Phenylketonuria from the perspectives of patients in Türkiye.

BACKGROUND: The present study aimed to determine the problems, unmet needs and expectations of phenylketonuria (PKU) patients in Türkiye regarding follow-up and treatment in order to provide data for future planning and implementations on PKU. METHODS: The study included patients diagnosed with PKU and/or their parents. They were informed about the study via phone calls and their verbal consents were obtained. Questions in the data collection forms, which were established separately for pediatric, adolescent, and adult age groups, were applied during the interviews and the answers were recorded. RESULTS: Among 182 classical PKU patients, 66 (36.3%) were in the pediatric group (0-12 years old), 44 (24.2%) were in the adolescent group (13-19 years old), and 72 (39.5%) were in the adult group (≥ 20 years old). In all patient groups, phenylalanine-restricted diet and medical nutrition products were the main options for treatment. The median of the last measured blood phenylalanine concentration (patient-reported) was 290 µmol/L, 425 µmol/L, and 750 µmol/L in the pediatric, adolescent, and adult groups, respectively. The frequency of blood testing for serum phenylalanine level according to the age groups was appropriate in nearly half of the patients. While the majority of the patients have been visiting the metabolism center they have been diagnosed with PKU for control, considerable proportion of the patients would like to change the center or the doctor they visit for control if they could. It was determined that nearly half of the patients had trouble in accessing the metabolism center. Treatment options' being limited and expensive were the major problems. The main requests of the patients and patient relatives included easier access to the metabolism centers and more options for treatment and diet. CONCLUSIONS: Access to the services should be easier to improve the patients' follow-up and treatment. There is need for low-cost, easily applicable, and accessible nutrition products and effective novel pharmacological agents. Focusing on these issues in health policies by providing pedagogic/psychological support, establishing support programs also comprising the families, and increasing the awareness activities were the key outcomes.

The effect of taurine on flap perfusion and viability in random pattern flaps in rats.

BACKGROUND: In present study, the effect of taurine on flap perfusion and viability was examined using the modified random pattern dorsal flap model (DFM). MATERIALS AND METHODS: Eighteen rats were included and divided equally (n=9) to taurine treatment and control groups in this study. Taurine treatments were given orally at a dose of 100 mg/kg/day. Taurine group received taurine, starting 3 days before the operation till the postoperative 3rd day. Angiographic images were recorded when the flaps were sutured back and on postoperative 5th and 7th days. Necrosis calculations were made with all the images obtained by the digital camera and the indocyanine green angiography. Fluorescence intensity, fluorescence filling rate and flow rate of DFM were calculated by the SPY device and the SPY-Q software. All flaps were analyzed histopathologically, also. RESULTS: Perioperative taurine treatment significantly reduced necrosis rates and increased the fluorescence density, the fluorescence filling rate and the flap filling rates in the DFM (p<0.05). Reduced amounts of necrosis, ulcer and polymorphonuclear leukocyte supported the beneficial effect of taurine histopathologically (p<0.05). CONCLUSIONS: Taurine may be used as an effective medical agent for prophylactic treatment options in flap surgery.

Regulatory Implications for considering flexible resources in network expansion planning: main lessons from regional cases in the H2020 FlexPlan project.

The FlexPlan Horizon2020 project aimed at establishing a new grid planning methodology which considers the opportunity to introduce new storage and flexibility resources in electricity transmission and distribution grids as an alternative to building new grid elements, in accordance with the intentions of the European Commission regulatory package "Clean Energy for all Europeans". FlexPlan creates a new innovative grid planning tool which is intended to go beyond the state of the art of planning methodologies by including the following innovative features: assessment of best planning strategy by analysing in one shot a high number of candidate expansion options provided by a pre-processor tool, simultaneous mid- and long-term planning assessment over three grid years (2030-2040-2050), incorporation of full range of cost benefit analysis criteria into the target function, integrated transmission distribution planning, embedded environmental analysis (air quality, carbon footprint, landscape constraints), probabilistic contingency methodologies in replacement of the traditional N-1 criterion, application of numerical decomposition techniques to reduce calculation efforts and analysis of variability of yearly RES and load time series through a Monte Carlo process. Six regional cases covering nearly the whole European continent are developed in order to cast a view on grid planning in Europe till 2050. The final step in FlexPlan was formulating guidelines for regulators and planning offices of system operators, by indicating to what extent system flexibility can contribute to reduce overall system costs (operational and investment) yet maintaining current system security levels and which regulatory provisions could foster such process. This paper focuses on the regulatory issues, which were uncovered during the initiation phase and of the project and refined in throughout six regional cases. In order to substantiate this, the paper explains in brief the developed and applied FlexPlan methodology and its testing in six regional cases.

