Frequency of CYP2C9 polymorphisms in polynesian people and potential relevance to management of gout with benzbromarone

ObjectivesGout is a major health problem in Polynesians and allopurinol, the drug of choice for the management gout, appears to be less effective in Polynesian patients. The uricosuric drug benzbromarone is an alternative treatment but CYP2C9 poor metabolisers (PMs) may be at a heightened risk of benzbromarone-induced hepatotoxicity. The objectives of this study were to determine the frequency of the PM alleles CYP2C9*2 and CYP2C9*3 in New Zealand (NZ) Caucasian and Polynesian gout cohorts; and then to test for novel CYP2C9 polymorphisms in Polynesians.MethodsEight hundred and fifty-two Caucasians (537 controls, 315 gout patients) and 1072 Māori and Pacific Island (Polynesian) people (620 controls, 452 gout patients) were genotyped for CYP2C9*2 and CYP2C9*3. Forty Polynesians were screened for novel CYP2C9 polymorphisms using whole genome sequencing.ResultsFrequency of CYP2C9 PM alleles was significantly higher in Caucasians compared to Polynesians (CYP2C9*2: 13.5% versus 3.1%; CYP2C9*3: 5.5% versus 1.6%, P < 1.2E-11). Within Polynesians, CYP2C9 PM alleles were rarer in Western Polynesians (Samoa, Tonga) than Eastern Polynesians (NZ and Cook Island Maori; CYP2C9*2: 0.6% versus 2.5%; CYP2C9*3: 0.4% versus 2.0%; P < 0.03). A total of 152 SNPs were found by sequencing. None of these variants were predicted by in silico analysis to significantly impact on CYP2C9 expression or activity.ConclusionProspective CYP2C9 genotyping of Caucasian gout patients may be warranted for benzbromarone, whereas the low frequencies of CYP2C9 PM alleles in Polynesians suggests that the CYP2C9 polymorphism may be of little or no relevance to benzbromarone prescribing in this population.     

Polyarticular sonographic assessment of gout: A hospital-based cross-sectional study

ObjectiveTo assess the sonographic frequency of synovial effusion, synovial hypertrophy, synovitis, and double contour sign at joints commonly affected by gout and whether these features differ according to serum urate levels, disease duration, and use of urate-lowering therapy.MethodsParticipants with gout were recruited from rheumatology clinics. A detailed clinical assessment was undertaken of gout history, co-morbidities, medication, alcohol consumption, height, weight, clinical synovitis, tophi, and serum urate. Sonographic examination of the metatarsophalangeal joints, ankles, knees, metacarpophalangeal joints, wrists and elbows for synovial effusion, synovial hypertrophy, synovitis and double contour sign was undertaken. The mean number of joints affected were compared according to serum urate (< 360 μmol/L versus ≥ 360 μmol/L), urate-lowering therapy (yes/no), and disease duration (≤ 5 years versus > 5 years).ResultsForty patients participated in the study. Synovial effusion, synovial hypertrophy, synovitis, and double contour sign were identified in 36 (90%), 38 (95%), 24 (62%) and 37 (93%) participants respectively. Synovial effusion was seen most frequently at the knee (right 70%, left 68%) followed by the first metatarsophalangeal (right 48%, left 40%) and lesser metatarsophalangeal joints (right 45%, left 35%). Synovial hypertrophy, synovitis, and double contour sign were seen most frequently at the first metatarsophalangeal joint (hypertrophy: right 65%, left 60%; synovitis: right 18%, left 18%; double contour: right 60%, left 68%). These findings did not differ according to serum urate, disease duration, or use of urate-lowering therapy.ConclusionPolyarticular sonography frequently identifies synovial effusion, synovial hypertrophy, synovitis and double contour sign in patients with gout, particularly at the metatarsophalangeal joints and knees.     

