The short-term impact of curative colorectal cancer treatment on physical activity, functional status and quality of life: A systematic review protocol

REVIEW QUESTION/OBJECTIVE The quantitative objectives are to identify the impact of curative colorectal cancer treatment (surgery or adjuvant therapy) on physical activity, functional status and quality of life within one year of treatment or diagnosis. INCLUSION CRITERIA Types of participants: This review will consider studies that include individuals aged 18 years and over who have been diagnosed with colorectal cancer. Types of intervention(s)/phenomena of interest: This review will consider studies that evaluate the impact of curative colorectal cancer treatment: surgery and/or adjuvant therapy. Types of outcomes: This review will consider studies that include the following outcome measures assessed within one year of diagnosis or treatment: Physical activity - any bodily movement produced by skeletal muscles resulting in energy expenditure. Physical activity is not exclusive to exercise; activities can also be walking, housework, occupational or leisure. Physical activity can be measured objectively using pedometers or accelerometers, or subjectively using self-reported measures. Functional status – measured as the capacity to perform all activities of daily living such as walking, showering, and eating; and instrumental activities of daily living such as (but not limited to) grocery shopping, housekeeping and laundry. Quality of life – defined as the individual meaning of mental, physical and psychosocial wellbeing, as measured by validated tools such as SF-36, EORTC-QLQ-C30, or FACT-C.

Effect of exercise referral schemes in primary care on physical activity and improving health outcomes: Systematic review and meta-analysis

Objective To assess the impact of exercise referral schemes on physical activity and health outcomes. Design Systematic review and meta-analysis. Data sources Medline, Embase, PsycINFO, Cochrane Library, ISI Web of Science, SPORTDiscus, and ongoing trial registries up to October 2009. We also checked study references. Study selection - Design: randomised controlled trials or non-randomised controlled (cluster or individual) studies published in peer review journals. - Population: sedentary individuals with or without medical diagnosis. - Exercise referral schemes defined as: clear referrals by primary care professionals to third party service providers to increase physical activity or exercise, physical activity or exercise programmes tailored to individuals, and initial assessment and monitoring throughout programmes. - Comparators: usual care, no intervention, or alternative exercise referral schemes. Results Eight randomised controlled trials met the inclusion criteria, comparing exercise referral schemes with usual care (six trials), alternative physical activity intervention (two), and an exercise referral scheme plus a self determination theory intervention (one). Compared with usual care, follow-up data for exercise referral schemes showed an increased number of participants who achieved 90-150 minutes of physical activity of at least moderate intensity per week (pooled relative risk 1.16, 95% confidence intervals 1.03 to 1.30) and a reduced level of depression (pooled standardised mean difference −0.82, −1.28 to −0.35). Evidence of a between group difference in physical activity of moderate or vigorous intensity or in other health outcomes was inconsistent at follow-up. We did not find any difference in outcomes between exercise referral schemes and the other two comparator groups. None of the included trials separately reported outcomes in individuals with specific medical diagnoses. Substantial heterogeneity in the quality and nature of the exercise referral schemes across studies might have contributed to the inconsistency in outcome findings. Conclusions Considerable uncertainty remains as to the effectiveness of exercise referral schemes for increasing physical activity, fitness, or health indicators, or whether they are an efficient use of resources for sedentary people with or without a medical diagnosis.

Improving diagnosis of tumor-induced osteomalacia with gallium-68 DOTATATE PET/CT

Context: Tumor-induced osteomalacia (TIO) is a rarely diagnosed disorder presenting with bone pain, fractures, muscle weakness, and moderate-to-severe hypophosphatemia resulting from fibroblast growth factor 23-mediated renal phosphate wasting. Tumors secreting fibroblast growth factor 23 are often small and difficult to find with conventional imaging. Objective: We studied the utility of 68Ga-DOTA-octreotate (DOTATATE) somatostatin receptor positron emission tomography (PET)/computed tomography (CT) imaging in the diagnosis of TIO. Design and Setting: A multicenter case series was conducted at tertiary referral hospitals. Patients and Methods: Six patients with TIO diagnosed between 2003 and 2012 in Australia were referred for DOTATATE PET imaging. We reviewed the clinical history, biochemistry, imaging characteristics, histopathology, and clinical outcome of each patient. Results: Each case demonstrated delayed diagnosis despite severe symptoms. DOTATATE PET/CT imaging demonstrated high uptake and localized the tumor with confidence in each case. After surgical excision, there was resolution of clinical symptoms and serum phosphate, except in one patient who demonstrated residual disease on PET/CT. All tumors demonstrated high somatostatin receptor subtype 2 cell surface receptor expression using immunohistochemistry. Conclusions: In patients with TIO, DOTATATE PET/CT can successfully localize phosphaturic mesenchymal tumors and may be a practical first step in functional imaging for this disorder. Serum phosphate should be measured routinely in patients with unexplained muscle weakness, bone pain, or stress fractures to allow earlier diagnosis of TIO. - See more at: http://press.endocrine.org/doi/abs/10.1210/jc.2012-3642#sthash.eXD0CopL.dpuf

