Metformin use and survival after colorectal cancer: A population-based cohort study.

Preclinical evidence suggests that metformin could delay cancer progression. Previous epidemiological studies however have been limited by small sample sizes and certain time-related biases. This study aimed to investigate whether colorectal cancer patients with type 2 diabetes who were exposed to metformin had reduced cancer-specific mortality. We conducted a retrospective cohort study of 1,197 colorectal cancer patients newly diagnosed from 1998 to 2009 (identified from English cancer registries) with type 2 diabetes (based upon Clinical Practice Research Datalink, CPRD, prescription and diagnosis records). In this cohort 382 colorectal cancer-specific deaths occurred up to 2012 from the Office of National Statistics (ONS) mortality data. Metformin use was identified from CPRD prescription records. Using time-dependent Cox regression models, unadjusted and adjusted hazard ratios (HR) and 95% CIs were calculated for the association between post-diagnostic exposure to metformin and colorectal cancer-specific mortality. Overall, there was no evidence of an association between metformin use and cancer-specific death before or after adjustment for potential confounders (adjusted HR 1.06, 95% CI 0.80, 1.40). In addition, after adjustment for confounders, there was also no evidence of associations between other diabetic medications and cancer-specific mortality including sulfonylureas (HR 1.14, 95% CI 0.86, 1.51), insulin use (HR 1.35, 95% CI 0.95, 1.93) or other anti-diabetic medications including thiazolidinediones (HR 0.73, 95% CI 0.46, 1.14). Similar associations were observed by duration of use and for all-cause mortality. This population-based study, the largest to date, does not support a protective association between metformin and survival in colorectal cancer patients.

Enzyme-induced Aggregation of Plasmonic Nanoparticles for the Development of Label-free and Ultrasensitive Detection of Bacterial DNA

Sensitive detection of pathogens is critical to ensure the safety of food supplies and to prevent bacterial disease infection and outbreak at the first onset. While conventional techniques such as cell culture, ELISA, PCR, etc. have been used as the predominant detection workhorses, they are however limited by either time-consuming procedure, complicated sample pre-treatment, expensive analysis and operation, or inability to be implemented at point-of-care testing. Here, we present our recently developed assay exploiting enzyme-induced aggregation of plasmonic gold nanoparticles (AuNPs) for label-free and ultrasensitive detection of bacterial DNA. In the experiments, AuNPs are first functionalized with specific, single-stranded RNA probes so that they exhibit high stability in solution even under high electrolytic condition thus exhibiting red color. When bacterial DNA is present in a sample, a DNA-RNA heteroduplex will be formed and subsequently prone to the RNase H cleavage on the RNA probe, allowing the DNA to liberate and hybridize with another RNA strand. This continuously happens until all of the RNA strands are cleaved, leaving the nanoparticles ‘unprotected’. The addition of NaCl will cause the ‘unprotected’ nanoparticles to aggregate, initiating a colour change from red to blue. The reaction is performed in a multi-well plate format, and the distinct colour signal can be discriminated by naked eye or simple optical spectroscopy. As a result, bacterial DNA as low as pM could be unambiguously detected, suggesting that the enzyme-induced aggregation of AuNPs assay is very easy to perform and sensitive, it will significantly benefit to development of fast and ultrasensitive methods that can be used for disease detection and diagnosis.

Differential Pharmacokinetics of Digoxin in Elderly Patients

Digoxin remains one of the most commonly prescribed of all cardiac medications. The main indications for digoxin usage include atrial fibrillation and heart failure; both these conditions are more prevalent in older patients. Given the aging population and the increasing incidence of heart failure we would expect prescribing of digoxin to remain as frequent or to even increase in older patients. Older patients are also more likely to develop toxicity and diagnosis of digoxin toxicity can be difficult in this group. Numerous components contribute to the development of toxicity in older patients, ranging from aging-related changes in renal function or body mass to polypharmacy and possible interactions with digoxin. It is therefore important to understand how the pharmacokinetics of digoxin may be altered in the older population. Application of basic pharmacological principles may be helpful in anticipating these problems. This review describes the pharmacokinetics of digoxin, the changes in pharmacokinetics with increasing age and how concomitant disease states or drug interactions may affect the pharmacokinetics of digoxin. Greater knowledge about the causes and prevention of digoxin toxicity should further reduce the morbidity and mortality arising from digoxin toxicity, especially in the elderly population.
For over 200 years debate has raged regarding the use of digitalis glycosides in cardiac disease. At present digoxin is the most commonly prescribed digitalis compound. This review describes the pharmacokinetics of digoxin and in particular how they are altered with increasing age. When considering the elderly population it is important to recognise the heterogeneity of response in this group, therefore there are no rules, with regards to prescribing, that can apply to the entire elderly population.