Palpable tophi and more comorbidities associated with adherence to urate-lowering medical therapy in a Chinese gout cohort

ObjectiveUrate-lowering therapy (ULT) nonadherence is common and problematic in gout. Since, sociocultural factors affect adherence, we analyzed a Chinese cohort.MethodsWe studied 903 Chinese gout patients aged 46.4 ± 14.7 years (mean ± SD), uniquely extending to assay of 2-year medication possession ratio (MPR) ≥80% defined as high adherence. Multivariable logistic regression analyses evaluated factors linked with adherence and ULT target attainment.ResultsCharacterization of ULT outcomes in this cohort revealed that after 2 years ULT, MPR ≥80% patients had better target serum urate (SU) achievement (from 23.3% to 71.0%, P < 0.001), lower flare frequency and palpable tophi compared to MPR < 80%. However, only 44.7% of cohort subjects had MPR ≥80%. Male sex (OR 3.68), gout onset age >60 years (OR 3.51), disease duration >5 years (OR 1.70), more comorbidities (OR 1.74), baseline palpable tophi (OR 1.53), SU < 6 mg/dL (360 μmol/L) (OR 1.92) and more frequent follow-up visits (OR 1.98) were significantly associated with high adherence. Nevertheless, significant independent risk factors for failed SU target achievement included male sex (OR 0.36) and more comorbidities (OR 0.85).ConclusionDespite adherence to ULT linked to better outcomes for flares and tophi, the more adherent Chinese male patients and those with more comorbidities had decreased target SU attainment. Differences in adherence of Chinese gout patients compared to several primarily Western studies emphasize the importance of not stereotyping gout patients for projected nonadherence. Results underline the dual importance of identifying gout patients more likely to be ULT-adherent and leveraging adherence to drive treatment to SU target.     

2020 recommendations from the French Society of Rheumatology for the management of gout: Urate-lowering therapy

ObjectiveTo develop French Society of Rheumatology-endorsed recommendations for the management of urate-lowering therapy (ULT).MethodsEvidence-based recommendations were developed by 9 rheumatologists (academic or community-based), 3 general practitioners, 1 cardiologist, 1 nephrologist and 1 patient, using a systematic literature search, one physical meeting to draft recommendations and two Delphi rounds to finalize them.ResultsA set of 3 overarching principles and 5 recommendations was elaborated. The overarching principles emphasize the importance of patient education, especially the need for explaining the objective of lowering serum urate (SU) level to obtain crystal dissolution, clinical symptoms disappearance and avoidance of complications. ULT is indicated as soon as the diagnosis of gout is established. SU level must be decreased below 300 μmol/l (50 mg/l) in all gout patients or at least below 360 μmol/l (60 ml/l) when the 300 μmol/l target cannot be reached, and must be maintained at these targets and monitored life-long. The choice of the ULT primarily relies on renal function: in patients whose estimated glomerular filtration rate (eGFR) is above 60 ml/min/1.73 m², first-line ULT is allopurinol; in those with eGFR between 30 and 60 ml/min/1.73 m², allopurinol use must be cautious and febuxostat can be considered as an alternative; and in those whose eGFR is below 30 ml/min/1.73 m², allopurinol must be avoided and febuxostat should be preferred. Prophylaxis of ULT-induced gout flares involves progressive increase of ULT dosage and low-dose colchicine for at least 6 months. Cardiovascular risk factors and diseases, the metabolic syndrome and chronic kidney disease must be screened and managed.ConclusionThese recommendations aim to provide simple and clear guidance for the management of ULT in France.     

