Effectiveness of heat treatment in rapid control of bed bugs in environmental conditions resembling their natural habitats.

We evaluated lethal temperatures and times for killing bed bugs in diverse covered and uncovered conditions simulating their natural habitats. A total of 5400 adult bed bugs were collected alive from 17 infested locations in Paris. They were morphologically identified in laboratory as Cimex lectularius. They were then distributed in multiple sets of 30 specimens to examine in covered (tissue, furniture, mattress or blanket) and uncovered (direct exposure) conditions and in diverse step-function temperatures (50, 55 and 60°C) and times (15, 30, 60 and 120 minutes), replicated three times. Effective mortality was observed in 1080 specimens exposed directly to 50°C for 60 minutes. In specimens covered by tissue (1080 specimens), furniture (1080) or mattress (1080), all were dead at 60°C within 60 minutes. The specimens covered by blanket (1080) at the same temperature were dead after 120 minutes. A 60-minutes delay in reaching to lethal temperature within blanket compared to uncovered thermometer was observed.

In vitro efficacy of five essential oils against Pediculus humanus capitis.

Treatment of head lice has relied mainly on the use of topical insecticides. Today, conventional topical pediculicides have suffered considerable loss of activity worldwide. There is increasing interest in the use of natural products such as essential oils for head louse control, and many of them are now incorporated into various over-the-counter products presented as pediculicides, often without proper evaluation. The aim of the present study was to assess the in vitro efficacy of five essential oils against adults of Pediculus humanus capitis using a contact filter paper toxicity bioassay. The chemical composition of the essential oils from wild bergamot, clove, lavender, tea tree, and Yunnan verbena was analyzed by gas chromatography-mass spectrometry. All treatments and controls were replicated three times on separate occasions over a period of 11 months. In all, 1239 living lice were collected from the scalp of 51 subjects, aged from 1 to 69 years. Clove oil, diluted either in coco oil or sunflower oil, demonstrated the best adulticidal activity, reaching > 90% mortality within 2 h in lice submitted to a 30-min contact. Yunnan verbena oil diluted in coco oil showed also a significant efficacy. Other essential oils showed a lower efficacy. The oil's major component(s) differed according to the tested oils and appeared chemically diverse. In the case of clove oil, the eugenol appeared as the main component. This study confirmed the potential interest of some of the essential oils tested, but not all, as products to include possibly in a pediculicidal formulation.

Doublet chemotherapy vs. single-agent therapy with 5FU in elderly patients with metastatic colorectal cancer. a meta-analysis.

BACKGROUND: The clinical benefit of first-line doublet chemotherapy (including oxaliplatin or irinotecan) compared to single-drug therapy (5FU) in elderly patients (>70 or >75 years old) with metastatic colorectal cancer (MCRC) is controversial. Therefore, we undertook a meta-analysis of all published phase III studies. MATERIAL AND METHODS: We performed a PubMed search using keywords metastatic colorectal cancer, phase III studies, oxaliplatin, irinotecan, survival. We also screened Society of Clinical Oncology (ASCO) and European Society of Medical Oncology (ESMO) proceedings. Few studies have been published corresponding to our inclusion criteria. The efficacy outcomes were overall survival (OS) and progression-free survival (PFS). Toxicity was also examined when available. Hazard ratios (HRs) with their 95 % confidence intervals (CI) were collected from the studies and pooled. By convention, HRs <1 corresponded to a better outcome for doublets. p values <0.05 were considered statistically significant. A fixed-effect model was used. We used Comprehensive Meta-Analysis Software (Biostat, Englewood, NJ, USA). RESULTS: This meta-analysis (MA) included five original studies (Mitry and Venderbosch for CAIRO both assessing irinotecan, De Gramont and Seymour for FOCUS2 and Ducreux assessing oxaliplatin) and an already published MA (Folprecht) of four trials comparing FOLFIRI with 5FU (Saltz, Douillard, Köhne and Seymour). Our MA included 1225 patients (70 % men). For age, we chose a cut-off of 70 years for oxaliplatin and a cut-off of 75 years for irinotecan. The performance status (PS) score was 0-1 in about 90 % of patients except for the studies by Mitry and Seymour FOCUS2 which both included 30 % of PS2 patients. Overall, doublet chemotherapy, compared to 5FU alone, did not improve OS (HR = 1.00; CI: 0.89-1.13) but significantly improved PFS (HR = 0.82; CI: 0.72-0.93). When assessed separately, FOLFIRI and FOLFOX both significantly improved PFS (HR = 0.83; 0.68-1.00 and HR = 0.81; 0.68-0.97, respectively). The main grade 3-4 toxicities for FOLFIRI were diarrhoea, nausea, vomiting and neutropenia, which occurred significantly more often than with 5FU alone. CONCLUSION: Addition of oxaliplatin or irinotecan to 5FU in metastatic CRC significantly improved PFS in elderly patients more than 70 years old but was associated with an increased risk of toxicity as shown for irinotecan.

