Concurrent Medication Use Research Articles

Clozapine-related EEG changes and seizures: dose and plasma-level relationships

Clozapine is a widely used atypical antipsychotic with a unique effectiveness in treatment-resistant schizophrenia. An important adverse effect is seizures, which have been observed at all stages of clozapine treatment. Valproate has traditionally been considered the drug of choice for the prophylaxis of clozapine seizures, however it may not be the most suitable choice for all patients. There is disagreement as to the best point to prescribe valproate or a suitable antiepileptic: as seizure prophylaxis at a certain clozapine dose or level, or only as remedial treatment. In this review, we examine the relevant literature with an aim to evaluate the following relationships: clozapine dose and electroencephalogram (EEG) abnormalities, plasma levels and EEG abnormalities, dose and occurrence of seizures and plasma levels and occurrence of seizures. Weighted linear regression models were fitted to investigate these relationships. There was a strong relationship between clozapine dose and plasma level and occurrence of clozapine-induced EEG abnormalities. However, a statistically significant relationship between dose and occurrence of seizures was not found. A relationship between clozapine plasma level and occurrence of seizures was not established because of the scarcity of useful data although our review found three case reports which suggested that there is a very substantial risk of seizures with clozapine plasma levels exceeding 1300 μg/l. Seizures are more common during the initiation phase of clozapine treatment, suggesting a slow titration to target plasma levels is desirable. An antiepileptic drug should be considered when the clozapine plasma level exceeds 500 μg/l, if the EEG shows clear epileptiform discharges, if seizures, myoclonic jerks or speech difficulties occur and when there is concurrent use of epileptogenic medication. The antiepileptics of choice for the treatment and prophylaxis of clozapine-induced seizures are valproate (particularly where there is mood disturbance) and lamotrigine (where there is resistance to clozapine).

Sleep Aid Prescribing Practices during Neoadjuvant or Adjuvant Chemotherapy for Breast Cancer

Sleep disruption is a common complaint in breast cancer patients receiving chemotherapy. We describe the sleep aid prescribing practices of oncologists treating women receiving adjuvant or neoadjuvant chemotherapy for breast cancer at a single institution. Subjects with early-stage breast cancer who received four cycles of neoadjuvant or adjuvant Adriamycin® and cyclophosphamide (AC) at the University of California, San Diego over a 2-year period were evaluated by retrospective chart review. Clinical data pertinent to sleep disorders and electronic prescriptions for sleep aids were collected using the electronic medical record. Of the 124 breast cancer subjects, 52.4% discussed sleep with their provider. Whereas 13.7% of subjects reported prior sleep aid use, 32.3% were prescribed sleep aids during chemotherapy, most commonly lorazepam (31.4%) and zolpidem (29.4%). Women prescribed sleep aids during chemotherapy were significantly more likely to discuss sleep with their provider, more likely to have been taking sleep aids previously, and more likely to be taking psychiatric medications. Sleep disturbances during AC chemotherapy for early-stage breast cancer are common and are frequently treated with sleep aid medications. We show that women with prior sleep aid use and concurrent psychiatric medication use were more likely to need sleep aids during chemotherapy, suggesting these are high-risk populations that could be targeted for intervention prospectively.

Concurrent herb-prescription medication use and health care provider disclosure among university students

To determine the extent to which college students are intermixing mood-altering herbs with prescription medications and whether they are disclosing this information to their health care providers. A nonrandom sample was drawn from the student body of a Northwestern state university (n=305). In November 2008 participants completed an online survey detailing herb use, disclosure to health care providers and herb/medicinal intermixing. There were no demographic differences between herb users and non-users. Most herb usage was self-prescribed (60%) and undisclosed to healthcare providers (only 25% of herb users disclosed to a healthcare provider). 34% of herb users used them to treat a mood disorder. Of herb users, 13% had simultaneously used herbs and prescription medication in the last year. In addition, herb users who intermixed herbs with prescription medications had higher depression and anxiety scores than those who did not intermix. College student herb use is primarily self prescribed and undisclosed to healthcare professionals, who may prescribe pharmaceuticals that interact negatively with herbals. Physician awareness and query is invaluable for the prevention of adverse herb and drug interactions.

