Monitoring plasma voriconazole levels following intravenous administration in critically ill patients: an observational study

Data relating to the pharmacokinetics of voriconazole in critically ill patients are lacking. A prospective observational study was conducted on 18 non-consecutive critically ill patients aged 24–97 years, comprising 12 patients with normal renal function (NRF) [creatinine clearance (CL_Cr) ≥60 mL/min] and 6 patients with moderate renal impairment (MRI) (CL_Cr 40–55 mL/min), administered voriconazole intravenously (6 mg/kg loading dose and 3–4 mg/kg twice daily thereafter) in order to determine the suitability of these doses in this patient population. Steady-state blood levels were monitored and liver and renal function were recorded throughout treatment. Large variability in patient plasma levels was observed, ranging from 37% at ≤1 mg/L (minimum inhibitory concentration at which, for most fungal pathogens, 90% of isolates are susceptible) to 19% at >5.5 mg/L. Moreover, maintaining trough concentrations above clinical breakpoints was not consistently achieved because 16/30 (53%) were ≤1 mg/L. In a few MRI patients, average concentrations were found to be significantly different compared with those of NRF patients administered the same dose, however this difference was not noted in pharmacokinetic parameters following dose normalisation. None of the patients experienced deterioration in renal or liver function. Recommended voriconazole doses are inadequate to achieve drug concentrations >1 μg/mL over the entire dosing interval in some critically ill patients.     

Omissions and errors during oxygen therapy of hospitalized patients in a large city of Greece

Omissions and errors are commonly found concerning hospital oxygen use and the use of nebulizers. The aim of the study was to record oxygen use in seven hospitals located in a large district city of Greece. Another aim was to record the use of nebulizers in the same hospitals. We included 105 head nurses (HNs) working in seven hospitals of a large city district of Greece. Data were collected after interviewing each HN using a questionnaire and completing an anonymous data form. Data are expressed as percentages and analyzed using the chi-square test. We found that 41% of HN believed O(2) is a gas that improves patient's dyspnea. The majority of the nurses (88.6%) stated that there was no protocol for O(2) therapy in the departments in which they worked. We found that O(2) therapy was commonly started, modified, discontinued by nurses in the absence of a medical order. Oxygen therapy was commonly not guided by arterial blood gas (ABG) analysis. We also found that there are no guidelines to prevent O(2) therapy interruption during intra-hospital transportation, and that few measures were taken to prevent O(2) explosion. In 95.2% of the departments the nebulizers were filled with tap water and were not changed on a daily basis (81.2%). Our results indicate that educational programmes, nursing protocols and guidelines are becoming mandatory in our country in order to ensure the proper use of O(2) therapy and nebulizers.     

Haemostatic profile of full-term, healthy, small for gestational age neonates

Background

Small for Gestational Age (SGA) neonates often appear with haemostatic alterations, principally due to hepatic dysfunction that results from chronic intrauterine hypoxia. Polycythaemia and thrombocytopenia are common findings in this neonatal population.

Study design

We performed a comparison of coagulation, natural inhibitors and fibrinolysis between SGA and Appropriate for Gestational Age (AGA) infants born full term [gestational age (G.A.) > 37 weeks]. Study population consisted of 188 healthy newborns, 90 of whom were SGA (62 females and 28 males), while the rest were the control group (44 females and 54 males). Blood samples were obtained within 30 minutes following birth and before the administration of vitamin K. Investigation included: PT, INR, APTT, fibrinogen, coagulation factors II, V, VII, VIII, IX, X, XI, XII, vWillebrand factor, protein C and free protein S, antithrombin (AT), APCR, tPA and PAI-1. The independent t-test was used to compare the differences between the values of haemostatic parameters.

Results

Statistical analysis revealed a significant prolongation in PT, INR, elevated levels of tPA (p < 0.015, 0.01 and 0.002 respectively) and a decrease in the values of XII and free protein S (p < 0.045 and 0.007 respectively) in SGA full term neonates. The two groups had similar demographic characteristics (except birth weight), without significant differences in the values of other haemostatic parameters.

Conclusions

Despite of statistically significant differences in PT, INR, values of tPA, XII and free protein S, levels of haemostatic factors range within laboratory references for healthy full term newborns. These findings were not accompanied with clinical manifestations of altered haemostasis.     

Anterior thigh flap extended hemipelvectomy and spinoiliac arthrodesis

We present the technique of anterior thigh flap extended external hemipelvectomy with spinoiliac arthrodesis in treatment of the patient with recurrent low-grade pelvic chondrosarcoma extending to the lower lumbar spine. Extended hemipelvectomy involves skeletal resection beyond the standard hemipelvectomy that is the SI joint by removal of contiguous musculoskeletal structures, such as elements of the sacral and lumbar spine or contralateral pelvic bone, in addition to the affected innominate bone. Spinoiliac arthrodesis reestablishes spinopelvic stability; the anterior thigh musculocutaneous flap provides reliable well-vascularized soft tissue coverage. This technique may serve an important role in the surgical management of patients with low-grade pelvic malignancies.     

