Posaconazole is indicated for prophylaxis and treatment of invasive aspergillosis. Therapeutic drug monitoring (TDM) of posaconazole is used to optimise drug exposure. The aim of this study was to analyse and describe the TDM practices and exposure of posaconazole tablets. Patients who received posaconazole for treatment or prophylaxis of fungal infections were included in the study. The following therapeutic window was defined: if concentration was low (<0.7 mg/L for prophylaxis or < 1.5 mg/L for treatment) or high (>3.75 mg/L), the hospital pharmacist provided the physician with dosage advice, which implementation to patient care was analysed. A longitudinal analysis was performed to analyse if different confounding variables had an effect on posaconazole concentrations. Forty‐seven patients were enrolled resulting in 217 posaconazole trough concentrations. A median of 3 (IQR 1‐7) samples was measured per patient. The median concentration was 1.7 mg/L (IQR 0.8‐2.7) for prophylaxis and 1.76 mg/L (IQR 1.3‐2.3) for treatment. Overall, 78 posaconazole concentrations were out of the therapeutic window. For 45 (54%) of these concentrations, a dosage change was recommended. In the longitudinal analysis, the laboratory markers and patient baseline variables did not have an effect on posaconazole concentrations. Adequate posaconazole exposure was shown in 64% (affected 28 patients) of the measured concentrations. TDM practice of posaconazole can be improved by increasing the implementation rate of dose recommendation by a multidisciplinary antifungal stewardship team. 相似文献
The predictive value of frailty and comorbidity, in addition to more readily available information, is not widely studied. We determined the incremental predictive value of frailty and comorbidity for mortality and institutionalization across both short and long prediction periods in persons with dementia.
Design
Longitudinal clinical cohort study with a follow-up of institutionalization and mortality occurrence across 7 years after baseline.
Setting and Participants
331 newly diagnosed dementia patients, originating from 3 Alzheimer centers (Amsterdam, Maastricht, and Nijmegen) in the Netherlands, contributed to the Clinical Course of Cognition and Comorbidity (4C) Study.
Measures
We measured comorbidity burden using the Cumulative Illness Rating Scale for Geriatrics (CIRS-G) and constructed a Frailty Index (FI) based on 35 items. Time-to-death and time-to-institutionalization from dementia diagnosis onward were verified through linkage to the Dutch population registry.
Results
After 7 years, 131 patients were institutionalized and 160 patients had died. Compared with a previously developed prediction model for survival in dementia, our Cox regression model showed a significant improvement in model concordance (U) after the addition of baseline CIRS-G or FI when examining mortality across 3 years (FI: U = 0.178, P = .005, CIRS-G: U = 0.180, P = .012), but not for mortality across 6 years (FI: U = 0.068, P = .176, CIRS-G: U = 0.084, P = .119). In a competing risk regression model for time-to-institutionalization, baseline CIRS-G and FI did not improve the prediction across any of the periods.
Conclusions
Characteristics such as frailty and comorbidity change over time and therefore their predictive value is likely maximized in the short term. These results call for a shift in our approach to prognostic modeling for chronic diseases, focusing on yearly predictions rather than a single prediction across multiple years. Our findings underline the importance of considering possible fluctuations in predictors over time by performing regular longitudinal assessments in future studies as well as in clinical practice. 相似文献
Ductal carcinoma in situ (DCIS) of the breast is a nonobligate precursor of invasive breast cancer, accounting for 20 % of screen-detected breast cancers. Little is known about the natural progression of DCIS because most patients undergo surgery upon diagnosis. Many DCIS patients are likely being overtreated, as it is believed that only around 50 % of DCIS will progress to invasive carcinoma. Robust prognostic markers for progression to invasive carcinoma are lacking. In the past, studies have investigated women who developed a recurrence after breast-conserving surgery (BCS) and compared them with those who did not. However, where there is no recurrence, the patient has probably been adequately treated. The present narrative review advocates a new research strategy, wherein only those patients with a recurrence are studied. Approximately half of the recurrences are invasive cancers, and half are DCIS. So-called “recurrences” are probably most often the result of residual disease. The new approach allows us to ask: why did some residual DCIS evolve to invasive cancers and others not? This novel strategy compares the group of patients that developed in situ recurrence with the group of patients that developed invasive recurrence after BCS. The differences between these groups could then be used to develop a robust risk stratification tool. This tool should estimate the risk of synchronous and metachronous invasive carcinoma when DCIS is diagnosed in a biopsy. Identification of DCIS patients at low risk for developing invasive carcinoma will individualize future therapy and prevent overtreatment. 相似文献