Plasma free carnitine in severe trauma: Influence of the association with traumatic brain injury

BackgroundMetabolic response to severe trauma requires early nutritional resuscitation. Carnitine is essential for lipolysis, the energy source during this hypercatabolic phase. However l-carnitine is not present in nutritional replacement solutions. Furthermore, free carnitine depletion, defined as carnitine plasma level under 36 μmol/L, was not adequately reported in adult patients with severe trauma. The aim of this study was to assess plasma free carnitine levels and factors of variation in severe trauma.MethodOur observational study concerned 38 trauma patients including 18 with traumatic brain injury (TBI). On the third day after trauma, plasma free carnitine concentration was determined (by enzymatic method) while patients received artificial nutrition.ResultsLow plasmatic free carnitine concentration was evidenced in 95% of the patients with a median value of 18 μmol/L (11–47). Univariate analysis showed that mean arterial pressure, serum urea, CKD-EPI and patients with TBI were significantly associated with plasma free carnitine concentration less than 18 μmol/L. Lower plasma free carnitine concentration was observed in the group of patients with TBI with 17.72 μmol/L (11–36) versus 21.5 μmol/L (11–47) for others patients (p = 0.031). Logistic regression analysis showed that severe trauma with TBI and CKD-EPI above 94 mL/min/1.73 m2 appeared to be independent predictor of lower free carnitine plasmatic concentration (Goodness of fit = 0.87 and AUC = 0.89).ConclusionOur observations support hypotheses that plasma free carnitine concentration is lowered in severe injured patients especially for TBI patients and patients with estimated GFR above 94 mL/min/1.73 m².     

Particulate matter (PM10) as a newly identified environmental risk factor for acute gout flares: A time-series study

ObjectivesThis study aimed to investigate the effect of short-term exposure to ambient particulate matter less than 10 μm in diameter (PM₁₀) on occurrence of acute gout flares in the general population and identify susceptible groups accordingly.MethodsThe data of emergency department (ED) cases with acute gout flare in Incheon city, Korea between January 1st 2008 and December 31st 2015 were collected from the National Health Insurance Service claims data. The levels of PM₁₀ and meterological measurements were provided by the Ministry of Environment and the National Meterological Office, respectively. To estimate the risk of daily ED visits due to acute gout flare, these time-series data set were analyzed using generalized additive models with Poisson distribution, including daily average PM₁₀ level, temperature, relative humidity, day of the week, national holiday, season, and date.ResultsThe risk of daily ED visits for acute gout flares per interquartile range increment of the average daily PM₁₀ levels significantly increased in the cumulative lag 0–7 model (relative risk, 1.018; 95% confidence interval, 1.008–1.027, P < 0.001). In particular, men aged ≥ 40 years and those with a history of diabetes mellitus or gout were significantly at a high risk of acute gout flares by subgroup analysis.ConclusionsOur time-series study demonstrated a modest, but significant effect of short-term exposure to PM₁₀ on ED visits for acute gout flares. Ambient PM₁₀ may be a newly identified environmental risk factor for acute gout flares.     

UltraSound evaluation in follow-up of urate-lowering therapy in gout phase 2 (USEFUL-2): Duration of flare prophylaxis

ObjectivesTo determine whether changes in ultrasonography (US) features of monosodium urate crystal deposition is associated with the number of gouty flares after stopping gout flare prophylaxis.MethodsWe performed a 1-year multicentre prospective study including patients with proven gout and US features of gout. The first phase of the study was a 6-month US follow-up after starting urate-lowering therapy (ULT) with gout flare prophylaxis. After 6 months of ULT, gout flare prophylaxis was stopped, followed by a clinical follow-up (M6 to 12) and ULT was maintained. Outcomes were the proportion of relapsing patients between M6 and M12 according to changes of US features of gout and determining a threshold decrease in tophus size according to the probability of relapse.ResultsWe included 79 gouty patients [mean (± SD) age 61.8 ± 14 years, 91% males, median disease duration 4 (IQR 1.5;10) years]. Among the 49 completers at M12, 23 (47%) experienced relapse. Decrease in tophus size ≥ 50% at M6 was more frequent without than with relapse (54% vs. 26%, P = 0.049). On ROC curve analysis, a threshold decrease of 50.8% in tophus size had the best sensitivity/specificity ratio to predict relapse [AUC 0.649 (95% confidence interval 0.488; 0.809)]. Probability of relapse was increased for patients with a decrease in tophus size < 50% between M0 and M6 [OR 3.35 (95% confidence interval 0.98; 11.44)].ConclusionA high reduction in US tophus size is associated with lower probability of relapse after stopping gout prophylaxis. US follow-up may be useful for managing ULT and gout flare prophylaxis.     

