Chemoprevention of colorectal cancer with nonsteroidal anti‐inflammatory drugs

Colorectal carcinoma is one of the commonest solid organ tumors in the world and its prevalence appears to be increasing in Asia. Recently, there has been much interest in various chemotherapeutic agents for the management of this condition, in particular nonsteroidal anti‐inflammatory drugs (NSAIDs). There is a large amount of data that suggest traditional NSAIDs, as well as the new cyclooxygenase (COX)‐2 selective inhibitors such as rofecoxib and celecoxib, have a role in the setting of primary and secondary prevention, and adjuvant therapy of both sporadic colorectal carcinoma and familial adenomatous polyposis. This review examines some of this data, as well as the potential problems and limitations of using these agents, particularly in light of the recent withdrawal of rofecoxib.     

Fight or flight: the ethics of emergency physician disaster response

Most disaster plans depend on using emergency physicians, nurses, emergency department support staff, and out-of-hospital personnel to maintain the health care system's front line during crises that involve personal risk to themselves or their families. Planners automatically assume that emergency health care workers will respond. However, we need to ask: Should they, and will they, work rather than flee? The answer involves basic moral and personal issues. This article identifies and examines the factors that influence health care workers' decisions in these situations. After reviewing physicians' response to past disasters and epidemics, we evaluate how much danger they actually faced. Next, we examine guidelines from medical professional organizations about physicians' duty to provide care despite personal risks, although we acknowledge that individuals will interpret and apply professional expectations and norms according to their own situation and values. The article goes on to articulate moral arguments for a duty to treat during disasters and social crises, as well as moral reasons that may limit or override such a duty. How fear influences behavior is examined, as are the institutional and social measures that can be taken to control fear and to encourage health professionals to provide treatment in crisis situations. Finally, the article emphasizes the importance of effective risk communication in enabling health care professionals and the public to make informed and defensible decisions during disasters. We conclude that the decision to stay or leave will ultimately depend on individuals' risk assessment and their value systems. Preparations for the next pandemic or disaster should include policies that encourage emergency physicians, who are inevitably among those at highest risk, to "stay and fight."     

Labetalol and Propranolol in Mild Hypertensives: Comparison of Blood Pressure and Plasma Volume Effects

Summary: Labetalol and propranolol in mild hypertensives: Comparison of blood pressure and plasma volume effects. S. N. Hunyor, G. E. Bauer, M. Ross and H. Larkin, Aust. N.Z. J. Med ., 1980, 10, pp. 162–166.
Labetalol administered in a small to moderate dose (first month 400 mg/day, second month average 585 mg/day) was effective in lowering blood pressure (BP) (-21/-18 mmHg, recumbent) in 11 of 13 mild essential hypertensives over an eight-week period, despite a significant (+294 ml) increase in plasma volume. The effect of propranolol (first month 160 mglday, second month average 234 mg/day) was significantly less on both blood pressure (-9/-9 mmHg) and plasma volume (+98 ml), although the pre-propranolol BP was lower and the final BP achieved on the two medications was comparable (labetalol 147/89 mmHg, propranolol 145/89
Six patients who continued labetalol for periods of up to 14 months had persistent plasma volume expansion. Three of these, taking a higher dose of labetalol, developed resistance to the drug's antihypertensive effect. Addition of a diuretic restored antihypertensive efficacy and led to a fall in plasma volume. No such plasma volume expansion was seen in six patients who were followed on long term propranolol therapy
Some plasma volume expansion with the combined alpha- beta-adrenoceptor blocker labetalol may be appropriate to its vasodilator action. Provided this effect is not excessive, it appears not to lead to resistance to its antihypertensive action. Small to moderate doses of labetalol would, therefore, seem effective without concomitant diuretic. Such sole use of labetalol could help minimise orthostatic symptoms which can be a major side effect of combination therapy     

Relationship of Urologic Complications With Health-Related Quality of Life and Perceived Value of Health in Men and Women With Type 1 Diabetes: The Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications (DCCT/EDIC) Cohort

OBJECTIVE

Limited information exists about the influence of urologic complications on health-related quality of life (HRQOL) in patients with type 1 diabetes.

RESEARCH DESIGN AND METHODS

We studied 664 men and 580 women from the Diabetes Control and Complications Trial/Epidemiology of Interventions and Complications Study: mean ages were 51.6 ± 6.6 and 50.6 ± 7.2 years and duration of diabetes was 29.5 ± 4.8 and 29.8 ± 5.1 years, respectively. We assessed associations of sexual dysfunction, lower urinary tract symptoms (LUTS), and, in women, urinary incontinence (UI) with general quality of life (SF-36), perceived value of health (EuroQol-5), diabetes-related quality of life (Diabetes Quality of Life Scale [DQOL]), and psychiatric symptoms (Symptom Checklist 90-R).

