Number of non‐diabetic drugs: a simple comorbidity indicator for diabetes?

Introduction: The number of nondiabetic drugs, taken by a patient with diabetes at any one point in time, has been validated in previous studies as a comorbidity indicator.Aim: The aim of the paper is to examine the relationship between this comorbidity indicator and health status in people with Type 2 diabetes.Method: The analysis presented is from a prospective cohort study of people with Type 2 diabetes before and after commencing insulin therapy, with simultaneous collection of health status, clinical and other comparative data. Results: Of the 48 people for whom both health status and drug data were available, 26 (54%) were taking at least one nondiabetic drug and 16 (33%) were taking 3 or more nondiabetic drugs, at the baseline assessment. There were no significant relationships between the number of nondiabetic drugs taken, and age, duration of diabetes or baseline HbA₁c measurements. However, there were statistically significant relationships between the number of nondiabetic drugs and health status, in terms of depression and physical function.Conclusion: Drug data are routinely recorded in primary care and therefore the number of nondiabetic drugs is a potentially widely available indicator. This indicator could be a useful, simple addition to datasets that not only proxies comorbidity but also relates to patients' physical function and depression status.     

Phase 2 study of bevacizumab plus carboplatin/nab-paclitaxel followed by bevacizumab plus nab‐paclitaxel for non‐squamous non‐small cell lung cancer with malignant pleural effusion

Investigational New Drugs - Objectives Vascular endothelial growth factor plays an important role in the pathogenesis of malignant pleural effusion (MPE). We previously showed the efficacy of...     

Sharp transients in the EEGs of non‐epileptic adult patients receiving sevoflurane

Objective: In this article unexpected EEG findings are described which were observed during EEG monitoring under sevoflurane anesthesia.Method: In seven nonepileptic adult patients sevoflurane was administered as inhalation anesthetic during routinely performed surgical operations. The EEG was recorded continuously as part of the standard monitoring process and served mainly as a dosage guide for anesthetics/narcotics.Main outcome measure: Occurrence of sharp transients in the EEG resembling distinctive waves which can be seen in epileptic disorders.Results: In six of the seven patients under 8.0 % sevoflurane, sharp transients were observed which appeared in very deep EEG stages, mostly with endtidal sevoflurane concentrations of 4.8 5.9 %. The findings are in accordance with observations in nonepileptic children from our clinic.Conclusions: The clinical significance of the observed EEG pattern under sevoflurane anesthesia is still unclear. Taking into consideration that convulsive and nonconvulsive status epilepticus can be followed by signs of brain damage, it would appear to be important to further investigate the phenomenon.     

Differences in perimenstrual symptoms between cocaine‐abusing and non‐cocaine‐abusing women

Cocaine abuse among women has become a major health problem in the United States, yet there is little information in the literature concerning the effects of this form of substance abuse on a woman's reproductive system. This study of 65 women in residential treatment for cocaine abuse and 65 non‐cocaine‐abusing women was undertaken to determine if there are differences in frequency or severity of perimenstrual symptoms between these two groups of women. Data were collected by questionnaire and included demographics, a substance use history, and the Menstrual Distress Questionnaire developed by Moos. Findings suggested that there are statistically significant differences in frequency and severity of perimenstrual symptoms between the two groups of women.     

Are systemic levels of non steroidal anti inflammatory drugs relevant to acute upper gastrointestinal haemorrhage?

