Reliability of computer-assisted periacetabular osteotomy using a minimally invasive approach

Background

Periacetabular osteotomy (PAO) is the treatment of choice for younger patients with developmental hip dysplasia. The procedure aims to normalize the joint configuration, reduce the peak-pressure, and delay the development of osteoarthritis. The procedure is technically demanding and no previous study has validated the use of computer navigation with a minimally invasive transsartorial approach.

Methods

Computer-assisted PAO was performed on ten patients. Patients underwent pre- and postoperative computed tomography (CT) scanning with a standardized protocol. Preoperative preparation consisted of outlining the lunate surface and segmenting the pelvis and femur from CT data. The Biomechanical Guidance System was used intra-operatively to automatically calculate diagnostic angles and peak-pressure measurements. Manual diagnostic angle measurements were performed based on pre- and postoperative CT. Differences in angle measurements were investigated with summary statistics, intraclass correlation coefficient, and Bland–Altman plots. The percentage postoperative change in peak-pressure was calculated.

Results

Intra-operative reported angle measurements show a good agreement with manual angle measurements with intraclass correlation coefficient between 0.94 and 0.98. Computer navigation reported angle measurements were significantly higher for the posterior sector angle (\(1.65^{\circ }\), \(p=0.001\)) and the acetabular anteversion angle (\(1.24^{\circ }\), \(p=0.004\)). No significant difference was found for the center-edge (\(p=0.056\)), acetabular index (\(p=0.212\)), and anterior sector angle (\(p=0.452\)). Peak-pressure after PAO decreased by a mean of 13% and was significantly different (\(p=0.008\)).

Conclusions

We found that computer navigation can reliably be used with a minimally invasive transsartorial approach PAO. Angle measurements generally agree with manual measurements and peak-pressure was shown to decrease postoperatively. With further development, the system will become a valuable tool in the operating room for both experienced and less experienced surgeons performing PAO. Further studies with a larger cohort and follow-up will allow us to investigate the association with peak-pressure and postoperative outcome and pave the way to clinical introduction.

     

Patient safety culture in out-of-hours primary care services in the Netherlands: a cross-sectional survey

Objective: To examine patient safety culture in Dutch out-of-hours primary care using the safety attitudes questionnaire (SAQ) which includes five factors: teamwork climate, safety climate, job satisfaction, perceptions of management and communication openness.

Design: Cross-sectional observational study using an anonymous web-survey. Setting Sixteen out-of-hours general practitioner (GP) cooperatives and two call centers in the Netherlands. Subjects Primary healthcare providers in out-of-hours services. Main outcome measures Mean scores on patient safety culture factors; association between patient safety culture and profession, gender, age, and working experience.

Results: Overall response rate was 43%. A total of 784 respondents were included; mainly GPs (N?=?470) and triage nurses (N?=?189). The healthcare providers were most positive about teamwork climate and job satisfaction, and less about communication openness and safety climate. The largest variation between clinics was found on safety climate; the lowest on teamwork climate. Triage nurses scored significantly higher than GPs on each of the five patient safety factors. Older healthcare providers scored significantly higher than younger on safety climate and perceptions of management. More working experience was positively related to higher teamwork climate and communication openness. Gender was not associated with any of the patient safety factors.

Conclusions: Our study showed that healthcare providers perceive patient safety culture in Dutch GP cooperatives positively, but there are differences related to the respondents’ profession, age and working experience. Recommendations for future studies are to examine reasons for these differences, to examine the effects of interventions to improve safety culture and to make international comparisons of safety culture.

• Key Points

• Creating a positive patient safety culture is assumed to be a prerequisite for quality and safety. We found that:

• ??healthcare providers in Dutch GP cooperatives perceive patient safety culture positively;

• ??triage nurses scored higher than GPs, and older and more experienced healthcare professionals scored higher than younger and less experienced professionals – on several patient safety culture factors; and

• ??within the GP cooperatives, safety climate and openness of communication had the largest potential for improvement.