Predictive factors of tumour necrosis inhibitor treatment persistence for rheumatoid arthritis: An observational study in 8052 patients

ObjectivesTo determine whether changes in ultrasonography (US) features of monosodium urate crystal deposition is associated with the number of gouty flares after stopping gout flare prophylaxis.MethodsWe performed a 1-year multicentre prospective study including patients with proven gout and US features of gout. The first phase of the study was a 6-month US follow-up after starting urate-lowering therapy (ULT) with gout flare prophylaxis. After 6 months of ULT, gout flare prophylaxis was stopped, followed by a clinical follow-up (M6 to 12) and ULT was maintained. Outcomes were the proportion of relapsing patients between M6 and M12 according to changes of US features of gout and determining a threshold decrease in tophus size according to the probability of relapse.ResultsWe included 79 gouty patients (mean [± SD] age 61.8 ± 14 years, 91% males, median disease duration 4 [IQR 1.5; 10] years). Among the 49 completers at M12, 23 (47%) experienced relapse. Decrease in tophus size ≥ 50% at M6 was more frequent without than with relapse (54% vs. 26%, P = 0.049). On ROC curve analysis, a threshold decrease of 50.8% in tophus size had the best sensitivity/specificity ratio to predict relapse. Probability of relapse was increased for patients with a decrease in tophus size <50% between M0 and M6 (OR 3.35 [95% confidence interval 0.98; 11.44]).ConclusionA high reduction in US tophus size is associated with low probability of relapse after stopping gout prophylaxis. US follow-up may be useful for managing ULT and gout flare prophylaxis.     

Évaluation de l’exposition aux radiations du chirurgien lors d’un TLIF mini-invasif : comparaison entre fluoroscopie et navigation O-arm

IntroductionTransforaminal lumbar interbody fusion with a minimally invasive approach (MIS TLIF) has become a very popular technique in the treatment of degenerative diseases of the lumbar spine, as it allows a decrease in muscle iatrogenic. However, iterative radiological controls inherent to this technique are responsible for a significant increase in exposure to ionizing radiation for the surgeon. New techniques for radiological guidance (O-arm navigation-assisted) would overcome this drawback, but this remains unproven.ObjectivesTo analyze the exposure of the surgeon to intraoperative X-ray during a MIS TLIF under fluoroscopy and under O-arm navigation-assisted.Materials and methodsThis prospective study was conducted at the University Hospital of Lille from February to May 2013. Twelve patients underwent a MIS TLIF for the treatment of low-grade spondylolisthesis; six under standard fluoroscopy (group 1) and six under O-arm system (group 2). Passive dosimeters (rings and glasses) and active dosimeters for thorax were used to measure the radiation exposure of the surgeon.ResultsFor group 1, the average time of fluoroscopy was 3.718 minutes (3.13–4.56) while no radioscopy was perform on group 2. For the first group, the average exposure dose was 12 μSv (5–20 μSv) on the thorax, 1168 μSv (510–2790 μSv) on the main hand and 179 μSv (103–486 μSv) on the lens. The exposure dose was measured zero on the second group.ConclusionThe maximum recommended doses can be reached, mainly for the lens. In addition to the radioprotection measures, O-arm navigation systems are safe alternatives to significantly reduce surgeon exposure.     

