Chronic anemia complicated by cardiac failure, pulmonary hypertension, and pericardial effusion: a case report.

BACKGROUND: Worldwide, iron deficiency anaemia (IDA) is the most common cause of anaemia. Iron deficiency alone has an association with heart failure and pulmonary hypertension. Chronic iron deficiency anemia triggers various physiologic adjustments, leading to hyperdynamic circulation and enhanced hypoxic pulmonary vasoconstriction. Those mechanisms may result in the development of high output cardiac failure and pulmonary hypertension; however, pericardial effusion remains a rare association. CASE PRESENTATION: A 44-year-old Nepalese man presented with fatigability and swollen ankles. Except for a hemorrhoidectomy 4 years ago, he had no comorbidities. Labs confirmed severe iron deficiency anemia (hemoglobin 1.8 grams per deciliter) likely secondary to hemorrhoids. An echocardiogram revealed high output cardiac failure, pericardial effusion, and severe pulmonary hypertension. He responded well to the correction of anemia and diuretics with the resolution of vascular complications. CONCLUSION: We report a unique presentation of chronic severe iron deficiency anemia complicated by heart failure, pulmonary hypertension, and pericardial effusion. We believe it to be the first-ever such case reported in the literature. These cardiovascular complications seem to result from internal homeostatic mechanisms against the chronic tissue hypoxemia observed in severe anemia. Furthermore, iron deficiency alone has an association with heart failure and pulmonary hypertension. After excluding other potential causes, we confirmed iron deficiency anaemia as the cause of those complications. The correction of anemia led to an excellent recovery without any sequelae. Our case report highlights the fact that management of such a case should be focused on underlying etiology rather than the complications.

Successful treatment of hereditary hypotrichosis simplex by platelet rich plasma injection with topical minoxidil 2.

Background: Hereditary hypotrichosis simplex is a rare genetic hair disease that affects the scalp. Failure to grow normal hair in terms of length and density is the main complaint of patients. Diagnosis usually established by exclusion of other congenital hair and other ectodermal disorders. Till now, no satisfactory treatment was used for the condition.Report: A 14 year old patient with hypotrichosis simplex was treated with combined platelet rich plasma injection and topical minoxidil 2% with marked improvement.Conclusion: While no satisfactory treatment presents for this condition, the use of platelet rich plasma injection can add new hope for hypotrichosis simplex patients.

Agomelatine improves streptozotocin-induced diabetic nephropathy through melatonin receptors/SIRT1 signaling pathway.

INTRODUCTION: Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD). Agomelatine, a melatonin receptor agonist, has a potent anti-inflammatory activity. The current study aimed to determine the ameliorative anti-inflammatory effect of agomelatine against DN. METHODS: We used 10 % fructose with streptozotocin (STZ) to induce DN in male Wistar rats. Diabetic rats were treated with agomelatine in presence or absence of melatonin receptor antagonist (luzindole) or Sirtuin1 (SIRT1) inhibitor (EX527). SIRT1 expression was measured by qRT-PCR and immunohistochemical analysis. The expression of nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), 5'adenosine monophosphate-activated protein kinase (AMPK), intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion protein-1 (VCAM-1), and monocyte chemoattractant protein-1 (MCP-1) were measured using ELISA. Histological assessment was performed using hematoxylin and eosin-stained renal sections. RESULTS: Fructose and STZ treatment induced diabetes, insulin resistance, and renal damage accompanied by reduced SIRT1 expression, increased NFκB activation, and decreased AMPK phosphorylation in the kidney. Agomelatine treatment improved kidney histology and function and upregulated SIRT1 expression (2-fold). Inhibition of melatonin receptors and SIRT1 activity increased NFκB phosphorylation (2.13 and 1.98-folds, respectively), reduced AMPK activation (0.51 and 0.53-folds, respectively), increased inflammatory markers ICAM-1 (2.16 and 2.23-folds, respectively), VCAM-1 (2.19 and 2.26-folds, respectively), and MCP-1(2.84 and 3.12-folds, respectively), and inhibited the ameliorative effect of agomelatine on kidney structure and function. CONCLUSION: Our findings reveal the ameliorative anti-inflammatory activity of agomelatine against STZ-induced DN and this effect is SIRT1- and melatonin receptor-dependent. Therefore, agomelatine may be beneficial to prevent the development of ESRD from diabetes mellitus.

