Potential Sexual Transmission of Zika Virus

In December 2013, during a Zika virus (ZIKV) outbreak in French Polynesia, a patient in Tahiti sought treatment for hematospermia, and ZIKV was isolated from his semen. ZIKV transmission by sexual intercourse has been previously suspected. This observation supports the possibility that ZIKV could be transmitted sexually.Zika virus (ZIKV) is a mosquitoborne arbovirus in the family Flaviviridae, genus Flavivirus. It was first isolated in 1947 from a rhesus monkey in the Zika forest of Uganda (1). Sporadic human cases were reported from the 1960s in Asia and Africa. The first reported large outbreak occurred in 2007 on Yap Island, Federated States of Micronesia (2). The largest known ZIKV outbreak reported started in October 2013 in French Polynesia, South Pacific (3), a territory of France comprising 67 inhabited islands; an estimated 28,000 persons (11% of the population) sought medical care for the illness (4). The most common symptoms of Zika fever are rash, fever, arthralgia, and conjunctivitis. Most of the patients had mild disease, but severe neurologic complications have been described in other patients in French Polynesia (5).     

Juvenile chronic pancreatitis--a cause of painless jaundice in a patient with multiple somatic abnormalities

Juvenile chronic pancreatitis presenting with painless obstructive jaundice is extremely rare. Pancreatic disease in association with multiple somatic abnormalities presenting in late childhood is uncommon. We report such a case.     

Type 2N von Willebrand disease

Type 2N von Willebrand disease (VWD) refers to patients with a factor VIII (FVIII) deficiency caused by a markedly decreased affinity of von Willebrand factor (VWF) for FVIII. It is inherited as an autosomal recessive trait but is clinically similar to mild hemophilia. The differential biologic diagnosis, which is of major importance for providing relevant genetic counseling and optimal treatment, is based on the measurement of plasma VWF capacity to bind FVIII. Molecular biology techniques have allowed the identification of 20 missense mutations in the VWF gene that cause type 2N VWD. All of them induce changes in amino acid residues located in the N-terminal part of mature VWF, which contains the FVIII binding site. Their identification may provide a genetic diagnosis. Theoretically, patients with type 2N VWD should be treated with products containing VWF that is able to stabilize their endogenous normal FVIII.     

Switching to darunavir/ritonavir 800/100 mg once‐daily containing regimen maintains virological control in fully suppressed pre‐treated patients infected with HIV‐1

The objective of this study was to evaluate the switch to once‐daily darunavir/ritonavir 800/100 mg in treatment‐experienced patients with suppressed HIV‐1 replication on a twice‐daily ritonavir‐boosted protease‐inhibitor (bid PI/r) containing regimen, that is in a setting where genotypic resistance test cannot be performed. In this open label, non‐comparative, multicenter study, patients on a bid PI/r‐containing triple combination, with suppressed viral replication, were switched to once‐daily darunavir/r 800/100 mg containing triple combination. The primary endpoint was the proportion of patients with plasma HIV‐RNA < 50 copies/ml 24 weeks after the switch. Intensive darunavir pharmacokinetic evaluation was performed at Week 4 (W4) in 11 patients. Eighty‐five patients were enrolled. All had HIV‐RNA < 50 copies/ml at screening with a pre‐exposure to a median of 2 PI/r (1–5). By intent‐to‐treat analysis (missing = failure), 78/85 patients (92%, 95% CI [83;96]) maintained an HIV‐RNA < 50 copies/ml at W24. Seven patients experienced protocol‐defined treatment failure between baseline and W24: Two had confirmed low‐level viral rebound, one discontinued study treatment for adverse event, three withdrew their consent, and one was lost to follow‐up. By on‐treatment analysis, 78/80 patients (97%, 95% CI [91;99]) maintained an HIV‐RNA < 50 copies/ml at W24. Results were similar at Week 48. The median area under the darunavir plasma concentration–time curve measured in 11 patients was 61,380 ng hr/ml; darunavir median trough concentration 1,340 ng/ml and darunavir half‐life was 12.2 hr. Tolerability of once‐daily darunavir/r 800/100 mg was excellent. Optimally suppressed, treatment‐experienced patients can switch safely from a twice‐daily PI/r regimen to a once‐daily darunavir/r 800/100 mg containing regimen. J. Med. Virol. 85:8–15, 2012. © 2012 Wiley Periodicals, Inc.     

Characterizing patient-oncologist communication in genomic tumor testing: The 21-gene recurrence score as an exemplar

ObjectiveWomen with early-stage, ER + breast cancer are recommend to receive genomic profiling tests, such as the 21-gene Recurrence Score (RS) test, to guide treatment decisions. We examined test- and treatment-related information discussed and the associations between RS categories and aspects of communication during patient-oncologist clinical encounters.MethodsAs part of a larger trial, clinical encounters (N = 46) were audiorecorded and coded for 1) RS- and treatment-related information, 2) shared decision making, 3) patient active participation, and 4) oncologist patient-centered communication. We examined differences by RS category using mixed models, adjusting for nesting within oncologist.ResultsPatients with a high RS were more likely to receive a chemotherapy recommendation (p < .01), hear about the risks/side effects of chemotherapy (p < .01), and offer their preferences (p = .02) than those with intermediate or low RS. Elements of shared decision making increased with RS. Oncologist patient-centered communication (M = 4.09/5, SD = .25) and patient active participation (M = 3.5/4, SD = 1.0) were high across RS.ConclusionFindings suggest that disease severity, rather than clinical uncertainty, impact treatment recommendations and shared decision making.Practice implicationsOncologists adjust test- and treatment-related information and shared decision making by disease severity. This information provides a framework to inform decision making in complex cancer and genomics settings.     