Small intestinal bacterial overgrowth and lactose intolerance contribute to irritable bowel syndrome symptomatology in Pakistan

Background /Aim:The symptoms of irritable bowel syndrome resemble those of small intestinal bacterial overgrowth (SIBO). The aim of this study was to determine the frequency of SIBO and lactose intolerance (LI) occurrence in patients with diarrhea-predominant irritable bowel syndrome (IBS-D) according to Rome III criteria.Patients and Methods:In this retrospective case-control study, patients over 18 years of age with altered bowel habit, bloating, and patients who had lactose Hydrogen breath test (H2BT) done were included. The “cases” were defined as patients who fulfill Rome III criteria for IBS-D, while “controls” were those having chronic nonspecific diarrhea (CNSD) who did not fulfill Rome III criteria for IBS-D. Demographic data, predominant bowel habit pattern, concurrent use of medications, etc., were noted.Results:Patients with IBS-D were 119 (51%) with a mean age of 35 ± 13 years, while those with CNSD were 115 (49%) with mean age 36 ± 15 years. Patients in both IBS-D and CNSD were comparable in gender, with male 87 (74%) and female 77 (64%). SIBO was documented by lactose H2BT in 32/234 (14%) cases. It was positive in 22/119 (19%) cases with IBS-D, while 10/115 (9%) cases had CNSD (P = 0.03). LI was positive in 43/234 (18%) cases. Of these, 25/119 (21%) cases had IBS-D and 18/115 (16%) cases had CNSD (P = 0.29).Conclusion:SIBO was seen in a significant number of our patients with IBS-D. There was no significant age or gender difference in patients with or without SIBO.

A Pilot Study of Qigong Practice and Upper Respiratory Illness in Elite Swimmers

Upper respiratory tract infections (URIs) are a common complaint in competitive swimmers and can adversely affect performance. No intervention has yet been shown to reduce URI incidence in intensively trained athletes. The University of Virginia varsity swim team received three weeks of training in qigong for the purpose of reducing stress and improving health. Our primary objective was to assess the relationship between qigong practice and symptoms of URI during a time when swimmers would be at high URI risk. Secondary objectives were to assess degree of compliance with a qigong practice regimen, to evaluate differences between qigong practitioners and non-practitioners, and to determine the response-rate and reliability of a newly developed internet-based, self-report survey. The design was observational, cross-sectional, and prospective. Weekly data on cold and flu symptoms, concurrent health problems and medication use, and qigong practice were gathered for seven weeks. Retrospective information on health and qigong training response was also collected. Participants were 27 of the 55 members of the University of Virginia Swim Team in the Virginia Athletic Department. Main outcomes were measures of aggregated cold/flu symptoms and Qigong practice. Survey completion was 100%, with no missing data, and reliability of the instrument was acceptable. Cold and flu symptoms showed a significant non-linear association with frequency of qigong practice (R(2) = 0.33, p < 0.01), with a strong, inverse relationship between practice frequency and symptom scores in swimmers who practised qigong at least once per week (R(2) = 0.70, p < 0.01). Qigong practitioners did not differ from non-practitioners in demographic or lifestyle characteristics, medical history, supplement or medication use, or belief in qigong. These preliminary findings suggest that qigong practice may be protective against URIs among elite swimmers who practice at least once per week.

Personalized Approaches to Clopidogrel Therapy

Clopidogrel is one of the most commonly prescribed medications worldwide. Recent advisories from the US Food and Drug Administration have drawn attention to the possibility of personalized decision-making for people who are candidates for clopidogrel. As is the case with antihypertensives, statins, and warfarin, common genetic sequence variants can influence clopidogrel metabolism and its effect on platelet activity. These genetic variants have, in multiple studies, been associated with adverse clinical outcomes. Concurrent medication use also influences how the body handles clopidogrel. Proton pump inhibitors, widely prescribed in conjunction with clopidogrel, may blunt its effectiveness. We address implications for bedside decision-making in light of accumulated data and current Food and Drug Administration advisories and conclude that genetic testing for CYP2C19 genotype and limitation of proton pump inhibitor interactions do not yet appear to offer an opportunity to optimize treatment given the current state of knowledge.