To improve the diagnostic accuracy of electroencephalography (EEG) criteria for nonconvulsive status epilepticus (NCSE), external validation of the recently proposed Salzburg criteria is paramount. We performed an external, retrospective, diagnostic accuracy study of the Salzburg criteria, using EEG recordings from patients with and without a clinical suspicion of having NCSE. Of the 191 EEG recordings, 12 (12%) was classified as an NCSE according to the reference standard. In the validation cohort, sensitivity was 67% and specificity was 89%. The positive predictive value was 47% and the negative predictive value was 95%. Ten patients in the control group (n = 93) were false positive, resulting in a specificity of 89.2%. The interrater agreement between the reference standards and between the scorers of the Salzburg criteria was moderate; disagreement occurred mainly in patients with an epileptic encephalopathy. The Salzburg criteria showed a lower diagnostic accuracy in our external validation study than in the original design, suggesting that they cannot replace the current practice of careful weighing of both clinical and EEG information on an individual basis. 相似文献
BackgroundPatients with traumatic intracranial hemorrhage (TIH) frequently receive repeat head CT scans (RHCT) to assess for progression of TIH. The utility of this practice has been brought into question, with some studies suggesting that in the absence of progressive neurologic symptoms, the RHCT does not lead to clinical interventions.MethodsThis was a retrospective review of consecutive patients with CT-documented TIH and GCS ≥ 13 presenting to an academic emergency department from 2009 to 2013. Demographic, historical, and physical exam variables, number of CT scans during admission were collected with primary outcomes of: neurological decline, worsening findings on repeat CT scan, and the need for neurosurgical intervention.ResultsOf these 1126 patients with mild traumatic intracranial hemorrhage, 975 had RHCT. Of these, 54 (5.5% (4.2–7.2 95 CI) had neurological decline, 73 (7.5% 5.9–9.3 95 CI) had hemorrhage progression on repeat CT scan, and 58 (5.9% 4.5–7.6 95 CI) required neurosurgical intervention. Only 3 patients (0.3% 0.1–0.9% 95 CI) underwent neurosurgical intervention due to hemorrhage progression on repeat CT scan without neurological decline. In this scenario, the number of RHCT scans needed to be performed to identify this one patient is 305.ConclusionsRHCT after initial findings of TIH and GCS ≥ 13 leading to a change to operative management in the absence of neurologic progression is a rare event. A protocol that includes selective RHCT including larger subdural hematomas or patients with coagulopathy (vitamin K inhibitors and anti-platelet agents) may be a topic for further study. 相似文献
The aim of this study was to evaluate the root canal shaping effect of instruments manufactured from nickel titanium, M-Wire, and Gold wire with different glide path preparation techniques.
Methods
One hundred thirty-five mesiobuccal canals of extracted human maxillary molars were randomly divided into 3 equal groups (N = 45) for glide path preparation with K-files (KF) (Dentsply Sirona, Ballaigues, Switzerland), One G (OG) files (Micro-Mega, Besançon, France), and ProGlider (PG) files (Dentsply Sirona). Specimens of each glide path group were further divided equally into 3 groups for instrumentation with ProTaper Next (PTN, Dentsply Sirona), One Shape (OS, Micro-Mega), and WaveOne Gold (WOG, Dentsply Sirona) systems (n = 15). Micro–computed tomographic imaging was used to scan teeth before instrumentation and after shaping to compare centering ratio and canal transportation values at the apical, midroot, and coronal levels and the overall changes in canal volume. Data sets were statistically analyzed (analysis of variance and Kruskal-Wallis H tests).
Results
The centering ratios for all groups were statistically similar at all levels. Apical canal transportation was significantly high for K/OS and K/PTN (P = .003). Midroot canal transportation was significantly high for K/PTN, K/OS, and OG/OS (P = .0003). Coronal canal transportation was significantly high for K/PTN and K/OS (P = .011). The highest change in canal volume was observed with all PTN groups and the lowest with PG/WOG (P = .06).
