Efficacy and tolerance of Menorest® compared to Premarin® in the treatment of postmenopausal women. A randomised,multicentre, double-blind,double-dummy study

Two-hundred and fourteen (214) menopausal women with moderate to severe vasomotor symptoms, aged 40–65 years, were randomised. After a 4-week treatment-free period, each woman received a continuous regimen of Menorest^® 50 twice weekly or Premarin^® 0.625 mg daily, for 12 weeks. Didrogesterone 10 mg was also given to all women for 12 days of every 28-day cycle. The objectives were to compare the efficacy and safety profiles of Menorest^® and an oral estrogen. A statistically significant reduction in the mean number of hot flushes occurred in each group compared to baseline with a decrease from 7.1 at baseline to 0.9 at 12 weeks in the Menorest^® group, and from 6.7 to 0.5 in the oral estrogen group; there was no statistically significant difference between the two groups (P = 0.36). With each successive treatment cycle, there was a continuous improvement in the number of hot flushes. The incidence and severity of menopausal symptoms were reduced in the same manner in both groups. There were no statistically significant differences in the mean plasma estradiol and estrone concentrations between the two treatment groups after 10 weeks of therapy. The mean estradiol to estrone ratio was similar in both groups, as was the number of adverse events observed. In summary, Menorest^® was as effective as an oral estrogen in alleviating menopausal symptoms.     

Evaluation of the BioFire® FilmArray® Meningitis/Encephalitis panel in an adult and pediatric Ugandan population

BackgroundMeningitis causes significant mortality in sub-Saharan Africa and limited diagnostics exist. We evaluated the utility of the BioFire® FilmArray® Meningitis/Encephalitis multiplex PCR panel (BioFire ME) in HIV-infected adults and HIV-infected and uninfected children presenting with suspected meningitis in Uganda.MethodsWe tested cerebrospinal fluid (CSF) using a stepwise meningitis diagnostic algorithm including BioFire ME. We determined the diagnostic performance of BioFire ME for cryptococcal meningitis, using cryptococcal antigen (CrAg) and CSF culture as reference standards, and assessed other central nervous system (CNS) pathogens identified by the panel.ResultsWe evaluated 328 adult and 42 pediatric CSF specimens using BioFire ME. Of the adult CSF samples tested, 258 were obtained at baseline, and 70 were obtained from repeat lumbar punctures in cryptococcal meningitis. For Cryptococcus, sensitivity was 82%, specificity was 98%, PPV was 98%, and NPV was 79% in baseline specimens using CSF CrAg as the reference standard. Among follow-up specimens, a negative BioFire ME for Cryptococcus predicted CSF culture sterility with 84% NPV. Overall sensitivity was decreased at low fungal burdens: 29% for 0–99 Cryptococcus CFU/mL compared to 94% for ≥100 CFU/mL in baseline specimens. Other pathogens detected included E. Coli, H. influenzae, S. pneumoniae, CMV, enterovirus, HSV, HHV-6, and VZV. Two specimens tested positive for S. pneumoniae and one for Cryptococcus in the pediatric population.ConclusionsMultiplex PCR is a promising rapid diagnostic test for meningitis in adults and children in resource-limited settings. Cryptococcus at low fungal burdens in CSF may be missed by BioFire ME.     

Molecular cloning and nucleotide sequencing of the 3′-terminal region of a South African isolate of ryegrass mosaic virus RNA and in vitro expression of the coat protein gene

Summary The 2094 nucleotides at the 3-terminus of a South African isolate of ryegrass mosaic virus (RGMV) was cloned and sequenced. Two putative poly-protein cleavage sites were found: Q/L and E/A, both of which are novel in thePotyviridae. The RGMV-SA cDNA was cloned into an expression vector, pUEX, and a fusion protein of 185 kDa was obtained which reacted strongly to anti-RGMV-SA antiserum. Alignment of the predicted amino acid sequence of RGMV-SA with those of otherPotyviridae members showed limited identity, indicating that RGMV-SA is a definite and distinct virus.     

