Predictors of refusal to participate: a longitudinal health survey of the elderly in Australia

Background

The loss of participants in longitudinal studies due to non-contact, refusal or death can introduce bias into the results of such studies. The study described here examines reasons for refusal over three waves of a survey of persons aged ≥ 70 years.

Methods

In a longitudinal study involving three waves, participants were compared to those who refused to participate but allowed an informant to be interviewed and to those who refused any participation.

Results

At Wave 1 both groups of Wave 2 non-participants had reported lower occupational status and fewer years of education, had achieved lower verbal IQ scores and cognitive performance scores and experienced some distress from the interview. Those with an informant interview only were in poorer physical health than those who participated and those who refused. Depression and anxiety symptoms were not associated with non-participation. Multivariate analyses found that verbal IQ and cognitive impairment predicted refusal. Results were very similar for refusers at both Waves 2 and 3.

Conclusions

Longitudinal studies of the elderly may over estimate cognitive performance because of the greater refusal rate of those with poorer performance. However, there is no evidence of bias with respect to anxiety or depression.     

Biofeedback in patients with ileoanal pouch dysfunction: a specialist centre experience

Objectives: To report outcomes following biofeedback for functional problems associated with an ileoanal pouch. Incontinence and evacuatory disorders associated with the ileoanal pouch can be particularly problematic and difficult to treat using conventional therapies. Biofeedback therapy is a behavioural treatment that offers a non-surgical approach as an alternative or adjunct for patients.

Materials and methods: This was a retrospective single centre study. We reviewed the notes of all patients attending for biofeedback at our institution between January 2012 and October 2017 and identified all those that did so for ileoanal pouch related problems. We recorded patient reported subjective improvements following biofeedback. The validated International Consultation on Incontinence Questionnaire was used to assess improvement in incontinent symptoms and the evacuatory disorder questionnaire was used to assess improvement in evacuatory disorders.

Results: Twenty-six patients with ileoanal pouch related problems underwent biofeedback. Based on patients’ feedback at next clinical encounter following biofeedback, nine reported much improvement, 11 reported some improvement and six reported no improvement. In the group treated for incontinence, quality of life improved significantly from a median pre-treatment score of 80 to a post-treatment score of 41 (p?=?.01). Biofeedback reduced pain, bloating straining and laxative use in patients with evacuatory disorders.

Conclusions: Biofeedback may be associated with significant improvement in quality of life as well as possible improvements in symptoms related to both incontinence and evacuatory disorders. It is probably an underused service. Further larger prospective studies are required to properly assess the efficacy of biofeedback in ileoanal pouch related dysfunction.     

Antitumor activities and on‐target toxicities mediated by a TRAIL receptor agonist following cotreatment with panobinostat

The recent development of novel targeted anticancer therapeutics such as histone deacetylase inhibitors (HDACi) and activators of the TRAIL pathway provide opportunities for the introduction of new treatment regimens in oncology. HDACi and recombinant TRAIL or agonistic anti‐TRAIL receptor antibodies have been shown to induce synergistic tumor cell apoptosis and some therapeutic activity in vivo. Herein, we have used syngeneic preclinical models of human solid cancers to demonstrate that the HDACi panobinostat can sensitize tumor cells to apoptosis mediated by the anti‐mouse TRAIL receptor antibody MD5‐1. We demonstrate that the combination of panobinostat and MD5‐1 can eradicate tumors grown subcutaneously and orthotopically in immunocompetent mice, while single agent treatment has minimal effect. However, escalation of the dose of panobinostat to enhance antitumor activity resulted in on‐target MD5‐1‐mediated gastrointestinal toxicities that were fatal to the treated mice. Studies performed in mice with knockout of the TRAIL receptor showed that these mice could tolerate doses of the panobinostat/MD5‐1 combination that were lethal in wild type mice resulting in superior tumor clearance. Given that clinical studies using HDACi and activators of the TRAIL pathway have been initiated, our preclinical data highlight the potential toxicities that could limit the use of such a treatment regimen. Our studies also demonstrate the power of using syngeneic in vivo tumor models as physiologically relevant preclinical systems to test the antitumor effects and identify potential side effects of novel anticancer regimens.     