The tired foot. The effects of physical activity, energy expenditure and sleep on the diabetic foot population

Background The most common pathway to development of diabetes foot ulcers is repetitive daily activity stress on the plantar surface of the neuropathic foot. Studies suggest an association between different diabetic foot complications and physical activity. However, to the best of the authors knowledge the steps/day and sleep patterns of people with diabetic foot ulcers has yet to be investigated. This observational study aims to investigate the physical activity and sleep patterns of three groups of adults with type 2 diabetes and different foot complications Methods Participants with type 2 diabetes were recruited into three groups: 1. those with no reported foot complications (DNIL), 2. those with diagnosis of neuropathy (DPN) and 3. those with a neuropathic ulcer (DFU). Exclusion criteria included peripheral arterial disease and mobility aid use. Participants wore a SenseWear Pro 3 Armband continuously for 7 days and completed an Epworth Sleepiness Scale. The Armband is a validated automated measure of activity (walking steps, average Metabolic Equivalent Task (MET), physical activity (>3 METs) duration), energy expenditure(kJ) (total and physical activity (>3 METs)) and sleep (duration). Data on age, sex, BMI, diabetes duration and HbA1c were also collected. Results Sixty-Six (14 DNIL, 22 DPN and 30 DFU's participants were recruited; 71% males, mean age 61(±12) years, diabetes duration 13(±9) years, HbA1c 8.3(±2.8), BMI 32.6(±5.9), average METs 1.2(0.2). Significant differences were reported in mean(SD) steps/day (5,859(±2,381) in DNIL; 5,007(±3,349) in DPN and 3,271(±2,417) in DFU's and daily energy expenditure (10,868(±1,307)kJ in DNIL; 11,060(±1,916)kJ in DPN and 13,006(± 3,559) in DFU's(p <0.05). No significant differences were reported for average METs, physical activity duration or energy expenditure, sleep time or Epworth score (p>0.1). Conclusions Preliminary findings suggest people with diabetes are sedentary. Results indicate that patients with a diabetic foot ulcer work significantly less than those with neuropathy or nil complications and use significantly more energy to do so. Sleep Parameters showed no differences. Recruitment is still on going.

Sedentariness and physical inactivity in diabetes: a case for home-based exercise prescription

Increasing proportions of the global population are being diagnosed with diabetes. It is anticipated that by 2030, 10% of the adult population worldwide will be living with this condition. Lifestyle factors can impact on the development, management and progression of diabetes. Obesity and sedentary living are contributory factors to the increased volume of diabetes. Physical activity offers those living with diabetes the opportunities to keep well and attain potentially more stable blood glucose control reducing the level of medical intervention required and delaying or preventing some of the life-changing complications that can derive from a diabetes diagnosis. Exercise interventions are effective in preventing and treating type-II diabetes. However, maintaining regular exercise routines, especially home-based exercises may provide a key for sustaining the health benefits.

Cost-effectiveness analysis of the diagnosis of meniscus tears.

