Diuretic-induced hyponatremia and osteoporotic fractures in patients admitted to the emergency department

Objective

Hyponatremia is a complication of diuretic treatment and has been recently identified as a novel factor associated with osteoporosis and fractures. The impact of diuretic-associated electrolyte disorders on osteoporotic fractures (OF) has rarely been studied systematically.

Design and setting

We conducted a study in patients presenting to the emergency department at the University Hospital Bern. In this retrospective case series analysis of prospectively gathered data, over a 2-year period we identified 10,823 adult (≥50 years) outpatients with a measured baseline serum sodium, at admission to the hospital. OF patients were compared to a control group without fractures using standard statistical methods.

Results

Four hundred and eighty (5%) patients had 547 OF. The OF group had a higher mean age (73 vs. 68 years, p < 0.0001), smaller proportion of men (37% vs. 58%, p < 0.0001), higher hospitalisation rate (83% vs. 62%, p < 0.0001) and longer hospital stay (8 vs. 6 days, p < 0.0001). Any diuretic agent (p < 0.0001), loop diurietics (p = 0.02), spironolactone (p = 0.02) and amiloride (p < 0.01) were used significantly more in OF patients, but not thiazides (p = 0.68). The prevalence of hyponatremia increased significantly (p < 0.0001) with the number of diuretics taken. Advanced age (odds ratio [OR] 1.04, p < 0.0001), hyponatremia (OR 1.46, p = 0.011) higher serum creatinine (OR 1.53, p = 0.0001), furosemide use alone (OR 1.40, p = 0.01) and co-treatment with amiloride (OR 2.22, p = 0.02) were associated with a higher risk for OF.

Conclusions

This study highlights the clinical association of hyponatremia during the use of certain diuretics (i.e. furosemide or in combination, i.e. amiloride) with an increased risk of osteoporosis associated fractures. Although evidence-based data is currently lacking a pragmatic approach concerning hyponatremia monitoring and correction appears reasonable in selected groups of patients.     

Scoping Review on Search Queries and Social Media for Disease Surveillance: A Chronology of Innovation

Background

The threat of a global pandemic posed by outbreaks of influenza H5N1 (1997) and Severe Acute Respiratory Syndrome (SARS, 2002), both diseases of zoonotic origin, provoked interest in improving early warning systems and reinforced the need for combining data from different sources. It led to the use of search query data from search engines such as Google and Yahoo! as an indicator of when and where influenza was occurring. This methodology has subsequently been extended to other diseases and has led to experimentation with new types of social media for disease surveillance.

Objective

The objective of this scoping review was to formally assess the current state of knowledge regarding the use of search queries and social media for disease surveillance in order to inform future work on early detection and more effective mitigation of the effects of foodborne illness.

Methods

Structured scoping review methods were used to identify, characterize, and evaluate all published primary research, expert review, and commentary articles regarding the use of social media in surveillance of infectious diseases from 2002-2011.

Results

Thirty-two primary research articles and 19 reviews and case studies were identified as relevant. Most relevant citations were peer-reviewed journal articles (29/32, 91%) published in 2010-11 (28/32, 88%) and reported use of a Google program for surveillance of influenza. Only four primary research articles investigated social media in the context of foodborne disease or gastroenteritis. Most authors (21/32 articles, 66%) reported that social media-based surveillance had comparable performance when compared to an existing surveillance program. The most commonly reported strengths of social media surveillance programs included their effectiveness (21/32, 66%) and rapid detection of disease (21/32, 66%). The most commonly reported weaknesses were the potential for false positive (16/32, 50%) and false negative (11/32, 34%) results. Most authors (24/32, 75%) recommended that social media programs should primarily be used to support existing surveillance programs.

Conclusions

The use of search queries and social media for disease surveillance are relatively recent phenomena (first reported in 2006). Both the tools themselves and the methodologies for exploiting them are evolving over time. While their accuracy, speed, and cost compare favorably with existing surveillance systems, the primary challenge is to refine the data signal by reducing surrounding noise. Further developments in digital disease surveillance have the potential to improve sensitivity and specificity, passively through advances in machine learning and actively through engagement of users. Adoption, even as supporting systems for existing surveillance, will entail a high level of familiarity with the tools and collaboration across jurisdictions.     