An original arthroscopic fixation of adult's tibial eminence fractures using the Tightrope® device: A report of 8 cases and review of literature

PurposeThe objective of this study is to asset the efficiency of the use of the Tightrope® device to treat isolated tibial spine fractures in adults.MethodsAll patients treated for isolated tibial spine fracture between November 2007 and February 2011 have been retrospectively included. The main judgment criteria was the post-operative knee laxity measured by Rolimeter® (Aircast) and the secondary criteria were the IKDC scores, the knee mobility, the Lachman test and the bone union. 8 patients have been included. The mean age was 34.2 years (± 12.5). The classification of Meyers and McKeever identified 5 types II, 2 types IIIa and 1 type IIIb. The mean follow-up period was 10 months.ResultsThe mean post-operative anterior knee laxity was 6 ± 2.14 mm for the operated side and 5.6 ± 1.85 mm for the opposite side. No significant difference was found (P = 0.73). According to the IKDC classification 3 patients were normal (A), 2 were nearly normal (B), 1 was abnormal (C) and 1 was very abnormal (D). The mean IKDC subjective score was 70.71 ± 17.56. All 8 fractures achieved union without elevation. 3 patients developed motion complications and 2 required an arthroscopic arthrolysis. No other significant complication was noted. The outcome was compared to the different series published during the last 10 years.ConclusionThe use of the Tightrope® device is a simple technique occurring a rigid fixation, allowing early rehabilitation with a high rate of arthrofibrosis.Level of evidenceLevel IV, case series.     

Correction to: Do habituation,host traits and seasonality have an impact on protist and helminth infections of wild western lowland gorillas?

Parasitology Research - Affiliation of Klára J. Petrželková was incorrectly assigned as 2, 9, 10 in the original version of this article when in fact it should have been 3, 9, 10....     

Evaluation of the COBAS® AmpliPrep/COBAS® TaqMan® HCV Test,v2.0 and comparison to assays used in routine clinical practice in an international multicenter clinical trial: The ExPECT study

BackgroundThe COBAS^® AmpliPrep^®/COBAS^® TaqMan^® HCV Test, v2.0 (CAP/CTM2) is used for HCV RNA viral load monitoring.ObjectivesThe performance of the CAP/CTM2 was compared to other widely used tests, including a manual version of the assay (the COBAS^® TaqMan^® HCV Test, v2.0 for use with the High Pure System, HPS/CTM2) predominantly used during phase III clinical trials for the new direct acting antiviral therapies.Study designLow HCV RNA level comparisons were performed across tests (Abbott Realtime HCV Test, ART; COBAS^® AmpliPrep^®/COBAS^® TaqMan^® HCV Test, v1.0, CAP/CTM1; CAP/CTM2; and HPS/CTM2) using dilutions of the 2nd HCV WHO International Standard. Additionally, the clinical performance of the CAP/CTM2 was evaluated with 421 leftover HCV RNA-positive routine clinical samples.ResultsAll quantifiable WHO dilutions were within ±0.3 log₁₀ IU/mL of the expected results across tests and the analytical sensitivity resulted in a limit of detection of 12 IU/mL (95% confidence interval, 10, 15). When clinical samples were tested the results for 87% (367 of 421) of all sample comparisons were within ±0.5 log₁₀ IU/mL. When low viral load results (25–3500 IU/mL) were compared, values obtained by the ART assay were significantly lower (p < 0.0001) than those obtained with the CAP/CTM2.ConclusionsThe new CAP/CTM2 showed good accuracy with comparable sensitivity to comparator assays. The new kit is well-suited for use in the routine diagnostic laboratory, especially for accurate monitoring of patients receiving triple therapy or interferone-free regimens.     

Assessment of adherence to highly active antiretroviral therapy in a cohort of African HIV-infected children in Abidjan, Côte d'Ivoire

African HIV-infected children benefit from access to antiretroviral treatments but little is known about their adherence. A cross-sectional assessment of adherence to highly active antiretroviral therapy was conducted among a group of children recruited in an observational cohort in Abidjan, C?te d'Ivoire. Adherence was determined by a 1-month recall by child or caregiver, with full adherence signifying no interruptions in the prior month. One-third reported less than full adherence. Undetectable viral load was associated with full adherence in a subset of children with a P value <10% (P = 0.098). As compared with children with full adherence, those with less than full adherence were significantly older and more likely to be taking efavirenz. These findings underscore the necessity of assessing and supporting children's adherence routinely in AIDS care institutions.     