A pharmaco-epidemiological study of migraine and antidepressant medications: Complete one year data from the Norwegian population

Background Migraine, depression and anxiety disorders have been associated with one another in several epidemiological studies. However, it is not known if or how these associations are reflected in the concurrent use of medications for migraine and depressive/anxiety disorders in the general population. The purpose of the present study was to identify groups of patients particularly likely to receive clinical treatment for both conditions. Methods Data from the Norwegian Prescription Database for 2006 were analysed for the purpose of ascertaining concurrence of prescriptions for migraine and depression/anxiety disorders. Data were subjected to analysis testing deviation from unity for the OR performed by a chi-square test. Results In the total Norwegian population ( N = 4640219) migraine drugs were prescribed to 81225 persons (1.8% of the population), antidepressant drugs to 257700 persons (5.6% of the population), and 11269 persons were prescribed both types of drugs. The prescription of antidepressants was significantly increased in patients receiving a prescription for a medication used to treat migraine (OR = 2.82 (95% CI = 2.76–2.88); chi-square p < 0.001), and this association was stronger for men than for women. Teenage women carried the highest risk for this co-morbid constellation (OR = 3.89 CI = 3.17–4.77); chi-square p < 0.001). Conclusion This study revealed a strong positive association between the prescription of migraine and antidepressant medications, and this association was generally most pronounced in men. However, teenage girls carried the highest risk of receiving both kinds of prescriptions, suggesting particular attentiveness is required in the clinical management of these patients.

Impact of Common Medications on Serum Total Prostate-Specific Antigen Levels: Analysis of the National Health and Nutrition Examination Survey

Previous studies suggest that some common medications alter prostate-specific antigen (PSA) levels. It remains unclear whether these reported medication effects are due to clinicodemographic factors or concurrent use of other medications. We investigated the impact of individual and combinations of common medications on PSA in a large cross-sectional study of the United States population. The study included men > or = 40 years old without prostate cancer from the 2003 to 2004 and 2005 to 2006 cycles of the National Health and Nutrition Examination Survey (NHANES). Men with recent prostate manipulation, prostatitis, and those on hormone therapy were excluded. Weighted multivariate linear regression was performed on log-transformed total PSA to determine the effect of the 10 most commonly prescribed medication classes, adjusting for potential confounders including demographics, clinical characteristics, physical examination, laboratory studies, and duration of medication use. In total, 1,864 men met inclusion criteria. Nonsteroidal anti-inflammatory drug (NSAID; P = .03), statin (P = .01), and thiazide diuretic (P = .025) intake was inversely related to PSA levels. Five years of NSAID, statin, and thiazide diuretic use was associated with PSA levels lower by 6%, 13%, and 26%, respectively. The combination of statins and thiazide diuretics showed the greatest reduction in PSA levels: 36% after 5 years. Concurrent calcium channel blocker use minimizes or negates the inverse relationship of statin use and PSA level. We found that men using NSAIDs, statins, and thiazide diuretics have reduced PSA levels by clinically relevant amounts. The impact of regularly consuming these common medications on prostate cancer screening is unknown.

Chart review of patients on valsartan-based single-pill combinations vs. ARB-based free combinations for BP goal achievement