Detection of chromosomes and estimation of aneuploidy in human spermatozoa using fluorescence in-situ hybridization

The development and application of fluorescence in-situ hybridization (FISH) has opened the way for comprehensive studies on numerical chromosome abnormalities in human spermatozoa. FISH can be rapidly applied to large numbers of spermatozoa and thus overcomes the major limitation of karyotyping spermatozoa after penetration of zona-free hamster oocytes. The simultaneous hybridization of two or more chromosome-specific probes to spermatozoa and subsequent detection of the bound probes using different fluorescent detection systems enables two or more chromosomes to be localized simultaneously in the same spermatozoon and provides a technique for undertaking reasonable estimates of aneuploidy. The most commonly used probes are those which bind to the centromeric region of specific chromosomes. Most studies to date have concentrated on estimating aneuploidy in spermatozoa from normospermic men, although reports are beginning to appear on aneuploidy in spermatozoa from subfertile and infertile men. Multi- probe FISH studies have generally reported disomy (hyperhaploidy) estimates of 0.05-0.2% per chromosome. There is preliminary evidence that some chromosomes such as X, Y and 21 are predisposed towards higher rates of non-disjunction during spermatogenesis. There are also suggestions of inter-donor variability in aneuploidy frequencies for specific chromosomes, although this requires confirmation in larger studies. While FISH is clearly a powerful technique that has many applications in reproductive medicine, it must also be realized that it does have limitations and the technology itself is still evolving and has yet to be fully validated on spermatozoa.      

Preliminary observations on polar body extrusion and pronuclear formation in human oocytes using time-lapse video cinematography

In this study, we have used time-lapse video cinematography to study fertilization in 50 human oocytes that had undergone intracytoplasmic sperm injection (ICSI). Time-lapse recording commenced shortly after ICSI and proceeded for 17-20 h. Oocytes were cultured in an environmental chamber which was maintained under standard culture conditions. Overall, 38 oocytes (76%) were fertilized normally, and the fertilization rate and embryo quality were not significantly different from 487 sibling oocytes cultured in a conventional incubator. Normal fertilization followed a defined course of events, although the timing of these events varied markedly between oocytes. In 35 of the 38 fertilized oocytes (92%), there were circular waves of granulation within the ooplasm which had a periodicity of 20-53 min. The sperm head decondensed during this granulation phase. The second polar body was then extruded, and this was followed by the central formation of the male pronucleus. The female pronucleus formed in the cytoplasm adjacent to the second polar body at the same time as, or slightly after, the male pronucleus, and was subsequently drawn towards the male pronucleus until the two abutted. Both pronuclei then increased in size, the nucleoli moved around within the pronuclei and some nucleoli coalesced. During pronuclear growth, the organelles contracted from the cortex towards the centre of the oocyte, leaving a clear cortical zone. The oocyte decreased in diameter from 112 to 106 microm (P < 0.0001) during the course of the observation period. The female pronucleus was significantly smaller in diameter than the male pronucleus (24.1 and 22.4 microm respectively, P = 0.008) and contained fewer nucleoli (4.2 and 7.0 respectively, P < 0.0001). After time-lapse recording, oocytes were cultured for 48 h prior to embryo transfer or cryopreservation. Embryo quality was related to fertilization events and periodicity of the cytoplasmic wave, and it was found that good quality embryos arose from oocytes that had more uniform timing from injection to pronuclear abuttal and tended to have a longer cytoplasmic wave. In conclusion, we have shown that time-lapse video cinematography is an excellent tool for studying fertilization and early embryo development, and have demonstrated that human fertilization comprises numerous complex dynamic events.      

Inhibition of CDK activity and PCNA-dependent DNA replication by p21 is blocked by interaction with the HPV-16 E7 oncoprotein

p21 inhibits cyclin-dependent kinase (CDK) activity and proliferating cell nuclear antigen (PCNA)-dependent DNA replication by binding to CDK/cyclin complexes and to PCNA through distinct domains. The human papillomavirus (HPV)-16 E7 oncoprotein (16E7) abrogated a DNA damage-induced cell cycle arrest in vivo, despite high levels of p21. Using cell lysates and purified proteins we show that 16E7 prevented p21 both from inhibiting CDK2/cyclin E activity and PCNA-dependent DNA replication, whereas the nononcogenic HPV-6 E7 had reduced effects. Inactivation of both inhibitory functions of p21 was attained through binding between 16E7 and sequences in the carboxy-terminal end of p21 that overlap with the PCNA-binding site and the second p21 cyclin-binding motif. These data imply that the carboxyl terminus of p21 simultaneously modulates both CDK activity and PCNA-dependent DNA replication and that a single protein, 16E7, can override this modulation to disrupt normal cell cycle control.     