Meta-analysis of telomere length in 19?713 subjects reveals high heritability,stronger maternal inheritance and a paternal age effect

Telomere length (TL) has been associated with aging and mortality, but individual differences are also influenced by genetic factors, with previous studies reporting heritability estimates ranging from 34 to 82%. Here we investigate the heritability, mode of inheritance and the influence of parental age at birth on TL in six large, independent cohort studies with a total of 19 713 participants. The meta-analysis estimate of TL heritability was 0.70 (95% CI 0.64–0.76) and is based on a pattern of results that is highly similar for twins and other family members. We observed a stronger mother–offspring (r=0.42; P-value=3.60 × 10⁻⁶¹) than father–offspring correlation (r=0.33; P-value=7.01 × 10⁻⁵), and a significant positive association with paternal age at offspring birth (β=0.005; P-value=7.01 × 10⁻⁵). Interestingly, a significant and quite substantial correlation in TL between spouses (r=0.25; P-value=2.82 × 10⁻³⁰) was seen, which appeared stronger in older spouse pairs (mean age ≥55 years; r=0.31; P-value=4.27 × 10⁻²³) than in younger pairs (mean age<55 years; r=0.20; P-value=3.24 × 10⁻¹⁰). In summary, we find a high and very consistent heritability estimate for TL, evidence for a maternal inheritance component and a positive association with paternal age.     

A review of epidural simulators: Where are we today?

Thirty-one central neural blockade simulators have been implemented into clinical practice over the last thirty years either commercially or for research. This review aims to provide a detailed evaluation of why we need epidural and spinal simulators in the first instance and then draws comparisons between computer-based and manikin-based simulators. This review covers thirty-one simulators in total; sixteen of which are solely epidural simulators, nine are for epidural plus spinal or lumbar puncture simulation, and six, which are solely lumbar puncture simulators. All hardware and software components of simulators are discussed, including actuators, sensors, graphics, haptics, and virtual reality based simulators. The purpose of this comparative review is to identify the direction for future epidural simulation by outlining necessary improvements to create the ideal epidural simulator. The weaknesses of existing simulators are discussed and their strengths identified so that these can be carried forward. This review aims to provide a foundation for the future creation of advanced simulators to enhance the training of epiduralists, enabling them to comprehensively practice epidural insertion in vitro before training on patients and ultimately reducing the potential risk of harm.     

Persistent neuropathic pain after inguinal herniorrhaphy depending on the procedure (open mesh v. laparoscopy): a propensity-matched analysis

Background

A greater incidence of persistent pain after inguinal herniorrhaphy is suspected with the open mesh procedure than with laparoscopy (transabdominal preperitoneal), but the involvement of neuropathy needs to be clarified.

Methods

We examined the cumulative incidence of neuropathic persistent pain, defined as self-report of pain at the surgical site with neuropathic aspects, within 6 months after surgery in 2 prospective subcohorts of a multicentre study. We compared open mesh with laparoscopy using different analysis, including a propensity-matched analysis with the propensity score built from a multivariable analysis using a generalized linear model.

Results

Considering the full patient sample (242 open mesh v. 126 laparoscopy), the raw odds ratio for neuropathic persistent pain after inguinal herniorrhaphy was 4.3. It reached 6.8 with the propensity-matched analysis conducted on pooled subgroups of 194 patients undergoing open mesh and 125 undergoing laparoscopy (95% confidence interval 1.5–30.4, p = 0.012). A risk factor analysis of these pooled subgroups revealed that history of peripheral neuropathy was an independent risk factor for persistent neuropathic pain, while older age was protective.

Conclusion

We found a greater risk of persistent pain with open mesh than with laparoscopy that may be explained by direct or indirect lesion of nerve terminations. Strategies to identify and preserve nerve terminations with the open mesh procedure are needed.     

Substitution of cysteine for phenylalanine 751 in mature von Willebrand factor is a novel candidate mutation in a family with type IIA von Willebrand disease

Summary Type IIA is a variant form of von Willebrand disease (vWD) characterized by the absence of von Willebrand factor (vWF) high molecular weight multimers in plasma. Most of the candidate missense mutations potentially responsible for type IIA vWD have been found clustered within a short segment of vWF, lying between Gly⁷⁴² and Glu⁸⁷⁵ of the mature subunit. The present work reports a single heterozygous T → G transversion in eight patients from a large type IIA vWD family, resulting in the substitution Phe⁷⁵¹→Cys. The absence of this mutation in 100 normal vWF genes as well as the lack, in these patients, of any other abnormality within the whole exon 28 encoding amino acids 463–921 of mature vWF, provide a strong support that this non-conservative mutation may be at the origin of the disease in this family. The presence of an additional cysteine at position 751 may induce a conformational change of the vWF subunit affecting either its ' in vivo ' sensitivity to proteolytic cleavage or, more likely, its intracellular transport as suggested by the abnormal multimeric pattern of platelet vWF observed in these patients.