Objective:To compare blood pressure (BP) goal achievement associated with the use of valsartan-based single pill combinations (SPCs) vs. angiotensin II receptor blocker (ARB)-based free combinations (FCs) among adult hypertension patients.Research design and methods:Data were collected from physician-administered chart review of adult hypertension patients in the South Central region. All patients had uncontrolled BP before initiating one of the index therapies (SPCs: valsartan/amlodipine or valsartan/hydrochlorothiazide [HCTZ], FCs: ARB + calcium channel blocker [CCB] or ARB + HCTZ) between 07/2008 and 06/2009. Up to three BP measures were collected starting from 45 days after the therapy initiation. BP goal was <130/80 mmHg for patients with diabetes, chronic renal disease or coronary heart disease; or <140/90 mmHg for patients without these comorbidities. The Kaplan–Meier method with log-rank test was used to compare rates of BP goal achievement associated with valsartan-based SPCs vs. ARB-based FCs over time. Cox proportional hazard models were used to estimate the likelihood of BP goal achievement associated with SPCs vs. FCs, controlling for demographics, baseline BP, hypertension history, comorbidities, prior and concurrent use of anti-hypertensive medications, and physician specialty.Results:The study included 812 patients: 414 on valsartan-based SPCs (209 on valsartan/amlodipine and 205 on valsartan/HCTZ) and 398 on ARB-based FCs (200 on ARB + CCB and 198 on ARB + HCTZ). The ARBs in the FC group included valsartan, losartan, olmesartan, telmisartan, irbesartan and candesartan. In the ARB FC group, the most commonly used ARB and CCB were valsartan (29.1%) and amlodipine (81.5%), respectively. During the observation period (81 days for valsartan SPC patients and 90 days for ARB FC patients), 65.9% of valsartan SPC patients and 55.8% of the ARB FC patients achieved BP goal. Over time, the rates of BP goal achievement were consistently higher among valsartan SPC vs. ARB FC patients (p = 0.01): 31.1% vs. 28.9% and 69.1% vs. 59.2% at month 3 and 6 after therapy initiation, respectively. Cox regression confirmed that valsartan SPC patients were more likely to achieve BP goal (HR = 1.22; p = 0.05). A similar trend was observed in the subgroup analyses comparing SPC of valsartan/amlodipine vs. FCs of ARB + CCB and SPC of valsartan/HCTZ vs. FCs of ARB + HCTZ.Limitations:Non-randomization of treatments, limited generalizability, and no records of BP measures within 45 days.Conclusions:Patients using valsartan-based SPCs were significantly more likely to achieve BP goal than those treated with ARB-based FCs in the real-world clinical practice in the South Central region. The significance was achieved at two-sided α = 0.05.

Discontinuation of Cholinesterase Inhibitor Treatment and Determinants thereof in the Netherlands

The cholinesterase inhibitors (ChEIs) rivastigmine and galantamine have been approved for the treatment of mild to moderate Alzheimer's disease in the Netherlands. Differences between ChEIs regarding persistence or the use of effective doses in daily clinical practice have been observed. However, most studies assessing ChEI discontinuation and associated determinants have been conducted in North America and there is a lack of knowledge about ChEI discontinuation and its determinants in daily clinical practice in Europe. To assess ChEI discontinuation in daily practice in the Netherlands and to seek its determinants, including suboptimal utilization. A retrospective cohort study was performed using data from the Dutch PHARMO Record Linkage System. Included patients were aged > or =50 years at first dispensing of a ChEI, had a first dispensing of a ChEI between 1998 and 2008, had a prior medication history of 12 months and had at least one subsequent dispensing of any kind of medication. The proportion of patients who discontinued ChEIs over 3 years was determined. Cox regression was used to assess determinants for early (< or =6 months) discontinuation and, separately, for late discontinuation during a subsequent 30-month follow-up among those persisting with treatment for >6 months. At 6 months, 30.8% of 3369 study patients had discontinued ChEIs, compared with 59.0% after 3 years. Thirty-five percent of patients taking rivastigmine reached the WHO-defined daily dose compared with 80% taking galantamine. At 6 months, compared with regular-dose rivastigmine, low-dose rivastigmine or low-dose galantamine was associated with an increased risk of early discontinuation, whereas regular-dose galantamine was associated with a decreased risk, as was concurrent use of cardiac medications, drugs for Parkinson's disease, propulsives, selective serotonin reuptake inhibitors and benzodiazepines. Associations of ChEI type/dose or co-medications with discontinuation among patients persisting for > 6 months differed somewhat from associations with discontinuation before 6 months. Fewer patients taking rivastigmine than those taking galantamine reached recommended doses. Furthermore, patients taking rivastigmine had an increased risk of early discontinuation compared with patients taking galantamine. Adverse effects leading to treatment intolerance and suboptimal utilization may have been contributing factors to these observed differences.