Animal model methodology: immunocompetent or leucopenic rats, which is the best? Results from a model of experimental pneumonia due to derepressed cephalosporinase-producing Enterobacter cloacae.

BACKGROUND: The aim of this study was to compare the bactericidal activity of cefepime plus amikacin against experimental pneumonia induced by a stably derepressed cephalosporinase-producing Enterobacter cloacae strain in immunocompetent and leucopenic rats. METHODS: Sixty Wistar rats were used. Leucopenia was induced in half of them by a single intravenous administration of 30 mg/kg cyclophosphamide, while the remaining rats received the same volume of saline. All rats were infected 96 h later by tracheal instillation of 8 log(10) colony-forming units of E. cloacae. Twelve rats (6 immunocompetent and 6 leucopenic) were sacrificed 6 h later to assess the initial bacterial burden to the lungs. Then, the remaining 48 rats received a combination of 60 mg/kg cefepime twice a day and 25 mg/kg amikacin once a day given intraperitoneally or the same volume of saline. Six rats per group (leucopenic or not, treated or not) were sacrificed 12 and 30 h after therapy started. RESULTS: Spontaneous bacterial clearance with time was observed only in immunocompetent rats. Compared to untreated animals, antibiotic administration induced a decrease in lung bacterial titres in immunocompetent and leucopenic rats. The difference was statistically significant only in leucopenic rats. CONCLUSIONS: The use of leucopenic rats reduced spontaneous bacterial clearance in the lungs and increased the bactericidal effect of the antibiotic combination and ultimately the confidence in the reliability of the results.

Clinical and epidemiological survey of tungiasis in Madagascar.

BACKGROUND: Tungiasis is a dermal parasitic infection, classified as a neglected tropical disease. Madagascar is one of endemic countries which have been committed for decades to control the tungiasis as a public health issue. Despite this medical importance, little is known about the prevalence and epidemiology of the disease in this country. METHODS: A descriptive cross-sectional survey was performed in two endemic foci of Antananarivo and Toamasina. RESULTS: In total, 2971 suspected individuals were surveyed. Of them, 643 individuals were excluded due to absence or refusing clinical examinations. Therefore, 2328 individuals with aforementioned criteria were clinically examined, 320 cases (13.7%) were found infected by Tunga penetrans. Of these 320 infected cases, 241 individuals came from rural regions against 79 from urban areas. The sex ratio of infected cases was 1.15 with an age average of 34.7 years old. Most of them were illiterate (185/320, 57.8%) with no habit of feet washing (210/320, 65.6%). The majority (198/320, 61.9%) inhabited in the houses constructed by falafa providing a suitable breeding location for Tunga ectoparasites. Based on clinical examination, most of the patients (298/320, 93.1%) had the lesions on their toes followed by those possessed the lesions on the plantar (140/320, 43.7%). The lesion stages of IV and V were observed in 49.1% (157/320) of visited patients which were more common in rural regions (86%) than in urban areas (14%). For treatment, removing the fleas using needle (122/320, 38.1%), followed by the application of petroleum (100/320, 31.2%) were among the most traditional remedies used by our patients. CONCLUSION: This investigation highlights a high burden of tungiasis in studied endemic foci in particular in rural regions. These results can be helpful in control management strategies against this parasitosis in Madagascar.