RESULTS

In both men and women, urologic complications adversely affected HRQOL and psychiatric symptoms, even after accounting for history of depression leading to treatment. Multivariable analyses accounting for the presence of diabetic retinopathy, neuropathy, and nephropathy also revealed substantial independent effects. In men, for example, the odds (95% CI) of a low DQOL score (≤25th percentile) were 3.01 (1.90–4.75) times greater with erectile dysfunction and 2.65 (1.68–4.18) times greater with LUTS and in women, 2.04 (1.25–3.35) times greater with sexual dysfunction and 2.71 (1.72–4.27) times greater with UI/LUTS combined compared with men and women without such complications. Similar effects were observed for the other measures.

CONCLUSIONS

Sexual dysfunction and urinary complications with type 1 diabetes are associated with decreased quality of life and perceived value of health and with higher levels of psychiatric symptoms, even after accounting for other diabetes complications and depression treatment.     

Xenophagy in Helicobacter pylori‐ and Epstein–Barr virus‐induced gastric cancer

Helicobacter pylori and Epstein–Barr virus (EBV) account for roughly 80% and 10%, respectively, of gastric carcinomas worldwide. Autophagy is an evolutionarily conserved and intricately regulated cellular process that involves the sequestration of cytoplasmic proteins and organelles into double‐membrane autophagosomes that eventually fuse with lysosomes for degradation of the engulfed content. Emerging evidence indicates that xenophagy, a form of selective autophagy, plays a crucial role in the pathogenesis of H. pylori‐ and EBV‐induced gastric cancer. Xenophagy specifically recognizes intracellular H. pylori and EBV and physically targets these pathogens to the autophagosomal–lysosomal pathway for degradation. In this connection, H. pylori or EBV‐induced dysregulation of autophagy may be causally linked to gastric tumourigenesis and therefore can be exploited as therapeutic targets. This review will discuss how H. pylori and EBV infection activate autophagy and how these pathogens evade recognition and degradation by the autophagic pathway. Elucidating the molecular aspects of H. pylori‐ and EBV‐induced autophagy will help us better understand the pathogenesis of gastric cancer and promote the development of autophagy modulators as antimicrobial agents. Published by John Wiley & Sons, Ltd     

What are the critical incidents that affect how people cope with being detained under Section 136 of the Mental Health Act (1983, 2007)?

Abstract

Purpose: Section 136 (S136) of the Mental Health Act (1983, 2007) provides legislative powers for police officers to detain those suspected of being ‘mentally disordered’ for a mental health assessment. Despite its increasing use, there is currently little qualitative research exploring detainee’s experiences.

Methodology: Participants recruited from NHS places of safety participated in a semi-structured interview. The novel application of Critical Incident Technique (CIT) within this study enabled the specific identification of critical incidents which mental health service users thought had either helped with, or worsened the S136 detention experience. A wish list of absent factors was also gathered.

Findings: Six categories of helpful critical incidents, seven categories of unhelpful critical incidents and five categories of wish-list items were identified. The importance of authentic relationships underpinned many categories, as well as challenging stigma, considering previous detentions; and receiving practical support.

Originality/value: The outlined study is the first of its kind to utilise CIT methodology to specifically identify critical incidents related to the process of S136 detention. These findings provide specific ways to improve the experience of detention informed directly by those who have been directly subjected to S136.

• Key points

• Take time to invest in meaningful relationships with those who are detained; asking about the individual’s life experience and their perception of its relationship to their current presenting difficulties.

• Identify the service user’s values -what’s important to them, and what gives meaning to their life – and discuss this in relation to what their worries, concerns or wishes may be for treatment.

• Discuss previous experiences of involuntary admission- this can support all parties involved to consider the impact of detention upon the individual, and services.

• Use problem-free discussions to normalise and help de-stigmatise mental health difficulties and support rapport building.

• Provide practical support, such as food, drink and routinely allow those who are detained to gather personal belongings such as a change of clothes or a book.

• Ensure advocacy services are always available and accessible for those who are detained under S136.

• Where possible, avoid the use of restrictive or stigmatising practices in front of the public where possible (e.g. use of handcuffs, police vehicles as transport) to minimise risk of increasing mental health stigma.