Protective effect of quercetin against 5-fluorouracil-induced cardiac impairments through activating Nrf2 and inhibiting NF-κB and caspase-3 activities.

5-Fluorouracil (5-FU) is a chemotherapy used to treat many types of cancer. Cardiotoxicity is one of the common drawbacks of 5-FU therapy. Quercetin (Qu) is a bioflavonoid with striking biological activities. This research aimed to assess the ameliorative effect of Qu against 5-FU-mediated cardiotoxicity. Thirty-five rats were allocated into five groups: control group (normal saline), 5-FU group (30 mg/kg, intraperitoneally), Qu group (50 mg/kg, oral), 25 mg/kg Qu+5-FU group, and 50 mg/kg Qu+5-FU. The experimental animals were received the above-mentioned drugs for 21 days. Results showed that 5-FU significantly elevated creatine kinase, lactate dehydrogenase, serum cholesterol and triglyceride, and upregulated troponin and renin mRNA expression. Additionally, cardiac oxidant/antioxidant imbalance was evident in elevated oxidants (malondialdehyde and nitric oxide) and depleted antioxidants (superoxide dismutase, catalase, glutathione peroxidase, and glutathione). 5-FU also downregulated the gene expression of nuclear factor erythroid 2-related factor 2. Furthermore, 5-FU significantly increased cardiac pro-inflammatory cytokines (tumor necrosis factor-alpha and interleukin-1 beta) and upregulated gene expression of nuclear factor kappa-B. 5-FU significantly enhanced cardiac apoptosis through upregulating caspase-3 expression and downregulating B-cell lymphoma 2. Immunohistochemical and histopathological examinations verified the above-mentioned findings. However, all these changes were significantly ameliorated in Qu pre-administered rats. Conclusively, Qu counteracted 5-FU-mediated cardiotoxicity through potent antioxidant, anti-inflammatory, and anti-apoptotic effects.

Olive Leaf Extract Attenuates Chlorpyrifos-Induced Neuro- and Reproductive Toxicity in Male Albino Rats.

Chlorpyrifos (CPF) is a common organophosphorus insecticide. It is associated with negative consequences such as neurotoxicity and reproductive injury. This study aimed to observe the ability of olive leaf extract to attenuate chlorpyrifos toxicity, which induced neuro- and reproductive toxicity in male albino rats. Olive leaf extract (OLE) exhibits potent antioxidant and antiapoptotic properties. Twenty-two mature male rats were divided into four groups: control (saline), CPF (9 mg/kg), OLE (150 mg/kg), and CPF + OLE. Treatment was administered orally for 80 days. The CPF significantly reduced serum sex hormones, sperm counts and motility, high oxidants (MDA), and depleted antioxidants (GSH, SOD, TAC) in the brain and testes homogenate; additionally, it decreased serum AChE and brain neurotransmitters, increased Bax, decreased Bcl-2, and boosted caspase-3 immune expression in neural and testicular cells. Immunological expression of Ki 67 in the cerebrum, cerebellum, choroid plexus, and hippocampus was reduced, and α-SMA in testicular tissue also decreased. Histopathological findings were consistent with the above impacts. OLE co-administration significantly normalized all these abnormalities. OLE showed significant protection against neural and reproductive damage caused by CPF.

Facial rejuvenation by microneedling with irradiated amniotic collagen matrix compared to platelet rich plasma.

Many modalities are used for treatment of facial wrinkles, such as microneedling that enhances collagen production, and platelet-rich plasma (PRP) which contains concentrated levels of growth factors. The human amniotic membrane isolated from the placentae of donors (during elective cesarean sections) has high levels of growth factors that help in rejuvenation by improving the migration and proliferation of keratinocytes, fibroblasts and increased collagen synthesis. Was to confirm the efficacy of irradiated amniotic collagen matrix (IACM) versus platelet rich plasma (PRP) delivered via microneedling in facial rejuvenation. The present study included 20 patients with facial wrinkles divided into two groups using split face technique: Group A subjected to microneedling with topical IACM on the right side of the face. Group B subjected to microneedling with topical PRP on the left side of the face. Patients received six sessions 2 weeks apart. Photos by Antera camera and skin biopsies were taken to assess the clinical results. There were a statistically significant improvement in both sides after than before treatment; with better improvement in patients treated with IACM more than patients treated with PRP using microneedling in both sides as proved clinically (assessed by WSRS and GAIS scale), pathologically (Orcein and Masson trichrome stain) and by Antera camera (texture and pigmentation). Microneedling using IACM is a new, safe and effective method for facial rejuvenation, more effective when compared to microneedling using PRP; in need for further studies to evaluate the correct dose and number of sessions to get the best outcome.