Fibrinogen is an independent predictor of mortality in major trauma patients: A five-year statewide cohort study

IntroductionFibrinogen may be reduced following traumatic injury due to loss from haemorrhage, increased consumption and reduced synthesis. In the absence of clinical trials, guidelines for fibrinogen replacement are based on expert opinion and vary internationally. We aimed to determine prevalence and predictors of low fibrinogen on admission in major trauma patients and investigate association of fibrinogen levels with patient outcomes.Patients and methodsData on all major trauma patients (January 2007–July 2011) identified through a prospective statewide trauma registry in Victoria, Australia were linked with laboratory and transfusion data. Major trauma included any of the following: death after injury, injury severity score (ISS) >15, admission to intensive care unit requiring mechanical ventilation, or urgent surgery for intrathoracic, intracranial, intra-abdominal procedures or fixation of pelvic or spinal fractures. Associations between initial fibrinogen level and in-hospital mortality were analysed using multiple logistic regression.ResultsOf 4773 patients identified, 114 (2.4%) had fibrinogen less than 1 g/L, 283 (5.9%) 1.0–1.5 g/L, 617 (12.9%) 1.6–1.9 g/L, 3024 (63.4%) 2–4 g/L and 735 (15%) >4 g/L. Median fibrinogen was 2.6 g/L (interquartile range 2.1–3.4). After adjusting for age, gender, ISS, injury type, pH, temperature, Glasgow Coma Score (GCS), initial international normalised ratio and platelet count, the lowest fibrinogen categories, compared with normal range, were associated with increased in-hospital mortality (adjusted odds ratio [OR] for less than 1 g/L 3.28 [95% CI 1.71–6.28, p < 0.01], 1–1.5 g/L adjusted OR 2.08 [95% CI 1.36–3.16, p < 0.01] and 1.6–1.9 g/L adjusted OR 1.39 [95% CI 0.97–2.00, p = 0.08]). Predictors of initial fibrinogen <1.5 g/L were younger age, lower GCS, systolic blood pressure <90 mmHg, chest decompression, penetrating injury, ISS >25 and lower pH and temperature.ConclusionsInitial fibrinogen levels less than the normal range are independently associated with higher in-hospital mortality in major trauma patients. Future studies are warranted to investigate whether earlier and/or greater fibrinogen replacement improves clinical outcomes.     

Percutaneous transluminal angioplasty alone versus stent placement for the treatment of transplant renal artery stenosis

PurposeThe purposes of this retrospective study were to assess the efficacy of endovascular techniques for the treatment of transplant renal artery stenosis (TRAS) by analyzing technical and clinical success and to compare the results of percutaneous transluminal angioplasty (PTA) alone to those of stenting.Materials and methodsA retrospective analysis was conducted on 31 patients who underwent endovascular treatment for TRAS between January 2012 and December 2017. There were 23 men and 8 women with a mean age of 60.5 ± 14 (SD) years (range: 24–81 years). Ten patients (10/31; 32%; 8 men, 2 women; median age, 63 years) were treated with PTA alone and 21/31 (68%; 15 men, 6 women; median age, 65 years) with metallic stent placement. Several variables including serum creatinine level, glomerular filtration rate, arterial blood pressure value, antihypertensive medication obtained before and after treatment were compared. Technical success was assessed for each procedure. Clinical success was defined as a 15% drop in serum creatinine level, a decrease greater than 15% in mean blood pressure values or a decrease greater than 10% in mean blood pressure values with a reduction in the number of antihypertensive drugs needed for hypertension control.ResultsTechnical success was obtained in all patients [31/31; 100%; 95% confidence interval (CI): 89–100%] and clinical success in 27/31 patients (87%; 95%CI: 71–95%). Four patients (4/31; 13%; 95%CI: 5–29%) underwent repeat endovascular intervention. Mean serum creatinine level and mean arterial blood pressure values were significantly lower after treatment (177.4 and 93.8 μmol/l, respectively) compared to before treatment (319.4 and 106.7 μmol/l, respectively) in the stent group but not in the group treated with PTA alone (P = 0.0012 and P = 0.002, respectively).ConclusionThe endovascular approach is safe and effective in the management of TRAS and stenting, depending on the morphology of the stenosis, should be the treatment of choice when possible.     