BACKGROUND: Diagnostic imaging represents the fastest growing segment of costs in the US health system. This study investigated the cost-effectiveness of alternative diagnostic approaches to meniscus tears of the knee, a highly prevalent disease that traditionally relies on MRI as part of the diagnostic strategy. PURPOSE: To identify the most efficient strategy for the diagnosis of meniscus tears. STUDY DESIGN: Economic and decision analysis; Level of evidence, 1. METHODS: A simple-decision model run as a cost-utility analysis was constructed to assess the value added by MRI in various combinations with patient history and physical examination (H&P). The model examined traumatic and degenerative tears in 2 distinct settings: primary care and orthopaedic sports medicine clinic. Strategies were compared using the incremental cost-effectiveness ratio (ICER). RESULTS: In both practice settings, H&P alone was widely preferred for degenerative meniscus tears. Performing MRI to confirm a positive H&P was preferred for traumatic tears in both practice settings, with a willingness to pay of less than US$50,000 per quality-adjusted life-year. Performing an MRI for all patients was not preferred in any reasonable clinical scenario. The prevalence of a meniscus tear in a clinician's patient population was influential. For traumatic tears, MRI to confirm a positive H&P was preferred when prevalence was less than 46.7%, with H&P preferred above that. For degenerative tears, H&P was preferred until the prevalence reaches 74.2%, and then MRI to confirm a negative was the preferred strategy. In both settings, MRI to confirm positive physical examination led to more than a 10-fold lower rate of unnecessary surgeries than did any other strategy, while MRI to confirm negative physical examination led to a 2.08 and 2.26 higher rate than H&P alone in primary care and orthopaedic clinics, respectively. CONCLUSION: For all practitioners, H&P is the preferred strategy for the suspected degenerative meniscus tear. An MRI to confirm a positive H&P is preferred for traumatic tears for all practitioners. Consideration should be given to implementing alternative diagnostic strategies as well as enhancing provider education in physical examination skills to improve the reliability of H&P as a diagnostic test. CLINICAL RELEVANCE: Alternative diagnostic strategies that do not include the use of MRI may result in decreased health care costs without harm to the patient and could possibly reduce unnecessary procedures.

Ex vivo diagnosis of lung cancer using a Raman miniprobe.

Lung cancer is the most common cause of cancer death. The conventional method of confirming the diagnosis is bronchoscopy, inspecting the airways of the patient with a fiber optic endoscope. A number of studies have shown that Raman spectroscopy can diagnose lung cancer in vitro. In this study, Raman spectra were obtained from ex vivo normal and malignant lung tissue using a minifiber optic Raman probe suitable for insertion into the working channel of a bronchoscope. Shifted subtracted Raman spectroscopy was used to reduce the fluorescence from the lung tissue. Using principal component analysis with a leave-one-out analysis, the tissues were classified accurately. This novel technique has the potential to obtain Raman spectra from tumors from patients with lung cancer in vivo.

Exploring and comparing the experience and coping behaviour of men and women with colorectal cancer at diagnosis and during surgery

Aim. This paper is a report of a study exploring and comparing the experience of men and women with colorectal cancer at diagnosis and during surgery.

Background. Men have higher incidence and mortality rates for nearly all cancers and frequently use health behaviours that reflect their masculinity. There has been minimal investigation into the influence of gender on the experience of a ‘shared’ cancer.

Methods. From November 2006 to November 2008, a qualitative study was conducted involving 38 individuals (24 men, 14 women) with colorectal cancer. Data were generated using semi-structured interviews at four time points over an 18-month period. This paper reports the participants’ experience at diagnosis and during surgery (time point 1) with the purpose of examining the impact of gender on this experience.

Findings. In general, men appeared more accepting of their diagnosis. The majority of females seemed more emotional and more affected by the physical side effects. However, there was variation in both gender groups, with some men and women portraying both ‘masculine’ and ‘feminine’ traits. There was also individual variation in relation to context.

Conclusions. It appears that many men may have been experiencing side effects and/or psychological distress that they were reluctant to discuss, particularly as some men portrayed typical ‘masculine’ traits in public, but felt able to open up in private. Nurses should not make assumptions based on the traditional view of masculinity, and should determine how each man wants to deal with their diagnosis and not presume that all men need to ‘open up’ about their illness.