Duration of adjuvant chemotherapy for patients with non-metastatic colorectal cancer.

BACKGROUND: Surgery of primary tumour is the backbone of colorectal cancer treatment (CRC). But in stage III cancer, metastatic or local relapse is often observed (50%). So, adjuvant treatment is always considered in this setting. The best treatment duration of hypothetic disease is not easy to define. Adjuvant chemotherapy for CRC actually lasts 6 months. The choice of optimal duration is based upon old studies using 5-fluorouracil (5FU). During the last ten years, results of major randomized controlled studies (RCTs) comparing different durations of treatments and different schedules in adjuvant setting were published. Several studies compared a 6-month chemotherapy with a longer treatment. Conversely, a single study by Chau et al compared a 6 month chemotherapy with continuous treatment lasting 3 months. But the optimal duration of these chemotherapies could be challenged. Even though the optimal duration of chemotherapy in CRC is a major issue, it has never been answered adequately. OBJECTIVES: To evaluate the optimal duration of adjuvant treatment, we performed a meta-analysis of all RCTs comparing two durations of adjuvant treatment, 6 months versus 9 to 12 months. SEARCH STRATEGY: Publications were identified from PubMed (February 28th, 2009), Embase, and the Cochrane Database of Clinical Controlled Trials (CENTRAL) in the Cochrane Library 2009 issue 1. Reviews and books were also scrutinized. Abstracts were reviewed from ASCO annual meetings proceedings from 1998 to 2009. SELECTION CRITERIA: Patients with surgically resected colorectal cancer with high risk of recurrence. DATA COLLECTION AND ANALYSIS: Several RCTs compared shorter versus longer durations of chemotherapy, 6 studies for overall survival (OS) and 7 studies for relapse free survival (RFS), for a total of 10326 patients, mean age 63.1 years, including 9826 colon and 500 rectum cancers. MAIN RESULTS: Treatments were always based on 5-FU. Two studies were excluded, an epidemiological study and a study comparing continuous treatment during 3 months with conventional chemotherapy during 6 months. The later because it compared 2 durations less than or equal to 6 months. Shorter duration of chemotherapy (3-6 months) compared with longer duration (9-12 months) was not associated to poorer RFS (RR =0.96, 95% CI : 0.90-1.02) and OS (RR = 0.96 ; 95% CI : 0.91-1.02). AUTHORS' CONCLUSIONS: The present meta-analysis confirmed that adjuvant chemotherapy of CRC should not last for more than 6 months. Prolonged duration would result in lower benefit to risk ratio. However, the results do not make it possible to favour either 3 or 6 month durations. They should help design a future RCT comparing different durations of continuous treatment.

Microsatellite instability does not predict the efficacy of chemotherapy in metastatic colorectal cancer. A systematic review and meta-analysis.

BACKGROUND: Microsatellite Instability (MSI) status is a good prognostic factor for colorectal cancer (CRC) but its predictive value for chemosensitivity remains controversial. A previous meta-analysis (MA) in the adjuvant setting showed that MSI-high (H) status did not predict the efficacy of chemotherapy. The predictive value of MSI status on the effect of metastatic chemotherapy was investigated by MA. PATIENTS AND METHODS: Studies were identified by electronic search through PubMed, Embase and ASCO proceedings online databases, using several key words (colorectal cancer, chemotherapy, microsatellite instability). For each study, the ratio of response rate (RR), complete (CR) and partial response (PR) divided by stable disease and progression was calculated. From 190 articles and 100 abstracts, only eight independent studies were selected. The data were analysed with a random-effect model (due to heterogeneity between studies) using EasyMA software. Statistical calculations were performed on six studies representing 964 patients (mean age 63 years; 91 MSI-H; 873 microsatellite stable (MSS) tumours). A total of 287 patients received 5-fluorouracil (5FU)-based chemotherapy, whereas 678 patients received combinations of 5FU or capecitabine with oxaliplatin and/or irinotecan. RESULTS: No benefit of metastatic chemotherapy in terms of RR for MSI-H patients compared with MSS patients was found. The global hazard ratio (HR) for RR was 0.82 (95% confidence interval, CI: 0.95; 0.65-1.03; p=0.09). CONCLUSION: MSI status does not predict the effect of chemotherapy which is similar in MSI-H and MSS metastatic CRC tumours.

