Neuro-cognitive impairment in breast cancer patients: pharmacological considerations

Post-chemotherapy cognitive impairment has been an issue of concern in cancer survivors. While most reviews are focused on patient-related factors, it is proposed that drug-related factors may also be determinants. The objective of this review is to study the relationship between the types and dose intensities of chemotherapy regimens on cognitive impairment in breast cancer patients through a systematic literature search. Eighteen prospective studies were selected. The types, dose intensities and durations of chemotherapy regimens received by subjects were compared against prevalence results obtained in individual studies. It was observed that the duration of impairment varied across different generations of chemotherapy regimens. Concurrent administration of multiple cytotoxic agents can lead to a synergistic decline on cognition. Current clinical evidence is insufficient to evaluate the relationship between the types, dose intensities of chemotherapy regimens and cognitive impairment. More investigation is needed to examine the role of pharmacological factors in chemotherapy-associated cognitive changes.     

New insights into mechanisms of action of carvedilol treatment in chronic heart failure patients--a matter of time for contractility

BackgroundIt is unclear whether improvement in left ventricular (LV) ejection fraction (LVEF) following treatment with a combined α₁,β₁,β₂-blockade can be attributed to improvement in LV contractility, to a reduction in afterload, and/or to improvements in LV remodeling and chamber size. We aimed to examine whether the observed improvement in LVEF following carvedilol treatment is due to changes in intrinsic myocardial contractility beyond changes in LV chamber size or loading conditions.Methods and ResultsIn 49 consecutive patients with chronic heart failure (HF), LVEF ≤35%, NYHA functional class II–IV, on angiotensin-converting enzyme inhibitors but not on ß-blockers, LV contractile performance and remodeling were assessed by comprehensive echocardiography at baseline and after 3 and 6 months of treatment with carvedilol. Carvedilol treatment resulted in significant improvements in LVEF, shortening fraction, and velocity of circumferential shortening (VCF_c). There were no significant changes in the mean arterial blood pressure or systemic vascular resistance index; but LV end-systolic wall stress (LVESS), effective arterial elastance, ventriculoarterial coupling, and LV end-diastolic and end-systolic dimensions and volumes were significantly reduced. Estimated end-systolic elastance, VCF_c-to-LVESS ratio, and pulsatile arterial compliance significantly improved after 6 months of treatment with carvedilol. The slope of the VCF_c relationship to LVESS worsened from 0 to 3 months, but significantly improved from 3 to 6 months.ConclusionsDespite an initial transient negative inotropic effect from 0 to 3 months, carvedilol treatment was associated with a positive inotropic effect with significant improvement in load-independent indexes of myocardial contractility beyond what can be attributed to changes in LV chamber size and load after 3 months. There were no changes in systemic vascular resistance with carvedilol treatment; however, improvement in pulsatile arterial compliance and ventriculoarterial coupling suggested enhanced cardiac mechanoenergetic performance along with improved systemic arterial compliance.     

Psychology of earthquake-induced stress cardiomyopathy, myocardial infarction and non-cardiac chest pain

Aims: To compare psychological factors in patients presenting to hospital with earthquake‐induced stress cardiomyopathy, myocardial infarction (MI) and non‐cardiac chest pain. We hypothesised that patients with stress cardiomyopathy and non‐cardiac chest pain would be more psychologically vulnerable than those with MI. Methods: Cardiology admitting staff in the week following the September 2010 Christchurch earthquake prospectively identified patients with earthquake‐precipitated chest pain. Males were excluded. All consenting women met diagnostic criteria for one of the three conditions. Patients underwent a semistructured interview with a senior clinical psychologist who was blind to the cardiac diagnosis. Premorbid psychological factors, experience of the earthquake and psychological response were assessed using a range of validated tools. Results: Seventeen women were included in the study, six with stress cardiomyopathy, five with MI and six with non‐cardiac chest pain. Earthquake experiences were notably similar across the groups. Patients with non‐cardiac chest pain scored high on the hospital anxiety and depression scale, the health anxiety questionnaire, the Eysenck neuroticism scale and the Impact of Event scale. Women with stress cardiomyopathy scored as the most psychologically robust. Depression and extroversion scores were the same across groups. Conclusion: Our hypothesis was incorrect. Women with non‐cardiac chest pain following an earthquake have higher anxiety and neuroticism scores than women with either MI or stress cardiomyopathy. Stress cardiomyopathy following an earthquake is not specific to psychologically vulnerable women. The psychology of natural disaster‐induced stress cardiomyopathy may differ from that of sporadic cases.     

Effectiveness of the BDProbeTec ET system for detection of Mycobacterium tuberculosis complex in sputum and bronchoalveolar lavage specimens