Steroid Injection and Biomarker Levels in the Treatment of Unicameral Bone Cysts: Can we Estimate the Result?

BACKGROUND: Steroid injection is a common method in the treatment of unicameral bone cysts (UBC). In this study, the relationship between the clinical results and inflammatory molecules' levels in the cyst fluid was evaluated after three repeated steroid injections in UBC subjects. METHODS: Twenty-one patients diagnosed with UBC were treated with methylprednisolone acetate (MPA) injections. Patients were given three injections, each containing MPA, 6-8 weeks apart. Plain radiographs were obtained and cyst healing was evaluated according to modified Neer classification. Cyst fluid samples were taken. Samples were taken at first and last operations and were studied using the ELISA method to examine IL-1ß, PGE2, MMP-1, and VEGF-A levels. RESULTS: There were 17 and 4 cases localized to the humerus and femur, respectively. The mean follow-up period was 36.9 months. Complete recovery was achieved in 13 patients (61.9%) receiving MPA. Four patients (19%) recovered with residual lesions. One patient (4.7%) did not respond to steroid injections at all. In three patients (14.2%) the cyst recurred. Results were satisfactory in 17 patients (80.9%) and totally unsuccessful in 4 patients (19%). IL-1ß, PGE2, and MMP-1 levels in cyst fluid were not affected by injection (p > 0.05), but VEGF-A levels decreased significantly with cyst healing (p = 0.01). CONCLUSION: Steroid injection is a good choice in the treatment of UBC because of its less aggressive and relatively good outcome. It may be considered to evaluate the response to treatment by performing biomarker monitoring especially VEGF-A in repeated injections. LEVEL OF EVIDENCE: Level II study.

Dipyrone attenuates cerebral vasospasm after experimental subarachnoid hemorrhage in rabbits.

BACKGROUND: The purpose of this study was to evaluate the effect of the systemic administration of dipyrone in a triple subarachnoid hemorrhage (SAH) model of cerebral vasospasm in rabbits. METHODS: Experimental subarachnoid hemorrhage was induced in rabbits by injecting autologous arterial blood into the cisterna magna. Digital subtraction angiographies (DSA) were performed before and after the first experimental SAH, and at 30, 45, 60 minutes and 72 hours after the first drug administration to measure the diameter of basilar artery. Intracisternal blood injections were repeated 24 and 48 hours after the first injection. Dipyrone (N.=20) or 0.9% NaCl (N.=20) was administered intravenously after initial SAH induction and repeated at 8-hour intervals intramuscularly. After sacrificing by perfusion-fixation, basilar arteries were removed and sectioned for transmission electron microscopic (TEM) examination. RESULTS: The average basilar artery diameter measured by DSA was 724±19 µm in the control, and 686±29 µm in treatment group before SAH. After SAH, mean basilar artery diameters decreased to 71% and 68% of their basal values, respectively. Dipyrone significantly attenuated the basilar artery diameter at one and 72 hours after the first drug administration, in comparison to the control group. TEM studies showed more edema in the endothelial cells of the basilar arteries of the control group when compared to the treatment group. CONCLUSIONS: Dipyrone showed a beneficial effect in autologous blood-induced basilar artery vasospasm in rabbits. These data support the idea that dipyrone can be a potential candidate drug to be tested in patients suffering from cerebral vasospasm secondary to subarachnoid hemorrhage.

Severe drug interactions and potentially inappropriate medication usage in elderly cancer patients.