Summary It is uncertain as to the extent which gastrointestinal (GI) haemorrhage related to NSAIDs is due to a local, topical effect or to an action related to systemic absorption. We hypothesised that, should systemic drug concentrations be of importance, plasma levels of NSAIDs might be higher in patients who had developed GI haemorrhage, from controls who had not.Ten patients with GI haemorrhage, who had ingested piroxicam (and no other NSAID), within the preceding 64 h, at the same dosage and on no new medication for the past 14 days, had blood taken at presentation for measurement of piroxicam concentrations. Plasma piroxicam concentrations were measured in 19 community dwelling controls, matched for age ±8 years, gender, daily piroxicam dosage, and time from last dose as their respective index case. All had been taking piroxicam for at least 3 months, and none had experienced GI adverse effects. Median plasma piroxicam concentrations in patients at 8.27 g/l, was higher than in controls at 5.06 g/l.These results suggest that a systemic component, at least with piroxicam, may play a significant (though not necessarily exclusive) role in causing major gastrointestinal haemorrhage.     

A review of the benefit–risk profile of gefitinib in Asian patients with advanced non‐small‐cell lung cancer

ABSTRACT

Background: Improvements in first-line therapy of advanced non-small-cell lung cancer (NSCLC) have increased the need for effective second-line treatment options. In a Phase II trial of the anticancer drug gefitinib (IRESSA), greater efficacy was observed in Japanese compared with non-Japanese patients. Furthermore, results from a placebo-controlled Phase III trial (IRESSA Survival Evaluation in Lung cancer [ISEL]) showed that treatment with gefitinib was not associated with a statistically significant improvement in survival in either the overall or adenocarcinoma co-primary populations, although there was marked heterogeneity in survival outcomes between patient groups, with patients of Asian origin achieving a significant survival benefit with gefitinib compared with placebo.

Objective: To review the benefit:risk profile of gefitinib in Asian patients with advanced NSCLC.

Research design and methods: We identified and reviewed 31 reports (each with ≥ 25 patients) of clinical experience with gefitinib 250?mg/day in Asia involving a total of > 2000 patients with refractory NSCLC in Japan, China, Korea and Taiwan by searching EMBASE and Medline databases for publications between 1 January 2003 and 1 July 2005.

Results and discussion: In the majority of these reports, objective response rates of > 25% and disease control rates of > 60% have been described. Treatment with gefitinib resulted in a median time to progression of > 3 months and a median survival time of > 6 months in most studies. These 31 reports also demonstrated the efficacy of gefitinib in patients with secondary brain metastases, those with poor performance status (PS) and in patients receiving the drug as first-line treatment. Female gender, adenocarcinoma histology, non-smoking history, good PS and the presence of multiple lung metastases are associated with improved responsiveness to gefitinib. Reflecting the results of previous clinical trials, the reports indicate that gefitinib is generally well tolerated by Asian patients. The incidence of interstitial lung disease appears to be higher in Japanese than non-Japanese patients, although the reasons for this are not clear. Recent findings regarding cellular and genetic factors that may underlie the increased responsiveness to gefitinib among Asian patients are discussed.     

Intravesical delivery of 5‐aminolevulinic acid from water‐in‐oil nano/submicron‐emulsion systems

The present work reports on the development of water‐in‐oil (w/o) emulsions for the intravesical administration of 5‐aminolevulinic acid (ALA). The physicochemical properties of droplet size, zeta potential, and viscosity of the emulsions are characterized and the ability of the emulsions to release ALA following in vitro application is tested. The delivery systems are administered intravesically for 1 and 3 h in rats to examine the drug accumulation in bladder tissue. The mean size and zeta potential of the emulsions are 50–200 nm and ?3 to ?14 mV, respectively. The loading of ALA into the emulsions resulted in a slower and sustained release. The release extent was found to be inversely related to the droplet size of the emulsions. The emulsions did not increase the drug permeation into tissues during short exposure duration (1 h). When the dwell time was extended to 3 h, the systems showed a 2.7‐fold increase in the ALA concentration in the bladder wall. Images of confocal laser scanning microscopy demonstrated a higher and deeper fluorescence signal, with emulsion administration, as compared to the aqueous control. Intravesical emulsion delivery provides a significant advantage for drugs targeting bladder tissues. © 2009 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 99: 2375–2385, 2010     

Does celecoxib improve the efficacy of chemotherapy for advanced non‐small cell lung cancer?