SARS-CoV replicates in primary human alveolar type II cell cultures but not in type I-like cells

Severe acute respiratory syndrome (SARS) is a disease characterized by diffuse alveolar damage. We isolated human alveolar type II cells and maintained them in a highly differentiated state. Type II cell cultures supported SARS-CoV replication as evidenced by RT-PCR detection of viral subgenomic RNA and an increase in virus titer. Virus titers were maximal by 24 h and peaked at approximately 10(5) pfu/mL. Two cell types within the cultures were infected. One cell type was type II cells, which were positive for SP-A, SP-C, cytokeratin, a type II cell-specific monoclonal antibody, and Ep-CAM. The other cell type was composed of spindle-shaped cells that were positive for vimentin and collagen III and likely fibroblasts. Viral replication was not detected in type I-like cells or macrophages. Hence, differentiated adult human alveolar type II cells were infectible but alveolar type I-like cells and alveolar macrophages did not support productive infection.     

A multipinhole small animal SPECT system with submillimeter spatial resolution

Single photon emission computed tomography (SPECT) is an important technology for molecular imaging studies of small animals. In this arena, there is an increasing demand for high performance imaging systems that offer improved spatial resolution and detection efficiency. We have designed a multipinhole small animal imaging system based on position sensitive avalanche photodiode (PSAPD) detectors with the goal of submillimeter spatial resolution and high detection efficiency, which will allow us to minimize the radiation dose to the animal and to shorten the time needed for the imaging study. Our design will use 8 x 24 mm2 PSAPD detector modules coupled to thallium-doped cesium iodide [CsI(Tl)] scintillators, which can achieve an intrinsic spatial resolution of 0.5 mm at 140 keV. These detectors will be arranged in rings of 24 modules each; the animal is positioned in the center of the 9 stationary detector rings which capture projection data from the animal with a cylindrical tungsten multipinhole collimator. The animal is supported on a bed which can be rocked about the central axis to increase angular sampling of the object. In contrast to conventional SPECT pinhole systems, in our design each pinhole views only a portion of the object. However, the ensemble of projection data from all of the multipinhole detectors provide angular sampling that is sufficient to reconstruct tomographic data from the object. The performance of this multipinhole PSAPD imaging system was simulated using a ray tracing program that models the appropriate point spread functions and then was compared against the performance of a dual-headed pinhole SPECT system. The detection efficiency of both systems was simulated and projection data of a hot rod phantom were generated and reconstructed to assess spatial resolution. Appropriate Poisson noise was added to the data to simulate an acquisition time of 15 min and an activity of 18.5 MBq distributed in the phantom. Both sets of data were reconstructed with an ML-EM reconstruction algorithm. In addition, the imaging performance of both systems was evaluated with a uniformity phantom and a realistic digital mouse phantom. Simulations show that our proposed system produces a spatial resolution of 0.8 mm and an average detection efficiency of 630 cps/MBq. In contrast, simulations of the dual-headed pinhole SPECT system produce a spatial resolution of 1.1 mm and an average detection efficiency of 53 cps/MBq. These results suggest that our novel design will achieve high spatial resolution and will improve the detection efficiency by more than an order of magnitude compared to a dual-headed pinhole SPECT system. We expect that this system can perform SPECT with submillimeter spatial resolution, high throughput, and low radiation dose suitable for in vivo imaging of small animals.     

The Washington Circle continuity of care performance measure: Predictive validity with adolescents discharged from residential treatment

This study examined the predictive validity of the Washington Circle (WC) continuity of care after long-term residential treatment performance measure, as well as the impact of assertive continuing care interventions on achieving continuity of care. This measure is a process measure that focuses on timely delivery of a minimal floor of services that are necessary to provide sufficient quality of treatment but should not be construed to be the optimal continuity of care after residential treatment for any specific adolescent. Participants included 342 adolescents who were admitted to long-term residential treatment and randomly assigned to either standard continuing care or an assertive continuing care condition. Overall, results provide initial support for the WC continuity of care after residential treatment performance measure as a useful predictor of 3-month recovery status. In addition, assignment to an assertive continuing care condition was found to significantly increase the likelihood of achieving continuity of care.     

Overview and update on molecular testing in non-small cell lung carcinoma utilizing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) samples

Lung carcinoma remains one of the most frequent and aggressive human neoplasms. Fortunately, in the last decades, the increasing knowledge of the molecular mechanisms leading to cancer development has allowed the use of targeted therapies with improvement of prognosis in many patients. Clinical management has also changed after the introduction of endobronchialultrasonographic bronchoscopy that allows a conservative staging of lung tumors, avoiding the need of mediastinoscopy for lymph node staging. Lung pathologists and cytopathologists are facing the challenge of giving the more comprehensive prognostic and predictive information with ever smaller tissue or cytological samples. The aim of this review is to summarize the molecular testing for non-small cell lung carcinoma and how pathologists can contribute to the patient's outcome with a conscious management of biological samples.