Home sleep apnea testing: comparison of manual and automated scoring across international sleep centers

Sleep and Breathing - To determine the agreement between the manual scoring of home sleep apnea tests (HSATs) by international sleep technologists and automated scoring systems. Fifteen HSATs,...     

Blood pressure response to treatment of obese vs non‐obese adults with sleep apnea

Many patients with obstructive sleep apnea (OSA), but not all, have a reduction in blood pressure (BP) with positive airway pressure (PAP) treatment. Our objective was to determine whether the BP response following PAP treatment is related to obesity. A total of 188 adults with OSA underwent 24‐hour BP monitoring and 24‐hour urinary norepinephrine collection at baseline. Obesity was assessed by waist circumference, body mass index, and abdominal visceral fat volume. Participants adherent to PAP treatment were reassessed after 4 months. Primary outcomes were 24‐hour mean arterial pressure (MAP) and 24‐hour urinary norepinephrine level. Obstructive sleep apnea participants had a significant reduction in 24‐hour MAP following PAP treatment (−1.22 [95% CI: −2.38, −0.06] mm Hg; P = .039). No significant correlations were present with any of the 3 obesity measures for BP or urinary norepinephrine measures at baseline in all OSA participants or for changes in BP measures in participants adherent to PAP treatment. Changes in BP measures following treatment were not correlated with baseline or change in urinary norepinephrine. Similar results were obtained when BP or urinary norepinephrine measures were compared between participants dichotomized using the sex‐specific median of each obesity measure. Greater reductions in urinary norepinephrine were correlated with higher waist circumference (rho = −0.21, P = .037), with a greater decrease from baseline in obese compared to non‐obese participants (−6.26 [−8.82, −3.69] vs −2.14 [−4.63, 0.35] ng/mg creatinine; P = .027). The results indicate that the BP response to PAP treatment in adults with OSA is not related to obesity or urinary norepinephrine levels.     

The prevalence and molecular basis of hemoglobinopathies in Cambodia

Blood counts, hemoglobin (Hb) high performance liquid chromatography (HPLC), and DNA analyses were performed on 260 children, aged 5 months to 16 years, at Siem Reap to assess the prevalence of thalassemia and other hemoglobinopathies in regional Cambodia. Hemoglobinopathies were present in 134 children (51.5%) with 20 abnormal genotypes identified. alpha-Thalassemia (thal) (35.4%) was the most prevalent disorder and the -alpha3.7 gene deletion was the most common alpha-globin gene abnormality. The - -SEA deletion and nondeletional forms of alpha-thal, Hb Constant Spring [Hb CS, alpha142, Term-->Gln, TAA-->CAA (alpha2)], Hb Paksé [alpha142, Term-->Tyr, TAA-->TAT (alpha2)] and triplicated alpha genes, were also present but at low frequencies. Hb E [beta26(B8)Glu-->Lys, GAG-->AAG] (28.8%) was the most common beta-globin gene abnormality, whilst beta-thal was only detected in two children (0.8% of cases). Although hemoglobinopathies were common, the majority of abnormalities detected (heterozygous -alpha3.7 and Hb E) were not clinically significant. On the basis of these findings, and with the majority of abnormalities being mild, it seems improbable that thalassemia represents a major health burden in this region of Cambodia.     

CXCL10- a path to β-cell death

The ability of the β-cells to control blood glucose levels depends on their function and mass. In both, type 1 and type 2 diabetes mellitus the main processes leading to β-cell failure are apoptosis and loss of function. Many studies demonstrate how cytokines and chemokines have an active role in triggering the immune-response against the β-cell population. In a recent study we have identified that the chemokine CXCL10 may play an active role in triggering β-cell destruction. We have identified the Toll like receptor 4 as the receptor for CXCL10 and as new pathway for the induction of β-cell apoptosis. Our findings may open new therapeutic approaches to fight onset and progression of the disease.     