Early diagnosis improves survival in kidney cancer

Kidney cancers account for 2-3% of all adult malignancies in the UK. Men are predominantly affected by renal cancer with an average age at diagnosis of 64 years. Renal (or clear) cell carcinoma (RCC) accounts for 90% of kidney cancers. Early diagnosis improves survival with five-year survival rates for renal cancer of 70-94% for localised tumours in the UK. RCC should be suspected in the presence of localising symptoms such as flank pain, a loin mass or haematuria; constitutional upset including weight loss, pyrexia and/or night sweats; or with unexplained laboratory tests. Smoking, obesity and hypertension are the most important and most common risk factors. Environmental exposure to asbestos, cadmium and trichloroethylene are less common risk factors. Patients on chronic dialysis and renal transplant recipients are at increased risk of RCC in their native kidneys. If kidney cancer is suspected on history, physical examination or initial screening tests then a red flag ultrasound examination of the renal tracts should be requested. Dipstick urinalysis is of great value as asymptomatic haematuria may be the only abnormal test in the presence of non-specific symptoms such as weight loss or loin pain. Visible or non-visible haematuria, in the absence of proteinuria, suggests an underlying structural abnormality is present in the kidneys, ureters or bladder. Surgical removal of RCCs, where feasible, may result in cure in up to 40-60% of cases. Individuals too frail for major surgery may benefit from thermal ablation and cryotherapy. Agents that target the VEGF and mTOR pathways are considered first line in the treatment of metastatic RCC. Sunitinib, recommended by NICE, is administered orally and acts by inhibiting the VEGF receptor.

A population-based study of adverse physical effects following prostate cancer treatments: Results from the PiCTure (Prostate cancer treatment – your experience) study

Background:

Men and clinicians need reliable population based information when making decisions about investigation and treatment of prostate cancer. In the absence of clearly preferred treatments, differences in outcomes become more important.

Aim:

To investigate rates of adverse physical effects among prostate cancer survivors 2-15 years post diagnosis by treatment, and estimate population burden.

Methods:

A cross sectional, postal survey to 6,559 survivors (all ages) diagnosed with primary, invasive prostate cancer (ICD10-C61), identified in Northern Ireland and the Republic of Ireland via cancer registries. Questions included symptoms at diagnosis, treatments received and adverse physical effects (impotence, urinary incontinence, bowel problems, breast changes, libido loss, hot flashes, fatigue) experienced ‘ever’ and ‘current’ i.e. at questionnaire completion. Physical effect levels were weighted by age, country and time since diagnosis for all prostate cancer survivors. Bonferroni corrections were applied to account for multiple comparisons.

Results:

Adjusted response rate 54%, (n=3,348). 75% reported at least one current physical effect (90% ever), with 29% reporting at least three. These varied by treatment. Current impotence was reported by 76% post-prostatectomy, 64% post-external beam radiotherapy with hormone therapy, with average for all survivors of 57%. Urinary incontinence (overall current level: 16%) was highest post-prostatectomy (current 28%, ever 70%). 42% of brachytherapy patients reported no current adverse physical effects; however 43% reported current impotence and 8% current incontinence. Current hot flashes (41%), breast changes (18%) and fatigue (28%) were reported more commonly by patients on hormone therapy.

Conclusions:

This study provides evidence that adverse physical effects following prostate cancer represent a significant public health burden; an estimated 1.6% of men over 45 is a prostate cancer survivor with a current adverse physical effect. This information should facilitate investigation and treatment decision-making and follow-up care of patients.

Patient-reported 'ever had' and 'current' long term physical symptoms following prostate cancer treatments

OBJECTIVE: To document prostate cancer patient reported 'ever experienced' and 'current' prevalence of disease specific physical symptoms stratified by primary treatment received.
PATIENTS: 3,348 prostate cancer survivors 2-15 years post diagnosis.
METHODS: Cross-sectional, postal survey of 6,559 survivors diagnosed 2-15 years ago with primary, invasive PCa (ICD10-C61) identified via national, population based cancer registries in Northern Ireland and Republic of Ireland. Questions included symptoms at diagnosis, primary treatments and physical symptoms (impotence/urinary incontinence/bowel problems/breast changes/loss of libido/hot flashes/fatigue) experienced 'ever' and at questionnaire completion ("current"). Symptom proportions were weighted by age, country and time since diagnosis. Bonferroni corrections were applied for multiple comparisons.
RESULTS: Adjusted response rate 54%; 75% reported at least one 'current' physical symptom ('ever':90%), with 29% reporting at least three. Prevalence varied by treatment; overall 57% reported current impotence; this was highest following radical prostatectomy (RP)76% followed by external beam radiotherapy with concurrent hormone therapy (HT); 64%. Urinary incontinence (overall 'current' 16%) was highest following RP ('current'28%, 'ever'70%). While 42% of brachytherapy patients reported no 'current' symptoms; 43% reported 'current' impotence and 8% 'current' incontinence. 'Current' hot flashes (41%), breast changes (18%) and fatigue (28%) were reported more often by patients on HT.
CONCLUSION: Symptoms following prostate cancer are common, often multiple, persist long-term and vary by treatment. They represent a significant health burden. An estimated 1.6% of men over 45 is a prostate cancer survivor currently experiencing an adverse physical symptom. Recognition and treatment of physical symptoms should be prioritised in patient follow-up. This information should facilitate men and clinicians when deciding about treatment as differences in survival between radical treatments is minimal.

