Clinical correlations of extraocular motility limitation pattern in orbital fracture cases: a retrospective cohort study in a level 1 trauma centre.

PURPOSE: Ocular pathology (OP) following orbital fracture can vary vastly in complexity and severity. Extra-ocular motility (EOM) limitations are frequently present in orbital trauma cases, with patterns of duction limitations being symmetrical or asymmetrical. The aim of this study was to identify if there was any association between increased OP following orbital fracture cases based on the pattern of EOM deficits. METHODS: This is a retrospective cohort study of patients with fractured orbits presenting with or without EOM limitations to a level 1 trauma center between August 2015 to January 2018. All pertinent elements of the ophthalmic examination were recorded. Outcome measures: Chi-square analyses assessed for association between symmetrical or asymmetrical EOM limitation and OP. Odds ratios were calculated with 95% confidence interval. RESULTS: 278 orbits with wall fractures were included in this study. A significant correlation between EOM limitation and increased OP following orbital trauma was found (p = 0.000081). Cases with symmetrical and asymmetrical EOM limitation were 7.9 (95%CI: 2.3-27.2) and 5.22 (95%CI: 1.9-13.9) times more likely to have OP than cases with no EOM limitation, respectively. With extraocular muscle entrapment excluded, cases with symmetrical limitations had a significantly higher incidence of OP than cases with asymmetrical limitations (p = 0.0161). CONCLUSIONS: OP is frequently observed in cases of orbital fracture. While any EOM limitations should prompt the clinicians to anticipate OP, intra-ocular injury may be more likely in cases of symmetrical EOM limitation. Future prospective studies are needed to further elucidate the relationship between EOM symmetricity and OP following orbital trauma.

Functional characterisation of twelve terpene synthases from actinobacteria.

Fifteen type I terpene synthase homologs from diverse actinobacteria that were selected based on a phylogenetic analysis of more than 4000 amino acid sequences were investigated for their products. For four enzymes with functions not previously reported from bacterial terpene synthases the products were isolated and their structures were elucidated by NMR spectroscopy, resulting in the discovery of the first terpene synthases for (+)-δ-cadinol and (+)-α-cadinene, besides the first two bacterial (-)-amorpha-4,11-diene synthases. For other terpene synthases with functions reported from bacteria before the products were identified by GC-MS. The characterised enzymes include a new epi-isozizaene synthase with monoterpene synthase side activity, a 7-epi-α-eudesmol synthase that also produces hedycaryol and germacrene A, and four more sesquiterpene synthases that produce mixtures of hedycaryol and germacrene A. Three phylogenetically related enzymes were in one case not expressed and in two cases inactive, suggesting pseudogenisation in the respective branch of the phylogenetic tree. Furthermore, a diterpene synthase for allokutznerene and a sesterterpene synthase for sesterviolene were identified.

[Acute pyelonephritis]. / Vignette diagnostique de l'étudiantLa pyélonéphrite aiguë.

The present review details the recommendations for the management of acute pyelonephritis in adults. Acute pyelonephritis corresponds to the infection of the upper urinary tract and is particularly common in women between the age of 15 and 65 years. Symptoms usually include fever, chills, flank pain, nausea and vomiting. There are different types of pyelonephritis, and their management may differ upon the patient's comorbidities and the pathogenic agent. The first step in the management of a patient with suspected acute pyelonephritis focuses on the need for hospitalization. Bacteriological samples should always be collected before the initiation of antibiotics. The antibiotic therapy will then be adapted according to the profile of the infecting pathogen.

Cette vignette reprend les recommandations de prise en charge de la pyélonéphrite aiguë (PNA) de l'adulte. La PNA est une infection urinaire haute, particulièrement fréquente chez la femme entre 15 et 65 ans. La symptomatologie typique associe fièvre, frissons, douleur au niveau de la loge rénale, nausées et vomissements. Il existe différents types de PNA dont la prise en charge peut varier selon les comorbidités du patient ou le type de bactéries. Devant toute PNA, la première étape est d'évaluer la nécessité d'une hospitalisation. Les prélèvements à visée bactériologique doivent toujours précéder l'initiation de l'antibiothérapie, dont le spectre sera adapté en fonction de la sensibilité antibiotique du germe mis en évidence.

Meningioma genomics: a therapeutic challenge for clinicians.