Efficiency of Fine-Needle Aspiration Compared with Other Sampling Techniques for Laboratory Diagnosis of Buruli Ulcer Disease

In accordance with recent WHO recommendations, this study evaluates the sensitivities of PCR and microscopy for fine-needle aspiration (FNA) versus techniques involving swabs and punch biopsy specimens and suggests that FNA can replace punch biopsies for nonulcerative lesions and may serve as an alternative for ulcerative lesions in cases where scarred edges prevent the collection of swabs.Buruli ulcer disease (BUD), caused by Mycobacterium ulcerans, is an emerging disease predominantly affecting West and Central Africa. BUD initially presents as a painless nodule, papule, and plaque (nonulcerative lesions), evolving into a painless ulcer with characteristically undermined edges (ulcerative lesions). Scarring and contractures may cause severe functional disability (9, 11, 12). Among the currently available diagnostic laboratory methods (microscopy, culture, PCR, and histopathology), PCR provides the highest sensitivity and is therefore regarded as the method of choice for laboratory confirmation. The WHO encourages all countries where BUD is endemic to ensure PCR confirmation of at least 50% of all cases (1, 12, 13). With the introduction of antimycobacterial treatment, laboratory confirmation of suspect cases became crucial for clinical management of the disease (6, 12-15). Swabs, punch biopsy specimens, and surgically excised tissue are suitable diagnostic samples (3, 5-7). Recently, the WHO recommended fine-needle aspiration (FNA) as a minimally invasive method for nonulcerative lesions as well as for ulcerative lesions where scarring of edges prevents collection of swab samples (15).The present study retrospectively compares the sensitivities of PCR and microscopy for FNA samples, swabs, punch biopsy specimens, and surgically excised tissue.From February 2008 until December 2008, 173 clinically suspected BUD cases from Ghana (n = 112) and Togo (n = 61) were included in the study. FNA was performed with 21-gauge needles by transdermal aspiration. The needle was inserted into the center of the nonulcerative lesions or the subcutaneous tissue of the ulcer (the maximal distance from the margins was 1 to 2 cm) and was moved back and forth about three times in different directions under suction without withdrawal of the needle. Swabs, 3-mm punch biopsy specimens, and surgically excised tissue were taken according to standardized procedures, and all samples were stored in transport media as previously described and forwarded to the laboratories (5). In Ghana, 68 swabs, 112 FNA samples, 108 punch biopsy specimens, and 14 surgically excised tissue samples were subjected to microscopy and dry-reagent-based IS2404 PCR at the Kumasi Centre for Collaborative Research in Tropical Medicine, Kumasi (5, 10). The samples from Togo (43 swabs, 61 FNA samples, 45 punch biopsy specimens, and 7 surgically excised tissue samples) were analyzed at the Centre National de Référence et de Traitement d''Ulcère de Buruli, Tsévié (microscopy), and the Department of Infectious Diseases and Tropical Medicine, University of Munich, Germany (IS2404 standard PCR), in accordance with standardized procedures (5, 10).One hundred ten suspects (63.6%) with 37 (33.6%) nonulcerative lesions and 73 (66.4%) ulcerative lesions were confirmed by at least one positive test result. The categories of the lesions according to the WHO definitions were known for 107 of these cases (12) (category I, 49 cases [45.8%]; category II, 44 cases [41.1%]; and category III, 14 cases [13.1%]).Among the 37 nonulcerative cases, the sensitivities of PCR, defined as the number of positive test results divided by the number of laboratory-confirmed cases (5), were 88.9% (32/36) for FNA samples and 87.5% (28/32) for punch biopsy specimens, and the sensitivities of microscopy were 58.3% (21/36) for FNA samples and 55.6% (15/27) for punch biopsy specimens. For both tests, there was no significant difference in sensitivity between the two types of samples (the P value for PCR [P_PCR] was 0.86, and the P value for microscopy [P_microscopy] was 0.83) (Table ​(Table11).

TABLE 1.