Sequential higher epidural catheter re-insertion after accidental dural puncture ameliorates the frequency and severity of post-dural puncture headache

ObjectivesThis cohort study aimed to evaluate the outcome of a hypothesis to use higher level for epidural catheter insertion and activation when an epidural tap was encountered at a lower level during epidural analgesia for labor pain.MethodsEpidural analgesia for labor pain was conducted using a mixture of 0.125% bupivacaine and fentanyl 5 μg/ml (10–15 ml) in 5-ml increments and maintained using continuous epidural infusion of 0.125% bupivacaine and fentanyl 2 μg/ml at rate of (5–15 ml/h), subsequently adjusted according to the patients needs. All cases had accidental dural puncture (ADP) were managed immediately with re-insertion of the needle at a higher level and completion of the procedure and maintained using continuous epidural infusion of 0.0625% bupivacaine and fentanyl 2 μg/ml at rate of (6–12 ml/h) for 24 h after delivery. Postpartum follow-up was conducted for 30 days to comment on the occurrence and severity of post-dural puncture headache (PDPH). All patients developed PDPH were followed daily until resolution of their headache.ResultsAbout 4800 parturient were enrolled in the study, ADP occurred in 24 patients with a frequency of 0.5%. All cases were immediately managed by re-insertion of the needle at a higher level and the procedure was successfully completed without new dural puncture, with 100% re-insertion success rate, and patients were maintained on continuous epidural infusion for 24 h. Throughout 30-day follow-up; only six of 24 patients developed PDPH with a success rate of re-insertion procedure as a prophylactic modality for PDPH after ADP of 75%. PDPH was relieved with bed rest, liberal fluids and paracetamol for 4 days in four patients, while the 5th patient continued to complain but the patient refused to undergo epidural blood patch (EBP) and headache started to subside and patient stopped to complain by the 10th day, and the last patient agreed to undergo EBP; and headache was relived immediately after 2 h.ConclusionIt could be concluded that re-insertion of epidural catheter at higher level of accidental dural puncture with epidural continuous infusion for 24 h could be considered as an efficient prophylactic modality to safe guard against PDPH with success rate of 75% and minimizes its severity if occurred.     

Intravenous dexamethasone as an adjunct to improve labor analgesia: A randomized,double-blinded,placebo controlled clinical trial

ObjectiveTo study the role of intravenous (i.v.) dexamethasone as an analgesic adjunct in labor analgesia.DesignDouble-blinded randomized controlled trial.SettingLabor analgesia in a tertiary-care teaching hospital.PatientsEighty consenting ASA I-II parturients, age > 18 year, nulliparous, single gestation, cephalic presentation at ≥ 36 wk. of gestation, in early spontaneous labor (cervical dilatation ≤ 5 cm) requesting epidural analgesia.InterventionsThe patients were randomized to two groups. The Dexa group received 8 mg of dexamethasone i.v. in 50 ml normal saline approximately 45 min before the procedure. Placebo group patients received 50 ml normal saline only. All patients underwent epidural labor analgesia per hospital protocol. After an initial bolus, they received continuous background infusion of 5 ml/h of 0.1% of levobupivacaine with 2 μg/ml of fentanyl, with the provision of patient controlled boluses of 5 ml of the same drug combination with a lockout interval of 12 min if needed.MeasurementsPrimary outcome measure: hourly average consumption of neuraxially administered levobupivacaine-fentanyl combination. Secondary outcomes and observations: pain score, maternal satisfaction, sensory and motor block characteristics, hemodynamic parameters of mother, fetal heart rate, duration of second stage of labor, mode of delivery, Apgar scores at 1 and 5 min, and adverse effects.Main resultsAverage hourly drug consumption was significantly lower in Dexa group as compared to Placebo group (10.34 ± 1.79 ml/h vs. 11.34 ± 1.83 ml/h; mean difference 1.007, 95% CI 0.199–1.815; P = 0.015). The median number of bolus doses was 4 (interquartile-range [IQR] 3–5.75) and 5 (IQR 3–6) in the Dexa and Placebo groups, respectively (P = 0.162). There was no significant difference between groups with regard to pain scores, maternal satisfaction and hemodynamics, mode of delivery, and adverse effects.ConclusionsI.v. dexamethasone significantly decreased hourly average drug consumption of levobupivacaine-fentanyl combination through the epidural route, demonstrating the epidural drug dose sparing effect during labor analgesia.     