PURPOSE: Due to more comorbidities, polypharmacy is common in elderly patients and drug interactions are inevitable. It is also challenging to treat an elderly patient with a diagnosis of cancer. Prevalence and clinical impacts of drug interactions and using potentially inappropriate medications (PIMs) have been studied in geriatric patients. However, these are not well defined in oncology practice. The purpose of this study is to define the prevalence of PIMs and severe drug interactions (SDIs) in elderly cancer patients and investigate the factors associated with them. METHODS: Patients more than 65 years of age in both inpatient and outpatient clinics were evaluated. Patient, disease characteristics, and medications used were collected by self reports and medical records. Drug interactions were checked with Lexicomp® and PIM was defined with 2012 update of Beers criteria. Severe drug interactions are defined with category D or X DIs. Logistic regression was used to compute odds ratios (ORs) and 95 % confidence intervals (CIs) for the association between SDIs, PIMs, and clinical parameters. RESULTS: Four hundered and forty-five elderly patients (286 outpatient, 159 inpatient), with a median age of 70 (65-89) were evaluated. SDIs were present in 156 (35.1 %) of patients, 81 (28.3 %), and 75 (47.2 %) for outpatient and inpatients, respectively (p < 0.001). PIMs were present in 117 (26.6 %) of the patients, 40 (14.2 %), and 77(48.4 %) for outpatient and inpatients, respectively (p < 0.001). In multivariate analysis; polypharmacy (≥5 drugs), inpatient status and diagnosis of lung cancer were associated with severe DIs. Polypharmacy, inpatient status, and bad performance score (ECOG 3-4) were associated with PIMs. CONCLUSIONS: Nearly one third of the elderly cancer patients are exposed to severe drug interactions and PIMs. Clinicians dealing with elderly cancer patients should be more cautious when prescribing/ planning drugs to this group of patients. More strategies should be developed in this group of patients to minimize the medications prescribed and prevent severe DIs.

Metamizole: an effective solution for vasospasm.

OBJECTIVE: Vasospasm is a major problem during microsurgery, and a variety of pharmacological agents are used to alleviate vasospasm. This study aimed to demonstrate the effect of metamizole on vasospasm and to compare it with lidocaine and papaverine, both of which are commonly used to correct vasospasm. METHODS: Thirty-five female rats were randomly divided into four groups: Group 1, 2, 3, and 4, which were the control (n = 8), metamizole (n = 9), papaverine (n = 9), and lidocaine (n = 9) treatment groups, respectively. Both femoral arteries of all of the rats were dissected, and they were immediately photographed. The pharmacological agents or saline in the control group were topically applied to the arteries, accordingly. The arteries were photographed again at time points 5, 10, 20 and 30 minutes after application of the agents. The images were transferred to a computer and the arteries' diameters were measured in mm. RESULTS: All of the pharmacological treatments increased the diameter of the arteries significantly during the observation period. However, comparison between the groups indicated that metamizole and papaverine produced significantly more vasodilation than the lidocaine group, for all time points measured after application. CONCLUSION: These findings show that topically applied metamizole is as effective as papaverine at alleviating vasospasm during the 30 minutes time interval. This administration may be considered as a good alternative to correct vasospasm during microsurgery.

Comparison of the effects of systemic sildenafil, tadalafil, and vardenafil treatments on skin flap survival in rats.

OBJECTIVE: The most important issue in flap surgery is flap viability. This study aimed to compare the effects of most commonly used phosphodiesterase type 5 (PDE5) inhibitors on flap survival. METHODS: A 3 × 9 cm flap was elevated from the dorsum of 32 Wistar albino rats. In the control group, saline was administered 2 hours before the flap elevation and continued for 2 days after the surgery. In the sildenafil, tadalafil, and vardenafil groups, the related drug was administered. Blood flow in the flaps was monitored with laser Doppler flowmetry. On postoperative day 7, flaps were photographed and biopsies were obtained. RESULTS: The ratios of flap necrosis area in the tadalafil, sildenafil, and vardenafil groups were lower than that in the control group, but without significant difference (p = 0.077). Histopathological evaluation revealed no significant difference among the groups. CONCLUSION: The ratio of flap necrosis area tended to be lower in the groups receiving oral PDE5 inhibitors than in the control group, although not statistically significant. The role of PDE5 inhibitors needs to be evaluated in larger studies before a conclusion can be made regarding their effects on flap viability.