     

Characterizing the PK/PD relationship for inhibition of capsaicin-induced dermal vasodilatation by MK-3207, an oral calcitonin gene related peptide receptor antagonist

Aims

Calcitonin gene related peptide (CGRP) receptor antagonists are effective acute migraine treatments. A capsaicin-induced dermal vasodilatation (CIDV) model has been developed to provide target-engagement information in healthy volunteers. In the model, CGRP release is provoked after dermal capsaicin application, by activating transient receptor potential vanilloid-type-1 (TRPV1) receptors at peripheral sensory nerves. Laser Doppler imaging is used to quantify CIDV and subsequent inhibition by CGRP receptor antagonists. We sought to evaluate a CGRP receptor antagonist, MK-3207, in the biomarker model and to assess the predictability of the CIDV response to migraine clinical efficacy.

Methods

An integrated population pharmacokinetic/pharmacodynamic (PK/PD) model was developed to describe the exposure−response relationship for CIDV inhibition by CGRP and TRPV1 receptor antagonists. MK-3207 dose−response predictions were made based on estimated potency from the PK/PD model and mean plasma concentrations observed at the doses investigated.

Results

The results suggested that a 20 mg dose of MK-3207 (EC₅₀ of 1.59 nm) would be required to attain the peripheral CIDV response at a target level that was shown previously to correlate with 2 h clinical efficacy based on phase 3 telcagepant clinical data, and that a plateau of the dose−response would be reached around 40–100 mg. These predictions provided a quantitative rationale for dose selection in a phase 2 clinical trial of MK-3207 and helped with interpretation of the efficacy results from the trial.

Conclusions

The integrated CIDV PK/PD model provides a useful platform for characterization of PK/PD relationships and predictions of dose−response relationships to aid in future development of CGRP and TRPV1 receptor antagonists.     

Synergistic interaction of the histone deacetylase inhibitor SAHA with the proteasome inhibitor bortezomib in mantle cell lymphoma

Objectives:  Mantle cell lymphoma (MCL) is an incurable B cell lymphoma, and novel treatment strategies are urgently needed. We evaluated the effects of combined treatment with the proteasome inhibitor bortezomib and the histone deacetylase inhibitor (HDACi) suberoylanilide hydroxamic acid (SAHA) on MCL. Bortezomib acts by targeting the proteasome, and – among other mechanisms – results in a reduced nuclear factor-kappa B (NF-κB) activity. HDACi promote histone acetylation, and also interfere with NF-κB signaling.
Methods:  Human MCL cell lines (JeKo-1, Granta-519 and Hbl-2) were exposed to bortezomib and/or SAHA. Cell viability and apoptosis were quantified by the MTT and annexin-V assay, respectively. Reactive oxygen species (ROS) were analyzed using the fluorophore H₂DCFDA. In addition, activated caspases, proteasome- and NF-κB activity were quantified.
Results:  Combined incubation with bortezomib and SAHA resulted in synergistic cytotoxic effects, as indicated by combination index values <1 using the median effect method of Chou and Talalay. The combination of both inhibitors led to a strong increase in apoptosis as compared to single agents and was accompanied by enhanced ROS generation, while each agent alone only modestly induced ROS. The free radical scavenger N -acetyl- l -cysteine blocked the ROS generation and reduced the apoptosis significantly. In addition, coexposure of bortezomib and SAHA led to increased caspase-3, -8 and -9 activity, marked reduction of proteasome activity and decrease of NF-κB activity.
Conclusions:  This is the first report giving evidence that SAHA and bortezomib synergistically induce apoptosis in MCL cells. These data build the framework for clinical trials using combined proteasome and histone deacetylase inhibition in the treatment of MCL.     