Conclusions
WOG manufactured from Gold wire combined with PG showed better root canal shaping ability and removed less dentin from the canal walls. The nickel-titanium (OS) and M-Wire (PTN) instruments used in combination with KF significantly transported more canals. PTN removed the most dentin from the canal walls regardless of the GPP technique. 相似文献
Purpose: Non-ambulatory persons with cerebral palsy are prone to low bone mineral density. In ambulatory persons with cerebral palsy, bone mineral density deficits are expected to be small or absent, but a consensus conclusion is lacking. In this systematic review bone mineral density in ambulatory persons with cerebral palsy (Gross Motor Function Classification Scales I–III) was studied.
Materials and methods: Medline, Embase, and Web of Science were searched. According to international guidelines, low bone mineral density was defined as Z-score?≤??2.0. In addition, we focused on Z-score?≤??1.0 because this may indicate a tendency towards low bone mineral density.
Results: We included 16 studies, comprising 465 patients aged 1–65?years. Moderate and conflicting evidence for low bone mineral density (Z-score?≤??2.0) was found for several body parts (total proximal femur, total body, distal femur, lumbar spine) in children with Gross Motor Function Classification Scales II and III. We found no evidence for low bone mineral density in children with Gross Motor Function Classification Scale I or adults, although there was a tendency towards low bone mineral density (Z-score?≤??1.0) for several body parts.
Conclusions: Although more high-quality research is needed, results indicate that deficits in bone mineral density are not restricted to non-ambulatory people with cerebral palsy.
Implications for Rehabilitation
Although more high-quality research is needed, including adults and fracture risk assessment, the current study indicates that deficits in bone mineral density are not restricted to non-ambulatory people with CP.
Health care professionals should be aware that optimal nutrition, supplements on indication, and an active lifestyle, preferably with weight-bearing activities, are important in ambulatory people with CP, also from a bone quality point-of-view.
If indicated, medication and fall prevention training should be prescribed.
Patient selection for open lower extremity revascularization in patients with chronic kidney disease (CKD) remains a clinical challenge. This study investigates the impact of CKD on early graft failure, postoperative complications, and mortality in patients undergoing lower extremity bypass for critical limb ischemia.
Methods
The National Surgical Quality Improvement Program database was queried for all patients with critical limb ischemia from 2012 to 2015 who underwent lower extremity bypass using the targeted vascular set. The glomerular filtration rate was calculated using the Chronic Kidney Disease Epidemiology Collaboration Study equation. CKD categories were determined from the National Kidney Foundation Kidney Disease Outcomes Quality Initiative staging criteria. Patients were classified into three groups: CKD stages 3 or lower (mild to moderate CKD), CKD stages 4 or 5 (severe CKD), and on hemodialysis (HD). Multiple variable analysis was used to examine graft failure, mortality, and postoperative complications.
Results
The Surgical Quality Improvement Program database identified 6978 patients who underwent infrainguinal lower extremity arterial bypass during the study period. There were 6101 patients (87.4%) with mild to moderate CKD, 327 (4.7%) with severe CKD, and 550 (7.9%) on HD. Patients with severe CKD and on HD were more likely to have revascularization for tissue loss (54.9% vs 68.8% and 74.7%; P < .01). Patients with severe CKD and those on HD had higher rates of early graft failure, postoperative myocardial infarction, and rates of reoperation. Multiple variable analysis confirmed these results showing that HD was associated with postoperative myocardial infarction, readmission, and increased mortality. It also demonstrated that severe CKD was associated with graft failure (odds ratio [OR], 1.67; 95% confidence interval [CI], 1.12-2.50; P = .01), postoperative myocardial infarction (OR, 2.16; 95% CI, 1.35-3.45; P < .01), and readmission (OR, 1.38; 95% CI, 1.06-1.80; P = .02). Other factors associated with graft failure include functional status (OR, 1.39; 95% CI, 1.08-1.80; P = .01), African American race (OR, 1.72; 95% CI, 1.39-2.13; P < .01), and distal bypass (OR, 1.33; 95% CI, 1.09-1.61; P < .01).
Conclusions
CKD is a significant predictor of perioperative morbidity after lower extremity bypass. Patients with severe CKD have worse postoperative outcomes without increased mortality. Those on HD have worse survival and postoperative outcomes. 相似文献