The value of epidural magnesium sulfate as an adjuvant to bupivacaine and fentanyl for labor analgesia

ObjectiveWe conducted this clinical study to assess the adjuvant effects of single dose magnesium sulfate (Mg) when administered epidurally during labor with fentanyl and bupivacaine.MethodsEighty healthy nulliparous women in labor requesting epidural analgesia were divided into two groups. Group 1 received bupivacaine 0.125% with magnesium sulfate 50 mg and fentanyl 50 μg as a loading dose; group 2, received bupivacaine 0.125% and fentanyl 50 μg only. Hemodynamic parameters, motor and sensory evaluation, cervical dilation at time of consenting, the progress of labor, the visual analog pain score (VAS), Apgar score, cord blood acid base status, side effects as nausea, vomiting, itching and respiratory depression were recorded. Fetal heart rate tracings were also documented.ResultsEpidural single dose magnesium sulfate added to bupivacaine and fentanyl in labor resulted in significantly faster onset and longer duration of epidural analgesia (169 ± 50 min) in comparison to those patients who received bupivacaine and fentanyl only (105 ± 41 min), also there was a significant reduction in the number of women requiring additional boluses of bupivacaine when Mg was added (P = 0.016). The two groups had no significant differences as regards maternal satisfaction score, maternal and neonatal adverse effects.ConclusionMagnesium sulfate added to bupivacaine and fentanyl for labor epidural analgesia resulted in faster onset, longer duration of action and reduced the break through pain.     

Changing thresholds and incidence of antibiotic treatment of cystic fibrosis pulmonary exacerbations, 1995–2005

BackgroundIncreased chronic therapy use and improved cystic fibrosis (CF) patient health should be accompanied by reduced pulmonary exacerbation-associated antibiotic treatment incidence.MethodsTreatment incidence rates and associated sign/symptom scores from 1995–2005 were studied in Epidemiologic Study of CF patients by route (± IV) and age (< 6, 6–12, 13–17, ≥ 18 years).ResultsOverall treatment incidence rate fell 0.0165 events/patient-year/year (P = .006); IV incidence fell 0.0179 (P < .001). Non-IV incidence increased in children ≤ 12 years (P ≤ .002) while significantly decreasing in older patients. Mean IV (P = .046) and non-IV (P = .004) treatment-associated clinical scores decreased in children < 6 years. Non-IV (but not IV) clinical scores decreased in older patients.ConclusionsIV incidence fell for all ages from 1995–2005; non-IV incidence increased in patients ≤ 12 years and fell in others. Average clinical treatment thresholds fell in children < 6 years; IV thresholds were unchanged in older patients; non-IV thresholds fell for patients ≥ 13 years. Decreases in treatment incidence were likely partially offset by lower treatment thresholds.     

Evaluation of febuxostat initiation during an acute gout attack: A prospective,randomized clinical trial