Novel In Vivo Assessment of Antimicrobial Efficacy of Ciprofloxacin Loaded Mesoporous Silica Nanoparticles against Salmonella typhimurium Infection.

Salmonella enterica serovar Typhimurium (S. typhimurium) is known for its intracellular survival, evading the robust inflammation and adaptive immune response of the host. The emergence of decreased ciprofloxacin (CIP) susceptibility (DCS) requires a prolonged antibiotic course with increased dosage, leading to threatening, adverse effects. Moreover, antibiotic-resistant bacteria can persist in biofilms, causing serious diseases. Hence, we validated the in vitro and in vivo efficacy of ciprofloxacin-loaded mesoporous silica nanoparticles (CIP-MSN) using a rat model of salmonella infection to compare the oral efficacy of 5 mg/kg body weight CIP-MSN and a traditional treatment regimen with 10 mg/kg CIP postinfection. Our results revealed that mesoporous silica particles can regulate the release rate of CIP with an MIC of 0.03125 mg/L against DCS S. typhimurium with a greater than 50% reduction of biofilm formation without significantly affecting the viable cells residing within the biofilm, and a sub-inhibitory concentration of CIP-MSN significantly reduced invA and FimA gene expressions. Furthermore, oral supplementation of CIP-MSN had an insignificant effect on all blood parameter values as well as on liver and kidney function parameters. MPO and NO activities that are key mediators of oxidative stress were abolished by CIP-MSN supplementation. Additionally, CIP-MSN supplementation has a promising role in attenuating the elevated secretion of pro-inflammatory cytokines and chemokines in serum from S. typhimurium-infected rats with a reduction in pro-apoptotic gene expression, resulting in reduced S. typhimurium-induced hepatic apoptosis. This counteracted the negative effects of the S. typhimurium challenge, as seen in a corrected histopathological picture of both the intestine and liver, along with increased bacterial clearance. We concluded that, compared with a normal ciprofloxacin treatment regime, MSN particles loaded with a half-dose of ciprofloxacin exhibited controlled release of the antibiotic, which can prolong the antibacterial effect.

Pulsed dye laser alone versus its combination with topical ivermectin 1% in treatment of Rosacea: a randomized comparative study.

BACKGROUND: While the etiology of rosacea is multifactorial, it is not surprising that treatment has been controversial. Pulsed dye laser (PDL) has been successfully used to treat vascular components of rosacea. Ivermectin 1% cream is an emerging treatment of rosacea. OBJECTIVE: To provide a comprehensive clinical and dermatoscopic comparative study between the efficacy and safety of pulsed dye laser alone versus its combination with topical ivermectin 1% in the treatment of rosacea. MATERIALS AND METHODS: Thirty Patients were randomly divided into two groups. Group A (n = 15) treated with 585 nm PDL, and group B (n = 15) treated with 585 nm PDL and topical ivermectin 1% cream. All patients received four laser treatments with a 4-week interval. The efficacy of treatment was assessed by photographs and dermoscopic photomicrographs at baseline and 3 months after the final treatment. The patient's level of satisfaction was also recorded. RESULTS: At the 3-month follow-up, group B induced better clinical improvement than group A. However, this difference was not significant. No serious adverse events were observed in either treatment group. CONCLUSION: This study supports the efficacy of PDL treatment for patients with rosacea. PDL could be more effective when combined with ivermectin 1% cream.

Evaluation of plasma exeresis as a new technique for non surgical treatment of dermatochalasis.

BACKGROUND: Dermatochalasis is frequently associated with tissue ageing and leads to multiple functional and cosmetic issues. There are several possible medical and surgical treatments available, such as blepharoplasty and laser therapy. OBJECTIVE: The aim of this work was to evaluate plasma exeresis as a new technique for nonsurgical treatment of dermatochalasis of the upper eyelid. PATIENT AND METHODS: This clinical trial included 40 female patients with dermatochalasis. Each patient received 3 sessions of treatment with the technology of plasma exeresis with one-month interval. Final evaluation was performed three months after the last session by 2 blinded dermatologists and 2 ophthalmologists, lid laxity according to facial laxity rating scale (FLRS), marginal crease distance (MCD) before and after treatment and patient satisfaction score. RESULTS: There was a significant decrease in eye lid laxity (FLRS) after treatment where p < .001; 36 (90%) patients had change and 4 (10%) patients without change in general. There was a significant increase in MCD after treatment (p = .001). CONCLUSION: Plasma exeresis seems to improve appearance of the upper eyelid, without any serious adverse events and could be a valid solution for dermatochalasis especially in mild and moderate cases.