Validation of an automated procedure to isolate human adipose tissue-derived cells by using the Sepax® technology

The stromal vascular fraction of adipose tissue has gained popularity as a source of autologous progenitor cells for tissue engineering and regenerative medicine applications. The aim of this study was to validate a newly developed, automated procedure to isolate adipose-derived mesenchymal stem/stromal cells (ASCs) from adult human lipoaspirates in a closed and clinical-grade device, based on the Sepax(?) technology. Using a total of 11 donors, this procedure was compared with the standard operator-based manual separation in terms of isolation yield, clonogenic fraction, phenotype, and differentiation potential of ASCs. As compared with the manual process, automation resulted in a 62% higher isolation yield, with 2.6±1.2×10(5) nucleated cells per mL of liposuction, and a 24% higher frequency of clonogenic progenitors. The variability in the isolation yield and clonogenicity across different preparations was reduced by 18% and 50%, respectively. The cytofluorimetric profile and in vitro differentiation capacity into mesenchymal lineages were comparable in the cells isolated using the two procedures. The new Sepax-based process thus allows an efficient isolation of ASCs with higher and more reproducible yields than the standard manual procedure, along with minimal operator intervention. These results are expected to facilitate the use of ASCs for clinical purposes, either within an intraoperative setting or in combination with further in vitro cell expansion/cultivation.     

Retrospective analysis of a clinical exome sequencing cohort reveals the mutational spectrum and identifies candidate disease–associated loci for BAFopathies

PurposeBRG1/BRM-associated factor (BAF) complex is a chromatin remodeling complex that plays a critical role in gene regulation. Defects in the genes encoding BAF subunits lead to BAFopathies, a group of neurodevelopmental disorders with extensive locus and phenotypic heterogeneity.MethodsWe retrospectively analyzed data from 16,243 patients referred for clinical exome sequencing (ES) with a focus on the BAF complex. We applied a genotype-first approach, combining predicted genic constraints to propose candidate BAFopathy genes.ResultsWe identified 127 patients carrying pathogenic variants, likely pathogenic variants, or de novo variants of unknown clinical significance in 11 known BAFopathy genes. Those include 34 patients molecularly diagnosed using ES reanalysis with new gene–disease evidence (n = 21) or variant reclassifications in known BAFopathy genes (n = 13). We also identified de novo or predicted loss-of-function variants in 4 candidate BAFopathy genes, including ACTL6A, BICRA (implicated in Coffin-Siris syndrome during this study), PBRM1, and SMARCC1.ConclusionWe report the mutational spectrum of BAFopathies in an ES cohort. A genotype-driven and pathway-based reanalysis of ES data identified new evidence for candidate genes involved in BAFopathies. Further mechanistic and phenotypic characterization of additional patients are warranted to confirm their roles in human disease and to delineate their associated phenotypic spectrums.     

The use of medical care and the prevalence of serious illness in an adult Prader–Willi syndrome cohort

IntroductionAdults with Prader–Willi syndrome (PWS) have an increased occurrence of several medical conditions. We report on the consequences of high morbidity rates such as prevalence rate of hospital admissions, medication use and surgery in a Dutch cohort of adults with PWS. Special attention is paid to causes and symptoms of serious illness.MethodParticipants were contacted via the Dutch Prader–Willi Parent Association and through physicians specializing in persons with ID. The persons with PWS and their main caregivers were visited at home. Information was collected through semi-structured interviews on 102 adults with PWS.ResultsThe need for medical care in the neonatal period is associated with hypotonia and feeding problems. Hospital admissions for respiratory tract infections are frequent. During childhood most hospital admissions were due to PWS syndrome specific surgery. During adolescence hospital admissions occurred for scoliosis surgery and endocrine evaluations. At adult age, hospitalization was associated with inguinal hernia surgery, diabetes mellitus, psychosis, erysipelas, water and drug intoxications. In the older group, respiratory infections were again the main reason for hospital admissions. Frequently used medications at adult age included psychotropics, laxatives, anti-diabetics and dermatologic preparations. Abnormal drinking patterns, problems with anesthesia, decreased ability to vomit, abnormal pain awareness and unpredictable fever responses were frequent and often lead to delayed diagnoses of serious conditions.DiscussionPeople with PWS are frequent users of medical-care. Reasons for hospitalization and medication use are age specific. Knowledge on the different presentation of symptoms in people with PWS is needed. In case of unexplained illness, disturbances of consciousness and behavioral changes in people with PWS, an infection should be ruled out in the first place. Information from this study may help in preventing conditions and recognizing conditions in an early stage. Adequate preventive management and treatment of PWS related morbidity, could reduce medical care use in the long term and could improve quality adjusted life years.     