ObjectiveThe diagnostic efficacy of the BDProbeTEC ET Mycobacterium tuberculosis (MTB) complex direct detection assay (DTB) performed on bronchoalveolar lavage (BAL) specimens and sputum smears was compared with acid-fast bacilli (AFB) smear microscopy.MethodAFB smear microscopy, DTB and culture results of 286 patients with pulmonary tuberculosis were retrospectively reviewed. A total of 120 patients provided expectorated sputum samples, and 166 patients provided BAL specimens. Culture results and clinical diagnosis were used as gold standards.ResultsThe sensitivity and specificity of the DTB assay in detecting MTB in sputum specimens was significantly higher compared to AFB smear microscopy (83.7% and 82.4%, vs. 75.6%, and 41.2%, respectively). The sensitivity and specificity of the DTB assay in detecting MTB in sputum samples was 77.2% and 100% compared to clinical diagnosis, while AFB smear had a sensitivity and specificity of 70.3% and 26.3%, respectively. Compared to culture, DTB had a sensitivity and specificity of 82.8% and 93.2%, respectively, in detecting MTB from BAL specimens; AFB smear had a sensitivity and specificity of 41.9% and 87.7%, respectively. Compared to clinical diagnosis, DTB had a sensitivity and specificity of 67.2% and 100%, respectively, in detecting MTB from BAL specimens; AFB smear had a sensitivity and specificity of 34.8% and 79.5%, respectively.ConclusionsThe superior performance of the DTB assay relative to AFB smear microscopy makes it a valuable tool to enable early diagnosis of MTB, thereby improving patient care and reducing transmission.     

Addressing different biases in analysing drug use on cancer risk in diabetes in non‐clinical trial settings—what,why and how?

Motivated by recent reports on associations between diabetes and cancer, many researchers have used administrative databases to examine risk association of cancer with drug use in patients with diabetes. Many of these studies suffered from major biases in study design and data analysis, which can lead to erroneous conclusions if these biases are not adjusted. This article discusses the sources and impacts of these biases and methods for correction of these biases. To avoid erroneous results, this article suggests performing sensitivity and specificity analysis as well as using a drug with a known effect on an outcome to ascertain the validity of the proposed methods. Using the Hong Kong Diabetes Registry, we illustrated the impacts of biases of drug use indication and prevalent user by examining the effects of statins on cardiovascular disease. We further showed that 'immortal time bias' may have a neutral impact on the estimated drug effect if the hazard is assumed to be constant over time. On the contrary, adjustment for 'immortal time bias' using time-dependent models may lead to misleading results biased towards against the treatment. However, artificial inclusion of immortal time in non-drug users to correct for immortal time bias may bias the result in favour of the therapy. In conclusion, drug use indication bias and prevalent user bias but not immortal time bias are major biases in the design and analysis of drug use effects among patients with diabetes in non-clinical trial settings.     

A systematic review on use of Chinese medicine and acupuncture for treatment of obesity

Obesity is a major health hazard and despite lifestyle modification, many patients frequently regain any lost body weight. The use of western anti‐obesity drugs has been limited by side effects including mood changes, suicidal thoughts, and gastrointestinal or cardiovascular complications. The effectiveness and safety of traditional Chinese medicine including Chinese herbal medicine (CHM) and acupuncture provide an alternative established therapy for this medical challenge. In this systematic review, we used standard methodologies to search, review, analyse and synthesize published data on the efficacy, safety and relapse of weight regain associated with use of CHM and acupuncture. We also examined the rationale, mechanisms and potential utility of these therapies. A total of 12 electronic databases, including Chinese, English, Korean and Japanese, were searched up to 28 February 2010. Randomized controlled trials (RCTs) for CHM and/or acupuncture with comparative controls were considered. We used the Jadad scale to assess methodological qualities, the random effect model in the pooled analysis of therapeutic efficacy to adjust for heterogeneity and funnel plots to explore publication bias. After screening 2,545 potential articles from the electronic databases, we identified 96 RCTs; comprising of 49 trials on CHM treatment, 44 trials on acupuncture treatment and 3 trials on combined therapy for appraisal. There were 4,861 subjects in the treatment groups and 3,821 in the control groups, with treatment duration ranging from 2 weeks to 4 months. Of the 77 publications written in Chinese, 75 had a Jadad score <3, while 16 of the 19 English publications had a Jadad score of >3. Efficacy was defined as body weight reduction ≥2 kg or body mass index (BMI) reduction ≥0.5 kg/m². Compared with placebo or lifestyle modification, CHM and acupuncture exhibited respective ‘risk ratio’ (RR) of 1.84 (95% CI: 1.37–2.46) and 2.14 (95% CI: 1.58–2.90) in favour of body weight reduction, with a mean difference in body weight reduction of 4.03 kg (95% CI: 2.22–5.85) and 2.76 kg (95% CI: 1.61–3.83) and a mean difference in BMI reduction of 1.32 kg m^–2 (95% CI: 0.78–1.85) and 2.02 kg m^–2 (95% CI: 0.94–3.10), respectively. Compared with the pharmacological treatments of sibutramine, fenfluramine or orlistat, CHM and acupuncture exhibited an RR of 1.11 (95% CI: 0.96–1.28) and 1.14 (95% CI: 1.03–1.25) in body weight reduction, mean difference in body weight reduction of 0.08 kg (95% CI: ?0.58 to 0.74) and 0.65 kg (95% CI: ?0.61 to 1.91), and mean difference in BMI reduction of 0.18 kg m^–2 (95% CI: ?0.39 to 0.75) and 0.83 kg m^–2 (95% CI: 0.29–1.37), respectively. There were fewer reports of adverse effects and relapses of weight regain in CHM intervention studies conducted in China than studies conducted outside China. CHM and acupuncture were more effective than placebo or lifestyle modification in reducing body weight. They had a similar efficacy as the Western anti‐obesity drugs but with fewer reported adverse effects. However, these conclusions were limited by small sample size and low quality of methodologies.