ObjectiveUrate-lowering treatment (ULT) is recommended in gout management. However, initiation of ULT during an acute gout flare is still inconclusive. This study aimed to evaluate the efficacy and safety of the ULT febuxostat administered at initiation of an acute gout attack.MethodsA prospective randomized controlled clinical trial was conducted for 12 weeks in primary gout patients who were admitted with acute gout attacks. Subjects were randomly assigned to the febuxostat group in which febuxostat, 40 mg daily, was administered in the primary care setting for attacks, or to the control group in which febuxostat, 40 mg daily, was administered after the attacks. All patients received adequate anti-inflammatory and analgesic therapies. Serum urate (SU) levels were monitored throughout the study. Pain, measured using a visual analogue scale (VAS), and gout recurrence rate were used as primary outcomes. Flare-related inflammation biomarkers were selected as secondary outcomes.ResultsFifty-two patients completed the study (febuxostat group: n = 28; control group: n = 24). No significant differences were detected in VAS scores between the two groups over the first 14-day observation period (P > 0.05). Administration of febuxostat decreased SU levels significantly during the first 2-week period. However, the gout recurrent rate or gout flare-related inflammation indicators did not change in the febuxostat or control groups. Treatment-related adverse events were mild and similar between groups.ConclusionInitiation of the urate-lowering drug febuxostat during an acute gout attack caused no significant difference in daily pain, recurrent flares, or adverse effects. The treatment significantly decreased SU levels in the early stage and might have potential long-term benefits in these patients.     

The effect of vitamin C intake on the risk of hyperuricemia and serum uric acid level in Korean Multi-Rural Communities Cohort

ObjectiveThe aim of this study was to determine the association between vitamin C intake and risk of hyperuricemia or serum uric acid levels in male and female subjects in the Korean Multi-Rural Communities Prospective Cohort.MethodsThis cross-sectional analysis was conducted in 9400 subjects enrolled in the Korean Multi-Rural Communities Cohort Study. The risk of hyperuricemia was assessed in five quintiles (Q1 to Q5) according to dietary and total vitamin C intake using multivariate-adjusted logistic regression models. Relationships between serum uric acid levels and vitamin C intake were evaluated using linear regression analysis after adjustment for covariates. Information about dietary components was collected using validated food frequency questionnaires.ResultsDietary vitamin C intake, but not total vitamin C intake, was significantly different between hyperuricemic and non-hyperuricemic subjects in males (P = 0.01) and females (P = 0.02). The risk of hyperuricemia decreased with increased dietary vitamin C intake in male and female subjects after multivariate adjustment (P for trend = 0.002 in males and P for trend = 0.02 in females). An effect of total vitamin C intake on hyperuricemia risk was identified in females (P for trend = 0.04), but not males (P for trend = 0.06). Serum uric acid level was linearly associated with total vitamin C intake in females (β = −0.0001, P = 0.01), but not with dietary vitamin C intake in either gender.ConclusionThis study showed that vitamin C intake might be in part responsible for hyperuricemia or serum uric acid level in the Korean Multi-Rural Communities Cohort.     

Hepatic dysfunction: A common occurrence in severely injured patients

BackgroundHepatic dysfunction (HD) is a common finding in critically ill patients. The underlying pathophysiological process is one of either cholestasis or hypoxic liver injury (HLI). Using serum bilirubin, our study aimed to determine the incidence of HD in a critically ill trauma population, identify risk factors and analyse the impact on outcomes.MethodsA retrospective observational study was performed on all patients admitted to the Level 1 Trauma Unit ICU at Inkosi Albert Luthuli Central Hospital in Durban, South Africa (IALCH) from 01/01/2012 until 31/12/2012. HD was defined as a total bilirubin greater than 34.2 μmol/l (2 mg/dL). Additional demographic, physiological, biochemical, and pharmaceutical risk factors for hepatic dysfunction were identified and recorded.ResultsTwo hundred and twenty five patients were included in the study of whom 48 (21.3%) developed HD. An increased duration of ventilation (median 15 days [inter-quartile range 6–19] vs 6 days [IQR 3–11] p < 0.001), prolonged length of stay (median 19 days [IQR 8.5–31] vs 7 days [IQR 3–13] p < 0.001), and higher mortality rate (31.3% vs. 14.7% p = 0.01) were all significantly associated with HD. Shock on admission was twice as common in patients developing HD (p < 0.001). The only drugs associated with HD were piperacillin-tazobactam (p < 0.001) and enalapril (p = 0.04). On multivariable analysis however, HD was not associated with mortality.ConclusionHD was common in our study population, and was associated with other organ dysfunction, increased mortality and length of stay.