Meningiomas are amongst the most commonly encountered intracranial tumors. The majority of these tumors arise intracranially, and the remaining incidents occur along the spinal cord. Meningiomas tend to grow gradually, with many tumors arising in inaccessible locations. Such sporadic behavior poses a therapeutic challenge to clinicians, causing incomplete tumor resections that often lead to recurrence. Therefore, ongoing research seeks to find alternative systematic treatments for meningiomas, with gene-based therapeutics of high interest. Subsequently, genetic studies characterized frequent somatic mutations in NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA. These genes are communally exhibited in 80% of sporadic meningiomas. In addition, other genes such as the DUSP family, the NR4 family, CMKOR, and FOSL2, have been identified as key players in spinal meningiomas. In this perspective, we aim to investigate current genetic-based studies, with the ongoing research mainly focused on the above NF2, TRAF7, KLF4, AKT1, SMO, and PIK3CA genes and their involved pathways. In addition, this perspective can serve as a potential cornerstone for future genetic analyses of meningioma cases.

Neurotrophic Effects of Mu Bie Zi (Momordica cochinchinensis) Seed Elucidated by High-Throughput Screening of Natural Products for NGF Mimetic Effects in PC-12 Cells.

Post-mitotic central nervous system (CNS) neurons have limited capacity for regeneration, creating a challenge in the development of effective therapeutics for spinal cord injury or neurodegenerative diseases. Furthermore, therapeutic use of human neurotrophic agents such as nerve growth factor (NGF) are limited due to hampered transport across the blood brain barrier (BBB) and a large number of peripheral side effects (e.g. neuro-inflammatory pain/tissue degeneration etc.). Therefore, there is a continued need for discovery of small molecule NGF mimetics that can penetrate the BBB and initiate CNS neuronal outgrowth/regeneration. In the current study, we conduct an exploratory high-through-put (HTP) screening of 1144 predominantly natural/herb products (947 natural herbs/plants/spices, 29 polyphenolics and 168 synthetic drugs) for ability to induce neurite outgrowth in PC12 dopaminergic cells grown on rat tail collagen, over 7 days. The data indicate a remarkably rare event-low hit ratio with only 1/1144 tested substances (<111.25 µg/mL) being capable of inducing neurite outgrowth in a dose dependent manner, identified as; Mu Bie Zi, Momordica cochinchinensis seed extract (MCS). To quantify the neurotrophic effects of MCS, 36 images (n = 6) (average of 340 cells per image), were numerically assessed for neurite length, neurite count/cell and min/max neurite length in microns (µm) using Image J software. The data show neurite elongation from 0.07 ± 0.02 µm (controls) to 5.5 ± 0.62 µm (NGF 0.5 µg/mL) and 3.39 ± 0.45 µm (138 µg/mL) in MCS, where the average maximum length per group extended from 3.58 ± 0.42 µm (controls) to 41.93 ± 3.14 µm (NGF) and 40.20 ± 2.72 µm (MCS). Imaging analysis using immunocytochemistry (ICC) confirmed that NGF and MCS had similar influence on 3-D orientation/expression of 160/200 kD neurofilament, tubulin and F-actin. These latent changes were associated with early rise in phosphorylated extracellular signal-regulated kinase (ERK) p-Erk1 (T202/Y204)/p-Erk2 (T185/Y187) at 60 min with mild changes in pAKT peaking at 5 min, and no indication of pMEK involvement. These findings demonstrate a remarkable infrequency of natural products or polyphenolic constituents to exert neurotrophic effects at low concentrations, and elucidate a unique property of MCS extract to do so. Future research will be required to delineate in depth mechanism of action of MCS, constituents responsible and potential for therapeutic application in CNS degenerative disease or injury.

Clinical and anatomic correlates of objectively measured zonular dehiscence in 427 postmortem pseudophakic eyes.