Glistenings and surface light scattering in intraocular lenses

Glistenings are fluid-filled microvacuoles that form within the intraocular lens (IOL) optic when the IOL is in an aqueous environment. They are observed in all types of IOLs but have been mainly associated with hydrophobic acrylic IOLs. Experimental and clinical studies suggest the various hydrophobic acrylic IOLs on the market exhibit different tendencies toward glistenings. Factors influencing glistening formation include IOL material composition, manufacturing technique, packaging, associated conditions such as glaucoma or those leading to breakdown of the blood-aqueous barrier, as well as concurrent use of ocular medications. Although the impact of glistenings on postoperative visual function and the evolution of glistenings in the late postoperative period remain controversial, IOL explantation has rarely been reported. The phenomenon of surface light scattering has also been described in association with hydrophobic acrylic IOLs. Its mechanism of formation is controversial but may be related to long-term phase separation water near the IOL surface, although not seen as microvacuoles. The author has no financial or proprietary interest in any material or method mentioned.

Rituximab‐induced late onset neutropenia in newly‐diagnosed B‐cell lymphoma correlates with Fc receptor FcγRIIIa 158(V/F) polymorphism

Rituximab is a commonly utilized treatment agent for B-cell lymphoma. Late onset neutropenia (LON) has been identified as a complication associated with rituximab, primarily in conjunction with hematopoietic stem cell transplantation (HSCT). Scant data exists regarding rituximab-related LON outside the spectrum of HSCT, including newly-diagnosed lymphoma. We examined a large cohort of newly-diagnosed B-cell lymphoma patients treated with rituximab-based therapy. We identified patients with LON and analyzed the characteristics and outcomes. Furthermore, we utilized multiplex PCR for the detection of the FcgRIIIa 158 V/F polymorphism and correlated this with LON. Eighty consecutive B-cell lymphoma patients were examined. Nine of 80 (11.3%) patients developed LON. The clinical course of LON was generally self-limiting without adverse events. The onset of LON occurred at a mean of 66 days after the last course of treatment, while the mean duration of LON was 97 days. Moreover, the V/V and V/F polymorphisms were significantly associated with the occurrence of LON (P 5 0.046) yielding an odds ratio for the development of LON of1.47 (95% CI 1.21-1.78). We identified an incidence of LON following frontline rituximab-based treatment of 11.3%. The FcgRIIIa polymorphism was highly associated with development of LON.

The myth of the superiority of concurrent combined treatments for anxiety disorders.

[Clin Psychol Sci Prac 17: 107–111, 2010] The treatment of anxiety disorders with combined cognitive-behavioral therapy (CBT) and pharmacological treatments has been an ongoing topic of discussion. Combined treatments have failed to demonstrate additive benefits despite their continued use in practice. Otto, McHugh, and Kantak (2010) suggest that concurrent use of medication and CBT affects the acute release of cortisol during the extinction phase of exposure therapy and, in turn, interferes with memory consolidation. This commentary expands on some of the psychological aspects of combined treatments for anxiety disorders to consider along with this new biochemical perspective.

Pulmonary manifestations of inflammatory bowel disease: Case presentations and review

Inflammatory bowel disease (IBD) is associated with a number of extraintestinal manifestations that may involve most organ systems. Extraintestinal manifestations are more common in Crohn disease (CD) and may include rheumatologic, ocular, dermatologic, biliary and pulmonary manifestations. The most common pulmonary manifestations of IBD are drug-induced lung disease. Other manifestations include parenchymal disease, pleuritis and overlap syndromes. We present a case series of 7 patients with non-infectious pulmonary manifestations of IBD, which included cryptogenic organizing pneumonia, usual interstitial pneumonitis (UIP), Langerhan's granulomatosis, and eosinophilic pneumonia. Concurrent extraintestinal manifestations present in these patients included arthralgia, iritis, and pyoderma gangrenosum. In most patients the development of pulmonary disease parallels that of the intestinal disease activity, extraintestinal manifestations and concurrent use of 5-ASA medications.