Aims

Clinical trials have reported conflicting results about whether celecoxib plus chemotherapy improves outcomes over chemotherapy alone in patients with advanced non‐small cell lung cancer.

Methods

We performed a meta‐analysis comparing the primary and secondary endpoints of treatment with celecoxib plus chemotherapy vs. chemotherapy alone in patients with advanced non‐small cell lung cancer.

Results

Six eligible trials (1181 patients) were selected from the 206 studies that were identified initially. A significant difference, favouring celecoxib plus chemotherapy over chemotherapy alone, was observed in the overall response rate [odds ratio (OR) 1.34; 95% confidence interval (CI) 1.08, 1.67; P = 0.009). However, there was no difference in the 1‐year survival rate (OR 1.08; 95% CI 0.86, 1.35; P = 0.512), clinical benefit (OR 1.05; 95% CI 1.88, 1.25; P = 0.613), complete response (OR 0.77; 95% CI 0.39, 1.51; P = 0.446) or partial response (OR 1.22; 95% CI 0.92, 1.63; P = 0.163). Toxicity did not differ significantly with the exception of the occurrence of leucopenia and thrombocytopenia.

Conclusions

Celecoxib plus chemotherapy appeared to improve the overall response rate compared with chemotherapy alone in the treatment of patients with advanced non‐small cell lung cancer. Further prospective randomized controlled trials are now needed.     

The law of mass action and the pharmacological concentration–effect curve: resolving the paradox of apparently non‐dose‐related adverse drug reactions

Background

Adverse drug reactions are sometimes described as being ‘non‐dose‐related’ because no relationship has been found between increasing doses and either the intensity of the response or the proportion of individuals in whom the response occurs; furthermore, hypersensitivity reactions are often regarded as being non‐dose‐related, even if different doses have not been studied. However, the law of mass action implies that all pharmacological effects are concentration related and should increase in intensity with increasing dose. We set out to explain this paradox.

Methods

We searched for published adverse drug reactions that have been described as non‐dose‐related and analysed them.

Results

We identified four categories of explanations that resolve the paradox: (i) the reaction is not real; it may have occurred by chance or there may be methodological problems, such as bias or confounding factors; (ii) the dose–response curve for the adverse effect reaches a maximum at doses lower than were studied (i.e. a hypersusceptibility reaction); this underpins the use of test doses to predict the possibility of an adverse reaction at therapeutic doses; (iii) susceptibility to the adverse reaction differs widely among individuals; and (iv) imprecision or inaccuracy in the measurement of either dose or effect obscures dose responsiveness. This last explanation encompasses: (a) reactions related to cumulative dose; (b) dissociation between dose and concentration through saturable pharmacokinetics; and (c) variability in the measurement of the effect.

Conclusions and implications

If an adverse drug reaction appears to be non‐dose‐related, the reasons should be sought, having these mechanisms in mind.     

French general practitioners' attitudes and prescription patterns toward buprenorphine maintenance treatment: does doctor shopping reflect buprenorphine misuse?

This study investigated attitudes toward buprenorphine maintenance treatment (BMT) among general practitioners (GPs) and their maintained patients' propensity to turn to several prescribers (doctor shopping), among a sample of 345 GPs prescribing BMT in South-Eastern France. Survey data were anonymously matched to administrative data that provided information about GPs' patients. A simultaneous equation model suggests that GPs' attitude influenced doctor shopping, not the reverse. Doctor shopping was lower among GPs who reported inducting BMT with 8 mg of buprenorphine per day or more, and was higher for GPs endorsing a stringent attitude toward patients. Thus doctor shopping should not be understood exclusively as a deviant behaviour. It is partially physician-driven, and further research is needed to assess whether it reflects patients' dissatisfaction toward inappropriate care supply and the difficulty to establish a good therapeutic relationship between an opiate-dependent patient and a general practitioner.