A successful compartmental approach for the treatment of breast cancer brain metastases.

BACKGROUND: Brain metastases are challenging daily practice in oncology and remain a compartmental problem since most anti-cancer drugs do not cross the blood-brain barrier at relevant pharmacological concentrations. METHODS: In a young woman with HER2-overexpressing breast cancer resistant to standard treatments, at the time of brain metastases progression, a ventricular reservoir was implanted for intrathecal drug injections and detailed pharmacokinetic studies. RESULTS: A first association of intrathecal trastuzumab with intravenous cisplatin was offered to the patient. For trastuzumab, the mean cerebrospinal fluid trough concentration of 53.4 mg/L reached relevant levels, enabling the stabilization of the metastases. Adding intravenous cisplatin was not beneficial, since the cerebrospinal fluid exposure was almost undetectable under 0.08 mg/L. We then offered the patient an intrathecal combination of trastuzumab and methotrexate, because of their in vitro synergic cytotoxicity. The cerebrospinal fluid peak of methotrexate was 1037 µmol/L at 2 h, and the concentrations remained above the theoretical therapeutic concentration. After 2 months of this drug combination, we obtained an excellent response on the brain metastases. CONCLUSION: Our preliminary study supports the interest of a compartmental approach through a direct administration of drugs into the cerebrospinal fluid for the treatment of breast cancer brain metastases.

Do drowning and anoxia kill head lice?

Chemical, physical, and mechanical methods are used to control human lice. Attempts have been made to eradicate head lice Pediculus humanus capitis by hot air, soaking in various fluids or asphyxiation using occlusive treatments. In this study, we assessed the maximum time that head lice can survive anoxia (oxygen deprivation) and their ability to survive prolonged water immersion. We also observed the ingress of fluids across louse tracheae and spiracle characteristics contrasting with those described in the literature. We showed that 100% of lice can withstand 8 h of anoxia and 12.2% survived 14 h of anoxia; survival was 48.9% in the untreated control group at 14 h. However, all lice had died following 16 h of anoxia. In contrast, the survival rate of water-immersed lice was significantly higher when compared with non-immersed lice after 6 h (100% vs. 76.6%, p = 0.0037), and 24 h (50.9% vs. 15.9%, p = 0.0003). Although water-immersed lice did not close their spiracles, water did not penetrate into the respiratory system. In contrast, immersion in colored dimeticone/cyclomethicone or colored ethanol resulted in penetration through the spiracles and spreading to the entire respiratory system within 30 min, leading to death in 100% of the lice.

Effects of statins on bone mineral density: a meta-analysis of clinical studies.

CONTEXT: Statins inhibit HMG-CoA reductase, preventing synthesis of mevalonate but also of isoprenoids, which affect osteoclast activity. Amino-bisphosphonates share this effect. In vitro and in vivo, statins show convincing anabolic and anti-resorptive bone effects. However, in a clinical meta-analysis (MA), they did not prevent hip fractures. OBJECTIVE AND DESIGN: Our meta-analysis studied the impact of statins on bone mineral density (BMD) at various sites and compared the effects of lipophilic and more hydrophilic statins. DATA SOURCES: Our PubMed and Embase queries using two keywords (statins, BMD) were updated to October 2006. DATA COLLECTION: Two readers independently collected BMDs from studies. DATA SYNTHESIS: Twenty-one studies, mostly observational (three randomized controlled trials and one pseudo-randomized study), were assessed. Two studies were excluded (no control groups). Three studies could not be analyzed. The sixteen studies analyzed mainly included postmenopausal osteopenic women (2971 patients under statins). Statins significantly increased BMD at total hip (TH) and femoral neck (FN). Effect sizes (ESs) were modest: 0.21 at TH (95% confidence interval [CI]: 0.16-0.25) and 0.20 at FN (CI: 0.08-0.28). Among women, statins acted similarly (ES: 0.20 for TH and 0.18 for FN; CI: 0.14-0.25 and 0.06-0.31 respectively); lipophilic statins (simvastatin, lovastatin) almost entirely caused this effect, at both TH (ES: 0.20; CI: 0.15-0.26) and FN (ES: 0.22; CI: 0.06-0.37). CONCLUSION: Our findings of modest but statistically significant beneficial effects of statins on hip BMD should promote large double-blind randomized controlled trials on their bone effects, in view of their major beneficial cardiovascular effects with excellent safety profile.