2044 THE IMPACT OF COMMON MEDICATIONS ON SERUM PROSTATE-SPECIFIC ANTIGEN LEVELS: ANALYSIS OF NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY

You have accessJournal of UrologyProstate Cancer: Markers I1 Apr 20102044 THE IMPACT OF COMMON MEDICATIONS ON SERUM PROSTATE-SPECIFIC ANTIGEN LEVELS: ANALYSIS OF NATIONAL HEALTH AND NUTRITION EXAMINATION SURVEY Steven Chang, Lauren Harshman, Jay Bhattacharya, and Joseph Presti Steven ChangSteven Chang More articles by this author , Lauren HarshmanLauren Harshman More articles by this author , Jay BhattacharyaJay Bhattacharya More articles by this author , and Joseph PrestiJoseph Presti More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2010.02.2091AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Previous studies suggest that some medications may lower serum prostate-specific antigen (PSA) levels. It remains unclear if these previously reported medication effects are due to sociodemographic factors, and clinical characteristics, or concurrent use of other medications. We investigated the impact of individual and combinations of common medications on serum total PSA in a large cross-sectional study of the civilian, non-institutionalized United States population. METHODS The study population included men at least 40 years of age without prostate cancer from the 2003-2004 and 2005-2006 cycles of the National Health and Nutrition Examination Survey (NHANES). We excluded men with recent prostate manipulation and those taking 5-alpha reductase inhibitors or hormone therapy. Weighted linear regression was performed on log-transformed serum total PSA to determine the effect of the 10 most commonly prescribed medication classes after adjusting for sociodemographic and clinical factors including physical examination, relevant laboratory studies, and duration of medication use. RESULTS 1,846 men met inclusion criteria. Nonsteroidal anti-inflammatory drugs (NSAIDs) (p=0.036), statins (p=0.008) and thiazide diuretics (p=0.032) were associated with lower total PSA levels. The models predicted that men regularly using NSAIDs, statins, and thiazide diuretics had total PSA levels reduced by 6%, 13%, and 27% at 5 years and 11%, 26%, and 47% at 10 years, respectively. The combined use of statins and thiazide diuretics was associated with the greatest decrease in total PSA levels: 36% and 59% after 5 and 10 years, respectively. The relationship of statin use and total PSA levels was negated with the concurrent use of calcium channel blockers. No other common medication demonstrated a relationship with total PSA levels. CONCLUSIONS Although most common medications are unrelated to total PSA level, men who consume NSAIDs, statins, and thiazide diuretics have reduced total PSA levels by clinically relevant amounts. The regular use of NSAIDs, statins, or thiazide diuretics may impact the quality of prostate cancer screening. Stanford, CA© 2010 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 183Issue 4SApril 2010Page: e793-e794 Advertisement Copyright & Permissions© 2010 by American Urological Association Education and Research, Inc.MetricsAuthor Information Steven Chang More articles by this author Lauren Harshman More articles by this author Jay Bhattacharya More articles by this author Joseph Presti More articles by this author Expand All Advertisement Advertisement PDF DownloadLoading ...

Angiotensin converting enzyme inhibitors may be protective against cardiac complications following anthracycline chemotherapy

Doxorubicin (DOX), despite causing cardiac toxicity, is an anthracycline chemotherapeutic agent that plays an important role in the treatment of breast cancer. Angiotensin-converting enzyme inhibitors (ACE-I) may protect against cardiac toxicity in patients receiving DOX chemotherapy. A total of 143 patients receiving DOX at the Masonic Comprehensive Cancer Clinic, University of Minnesota, who had two or more multigated blood pool imaging (MUGA) scans or echocardiograms performed between 2004 and 2007 were identified and reviewed. Patients with a 10% absolute drop in their ejection fraction (EF) or more to below 55% were identified and compared with those that did not have a 10% decline in EF. Impact of patient variables and the use of concurrent medications on EF drop were evaluated using logistic regression. Median age was 52 years old. 85 (60%) were female. Cancer diagnosis was breast (n = 26), lymphoma (n = 92), and other (n = 25). In spite of a similar baseline EF in all the patients, 22/142 (15%) patients had a significant drop in EF during DOX chemotherapy. Adjusting for age, the odds ratio of EF drop associated with the use of ACE-I is 0.267 (P = 0.0940), suggesting that ACE-I has a protective effect. Cumulative DOX dose, the use of beta-blockers, or aspirin did not appear to be predictive or protective. Although not statistically significant, this study suggests that the use of ACE-I when given with DOX chemotherapy protects against DOX chemotherapy and warrants further investigation.