Critical appraisal of air pouch infection model in rats.

The aim of this study was to assess the efficacy and pharmacokinetic profiles of gentamicin, vancomycin, and levofloxacin in a rat air pouch model, in which Staphylococcus aureus (ATCC 25293) was used as the test organism. Antibiotic treatments (i.p.) were started 1 hour after bacterial inoculation and continued for 5 days. Bacterial counts and antibiotic concentrations were determined in pouch exudates that were obtained on the 5th day of antibiotic treatment. The following observations were made: 1) The concentrations of gentamicin or vancomycin in the exudate were found to be below the detection limit. 2) Levofloxacin and ciprofloxacin exhibited a dose-dependent effect on bacterial counts in the exudate. 3) The antibacterial efficacy of levofloxacin was found to be enhanced when the total daily dose of 10 mg was divided into smaller parts. The present study also showed that the air pouch infection model was a valuable tool to assess the pharmacokinetic and pharmacodynamic properties of antibiotics.

The effect of resveratrol on blood pressure in a rat model of preeclampsia.

OBJECTIVE: To examine the hypothesis that resveratrol administration could result in blood pressure and blood flow decrease in a rat preeclampsia model. MATERIALS AND METHODS: Desoxycorticosterone acetate (DOCA) was used to produce hypertension. The Wistar albino rats were divided randomly into three groups: control (n = 12), DOCA injected (n = 11), and DOCA injected and resveratrol treated (n = 13). Rats were sacrificed on gestational day 16-20. The systolic blood pressure was measured by the tail-cuff method. Urine protein was expressed as protein/creatinine. Laser Doppler measurements of the blood flow were made in one placenta, the left kidney and both parietal lobes of brain. Placentas were examined by light microscopy. RESULTS: DOCA injected group exhibited significant differences in blood pressure and protein/creatinine. Mean blood pressure in DOCA-treated rats was 130.1 ± 12.9 mmHg at baseline and 148.4 ± 20.1 mmHg at the time of euthanization (p = 0.044). Resveratrol did not significantly affect blood pressure, placental and renal blood flows. There were also no significant differences in placental pathology parameters among the three groups. CONCLUSION: The present study demonstrated that resveratrol did not decrease blood pressure, and did not result in a significant response in blood flows and placental pathology parameters.

Does adjuvant antibiotic treatment after drainage of anorectal abscess prevent development of anal fistulas? A randomized, placebo-controlled, double-blind, multicenter study.

BACKGROUND: The risk of fistula formation is a major concern after incision and drainage of an anorectal abscess. OBJECTIVE: Our objective was to the test the effects of antibiotic treatment on fistula formation after incision and drainage of anorectal abscesses. DESIGN: Randomized, placebo-controlled, double-blind study. SETTING: Multicenter trial at 3 teaching hospitals in Turkey. PATIENTS: Patients who underwent abscess drainage between September 2005 and January 2008 were evaluated for eligibility. Exclusion criteria included penicillin allergy, antimicrobial agent usage before enrolment, other infection, previous anorectal surgery, inflammatory bowel disease, suspicion of Fournier gangrene, secondary and recurrent anorectal abscesses, anal fistula at time of the surgery, immune compromised states, and pregnancy. INTERVENTION: Patients were randomly assigned to receive placebo or amoxicillin-clavulanic acid combination treatment for 10 days after abscess drainage. MAIN OUTCOME MEASURES: The primary end point was rate of anorectal fistula formation at 1-year follow-up. RESULTS: : Of 334 patients assessed for eligibility, 183 entered the study (placebo, 92; antibiotics, 91). Data were available for per-protocol analysis from 151 patients (placebo, 76; antibiotics, 75) with a mean age of 37.6 years; 118 patients (78.1%) were men. Overall, 45 patients (29.8%) developed anal fistulas during 1-year follow-up. Fistula formation occurred in 17 patients (22.4%) in the placebo group and in 28 patients (37.3%) in the antibiotic group (P = .044). Risk of fistula formation was increased in patients with ischiorectal abscess (odds ratio, 7.82) or intersphincteric abscess (odds ratio, 3.35) compared with perianal abscess. CONCLUSION: Antibiotic treatment following the drainage of an anorectal abscess has no protective effect regarding risk of fistula formation.