Using EasyMatch® to anticipate the identification of an HLA identical unrelated donor: A validated efficient time and cost saving method

In the absence of an HLA matched familial donor, a search for an unrelated donor or cord blood unit is initiated through worldwide registries. Although a first look-up on available HLA information of donors in the “book” at BMDW (Bone Marrow Donor Worldwide) can provide a good estimation of the number of compatible donors, the variety of resolution typing levels requires confirmatory typing (CT) which are expensive and time consuming. In order to help recipient centers in their work. The French donor registry (France Greffe de Moelle/Agence de la Biomedecine) has recently developed a software program called “EasyMatch®” that uses haplotype frequencies to compute the likelihood of phenotypic match in donors according to various typing resolution levels.The goal of our study is to report a single monocentric user-experience with EasyMatch®, demonstrating that its routine use reduced the cost and the delay of the donor search in our center, allowing the definition of a new strategy to search compatible unrelated donors.The strategy was first established on a retrospective cohort of 217 recipients (185 adults and 32 children = before score) and then validated on a prospective cohort of 171 recipients (160 adults and 11 children = after score).For all patients, we calculated the delay between the registration day and the donor identification day, and the number of CT requested to the donor centre. Considering both groups, we could observe a significant decrease of the number of CT from 8 to 2 (p < 0,001), and a significant decrease of the median delay to identify a suitable donor from 43 to 31 days (p < 0.0001).EasyMatch® estimates the number of potentially identical donors, but doesn’t foresee availability of the donors. It provides us an easy tracking of mismatches, an estimation of the number of potential donors, the selection of population following ethnic origin of patients and a high prediction when probability is high or low. It affords a new approach of donor search in our daily work and improves the efficiency in the great challenge of the compatible donor identification.     

Introduction of East African cassava mosaic Zanzibar virus to Oman harks back to “Zanzibar, the capital of Oman”

Cassava mosaic disease (CMD) is the most devastating disease of the subsistence crop cassava (Manihot esculenta) across Africa and the Indian subcontinent. The disease is caused by viruses of the genus Begomovirus (family Geminiviridae)—seven species have been identified so far. The Sultanate of Oman is unusual among countries in Arabia in growing cassava on a small scale for local consumption. During a recent survey in A’Seeb wilayat of Muscat governorate, Oman, cassava plants were identified with symptoms typical of CMD. A begomovirus, East African cassava mosaic Zanzibar virus (EACMZV), was isolated from symptomatic plants. This virus was previously only known to occur in Zanzibar and Kenya. During the 19th Century, Zanzibar was governed by Oman and was so important that the Sultan of Oman moved his capital there from Muscat. After a period of colonial rule, the governing Arab elite was overthrown, following independence in the 1960s, and many expatriate Omanis returned to their homeland. Having gained a liking for the local Zanzibar cuisine, it appears that returning Omanis did not wish to do without dishes made from one particular favorite, cassava. Consequently, they carried planting material back to Oman for cultivation in their kitchen gardens. The evidence suggests that this material harbored EACMZV. Recently, Oman has been shown to be a nexus for geminiviruses and their associated satellites from diverse geographic origins. With their propensity to recombine, a major mechanism for evolution of geminiviruses, and the fact that Oman (and several other Arabian countries) is a major hub for trade and travel by air and sea, the possibility of onward spread is worrying.     