Sensitivities of dry-reagent-based IS2404 PCR and microscopic examination^a

It's like being in another world--patients' lived experience of magnetic resonance imaging

Aim. The aim of this study was to illuminate patients’ lived experience during magnetic resonance imaging. Background. Magnetic resonance imaging has increased in importance since the early 1980s and is today a common useful diagnostic tool. Although magnetic resonance imaging are non‐invasive and considered painless, many patients experience anxiety, sometimes so strong that the scan has to be terminated. Design and methods. The study had an inductive design and a hermeneutic phenomenological methodology was used. Results. The essential theme of going through magnetic resonance imaging was a feeling of being in another world. The strange environment and isolation inside the scanner made the participants’ experiences unusual, with varying degrees of difficulty dealing with it. Being in the other world caused a threat to the participants’ self‐control. There was a relation between threat to self‐control, effort and need for support in the sense that the magnitude of threat to self‐control had an impact on the effort it took to handle the situation and on the need for support, and conversely that the support received could affect the effort and threat to self‐control. Conclusions. The study shows that the information received and the interaction between patients and staff have a significant influence on patients’ lived experiences. Relevance to clinical practice. The individual experience of threat to self‐control requires the need for support to be individualized and care need to be adjusted for each patient.     

Predictive testing for hereditary non-polyposis colorectal cancer: motivation, illness representations and short-term psychological impact

This paper describes the motivation, recall of cancer risks, and illness representations of 40 individuals who had a predictive test for hereditary non-polyposis colorectal cancer (HNPCC) as well as the short-term impact of predictive testing by means of a semi-structured interview and self-report questionnaires. The main motives for predictive testing were early detection of cancer, knowledge of the children's risk and reduction of uncertainty. Overall, recall of cancer risks was good. Measurements of illness representations revealed low perceptions of "threat" of cancer and high confidence in the controllability of the disease. Distress was within normal ranges. Distress decreased significantly from pre- to post-test in non-carriers and did not in carriers. It also decreased in individuals for whom "reducing uncertainty" was a very important motive for the test, not in the others. Although part of the carriers did not have colonoscopies, all carriers intended to have regular colonoscopies in the future.     

Neural network classification of otoneurological data and its visualization

When complex data is distributed in a biased manner between disease classes, classification accuracy can be increased with a network set of perceptron neural networks developed by us. A novel projection method is also introduced for the visual classification of the data to elucidate its features and disease class distribution. The set of the perceptron neural networks and the projection method were tested with otoneurological data and they improved average sensitivity and positive predictive value at least 10% up to 85% and 83%, compared to our earlier neural network classifications with the same data. The methods were also experimented with two additional data sets, which included diagnostically very difficult cases.     

TMC647055, a Potent Nonnucleoside Hepatitis C Virus NS5B Polymerase Inhibitor with Cross-Genotypic Coverage

Hepatitis C virus (HCV) infection is a major global health burden and is associated with an increased risk of liver cirrhosis and hepatocellular carcinoma. There remains an unmet medical need for efficacious and safe direct antivirals with complementary modes of action for combination in treatment regimens to deliver a high cure rate with a short duration of treatment for HCV patients. Here we report the in vitro inhibitory activity, mode of action, binding kinetics, and resistance profile of TMC647055, a novel and potent nonnucleoside inhibitor of the HCV NS5B RNA-dependent RNA polymerase. In vitro combination studies with an HCV NS3/4A protease inhibitor demonstrated potent suppression of HCV RNA replication, confirming the potential for combination of these two classes in the treatment of chronic HCV infection. TMC647055 is a potent nonnucleoside NS5B polymerase inhibitor of HCV replication with a promising in vitro biochemical, kinetic, and virological profile that is currently undergoing clinical evaluation.     

The constraints of the ordinary: 'being with' in the context of end-of-life nursing care

The concept of 'being with' was an essential part of the hospice philosophy developed by Cicely Saunders, and one that she believed was a key element in the care of the dying. In Saunders' philosophy, 'being with' is a specific moment of engagement between a health professional and a patient whereby the patient has the opportunity to examine and express their thoughts and feelings relating to their imminent death. This study examined how 'being with' was implemented as a part of ordinary day-to-day practice in a hospice in Scotland. The study was based on the principles of ethnomethodology, which aims to reveal embedded and taken-for-granted rules and behaviours that determine practice. The data collection and analysis revealed that the nursing practice was constructed in such a way that 'being with', as Saunders understood it, could not be initiated either by a member of the nursing staff or by the patients. By adopting the philosophical framework of Heidegger, the study offers an understanding of how the nursing staff had developed 'being with' as provision of comfort in order to protect both themselves and the patients from engaging with painful emotions associated with facing death.