Evaluation of adding platelet-rich plasma to combined medical therapy in androgenetic alopecia.

BACKGROUND: Androgenetic alopecia (AGA) is a common hair loss disorder. OBJECTIVES: To evaluate the therapeutic effects of platelet-rich plasma (PRP) in androgenetic alopecia. METHODS: This study was done on 126 AGA patients, 42 patients survived as control group who received medical treatment, only other 84 patients were subdivided into two groups, and they received PRP sessions as co-adjuvant therapy using different methods administration. Patients were evaluated clinically, by dermoscopy and by digital dermoscopy to measure hair density and diameters before and after treatment. RESULTS: PRP-treated patients showed statistically significant increase in hair density and diameter measurements than control group. These results increased by using microneedling as a method of PRP administration. CONCLUSION: In AGA, the addition of "PRP with microneedling" to the combined medical treatment increases its efficacy and shortens the time needed for optimum improvement. STUDY DESIGN: Single-blinded randomized controlled study.

Immunotherapy in cutaneous warts: comparative clinical Study between MMR vaccine, tuberculin, and BCG Vaccine.

BACKGROUND: Warts are common viral infection of the skin. Treating warts are still an ongoing challenge and no general agreement is reached, on the best treatment, despite different therapeutic approaches. Intralesional (IL) immunotherapy has recently been shown to be effective in treating various wart forms. AIMS: To assess the efficacy and safety of IL tuberculin, IL MMR vaccine, and intradermal (ID) BCG vaccination in treating viral warts. PATIENTS AND METHODS: Sixty patients with single or multiple warts were divided equally into three groups. Group A received IL MMR vaccine, and group B received IL tuberculin every 3 weeks (maximum 3 times). Group C received ID BCG vaccination in the arm with one month interval (maximum 3 times). Recurrence was followed up for 6 months. RESULTS: In group A, complete response occurred in 30%, partial response in 5%, and no response in 65%. In group B, complete response occurred in 45%, partial response in 20%, minimal response in 10% and no response in 25%. In group C, complete response occurred in 70%, partial response in 5%, minimal response in 5%, and no response in 20%. No recurrence was observed in group A and B but occurred in one patient in group C with the same lesion. CONCLUSIONS: Immunotherapy by IL tuberculin and ID BCG vaccination are safe, effective, and inexpensive techniques in treating all types of warts even if recalcitrant or multiple but immunotherapy by IL MMR vaccine has shown less effectiveness and less safety technique.

Effect of acute gold nanorods on reproductive function in male albino rats: histological, morphometric, hormonal, and redox balance parameters.

In this study, we investigated the effect of acute administration of gold nanorods (AuNRs) on testicular function, sexual hormones, and oxidative stress parameters in male albino rats. Forty mature male albino rats were divided into two equal groups (n = 20/each). The first group received 1 ml saline solution intraperitoneally (i.p.). The second group received single i.p. injection of 75 µg 50 nm AuNRs/kg/bwt. Five rats from each group were sacrificed on days 1, 3, 7, and 14 post treatment and blood samples were collected for hormonal and biochemical analysis. Testes were collected from each group at each time point for histopathology, morphometric, and transmission electron microscope analyses of testis and epididymis. Results indicated that i.p. injection of AuNRs did not produce any histopathological changes. Morphometric analysis of testicular samples revealed that the height of lining epithelium was significantly (P < 0.05) higher in AuNR group on days 3 and 14 post treatment, and the minor axis of seminiferous tubules was higher (P < 0.05) in AuNR-injected rats than in control group. For the epididymis, the number of spermatozoa was significantly (P < 0.05) higher on days 7 and 14 after AuNR injection when compared with control rats. AuNRs were not detected by TEM at all time points of the experiment. Serum analysis demonstrated that total and free testosterone values significantly (P < 0.05) increased on days 1, 3, 7, and 14 post AuNR injection. LH was higher (P < 0.05) in AuNRs-injected rats on days 3, 7, and 14 post injection, while FSH values were higher (P < 0.05) in AuNR group on days 3 and 14. Malondialdehyde significantly (P < 0.05) decreased on days 3, 7, and 14 in AuNR group, while catalase, glutathione peroxidase, and superoxide dismutase values were significantly (P < 0.05) elevated on days 3, 7, and 14 in AuNRs-injected rats compared with control group. In conclusion, intraperitoneal injection of 50 nm AuNRs is safe on the reproductive function and has an antioxidant action.