Microvessel density as a prognostic factor in women with breast cancer: a systematic review of the literature and meta-analysis.

We performed a meta-analysis of all 87 published studies linking intratumoral microvessel density (MVD), reflecting angiogenesis, to relapse-free survival (RFS) and overall survival (OS). With median MVD as cutoff, MVD impact was measured by risk ratio (RR) between the two survival distributions. Seventeen studies did not mention survival data or fit inclusion criteria. Twenty-two were multiple publications of the same series, leaving 43 independent studies (8936 patients). MVD was assessed by immunohistochemistry, using antibodies against factor VIII (27 studies; n = 5262), CD31 (10 studies; n = 2296), or CD34 (8 studies; n = 1726). MVD might be a better prognostic factor when assessed by CD31 or CD34 versus factor VIII (P = 0.11). For RFS, statistical calculations were performed in 25 studies (6501 patients). High MVD significantly predicted poor survival [RR = 1.54 for RFS and OS with the same 95% confidence interval (CI), 1.29-1.84]. Twenty-two studies analyzed separately lymph node-negative patients (n = 3580), for whom predictors of poor survival are requested. This latter meta-analysis included 15 studies for RFS (2727 patients) and 11 for OS (1926 patients). High MVD significantly predicted poor survival [RR = 1.99 for RFS (95% CI, 1.33-2.98) and RR = 1.54 for OS (95% CI, 1.01-2.33)]. Between-study variations could result from patient selection criteria, techniques to stain and count microvessels, and cutoff selection. MVD was a significant although weak prognostic factor in women with breast cancer. Standardization of MVD assessment is needed.

Is There a Survival Benefit of First-Line Epidermal Growth Factor Receptor Tyrosine-Kinase Inhibitor Monotherapy Versus Chemotherapy in Patients with Advanced Non-Small-Cell Lung Cancer?: A Meta-Analysis.

BACKGROUND: Tyrosine-kinase inhibitors (TKIs) markedly improve progression-free survival (PFS) of patients with advanced non-small-cell lung cancer (NSCLC) mutated for epidermal growth factor receptor (EGFR). Results on overall survival (OS) are less clear-cut. We performed a publication-based meta-analysis to address further this issue. METHODS: We did a PubMed query using keywords simultaneously (lung neoplasm, tyrosine kinase inhibitors, epidermal growth factor receptor mutation, survival, and randomized controlled trials). We also searched for relevant abstracts in annual proceedings of ASCO, ESMO, and WCLC meetings. We cross-checked all references from all eligible articles. Only phase III randomized controlled trials comparing TKI monotherapy and platinum-based doublet chemotherapy in first-line treatment of metastatic or advanced NSCLC were included. We used EasyMA software to perform statistical analyses. A random effect model was used in case of heterogeneity between studies (and a fixed effect model in absence of heterogeneity). RESULTS: The eight eligible studies included 2962 patients (780 males, 2182 females, mostly Asian, median age 60 years), 2909 adenocarcinomas (98 %), 1739 mutated tumors (897 exon 19 deletion, 699 L858 mutation), 448 stage IIIB, and 2222 stage IV (75 %) tumours and 2453 never smokers (83 %). Four studies assessed gefitinib, two studies assessed erlotinib, and two studies assessed afatinib. Chemotherapies were doublets including a platinum salt. All studies included patients with EGFR mutations, but six studies included only EGFR mutated patients. OS was similar among patients who first received TKI or chemotherapy (HR 0.98, 95 % CI 0.87-1.10, fixed effect model). Conversely, compared with chemotherapy, EGFR TKIs significantly improved PFS in patients with EGFR-mutated tumours (HR 0.37, 95 % CI 0.29-0.49, random effect model). Concerning side effects, rash (RR 6.29, 95 % CI 4.05-9.77), diarrhoea (RR 3.51, 95 % CI 2.15-5.75), stomatitis (RR 3.57, 95 % CI 1.81-7.04), and interstitial lung disease (RR 6.07, 95 % CI 1.66-22.2) were significantly more frequent after TKIs. As expected, fatigue (RR 0.38, 95 % CI 0.32-0.45), nausea/vomiting (RR 0.19, 95 % CI 0.11-0.32), and haematological disorders, including thrombocytopenia (RR 0.18, 95 % CI 0.09-0.35), anaemia (RR 0.22, 95 % CI 0.15-0.33), and grade 3-4 neutropenia (RR 0.06, 95 % CI 0.04-0.08), were significantly more frequent after chemotherapy. CONCLUSION: The major discrepancy between a similar OS and a markedly improved PFS after first-line TKI compared with chemotherapy could be related to the high level of crossing-over between both groups.