OBJECTIVE: This study aims to objectively measure the degree of zonular dehiscence in postmortem eyes and to assess for clinical and anatomic correlates. DESIGN: Cross-sectional study. MATERIALS: Four hundred and twenty-seven postmortem pseudophakic human eyes. METHODS: Eyes were obtained from the Lions Gift of Sight Eye Bank. Microscope photographs were taken of the eyes in Miyake-Apple view, and region-of-interest analysis was performed using ImageJ to measure the area, circumference, and diameter of the capsular bag, the ciliary ring, and the capsulorhexis. Clinical and anatomic parameters were assessed using simple linear regression analysis and one-way analysis of variance with post hoc Bonferroni testing. Zonular dehiscence was measured via 2 surrogates: capsule area over ciliary ring area ratio (CCR) and capsule-ciliary ring decentration (CCD). Low CCR and high CCD indicate more zonular dehiscence. RESULTS: CCR was significantly inversely correlated with smaller capsulorhexi (p = 0.012), lower intraocular lens power (p < 0.00001), younger age at death (p = 0.00002), and a longer cataract-to-death time (p = 0.00786). CCR also was significantly lower in glaucomatous cases (p = 0.0291). CCD was significantly correlated with longer cataract-to-death time (p = 0.000864), larger ciliary ring area (p = 0.001), more posterior capsule opacification (p = 0.0234), and higher Soemmering's ring opacity (p = 0.0003). There was also significantly more decentration in male eyes than in female eyes (p = 0.00852). CONCLUSIONS: CCR and CCD are novel measures of zonular dehiscence in postmortem eyes, with many interesting correlates. An enlarged ciliary ring area is possibly associated with zonular dehiscence in pseudophakic eyes and may be a quantifiable surrogate in vivo.

Hydroxychloroquine lung pharmacokinetics in critically ill patients with COVID-19.

Different dosage regimens of hydroxychloroquine (HCQ) have been used to manage COVID-19 (coronavirus disease 2019) patients, with no information on lung exposure in this population. The aim of our study was to evaluate HCQ concentrations in the lung epithelial lining fluid (ELF) in patients infected with SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2), the virus that causes COVID-19. This was a retrospective, observational, multicentre, pharmacokinetic study of HCQ in critically ill COVID-19 patients. No additional interventions or additional samples compared with standard care of these patients were conducted in our teaching hospital. We included all intubated COVID-19 patients treated with crushed HCQ tablets, regardless of the dosage administered by nasogastric tube. Blood and bronchoalveolar lavage samples (n = 28) were collected from 22 COVID-19 patients and total HCQ concentrations in ELF were estimated. Median (interquartile range) HCQ plasma concentrations were 0.09 (0.06-0.14) mg/L and 0.07 (0.05-0.08) mg/L for 400 mg × 1/day and 200 mg × 3/day, respectively. Median HCQ ELF concentrations were 3.74 (1.10-7.26) mg/L and 1.81 (1.20-7.25) for 400 mg × 1/day and 200 mg × 3/day, respectively. The median ratio of ELF/plasma concentrations was 40.0 (7.3-162.7) and 21.2 (18.4-109.5) for 400 mg × 1/day and 200 mg × 3/day, respectively. ELF exposure is likely to be underestimated from HCQ concentrations in plasma. In clinical practice, low plasma concentrations should not induce an increase in drug dosage because lung exposure may already be high.

Effect of Phase Change Material Cooling Vests on Body Thermoregulation and Thermal Comfort of Patients With Paraplegia: A Human Subject Experimental Study.

STUDY DESIGN: Randomized experimental study. OBJECTIVE: Compared to able-bodied people, patients with paraplegia due to thoracic spinal cord injury (SCI) are at an increased risk of heat illnesses during exercise due to impaired thermoregulatory responses. To overcome this limitation, we investigated the performance of three phase change material (PCM) cooling vests of different melting temperatures (Eijsvogels, #49) and coverage area of the trunk. METHODS: Sixteen participants were divided into three groups according to their injury level. All were tested for V20 full vest (20°C Tm, 75% coverage). Mid-thoracic and high-thoracic groups were tested for V14 vest (14°C Tm, 75% coverage). The mid-thoracic group was tested for V20 half vest (20°C Tm, 50% coverage). The participants performed a 30-min arm-crank exercise followed by a recovery period inside a controlled hot climatic chamber. The heart rate, segmental skin (Tskin), and core temperature (Tcore) values were recorded, and subjective questionnaires were taken. RESULTS: Compared to no vest (NV) test, all the vests showed an effective decrease in Tskin values of the trunk. However, the decrease in Tskin was not enough to induce a significant decrease in Tcore in all three groups. Mid-thoracic and low-thoracic groups showed a reduction in the increasing Tcore by the end of the exercise and recovery period. Finally, the level of thermal comfort was enhanced for the three groups. CONCLUSION: The effectiveness of cooling vests for persons with paraplegia is dependent on injury level and thus the ratio of sensate to insensate skin. Future studies necessitate the investigation of the cooling effects of PCM vests at a lower Tm with a larger sample size.