Diabetes and its effects on wound healing

This article discusses the reasons why wounds in people with diabetes take longer to heal and are more susceptible to complications. The physiology of the wound healing process, and how this is affected by diabetes, is outlined. The article also explains why wounds in patients with diabetes are more prone to infection and discusses preventive measures.     

Lymphangiogenesis and cancer

Historically, lymphatic vessels were considered passive participants in tumor metastasis by simply providing channels for tumor cells to transit to draining lymph nodes. The discovery of several key lymphatic-specific molecular markers and an increased availability of in vitro and in vivo experimental systems to study lymphatic biology have however highlighted a much more complex, active role for the lymphatic vasculature in metastatic tumor spread. This review will briefly describe the lymphatic system and lymphangiogenesis and then focus on the role of the lymphatic system in cancer metastasis. The progression of our understanding from the lymphatic system as a somewhat passive conduit for metastasis to an active participant in metastatic tumor dissemination, regulated by a complex array of lymphangiogenic factors, chemokines, and immune cell subsets, will be described.     

A Herpesvirus saimiri-based vector expressing TRAIL induces cell death in human carcinoma cell lines and multicellular spheroid cultures

Herpesvirus saimiri (HVS) is capable of infecting a range of human carcinoma cell types with high efficiency and the viral genome persists as high copy number, circular, non-integrated episomes which segregate to progeny upon cell division. This allows HVS-based vectors to stably transduce a dividing cell population and provide sustained transgene expression for an extended period of time both in vitro and in vivo. Moreover, the insertion of a bacterial artificial chromosome cassette into the HVS genome simplifies the incorporation of large amounts of heterologous DNA for gene delivery. Herein we have produced a recombinant HVS-based vector containing full-length human TRAIL under the control of the α-survivin promoter, and subsequently challenged a variety of cancer cell lines with this vector. The TRAIL transgene was expressed in infected colorectal SW480 cells, causing considerable apoptosis induction. Apoptosis was also observed when several other cancer cell lines derived from different tissues were infected. Moreover, co-treatment with Jak inhibitor AG490 led to the disruption of spheroid cultures grown from the melanoma Mel888 line. These data suggest that an HVS gene therapy vector expressing TRAIL could be an effective treatment against cancer.     

Urine pH is an indicator of dietary acid-base load, fruit and vegetables and meat intakes: results from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk population study

Evidence exists that a more acidic diet is detrimental to bone health. Although more precise methods exist for measurement of acid-base balance, urine pH reflects acid-base balance and is readily measurable but has not been related to habitual dietary intake in general populations. The present study investigated the relationship between urine pH and dietary acid-base load (potential renal acid load; PRAL) and its contributory food groups (fruit and vegetables, meats, cereal and dairy foods). There were 22,034 men and women aged 39-78 years living in Norfolk (UK) with casual urine samples and dietary intakes from the European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk FFQ. A sub-study (n 363) compared pH in casual samples and 24 h urine and intakes from a 7 d diary and the FFQ. A more alkaline diet (low PRAL), high fruit and vegetable intake and lower consumption of meat was significantly associated with a more alkaline urine pH before and after adjustment for age, BMI, physical activity and smoking habit and also after excluding for urinary protein, glucose, ketones, diagnosed high blood pressure and diuretic medication. In the sub-study the strongest relationship was found between the 24 h urine and the 7 d diary. In conclusion, a more alkaline diet, higher fruit and vegetable and lower meat intake were related to more alkaline urine with a magnitude similar to intervention studies. As urine pH relates to dietary acid-base load its use to monitor change in consumption of fruit and vegetables, in individuals, warrants further investigation.