Management of large-vessel vasculitis with FDG-PET: a systematic literature review and meta-analysis.

We aimed to clarify the role of 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in the management of large-vessel vasculitis (LVV), focusing on 3 issues which are as follows: describe and determine the different FDG-PET criteria for the diagnosis of vascular inflammation, the performance of FDG-PET for the diagnosis of large-vessel inflammation in giant cell arteritis (GCA) patients, and the performance of FDG-PET to evaluate the disease inflammatory activity in Takayasu arteritis (TA) patients. MEDLINE, Cochrane Library, and EMBASE database were searched for articles that evaluated the value of FDG-PET in LVV, from January 2000 to December 2013. Inclusion criteria were American College of Rheumatology criteria for GCA or TA, definition PET positivity threshold, and >4 cases included. Sensitivity (Se) and specificity (Sp) of FDG-PET for the diagnosis of large-vessel inflammation were calculated from each included individual study, and then pooled for meta-analysis with a random-effects model. Twenty-one studies (413 patients, 299 controls) were included in the systematic review. FDG-PET showed FDG vascular uptake in 70% (288/413) of patients and 7% (22/299) of controls. Only vascular uptake equal to or higher than the liver uptake was significantly different between GCA/TA patients and controls (P < 0.001). The meta-analysis of GCA patients (4 studies, 57 patients) shows that FDG-PET has high Se and Sp for the diagnosis of large-vessel inflammation in GCA patients in comparison to controls, with a pooled Se at 90% (95% confidence interval [CI], 79%-93%) and a pooled Sp at 98% (95% CI, 94%-99%). The meta-analysis of TA patients (7 studies, 191 patients) shows that FDG-PET has a pooled Se at 87% (95% CI, 78%-93%) and Sp at 73% (95% CI, 63%-81%) for the assessment of disease activity in TA, with up to 84% Sp, with studies using National Institutes of Health criteria as the disease activity assessment scale. FDG-PET showed good performances in the diagnosis of large-vessel inflammation, with higher accuracy in GCA patients than in TA patients. Although a vascular uptake equal to or higher than the liver uptake appears to be a good criterion for the diagnosis of vascular inflammation, further studies are needed to define the threshold of significance as well as the clinical significance of the vascular uptake.

In vitro evaluation and biodistribution of a 99mTc-labeled anti-VEGF peptide targeting neuropilin-1.

Neuropilins (NRP) are receptors of angiogenic vascular endothelial growth factor (VEGF). Their overexpression was correlated with tumor angiogenesis and growth suggesting that their specific targeting could provide a new marker of tumor progression. Here, we observed in vitro that new (99m)Tc-labeled derivative of anti-VEGF heptapeptide, ATWLPPR, binds to NRP1 but not to NRP2. Our radiotracer is stable up to 24 h in human serum and in cysteine challenge. But, its too low affinity and too fast extraction indicate further improvement to give a successful imaging of tumor in vivo.