Leishmaniasis in Cameroon: what is known and is done so far? A protocol for systematic review.

INTRODUCTION: The first visceral and cutaneous leishmaniasis cases were reported in Cameroon since more than six decades. However, interest in the disease has decreased over time and data on its epidemiology across the country are scanty. This systematic review aims to update data on what is known and done so far on leishmaniasis in Cameroon. METHODS AND ANALYSIS: PubMed/MEDLINE, EMBASE and Web of Science will be searched from inception onwards. Grey literature will be identified through Google Scholar searches, dissertation databases and other relevant documents such as report of the National Control Program. Searches will be conducted between January and February 2021. All studies reporting endemicity, distribution, infecting species, vectors and reservoirs will be eligible. The main outcomes will be epidemiological data (infection rate, distribution, infecting species, vectors and animal reservoir), while the secondary outcomes will be the cases management (diagnostic, treatment, reporting, intervention…). Two reviewers will independently screen eligible papers, and potential conflicts will be resolved by involving a third reviewer as an adjudicator. Methodological quality including bias will be appraised using a methodological quality critical appraisal checklist proposed in the Joanna Briggs Institute systematic review methods manual. A narrative synthesis will describe quality and content of the epidemiological evidence. Data on prevalence and vectors will be used to draw thematic maps of the distribution of leishmaniasis in Cameroon. ETHICS AND DISSEMINATION: This study will not require ethical approval as it will be based on already published or unpublished data. The final report of this review will be published in a peer-reviewed journal, and the outcomes will be used (1) as baseline information to design further studies that will help to better refine the epidemiological situation of leishmaniasis in Cameroon, and (2) to inform both programme managers and policy-makers of the situation of leishmaniasis in the country. SYSTEMATIC REVIEW REGISTRATION: This protocol was registered with the International Prospective Register of Systematic reviews (PROSPERO; registration number: CRD42020211864) database.

Role of connexins in spinal cord injury: An update.

Connexins (Cxs) are a family of transmembrane proteins that assemble into groups of six, forming what is known as a connexon or a hemichannel. Connexins are named based on their molecular weight, e.g. Cx43 is the connexin protein that weighs 43 kDa. Two hemichannels, each from a different cell, can link up end-to-end forming a gap junction. In the nervous system, gap junctions facilitate metabolite exchange between neighboring cells, in addition to electrical and chemical impulses. Many animal studies have been conducted to investigate the role of different types of Cxs in spinal cord injury (SCI) - most notably Cx43 - and the potential for targeting them with inhibitors. In this review, the authors discuss these studies and provide an update on recent connexin specific pharmacological agents that may potentially pave the way for the use of connexin inhibition in the management of SCI in humans, if more translational studies are done.

Gender and neglected tropical disease front-line workers: Data from 16 countries.

BACKGROUND: Delivery of preventive chemotherapy (PC) through mass drug administration (MDA) is used to control or eliminate five of the most common neglected tropical diseases (NTDs). The success of an MDA campaign relies on the ability of drug distributors and their supervisors-the NTD front-line workers-to reach populations at risk of NTDs. In the past, our understanding of the demographics of these workers has been limited, but with increased access to sex-disaggregated data, we begin to explore the implications of gender and sex for the success of NTD front-line workers. METHODOLOGY/PRINCIPAL FINDINGS: We reviewed data collected by USAID-supported NTD projects from national NTD programs from fiscal years (FY) 2012-2017 to assess availability of sex-disaggregated data on the workforce. What we found was sex-disaggregated data on 2,984,908 trainees trained with financial support from the project. We then analyzed the percentage of males and females trained by job category, country, and fiscal year. During FY12, 59% of these data were disaggregated by sex, which increased to nearly 100% by FY15 and was sustained through FY17. In FY17, 43% of trainees were female, with just four countries reporting more females than males trained as drug distributors and three countries reporting more females than males trained as trainers/supervisors. Except for two countries, there were no clear trends over time in changes to the percent of females trained. CONCLUSIONS/SIGNIFICANCE: There has been a rapid increase in availability of sex-disaggregated data, but little increase in recruitment of female workers in countries included in this study. Women continue to be under-represented in the NTD workforce, and while there are often valid reasons for this distribution, we need to test this norm and better understand gender dynamics within NTD programs to increase equity.

Cefepime in intensive care unit patients: validation of a population pharmacokinetic approach and influence of covariables.