Visceral leishmaniasis: current status of control,diagnosis, and treatment,and a proposed research and development agenda

Visceral leishmaniasis is common in less developed countries, with an estimated 500000 new cases each year. Because of the diversity of epidemiological situations, no single diagnosis, treatment, or control will be suitable for all. Control measures through case finding, treatment, and vector control are seldom used, even where they could be useful. There is a place for a vaccine, and new imaginative approaches are needed. HIV co-infection is changing the epidemiology and presents problems for diagnosis and case management. Field diagnosis is difficult; simpler, less invasive tests are needed. Current treatments require long courses and parenteral administration, and most are expensive. Resistance is making the mainstay of treatment, agents based on pentavalent antimony, useless in northeastern India, where disease incidence is highest. Second-line drugs (pentamidine and amphotericin B) are limited by toxicity and availability, and newer formulations of amphotericin B are not affordable. The first effective oral drug, miltefosine, has been licensed in India, but the development of other drugs in clinical phases (paromomycin and sitamaquine) is slow. No novel compound is in the pipeline. Drug combinations must be developed to prevent drug resistance. Despite these urgent needs, research and development has been neglected, because a disease that mainly affects the poor ranks as a low priority in the private sector, and the public sector currently struggles to undertake the development of drugs and diagnostics in the absence of adequate funds and infrastructure. This article reviews the current situation and perspectives for diagnosis, treatment, and control of visceral leishmaniasis, and lists some priorities for research and development.     

Hypoplastic left heart syndrome and 45X karyotype

A review of 63 patients with 45X karyotype (Turner's syndrome) admitted to a hospital from 1972 to 1985 showed that 20 (32%) had one or more major cardiac malformations (mostly coarctation and aortic stenosis). Four (20%) died in the neonatal. One infant had mitral stenosis and severe aortic stenosis and died at the age of 35 days. The three (15%) other patients who died had a typical hypoplastic left heart syndrome, with an atretic aortic valve in two and pinpoint aortic valve in one. Turner's syndrome was clinically suspected in three of the cases. One of these had mosaicism (46XX,45X) the others had a 45X pattern. During the same period (1972-85) 39 patients (14 girls and 25 boys) were admitted with diagnosis of hypoplastic left heart syndrome. Three (21.4%) girls had a 45X karyotype. The high incidence of hypoplastic left heart syndrome in Turner's syndrome and of Turner's syndrome in girls with hypoplastic left heart syndrome suggests that hypoplastic left heart syndrome can be another expression of the 45X karyotype.     

Increased Risk of HIV in Women Experiencing Physical Partner Violence in Nairobi,Kenya

As part of a study on etiology of sexually transmitted infections (STI) among 520 women presenting at the STI clinic in Nairobi, data on partner violence and its correlates were analyzed. Prevalence of lifetime physical violence was 26%, mainly by an intimate partner (74%). HIV seropositive women had an almost twofold increase in lifetime partner violence. Women with more risky sexual behavior such as early sexual debut, number of sex partners, history of condom use and of STI, experienced more partner violence. Parity and miscarriage were associated with a history of lifetime violence. We found an inverse association between schooling and level of violence. Six percent of the women had been raped. Gender-based violence screening and services should be integrated into voluntary counseling and testing programs as well as in reproductive health programs. Multi-sector approaches are needed to change prevailing attitudes towards violence against women. An erratum to this article can be found at     

Antibiotic susceptibility of Atopobium vaginae

Background  

Previous studies have indicated that a recently described anaerobic bacterium, Atopobium vaginae is associated with bacterial vaginosis (BV). Thus far the four isolates of this fastidious micro-organism were found to be highly resistant to metronidazole and susceptible for clindamycin, two antibiotics preferred for the treatment of BV.     

Brief Report: Associations Between Autism Characteristics,Written and Spoken Communication Skills,and Social Interaction Skills in Preschool-Age Children on the Autism Spectrum

Journal of Autism and Developmental Disorders - We used parent-report data from a prospective longitudinal study to better understand the early strengths in written skills often observed in...