The “muscular hernia sign”: an original ultrasonographic sign to detect lesions of the forearm’s interosseous membrane

The total disruption of the forearm’s interosseous membrane can lead to an Essex-Lopresti syndrome. The diagnosis must be done early for a better prognostic. Incomplete lesions can aggravate and an early diagnosis of incomplete lesions is a challenging problem. Magnetic resonance imaging is the gold standard but remains expensive, and is hard to obtain in an emergency. On the contrary, ultrasonography is cheap, accessible in an emergency, and dynamical tests can be performed easily. Twelve fresh frozen forearms were randomized in four groups. The membrane was divided into three parts (proximal, middle, and distal thirds). Each group was prepared with variable patterns of lesions. Two radiologists performed an ultrasonographic (US) examination of these forearms. They were blinded with respect to the lesional status of the forearms. Each examination consisted of two stages: static and dynamic. During the dynamic examination, the radiologist looked for the “muscular hernia sign”. The results of their examinations were compared with the real lesional status. The static examination was very efficient in the proximal and middle parts of the membrane, and less reliable in the distal third. With the dynamical examination, no mistake occurred at the proximal and middle parts of the forearm, and there was only one at the distal part. The US examination of the interosseous membrane is very efficient to detect incomplete lesions, mostly, if dynamical tests are performed looking for a “muscular hernia sign”.     

Whole genome analyses of African G2, G8, G9, and G12 rotavirus strains using sequence-independent amplification and 454® pyrosequencing

High mortality rates caused by rotaviruses are associated with several strains such as G2, G8, G9, and G12 rotaviruses. Rotaviruses with G9 and G12 genotypes emerged worldwide in the past two decades. G2 and G8 rotaviruses are however also characterized frequently across Africa. To understand the genetic constellation of African G2, G8, G9, and G12 rotavirus strains and their possible origin, sequence‐independent cDNA synthesis, amplification, and 454^® pyrosequencing of the whole genomes of five human African rotavirus strains were performed. RotaC and phylogenetic analysis were used to assign and confirm the genotypes of the strains. Strains RVA/Human‐wt/MWI/1473/2001/G8P[4], RVA/Human‐wt/ZAF/3203WC/2009/G2P[4], RVA/Human‐wt/ZAF/3133WC/2009/G12P[4], RVA/Human‐wt/ZAF/3176WC/2009/G12P[6], and RVA/Human‐wt/ZAF/GR10924/1999/G9P[6] were assigned G8‐P[4]‐I2‐R2‐C2‐M2‐A2‐N2‐T2‐E2‐H2, G2‐P[4]‐I2‐R2‐C2‐M2‐A2‐N2‐T2‐E2‐H2, G12‐P[4]‐I1‐R1‐C1‐M1‐A1‐N1‐T1‐E1‐H1, G12‐P[6]‐I1‐R1‐C1‐M1‐A1‐N1‐T1‐E1‐H1, and G9‐P[6]‐I2‐R2‐C2‐M2‐A2‐N2‐T2‐E2‐H2 genotypes, respectively. The detection of both Wa‐ and DS‐1‐like genotypes in strain RVA/Human‐wt/ZAF/3133WC/2009/G12P[4] and Wa‐like, DS‐1‐like and P[6] genotypes in strain RVA/Human‐wt/ZAF/GR10924/1999/G9P[6] implies that these two strains were generated through intergenogroup genome reassortment. The close similarity of the genome segments of strain RVA/Human‐wt/MWI/1473/2001/G8P[4] to artiodactyl‐like, human‐bovine reassortant strains and human rotavirus strains suggests that it originated from or shares a common origin with bovine strains. It is therefore possible that this strain might have emerged through interspecies genome reassortment between human and artiodactyl rotaviruses. This study illustrates the swift characterization of all the 11 rotavirus genome segments by using a single set of universal primers for cDNA synthesis followed by 454^® pyrosequencing and RotaC analysis. J. Med. Virol. 83:2018–2042, 2011. © 2011 Wiley‐Liss, Inc.     