AIM: The purpose of our study was to define and validate a population-pharmacokinetic model including the influence of patients' characteristics on the pharmacokinetics of cefepime. PATIENTS AND METHODS: A total of 55 patients were randomized in Group 1 (34 patients, 320 cefepime concentrations) for the model building and Group 2 (21 patients, 196 cefepime concentrations) for the validation group. They received cefepime as 2 g A 2 or as 4 g continuously. The population pharmacokinetic analysis was carried out using NONMEM and a baseline model was constructed for studying the influence of demographic and biological variables. The model was then validated by a comparison of the predicted and observed concentrations in Group 2. A final model was elaborated from the whole population. RESULTS: Total clearance (CL) was significantly correlated with the serum creatinine (CREA) and the central volume of distribution (V1) was correlated with the body weight (WT). The final model was: CL = 7.14 + (-0.0133 A CREA). V1 = (-16.8) + (0.475 A WT). Q (intercompartmental clearance) = 10.5. V2 = 18.1. The mean pharmacokinetic parameters and their individual variability were: CL (8.24 l/h, 45%), V1 (20.89 l, 60%), V2 (17.95 l, 49%), total volume (38.85 l, 42%) and Q (10.56 l/h, 9%). The bias (1.07 mg/l, IC 95% = -40.46 -+42.60), precision (21.19%) and AFE (1.15) demonstrated the performance of the model. CONCLUSION: We have developed and validated a pharmacokinetic model to estimate cefepime concentrations. We showed that serum creatinine and body weight are factors that may influence the standard dose of cefepime. Our model enabled us to predict cefepime concentrations in other patients.

3-month prognostic impact of severe acute renal failure under veno-venous ECMO support: Importance of time of onset.

PURPOSE: Veno-venous ECMO is increasingly used for the management of refractory ARDS. In this context, acute kidney injury (AKI) is a major and frequent complication, often associated with poor outcome. We aimed to identify characteristics associated with severe renal failure (Kidney Disease Improving Global Outcome (KDIGO) 3) and its impact on 3-month outcome. METHODS: Between May 2009 and April 2016, 60 adult patients requiring VV-ECMO in our University Hospital were prospectively included. RESULTS: AKI occurrence was frequent (75%; n=45), 51% of patients (n=31) developed KDIGO 3 - predominantly prior to ECMO insertion - and renal replacement therapy was required in 43% (n=26) of cases. KDIGO 3 was associated with a lower mechanical ventilation weaning rate (24% vs 68% for patients with no AKI or other stages of AKI; p<0.001) and a higher 90-day mortality rate (72% vs 32%, p=0.002). Multivariate logistic regression suggested that KDIGO 3 occurrence prior to ECMO insertion, as well as PaCO2>57mmHg and mSOFA>12 were independent risks factors for 90-day mortality. CONCLUSION: KDIGO 3 AKI occurrence is correlated with the severity of patients' clinical condition prior to ECMO insertion and is negatively associated with 90-day survival.

Convergent peptide libraries, or mixotopes, to elicit or to identify specific immune responses.

Many recent studies have demonstrated the flexibility of epitope recognition by the immune system. This can be explored using a particular type of combinatorial peptide library, termed as 'convergent', consisting essentially of closely related molecular species; from this a fuzzy set can be constructed, which comprises several variants of a peptide that would act in synchrony to represent a model antigen and its recognition by the immune system.

Interleukin-12 expression enhances vesicular stomatitis virus oncolytic therapy in murine squamous cell carcinoma.