Effect of systemic piracetam treatment on flap survival and vascular endothelial growth factor expression after ischemia-reperfusion injury.

The effects of piracetam on flap survival, ischemia-reperfusion (I/R) injury, and vascular endothelial growth factor (VEGF) expression were evaluated in this study. Unipedicled epigastric flap model was used in 36 rats and was evaluated within 4 groups. The flap was elevated and untreated in Group 1. Postoperative piracetam treatment was given for 7 days in Group 2. In Group 3, 4 hours of ischemia and 2 hours of reperfusion were applied. I/R was applied to Group 4 and piracetam was given 30 minutes before reperfusion and postoperatively for 7 days. Laser Doppler flowmetry was used to measure blood flow changes. VEGF expression was determined using immunohistochemical methods on tissue samples taken after the completion of 2 hours reperfusion in groups 3 and 4. Flap necrosis was measured on the day 7 in all groups. Blood flow rates did not show significant difference between piracetam treated and untreated I/R groups. Piracetam significantly reduced necrosis area both in ischemic and nonischemic flaps ( P < 0.05). VEGF expression was significantly increased in piracetam-treated Group 4 compared with Group 3 ( P = 0.005). This experimental study demonstrates that systemic piracetam treatment improves survival of pedicled flaps, reduces necrosis amounts, and increases VEGF expression in I/R induced flaps.

The role of metamizol induction for the detection of perfusion reversibility on thallium-201 myocardial perfusion scintigraphy.

OBJECTIVE: Metamizol, probably with its vascular smooth muscle relaxant effect, enhances rest myocardial perfusion with the use of technetium-99m-methoxyisobutylisonitrile. We aimed to investigate whether metamizol induction is also able to increase the detectability of the ischemic/jeopardized myocardium during thallium-201 myocardial perfusion scintigraphy (MPS). METHODS: Twenty patients who had partially reversible/irreversible perfusion defects on their routine stress-redistribution-reinjection thallium-201 MPS were enrolled and metamizol-induced thallium-201 MPS (111 MBq thallium-201 was injected 45 min after 1 g oral metamizol) was acquired (10 min, 1 and 3 h later). Routine MPS and metamizol-induced MPS images were interpreted on the model of 17 segments using a visual uptake score (VUS; 0=normal, 1=mild, 2=moderate, 3=significant decreases, 4=no uptake). Thallium-201 uptake ratios (mean counts in the region of the perfusion defect/mean counts in the region of the normal-perfused wall) were calculated for each MPS. Blood pressure was monitored at 15-min intervals. MPS were compared with coronary angiography results. RESULTS: Visual uptake score and thallium-201 uptake ratio results indicated that in the first and third hour metamizol-induced thallium-201 uptake was significantly higher (P<0.001) than the redistribution/reinjection studies in 26 ischemic myocardial walls. Fourteen myocardial walls showed no thallium-201 uptake on either MPS and were considered as myocardial infarction. Statistically significant but asymptomatic decreases in blood pressure were observed. Coronary angiography results were in concordance with metamizol-induced MPS. CONCLUSION: Metamizol increases the detectability of ischemic/viable myocardium during MPS with thallium-201 and could be used with MPS.

Beta-estradiol reduces lipid peroxidation and depth of injury in cold-induced brain injury model.