Effect of Bone Marrow-Derived Mesenchymal Stem Cells on Ischaemic-Reperfused Hearts in Adult Rats with Established Chronic Kidney Disease.

BACKGROUND AND OBJECTIVES: Bone marrow-derived mesenchymal stem cells (BM-MSCs) are adult multipotent non-haematopoietic stem cells that have regeneration potential. The current study aimed to detect the ability of BM-MSCs to improve kidney and cardiac functions in adult rats with established chronic kidney disease. METHODS: Rats were divided into sham-operated control, untreated sub totally nephrectomised and treated sub totally nephrectomised groups. Body weight, kidney and cardiac tissue weights, plasma creatinine and urea levels and arterial blood pressure were measured. ECG was recorded, and an in vitro isolated heart study was performed. RESULTS: Stem cell treatment decreased the elevated plasma creatinine and urea levels and decreased systolic, diastolic and mean arterial blood pressure values. These changes were accompanied by a decrease in glomerular hypertrophy with apparent normal renal parenchyma. Additionally, BM-MSCs shortened Q-To and Q-Tc intervals, all time to peak tension values, the half relaxation value at 30 min of reperfusion and the contraction time at 15 and 30 min of reperfusion. Moreover, stem cell treatment significantly increased the heart rate, QRS voltage, the peak tension at the 15- and 30-min reperfusion time points and the peak tension per left ventricle at the 30-min reperfusion time point compared to the pre-ischaemia baseline. BM-MSCs resolve inter muscular oedema and lead to the re-appearance of normal cardiomyocytes. This improvement occurs with the observations of BM-MSCs in renal and heart tissues. CONCLUSIONS: BM-MSCs can attenuate chronic kidney disease progression and the associated cardiac electrophysiological and inotropic dysfunction.

Serum-soluble CXCL16 in juvenile systemic lupus erythematosus: a promising predictor of disease severity and lupus nephritis.

Juvenile systemic lupus erythematosus (jSLE) is a multisystem autoimmune disease of unpredicted course and prognosis. Rates of organ involvement in SLE are higher in children, and overt lupus nephropathy is more often a presenting manifestation of SLE in children than adults. Inflammatory soluble chemokine CXC motif-ligand 16 (sCXCL16) is an important pathogenic mediator in inflammatory diseases as SLE. Herein, we aimed to evaluate serum level of sCXCL16 in jSLE patients in comparison to healthy controls and to correlate it with disease activity and extent of cutaneous and renal affection, to detect its possible role in disease pathogenesis. Serum level of sCXCL16 was determined by ELISA in 27 patients with jSLE (mean age 12.35 years ± 2.26 SD) in addition to 30 age- and sex-matched healthy controls and correlated with clinical and laboratory parameters in lupus group. Serum sCXCL16 was significantly higher in jSLE patients than controls (P ≤ 0.001), and it correlated positively with SLE disease activity, severity of lupus nephritis, 24-h urinary protein, anti-dsDNA titre, blood pressure, and ESR, while it correlated negatively with serum C3 levels. Serum sCXCL16 was higher in jSLE patients with alopecia and malar erythema. Serum sCXCL16 might play a role in inflammatory pathogenesis of jSLE particularly in periods of disease activity. It might serve as a future useful laboratory test for detection of jSLE activity, renal insult, and its severity which might limit the need for invasive renal biopsies in such a delicate patient population.

Pulsed dye laser versus intense pulsed light in melasma: a split-face comparative study.