OBJECTIVES: Replication-competent, vesicular stomatitis virus (VSV) has been demonstrated to be an effective oncolytic agent in a variety of malignant tumors. Cytokine gene transfer has also been used as immunomodulatory therapy for cancer. To test the use of combining these two approaches, an oncolytic VSV vector (rVSV-IL12) was designed to express the murine interleukin 12 (IL12) gene. This cytokine-carrying oncolytic virus was compared with an analogous noncytokine-carrying fusogenic virus (rVSV-F) in the treatment of murine SCC VII squamous cell carcinoma (SCC). STUDY DESIGN AND SETTING: The authors performed in vitro testing of recombinant VSV-F and recombinant VSV-IL12 in SCC cell lines. In vivo testing of multiple direct intratumoral injections of rVSV-F or rVSV-IL12 in an orthotopic floor of mouth murine model was performed. Each cell line was tested using rVSV-F or rVSV-IL12 at multiplicity of infection of 0.01. The ability of each virus to replicate was tested by real-time reverse transcriptase-polymerase chain reaction over 48 hours to determine viral copies of RNA. Cell survival was determined by MTT assay over 72 hours. IL12 expression by rVSV-IL12-treated cells was determined by enzyme-linked immunosorbent assay. RESULTS: Both viruses demonstrated similar infection efficiency, viral replication, and cytotoxicity in vitro. In an SCC VII orthotopic floor of mouth model in immunocompetent C3H/HeJ mice, multiple intratumoral injections with each virus caused a significant reduction in tumor volume when compared with saline injections alone. The rVSV-IL12-treated tumors showed a striking reduction in tumor volume when compared with rVSV-F and saline-treated tumors (P < .005). This striking reduction in tumor volume translated into a substantial survival benefit in rVSV-IL12-treated animals. No treatment-related toxicity was observed in either group. CONCLUSION/SIGNIFICANCE: rVSV-IL12 is a novel oncolytic vesicular stomatitis virus that effectively expresses IL12 and significantly enhances the treatment of head and neck murine carcinoma. Such combined oncolytic and immunomodulatory strategies hold promise in the treatment of head and neck cancers.

Acute interstitial nephritis after cocaine sniffing.

We report the case of a 42-year-old man who developed biopsy-confirmed acute interstitial nephritis (AIN) after cocaine sniffing. He required a few hemodialysis sessions but fully recovered within 3 weeks after cocaine withdrawal and a short course of corticosteroids. AIN should be recognized as a potential cause of acute renal failure in cocaine users, and a history of cocaine use should be carefully elicited in patients with unexplained AIN.

Ghrelin reduces hepatic mitochondrial fatty acid beta oxidation.

Ghrelin is a 28-amino-acid peptide secreted during starvation by gastric cells. Ghrelin physiologically induces food intake and seems to alter lipid and glucid metabolism in several tissues such as adipose tissue and liver. Liver has a key position in lipid metabolism as it allows the metabolic orientation of fatty acids between oxidation and esterification. We investigated the effects of peripheral ghrelin administration on 2 crucial parameters of fatty acid oxidation: the levocarnitine (L-carnitine)-dependent entry of the fatty acids in the mitochondria and the mitochondrial fatty acid oxidation. Ghrelin was either given to rats prior to the hepatocyte preparation and culture or used to treat hepatocytes prepared from control animals. Direct incubation of ghrelin to raw hepatocytes did not induce any change in the studied parameters. In hepatocytes prepared from 3 nmol ghrelin-treated rats, a 44% reduction of the mitochondrial fatty acid oxidation while no alteration of the L-carnitine-related parameters were observed. These results suggested (a) that ghrelin has no direct effect on liver, and (b) that when administrated to a whole organism, ghrelin may alter the lipid metabolism and the energy balance through a marked decrease in liver fatty acid oxidation.

Intermittent administration of ceftazidime to burns patients: influence of glomerular filtration.

OBJECTIVE: The pharmacokinetics of ceftazidime, the antibiotic of choice for treating acute P. aeruginosa infections, may be modified in burns patients. The aim of this study was to identify the factors causing variations in the serum antibiotic concentrations in bums patients. METHODS: 30 patients with serious burns were randomly divided into two groups. Group 1 received a dose of ceftazidime of 2 x 3 g/24 hours. The second group received the same dose but divided into 6 administrations. Blood samples were taken at 24 (M1) and 48 hours (M2) after the start of treatment and the peak and trough serum concentrations of ceftazidime measured by HPLC. Depending on the results, frequency and/or dose was modified to obtain trough concentrations (Cmin) equal to 16 mg/l, i.e. 4 times the MIC. Either the same dose was maintained, but mostly divided up, or it was increased to 1 g x 8 administrations or it was decreased to 1 g x 4 or 1 g x 3. The serum concentrations of ceftazidime obtained were analyzed taking into account the characteristics of the burns patients (multivariate correlation). RESULTS: From the first sample (M1) Cmin was lower than the target concentration in 50% of the patients in Group 1 and 20% in Group 2. The modification of the dosing regimen put into place after the first analysis, led to the patients being further divided into four groups before the second blood sampling. Finally, 5 patients ended up in Group 1. In all patients and for all administration times, a negative correlation was found between Cmin and the creatinine clearance, calculated by using Cockcroft's formula. CONCLUSION: This study highlights the peculiarities of ceftazidime pharmacokinetics seen in burns patients with high interindividual variability. Based on Cmin monitoring and a predefined therapeutic range, dose adjustment was often required. Ceftazidime clearance is correlated with creatinine clearance (Cockcroft's formula), suggesting that this parameter could be used for a priori or a posteriori dose individualization. To respect the summary of the product characteristics (SPC) and reduce the variability in trough concentrations, the dose should be fractionated (1 g x 6) over a 24-hour period or even given as a continuous infusion. Trough concentrations must be evaluated to adapt the dosage regimen to attain target concentrations of 4 x the MIC.