Synthesis of new Aβ-ligands useful in diagnosis of Alzheimer's disease

Alzheimer’s disease is a chronic progressive neurodegenerative disease and is the most common form of dementia (estimated 50−60% of all cases), associated with loss of memory (in particular episodic memory), cognitive decline, and behavioural and physical disability, ultimately leading to death. Alzheimer’s disease is a complex disease, mostly occurring sporadically with no apparent inheritance and being the age the main risk factor. The production and accumulation of amyloid-beta peptide in the central nervous system is a key event in the development of Alzheimer’s disease. This project is devoted to the synthesis of amyloid-beta ligands, fluorophores and blood brain barrier-transporters for diagnosis and therapy of Alzheimer’s disease. Different amyloid-beta ligands will be synthesized and their ability to interact with amyloid-beta plaques will be studied with nuclear magnetic resonance techniques and a process of lead optimization will be performed. Many natural and synthetic compounds able to interact as amyloid-beta ligands have been identified. Among them, a set of small molecules in which aromatic moieties seem to play a key role to inhibit amyloid-beta aggregation, in particular heteroaromatic polycyclic compounds such as tetracyclines. Nevertheless tetracyclines suffer from chemical instability, low water solubility and possess, in this contest, undesired anti-bacterial activity. In order to overcome these limitations, one of our goals is to synthesize tetracyclines analogues bearing a polycyclic structure with improved chemical stability and water solubility, possibly lacking antibacterial activity but conserving the ability to interact with amyloid-beta peptides. Known tetracyclines have in common a fourth cycle without an aromatic character and with different functionalisations. We aim to synthesize derivatives in which this cycle is represented by a sugar moiety, thus bearing different derivatisable positions or create derivatives in which we will increase or decrease the number of fused rings. In order to generate a potential drug-tool candidate, these molecules should also possess the correct chemical-physical characteristics. The glycidic moiety, not being directly involved in the binding, it assures further possible derivatizations, such as conjugation to others molecular entities (nanoparticles, polymeric supports, etc.), and functionalization with chemical groups able to modulate the hydro/lipophilicity. In order to be useful such compounds should perform their action within the brain, therefore they have to be able to cross the blood brain barrier, and to be somehow detected for diagnostic purposes.

New approaches for the diagnosis of human papillomavirus infection:relevance for clinical practice and cancer prevention

Tese de doutoramento, Biologia (Microbiologia), Universidade de Lisboa, Faculdade de Ciências, 2014

Physical therapy with drug treatment in bell palsy: a focused review

ABSTRACT: The physical therapy (PT) associated with standard drug treatment (SDT) in Bell palsy has never been investigated. Randomized controlled trials or quasirandomized controlled trials have compared facial PT (except treatments such as acupuncture and osteopathic) combined with SDT against a control group with SDT alone. Participants included those older than 15 yrs with a clinical diagnosis of Bell palsy, and the primary outcome measure was motor function recovery by the House-Brackmann scale. The methodologic quality of each study was also independently assessed by two reviewers using the PEDro scale. Four studies met the inclusion criteria. Three trials indicate that PT in association with SDT supports higher motor function recovery than SDT alone between 15 days and 1 yr of follow-up. On the other hand, one trial showed that electrical stimulation added to conventional PT with SDT did not influence treatment outcomes. The present review suggests that the current practice of Bell palsy treatment by PT associated with SDT seems to have a positive effect on grade and time recovery compared with SDT alone. However, there is very little quality evidence from randomized controlled trials, and such evidence is insufficient to decide whether combined treatment is beneficial in the management of Bell palsy.