Portal vein thrombosis after laparoscopic splenectomy for systemic mastocytosis: a case report and review of the literature

INTRODUCTION: Laparoscopic splenectomy has become the surgical procedure of choice for various diseases of the spleen. Portal vein thrombosis (PVT) after splenectomy occurs in 0.5% to 22% of patients. Symptoms are nonspecific and include fever, abdominal pain, and epigastric distress. Risk factors for PVT after splenectomy include underlying hematologic disorders, massive splenectomy, and other hypercoagulable states. METHODS: We describe a case of PVT in a woman who underwent laparoscopic splenectomy for symptomatic splenomegaly secondary to systemic mastocytosis. The patient was discharged from the hospital without anticoagulation and experienced nonspecific symptoms beginning 10 days postoperatively. Diagnosis of PVT was made by contrast-enhanced abdominal computed tomography. The patient had no underlying risk factors. Anticoagulation treatment facilitated recanalization of the portal vein and this was verified by Doppler ultrasound at follow-up. CONCLUSIONS: PVT after laparoscopic splenectomy is not uncommon. Signs and symptoms are vague and require a high index of suspicion for timely diagnosis. Anticoagulation is the treatment of choice and allows recanalization of the portal system in the majority of cases.     

The natural history of a mistreated ipsilateral Galeazzi and Monteggia lesion: report of a case 39 years post-injury

Galeazzi injury combined with ipsilateral Monteggia lesion is extremely rare. A 45-year-old male patient with a mistreated Galeazzi lesion combined with an ipsilateral Monteggia fracture at the age of 6 is presented. Thirty-nine years post-injury his elbow was asymptomatic and stable and his distal radioulnar and radiocarpal joints were also asymptomatic. The strength of the limb was equal to the unaffected contralateral upper limb and he was able to work manually as a waiter for the last 20 years without any problem. The only obvious defect was a 30 degrees lack of elbow flexion and a 10 degrees lack of forearm pronation in comparison to the normal side.     

Re-writing Oral Pharmacokinetics Using Physiologically Based Finite Time Pharmacokinetic (PBFTPK) Models

Pharmaceutical Research - To develop physiologically based finite time pharmacokinetic (PBFTPK) models for the analysis of oral pharmacokinetic data. The models are based on the passive drug...     

Evaluation of sexual function in hypertensive men receiving treatment: a review of current guidelines recommendation

IntroductionIt has been suggested that some classes of antihypertensive drugs may induce or exacerbate sexual and/or erectile dysfunction (ED) more than others. Sexually related side effects of antihypertensive treatment may compromise patient's and partner's quality of life. Often, these side effects can lead to withdrawal or poor compliance with therapy resulting in abnormal blood pressure and associated morbidity.AimThe aim of this study was to evaluate whether hypertension clinical practice guidelines (CPGs) address ED and/or other sexual issues as either an adverse outcome of chosen therapy or as a factor to consider in treatment decision.MethodsHypertension CPGs were identified by searching PubMed (from 2000 to current), the World Wide Web, bibliographies of retrieved guidelines, and official home pages of major medical societies.Main Outcome MeasuresThe main outcome measures used for this study were guidelines assessment using a set of author‐determined survey questions.ResultsTwelve CPGs were identified and analyzed. From these 12, only three emphasized the importance of assessing sexual function prior to initiation and/or follow‐up of antihypertensive therapy; only five described potential sexual side effects associated with some drugs; only two provided specific management recommendations on commencing antihypertensive therapy in sexually active men or those with preexisting ED and address the timeline of the potential drug‐induced impairment of sexual function.ConclusionsOnly a minority of CPGs for the treatment of hypertension consider ED or other sexual issues as either an adverse outcome or as a factor to consider in treatment. Sexual function is an important aspect of quality of life for both the individual and his partner. It is therefore imperative to select therapy with the least possible potential for causing sexual sequelae and enable the best achievable balance between therapeutic efficacy, quality of life, and therapeutic compliance. Based on these results, our proposed algorithm attempts to effectively apply available evidence to clinical practice. Karavitakis M, Komninos C, Theodorakis PN, Politis V, Lefakis G, Mitsios K, Koritsiadis S, and Doumanis G. Evaluation of sexual function in hypertensive men receiving treatment: A review of current guidelines recommendation. J Sex Med 2011;8:2405–2414.