The inferential monitoring of the screw disturbance torque to predict process fluctuations in polymer extrusion

Polymer extrusion is one of the major methods of processing polymer materials and advanced process monitoring is important to ensure good product quality. However, commonly used process monitoring devices, e.g. temperature and pressure sensors, are limited in providing information on process dynamics inside an extruder barrel. Screw load torque dynamics, which may occur due to changes in solids conveying, melting, mixing, melt conveying, etc., are believed to be a useful indicator of process fluctuations inside the extruder barrel. However, practical measurement of the screw load torque is difficult to achieve. In this work, inferential monitoring of the screw load torque signal in an extruder was shown to be possible by monitoring the motor current (armature and/or field) and simulation studies were used to check the accuracy of the proposed method. The ability of this signal to aid identification and diagnosis of process issues was explored through an experimental investigation. Power spectral density and wavelet frequency analysis were implemented together with a covariance analysis. It was shown that the torque signal is dominated by the solid friction in the extruder and hence it did not correlate well with melting fluctuations. However, it is useful for online identification of solids conveying issues.

Economic aspects of pharmacotherapy for chronic constipation

Constipation is one of the most common digestive complaints. It is a symptom, not a disease. The subjectivity that this involves means that assessments of clinical epidemiology, socioeconomic costs and pharmacotherapy are difficult, since there is no definition of 'normal' bowel habit. Although constipation can affect all ages, the problem increases with age, and is of particular concern for those who are frail and in long term care. Cultural influences may affect the prevalence in older people. Drug therapy of constipation cannot be considered in isolation, since there are issues in the prevention of constipation and the principles of good management that also apply. Furthermore, some consideration of the pathophysiology and diagnosis is important. This is because a number of remediable causes can be identified, and the diagnostic process involves patient education, which in turn may be effective in reducing costs. It is the complaint of constipation which leads either to self-medication or to consultation with the medical profession. Both of these courses of action have a significant influence on utilisation of laxatives (cathartics), obtained both over-the-counter and by prescription. Although there are a large number of laxative preparations available, therapy has changed little in half a century. Costs may vary considerably, and with such a significant problem there is a need for comparative studies. However, study methodologies are difficult, and a significant placebo response may be found. Education and preventive measures have been shown to reduce laxative use and costs in institutions. Unfortunately, there are few comparative studies of individual laxatives and even fewer cost-effectiveness studies. Those that there are have been based in institutions, and so extrapolation to other situations may be difficult. In general, little attention is given to constipation. It is, however, an area with significant resource implications in which education and preventive measures have been shown to be beneficial. Even so, there is still a need for good comparative studies, particularly where cost effectiveness is concerned.

Microneedle-Mediated Minimally Invasive Patient Monitoring

Background: The emerging field of microneedle-based minimally invasive patient monitoring and diagnosis is reviewed. Microneedle arrays consist of rows of micron-scale projections attached to a solid support. They have been widely investigated for transdermal drug and vaccine delivery applications since the late 1990s. However, researchers and clinicians have recently realized the great potential of microneedles for extraction of skin interstitial fluid and, less commonly, blood, for enhanced monitoring of patient health.

Methods: We reviewed the journal and patent literature, and summarized the findings and provided technical insights and critical analysis.

Results: We describe the basic concepts in detail and extensively review the work performed to date.

Conclusions: It is our view that microneedles will have an important role to play in clinical management of patients and will ultimately improve therapeutic outcomes for people worldwide.

Use of eye care services among diabetic patients in urban Indonesia.

OBJECTIVES:

To assess the use of eye care and its predictors among diabetic patients in Indonesia.

METHODS:

Diabetic patients aged 18 years and older were recruited consecutively from a university clinic and 2 community clinics in Jakarta, Indonesia. Information obtained by questionnaire and record review included demographic and socioeconomic status, knowledge about diabetic retinopathy, and ocular and medical history. The main outcome was self-reported or record history of an eye examination by an eye care professional with dilation of the pupil within the preceding year.

RESULTS:

Among 196 participants (mean [SD] age, 58.4 [9.4] years; 61.5% female), 166 (84.7%) had not undergone ocular examination in the last year, including 100 of 119 patients (84.0%) at the university clinic. Fewer than half (82 of 166 [49.4%]) of all patients reported being told of the need for eye examinations by their physician. In regression analyses, factors associated with having an eye examination were higher diabetic retinopathy knowledge score (odds ratio = 1.52; P = .01) and years since being diagnosed as having diabetes (odds ratio = 1.71 for third vs first tertile; P = .02). Education, income, health insurance status, and diagnosis of diabetic retinopathy were not predictive of examination. The most common reasons given by subjects for not having had eye examinations concerned lack of knowledge about the need for care (97 of 160 subjects [60.6%]), while financial barriers were cited by only 22 of 160 subjects (13.8%).

CONCLUSION:

The low proportion of diabetic subjects receiving recommended annual eye examinations in Indonesia might be improved through patient and physician education.