same visit. METHODS: This was a prospective cohort study performed over 2 years (March 2004-2006) at an antenatal clinic at a large tertiary hospital in Victoria, Australia. Those recruited were 697 asymptomatic women who attended their first antenatal visit between 6 (+2 days) and 11(+6 days) weeks of gestation, where evidence of fetal cardiac activity of a singleton was obtained by office ultrasonography. The main outcome measure was rates of miscarriage, stratified by gestation at presentation. RESULTS: One case was lost to follow-up. The risk of miscarriage among the entire cohort was 11 of 696 (1.6%). The risk fell rapidly with advancing gestation; 9.4% at 6 (completed) weeks of gestation, 4.2% at 7 weeks, 1.5% at 8 weeks, 0.5% at 9 weeks and 0.7% at 10 weeks (chi(2); test for trend P=.001). Most who miscarried received their ultrasound diagnoses many weeks after their visit; five (45%) were diagnosed in the second trimester, and all but one received their ultrasound diagnoses after 10 weeks of gestation. CONCLUSION: For women without symptoms, the risk of miscarriage after attending a first antenatal visit between 6 and 11 weeks is low (1.6% or less), especially if they present at 8 weeks of gestation and beyond. Our data could be used to reassure such women that the probability of progressing to later than 20 weeks of gestation is very good.

The prevalence of inherited thrombophilic polymorphisms in an asymptomatic Australian antenatal population.

AIM: Inherited thrombophilic polymorphisms have been linked to pregnancy-related thromboembolism and other adverse pregnancy outcomes. As there are limited data on the prevalence of these polymorphisms in Australian populations, we aimed to assess this in an antenatal population. METHODS: Healthy nulliparous women (n = 2031) were recruited to this study. The women had no past or family history of venous thromboembolism. Women were excluded if they or a family member was known to be a carrier of any thrombophilic marker. Genotyping from venous blood for the factor V Leiden, prothrombin 20210A, MTHFR 677 and 1298 and thrombomodulin C1418T polymorphisms was undertaken. RESULTS: Key findings were that 107 of 2019 (5.30, 95% confidence interval 4.36-6.37%) women tested were heterozygous carriers of factor V Leiden and one was homozygous (0.05, 0-0.27%); 2.43% of women were heterozygous carriers of the prothrombin gene mutation (1.80-3.20%) while no women were homozygous for this mutation; 11.62% (10.22-13.02%) and 9.98% (8.67-11.29%) were homozygous for the MTHFR 677 and 1298 polymorphisms, respectively, and 3.43% (2.63-4.22%) of women were homozygous for the thrombomodulin polymorphism. CONCLUSIONS: The prevalence of these polymorphisms is consistent with previously published data in Caucasian populations. These data will provide the basis for further assessment of the relationship between poor pregnancy outcome and these inherited thrombophilic polymorphisms in an asymptomatic antenatal population.

Ascertaining women's choice of title during pregnancy and childbirth.

METHODS: A questionnaire was administered to 958 women attending the antenatal clinic at Mercy Hospital for Women, Melbourne, to ascertain their choice of title during pregnancy Midwifery, nursing and medical staff (376 in total) were also invited to respond to a similar questionnaire. RESULTS: The response rate was 73.6% from the survey of all women who were overwhelmingly in favour of being called 'patient' as their first choice (34%), followed by 'other' (20%) and then 'mother' (19%). Virtually all women requesting 'other' wished to be called by their name. Women wishing to be called 'patient' for first choice did not significantly differ from the remainder of the study group in age, gestation, number of previous pregnancies, or number of children. When women from the Family Birth Centre (FBC) were analysed as a separate group, they had a clear preference to be called 'other' (unanimously, by their name) than the general antenatal population (odds ratio (OR) 5.1; 95% confidence interval (CI) 3.1, 8.3; p < 0.0001). The staff survey, with a response rate of 84%, also demonstrated that 'patient' was the most popular first choice for patient title. Medical staff were significantly more likely to choose 'patient' (OR 4.2, 95% CI 2.3, 7.7; p < 0.0001), though the term 'patient' was the preferred choice of all staff.