Thiazide-Induced Hyponatremia

The importance of thiazide-induced hyponatremia (TIH) is reemerging because thiazide diuretic prescription seems to be increasing after the guidelines recommending thiazides as first-line treatment of essential hypertension have been introduced. Thiazide diuretics act by inhibiting reabsorption of Na+ and Cl- from the distal convoluted tubule by blocking the thiazide-sensitive Na+/Cl- cotransporter. Thus, they inhibit electrolyte transport in the diluting segment and may impair urinary dilution in some vulnerable groups. Risk factors predisposing to TIH are old age, women, reduced body masses, and concurrent use of other medications that impair water excretion. While taking thiazides, the elderly may have a greater defect in water excretion after a water load compared with young subjects. Hyponatremia is usually induced within 2 weeks of starting the thiazide diuretic, but it can occur any time during thiazide therapy when subsequent contributory factors are complicated, such as reduction of renal function with aging, ingestion of other drugs that affect free water clearance, or changes in water or sodium intake. While some patients are volume depleted on presentation, most appear euvolemic. Notably serum levels of uric acid, creatinine and urea nitrogen are usually normal or low, suggestive of syndrome of inappropriate secretion of antidiuretic hormone. Despite numerous studies, the pathophysiological mechanisms underlying TIH are unclear. Although the traditional view is that diuretic-induced sodium or volume loss results in vasopressin-induced water retention, the following 3 main factors are implicated in TIH: stimulation of vasopressin secretion, reduced free-water clearance, and increased water intake. These factors will be discussed in this review.

No Increase in Breast Cancer Recurrence with Concurrent Use of Tamoxifen and Some CYP2D6-Inhibiting Medications

Tamoxifen reduces recurrence risk among women treated for estrogen receptor-positive breast cancer. Its effectiveness partly depends on metabolic activation via cytochrome P450 2D6 (CYP2D6). Some medications compromise CYP2D6 activity and may lower plasma concentrations of active tamoxifen metabolites. We studied the association between concurrent use of tamoxifen and CYP2D6-inhibiting medications and breast cancer recurrence among Danish women diagnosed with early-stage, estrogen receptor-positive breast cancer. Using the Danish Breast Cancer Cooperative Group Registry, we identified 366 cases with local or distant breast cancer recurrence and 366 matched breast cancer controls. We ascertained concurrent prescription of CYP2D6-inhibiting medications during tamoxifen treatment by linking to the national prescription database covering all Danish pharmacies. We computed the breast cancer recurrence odds ratio (OR) and 95% confidence interval for each medication. The pooled recurrence OR was null (OR, 1.0; 95% confidence interval, 0.8-1.3); recurrence ORs for individual drugs ranged from 0.3 to 3.4. The individual ORs followed the pattern expected under a null-centered Gaussian distribution. Null associations were apparent for all drugs after empirical Bayes adjustment for multiple comparisons. Together, these results provide evidence for a null association between drug-compromised CYP2D6 activity and breast cancer recurrence among tamoxifen-treated women.

Obstructive sleep apnoea is associated with diabetes in sleepy subjects

Background:Although obstructive sleep apnoea (OSA) has been linked to insulin resistance and glucose intolerance, it is unclear whether there is an independent association between OSA and diabetes mellitus (DM) and...

A fixed dose combination of ibuprofen and famotidine

The NSAID class of medications is frequently used for mild to moderate pain. While overall safe, NSAIDs have several important adverse effects including esophageal, gastric and duodenal ulceration which limit their use. This has led to the development of NSAIDs with either less gastrointestinal side effects or concurrent use of medications to prevent NSAID gastrointestinal side effects. While several classes of medications exist for the prevention of gastrointestinal side effects, few combination treatments are available in a single pill. Towards this end, a combination pill of ibuprofen and famotidine (HZT-501, Horizon Therapeutics, Skokie, IL. USA) has been developed.