Pharmacokinetics of ceftazidime and cefepime in burn patients: the importance of age and creatinine clearance.

AIM: The standard dosage recommendations for beta-lactam antibiotics can result in very low drug levels in intensive care (IC) patients and burn patients in the absence of renal dysfunction. We studied the pharmacokinetic parameters and serum concentrations of ceftazidime (CF) and cefepime (CE) in burn patients and analyzed the modifications according to clinical and biological parameters and in particular age and creatinine clearance. MATERIAL AND METHODS: Two pharmacokinetic studies were carried out with daily doses of 1 g x 6 for CF (n = 17) and 2 g x 3 for CE (n = 13). Creatinine clearance (CL(CR)) was both estimated and measured. Blood was sampled at steady state after an initial and a subsequent antibiotic dose. C(max) (maximal) and C(min) (minimal) concentrations were measured by HPLC. The influence of clinical and biological data was analyzed using ANOVA, ANCOVA and stepwise multiple linear regression. RESULTS: The ratio of C(min) to the low MIC break point (4 mg/l) was lower than 4 in 52% of subjects receiving CF and in 80% of subjects receiving CE. The C(min) of CF was correlated with measured CL(CR) and was higher in mechanically ventilated patients than in non-ventilated patients. The clearance of CF was correlated with age. The C(min) of CE was correlated with age and drug clearance with measured CL(CR). Therefore dosage adjustment of these drugs in burn patients needs to take into account age, measured creatinine clearance and the danger of low concentrations occurring when the creatinine clearance is greater than 120 ml x min(-1). CONCLUSION: In burn patients, the pharmacokinetic disposition of CF and CE was much more variable than in healthy subjects. Age and CL(CR) were predictors of the disposition of these antibiotics. Shortening the dosage interval or using continuous infusions will prevent low serum levels and keep trough levels above the MIC for longer periods of time. In view of the lack of a bedside measurement technique for ceftazidime and cefepime levels, we suggest a more frequent use of measured CL(CR) in order to attain efficacious clinical concentrations.

Prevalence and Characteristics of Hepatitis Delta Virus Infection in a Tertiary Hospital Setting in Cameroon.

BACKGROUND/AIMS: Hepatitis B virus (HBV) and hepatitis D virus (HDV) coinfection is associated with more severe liver disease than HBV alone. More knowledge on the epidemiology and clinical impact of HDV-infected individuals is needed in Cameroon.We aimed at determining the frequency of anti-HDV antibody testing in hepatitis B surface antigen (HBsAg) positive patients, the proportion of anti-HDV positivity, and the characteristics of anti-HDV positive compared to anti-HDV negative patients in a tertiary hospital setting in Cameroon. METHODS: A cross-sectional study was conducted. Clinical records of chronic HBV-infected patients attending the gastroenterology unit at the Douala General Hospital from 2010 to 2014 were reviewed. RESULTS: Of 365 files of HBsAg-positive patients defined as chronic HBV infection, 80.5% (294) were tested for anti-HDV antibodies, among whom 10.5% (31/294) were positive. Median aspartate aminotransferase (P < 0.0001), alanine aminotransferase (P < 0.0001), and gamma glutaryl transpeptidase (P < 0.0001) were significantly higher while platelets count (P < 0.002) and prothrombin time (P < 0.0001) were significantly lower in anti-HDV positive compared to anti-HDV negative patients. Liver necroinflammation (P < 0.0001), fibrosis score (P < 0.0001), and decompensated cirrhosis (P < 0.0001) were also significantly associated with anti-HDV positivity. CONCLUSION: The proportion of anti-HDV antibody positivity remains high in this setting and was significantly associated with more severe liver disease compared to those who were anti-HDV negative. More studies are needed to evaluate rates of HDV testing in other centers in Cameroon and the subregion. Preventive strategies for HBV prevention, which also apply to HDV, must still be reinforced by healthcare providers and policy makers.