Estrogen has neuroprotective effects in neurodegenerative disorders and models of neuronal damage. The effectiveness of estradiol (EST) (1 mg/kg and 10 mg/kg doses) in cold-induced brain injury (CIB) model was evaluated and compared with standard dexamethasone treatment. Forty-eight male Wistar rats (250-300 g) were randomly divided into 6 groups: sham operated, CIB + no treatment, CIB + 1 mg/kg dexamethasone, CIB + 1 mg/kg EST, CIB + 10 mg/kg EST, CIB + vehicle (ethanol). Rats were placed on stereotaxic frame and a craniotomy of 5 mm diameter was performed on the parietal lob under general anesthesia (ketamine+xylazine). A metal probe of 5 mm diameter was cooled (2 min) in liquid nitrogen (-190 degrees C) and was applied on the craniotomy area for 3 min. The treatment was started immediately after the CIB. Twenty-four hours later the whole brain was isolated and study parameters were assessed. The parameters were tissue wet/dry weight ratio, lipid peroxidation, and histopathological examination of the depth of injury. Both 1 mg/kg dexamethasone and 1mg/kg EST treatment significantly reduced all the measured injury parameters, whereas 10 mg/kg EST had no effect on any of the parameters. This study shows that EST at lower concentrations is beneficial in this model of cold-induced brain injury. However, the effect of EST is dual and higher concentrations, in contrast, do not affect or even may be detrimental in brain injury.

[Quality of life in major depressive disorder: a cross-sectional study]. / Major Depresif Bozuklukta Yasam Kalitesi: Kesitsel Bir Calisma.

OBJECTIVE: To investigate quality of life and its association with depression in patients with major depressive disorder. METHOD: The study included 74 patients diagnosed with major depressive disorder according to DSM-IV. The Hamilton Depression Rating Scale (HAM-D) was used to assess the severity of depression; and the, Medical Outcomes Study Short Form-36 (MOS SF-36) and EuroQol 5-D (EQ-5D) were used to measure quality of life. RESULTS: In the assessment of quality of life, it was determined that Patients with major depressive disorder scored significantly lower on all domains of MOS SF-36 compared to Turkish normative data. The depressive disorder patients had lower EQ-5D health utility index scores, in comparison to Turkish normative data. There was a significant negative correlation between mean HAM-D score and all domains of MOS SF-36 and EQ-5D health utility index scores. When quality of life in depressive patients was compared according to episode type, patients with recurrent type major depressive disorder had lower quality of life in terms of physical functioning, general health perception, and physical component summary score than patients with single episode type major depressive disorder. CONCLUSION: All domains of quality of life were lower in patients with major depressive disorder and quality of life decreased as severity of depression increased. Physical health perception was impaired to a greater degree in patients with recurrent major depressive disorder when compared with single episode depressive patients.

99mTc sestamibi myocardial perfusion scintigraphy with the novel use of metamizol for the detection of perfusion reversibility.

PURPOSE: This study aims to investigate whether induction with metamizol, an analgesic-antipyretic drug having spasmolitic activity, could be used to increase the detectability of ischemic/jeopardized myocardium during MPS (myocardial perfusion scintigraphy). MATERIALS AND METHODS: Metamizol-enhanced rest MPS (45 min after administration of 1 g metamizol orally, 740 MBq (99m)Tc sestamibi was injected, MPS was acquired 45 min later) was performed in 21 patients who had perfusion defects on their previous stress-rest (99m)Tc sestamibi MPS. Blood pressure was monitored at 15-min intervals. Stress, rest, metamizol-rest MPS images were interpreted on the model of 20 segments using a visual uptake score (VUS; 0 = normal, 1 = mild, 2 = moderate, 3 = significant decreases, 4 = no uptake). (99m)Tc sestamibi uptake ratios (MIBI-UR; mean counts in the region of the perfusion defect/mean counts in the region of the normal-perfused wall) were obtained on each MPS and compared with each other. Average MIBI-UR in each scintigraphic examination was calculated. MPS were compared with coronary angiography results. RESULTS: VUS and MIBI-UR results showed that metamizol-rest MPS displayed the defect reversibility better than rest MPS. Of the 14 segments with fixed perfusion defects on stress-rest MPS, 8 showed improvement of perfusion after metamizol induction. In 33 segments, lesion reversibility was better delineated on metamizol-rest MPS. Metamizol-induced sestamibi uptake was significantly higher (p < 0.001) than stress/baseline rest examinations as calculated by the MIBI-UR. Blood pressure remained unaltered. Coronary angiography results were in concordance with metamizol induced MPS. CONCLUSIONS: Metamizol-enhanced rest MPS increases detectability of ischemic/viable myocardium during MPS. Metamizol should be discontinued like nitrates before stress MPS since it may mask the visualization of ischemic perfusion defects.