The experience of labor, maternal perception of the infant, and the mother’s postpartum mood in a low-risk community cohort

Postpartum negative mood interferes with maternal–infant bonding and carries long-term negative consequences for infant growth. We examined the effects of birth-related risks on mother’s postpartum anxiety and depression. A community cohort of 1,844 low-risk women who delivered a singleton term baby completed measures assessing delivery, emotions during labor, attitudes toward pregnancy and infant, mood regulation, and postpartum anxiety and depression. Under conditions of low risk, 20.5% of parturient women reported high levels of depressive symptoms. Following Cesarean Section Delivery (CSD), 23% reported high depressive symptoms, compared to 19% following Vaginal Delivery (VGD), and 21% after Assisted Vaginal Delivery (AVGD). State anxiety was highest in CSD and lowest in VGD. Mothers undergoing CSD experienced labor as most negative, reported highest somatic symptoms during the last trimester, and were least efficient in regulating negative mood. Postpartum depression was independently associated with higher maternal age, CSD, labor pain, lower negative and higher positive emotions during labor, inefficient mood regulation, somatic symptoms, and more negative and less positive perception of fetus during last trimester. Results demonstrate that elevated depressive symptoms are prevalent in the postpartum even under optimal socioeconomic and health conditions and increase following CSD. Interventions to increase positive infant-related perceptions and emotions may be especially important for promoting bond formation following CSD.     

A prospective study to assess the diagnostic performance of the Sofia® Immunoassay for Influenza and RSV detection.

BackgroundRespiratory viruses RSV and influenza A and B viruses are responsible for important disease outbreaks during the winter season in temperate climate regions. Rapid diagnostic tests (RDTs) are assays designed to yield a rapid diagnosis, which facilitates patient management. The Sofia Influenza A + B Fluorescence Immunoassay and Sofia RSV Fluorescence Immunoassay are RDTs for Influenza and RSV detection that employ a new technology to enhance their sensitivity.ObjectivesSensitivity, specificity and positive and negative predictive values of the assays were calculated compared with the reference diagnostic method: real-time RT-PCR.Study designA prospective evaluation was carried out on 1065 respiratory samples for Sofia Influenza A + B FIA and on 261 samples for Sofia RSV FIA from November 2013 to April 2014.ResultsThe sensitivities of the Sofia Influenza A + B FIA for influenza A and influenza B detection were, respectively, 75.3% (244/324) and 50.0% (8/16). The sensitivity of the Sofia RSV FIA was 92.1% (128/139). There were no differences in Sofia FIA performance depending on the virus subtype.ConclusionsThe results showed high sensitivity and specificity values for influenza A and RSV detection, but values were lower for influenza B. More information is needed regarding the performance for influenza B given the small number of positive samples assessed.     

Performance of the Genotype® MTBDRPlus assay in the diagnosis of tuberculosis and drug resistance in Samara, Russian Federation

Background

Russia is a high tuberculosis (TB) burden country with a high prevalence of multidrug resistant tuberculosis (MDRTB). Molecular assays for detection of MDRTB on clinical specimens are not widely available in Russia.

Results

We performed an evaluation of the GenoType^® MTBDRplus assay (HAIN Lifescience GmbH, Germany) on a total of 168 sputum specimens from individual patients at a public health laboratory in Central Russia, as a model of a middle income site in a region with high levels of drug resistance. Phenotypic drug resistance tests (DST) were performed on cultures derived from the same sputum specimens using the BACTEC 960 liquid media system. Interpretable GenoType^® MTBDRplus results were obtained for 154(91.7%) specimens with readability rates significantly higher in sputum specimens graded 2+ and 3+ compared to 1+ (RR = 1.17 95%CI 1.04–1.32). The sensitivity and specificity of the assay for the detection of rifampicin (RIF) and isoniazid (INH) resistance and MDR was 96.2%, 97.4%, 97.1% and 90.7%, 83.3%, 88.9% respectively. Mutations in codon 531 of the rpoB gene and codon 315 of the katG gene dominated in RIF and INH resistant strains respectively. Disagreements between phenotypical and molecular tests results (12 samples) could be explained by the presence of rare mutations in strains circulating in Russia and simultaneous presence of resistant and sensitive bacilli in sputum specimens (heteroresistance).

Conclusion

High sensitivity, short turnaround times and the potential for screening large numbers of specimens rapidly, make the GenoType^® MTBDRplus assay suitable as a first-line screening assay for drug resistant TB.