BACKGROUND: Recent reports suggest that melasma may have a vascular component. Vascular targeting lasers and light treatment can be a therapeutic option that will provide benefits to the patients. OBJECTIVES: To compare the efficacy and tolerability of pulsed dye laser (PDL) and intense pulsed light in treatment of melasma. PATIENTS AND METHODS: Twenty-eight Egyptian female patients with melasma were treated with PDL on the right hemiface (Group A) and with the intense pulsed light on the left hemiface (Group B). Clinical assessment was performed according to the hemifacial modified Melasma Area and Severity Index score (mMASI). Tissue biopsies were taken from patients for immunohistochemical staining with vascular endothelial growth factor (VEGF) antibody. RESULTS: The hemifacial mMASI score was significantly reduced after treatment in studied groups with no statistically significant difference. Intense pulsed light (IPL) group showed higher efficacy of treatment than PDL group in the epidermal melasma and in melasma lesions which had a vascular component. The expression level and intensity score of VEGF were significantly reduced after treatment in both groups. CONCLUSIONS: Both PDL and IPL were effective and safe treatment modalities for lightening of melasma. VEGF can be proved as a possible mechanism underlying the action of both PDL and IPL on melasma.

Modulators of very low voriconazole concentrations in routine therapeutic drug monitoring.

Very low voriconazole concentrations are commonly observed during therapeutic drug monitoring. Possible mechanisms include inappropriate dose selection, rapid metabolism (as a result of genetic polymorphisms or enzyme induction), and also nonadherence. We aimed to develop a method to distinguish between rapid metabolism of and nonadherence to voriconazole by quantification of voriconazole metabolites. In addition, the relevance of common genetic polymorphisms of CYP2C19 was assessed. In a retrospective study, samples with voriconazole concentrations 0.2 µg/mL or less in routine therapeutic drug monitoring (as quantified by high-performance liquid chromatography) were evaluated. Voriconazole and its N-oxide metabolite were quantified in residual blood using a highly sensitive liquid chromatography-tandem mass spectroscopy method (lower limit of quantitation = 0.03 µg/mL). Genetic polymorphisms of CYP2C19 were determined by real-time polymerase chain reaction using the hybridization probe format and the polymerase chain reaction-random fragment length polymorphism format. A total of 747 routine therapeutic drug monitoring plasma/blood samples of 335 patients treated with systemic voriconazole were analyzed and in 18.7% of all samples, voriconazole concentrations 0.2 µg/mL or less were found. In 32 samples (30 patients) with adequate dosage and timing of blood withdrawal, nonadherence was strongly suspected in seven patients because voriconazole-N-oxide concentrations were below 0.03 µg/mL, which was not observed in a reference group of 51 healthy volunteers with controlled drug intake. In 10 patients, of whom EDTA blood was available, the ultrarapid metabolizer genotype (CYP2C19*1\*17, CYP2C19*17\*17) was found in 80% and its prevalence was significantly higher as compared to a reference group (P = 0.02). In conclusion, quantification of voriconazole-N-oxide allowed for detection of suspected nonadherence in one of four patients with very low voriconazole concentrations. In the remaining patients, ultrarapid metabolism resulting from the CYP2C19*17 polymorphism appears to play a major role. Thus, in the case of voriconazole therapy failure, both nonadherence and genetic factors have to be considered.

Appropriateness of timing of drug administration in electronic prescriptions.

INTRODUCTION: For a small number of drugs circadian variability has been shown to modify efficacy, safety, or pharmacokinetics. OBJECTIVE OF THE STUDY: We aimed to develop a database containing optimum timing of drug administration and to test how well such information is considered in daily practice. SETTING: University hospital providing primary and tertiary care. METHODS: We included data of randomised controlled trials collected from Embase and Medline studying the impact of the timing of drug administration on pharmacodynamics, pharmacokinetics, and adverse events. Data were analysed and weighed according to an algorithm considering trial design and assessed endpoints. Each branch of the algorithm led to a specific recommendation as to the time of the day the drug should be administered. A second algorithm was used to establish a recommendation if studies differed in their conclusion. Subsequently we retrospectively analysed the dosing time in consecutive electronic prescriptions issued at our institution in 2007. RESULTS: For 30 active compounds randomised controlled trials were published assessing optimum timing of their administration. In 33% of them timing had no impact on clinical endpoints while the administration at a certain time of the day significantly improved the outcome of another 64% no clear statement was made for one drug (ketoprofen). We then analysed 478,864 electronic prescriptions. Two percent of them contained drugs with known circadian variability. Only in 14% the suggested time was considered with a range between 0% for telmisartan (bedtime administration) and 85% for perindopril (morning administration). CONCLUSION: Thus far, dedicated studies on circadian responsiveness to drugs are sparse and for the few drugs with unequivocal evidence this information is only rarely considered in daily practice. Integration of circadian dosing information into a clinical decision support system linked to electronic prescribing may be one promising way to make this information widely accessible.