Efficacy and safety of topical nimesulide in the treatment of knee osteoarthritis.

BACKGROUND: Osteoarthritis (OA) affects mainly older people who are more sensitive to adverse effects of classic nonsteroidal anti-inflammatory drugs. Recent publications indicate that topically applied nonsteroidal anti-inflammatory drugs are effective and much safer than their oral analogues. OBJECTIVES: In this double-blind, randomized, placebo-controlled study design, we aimed to investigate whether topical nimesulide treatment has any beneficial effect in knee OA patients. METHODS: Seventy-four adult knee OA outpatients were enrolled. We used Western Ontario and McMaster Universities OA Index (WOMAC), Nottingham Health Profile (NHP), and patient and physician global satisfaction scores. WOMAC and NHP scores were measured at the initial and final visit. Treatment group received topical nimesulide gel 1% on the knee skin 3 times a day whereas placebo group received an identical-appearing gel for 30 days. RESULTS: There was a significant improvement in the nimesulide treatment group for all 3 parameters and overall score of WOMAC between pretreatment and posttreatment values. The overall WOMAC scores was significantly better than placebo (P = 0.03), but physical functioning, stiffness, and pain scales did not reach statistical significance. For the NHP scores there was an improvement at "energy level," "pain," "physical motion," and "NHP distress" scores in the treatment group whereas no improvement was found in the placebo group. Between-group differences were not significant. Both patient and physician satisfaction scores were significantly better in the treatment group. CONCLUSION: This study shows that topical nimesulide gel can have beneficial effects and can improve quality of life in patients with knee OA.

Cost-minimization analysis comparing topiramate with standard treatments in migraine prophylaxis.

Migraine is a common disorder with a relatively high burden of disease from the perspective of both society and the individual patient. Optimizing the use of prophylactic treatment may decrease the frequency and severity of attacks thus reducing the burden of disease. In this regard, topiramate has been found to be as effective as propranolol in the prevention of migraine attacks. In the present study, a cost-minimization analysis was performed. Monthly preventive medication cost and price per migraine attack reduced were used as measures. In comparison with propranolol and flunarizine, topiramate was identified as being the most costly option for migraine prophylaxis with a monthly drug cost of USD 24.97-45.04 as compared with propranolol (USD 1.72-6.87) and flunarizine (USD 6.09-12.18). Current treatment options would appear to offer better value for money in achieving effective migraine prophylaxis unless additional benefits can be identified for topiramate in this patient group.

Vancomycin elimination in human infants with intrauterine growth retardation.

BACKGROUND: Intrauterine growth retardation (IUGR) results in substantial decrease in nephron number and renal and hepatic organ mass in experimental animals and newborn infants. Because the liver and the kidneys are the major organs for drug biotransformation and elimination, any decrease in their size and function may lead to impaired metabolism and elimination of drugs in newborns with IUGR. Our objective was to test the hypothesis that IUGR results in prolonged renal elimination of vancomycin in newborns. METHODS: Small for gestational age (SGA) infants (n = 20) were matched with appropriate for gestational age (AGA) infants (n = 123). Steady state peak and trough serum concentrations were used to calculate vancomycin clearance (Cl), volume of distribution (Vd) and half-life (t(1/2)) for each subject. Pharmacokinetic profiles were compared between groups. RESULTS: Overall, Cl, Vd and t(1/2) of vancomycin were the same between groups. However, stratification showed decreased Cl in those SGA versus AGA newborns 3-4 weeks old and in those newborns with a postconceptional age of 27-29 weeks. There was no difference in Vd, normalized for weight, between SGA and AGA babies. The half-life of vancomycin was similar across most groups but was prolonged in SGA newborns aged 3-4 weeks. CONCLUSIONS: Vancomycin Cl differs between SGA and AGA newborns. This difference is greatest early in life and normalizes between groups after the fourth week of life or after 29 weeks postconceptionally. Normalized Vd is similar between SGA and AGA newborns. The elimination of vancomycin is comparable between SGA and AGA infants, except before the fifth week of life, when SGA newborns may eliminate the drug more slowly. Specific vancomycin dose recommendations for SGA versus AGA neonates may therefore be justified during the first month of life.