[Areas of application for teledermatology]. / Anwendungsbereiche der Teledermatologie.

BACKGROUND: In recent years, the introduction of the E­Health Act and the relaxation of the ban on remote treatment has improved the framework for telemedicine in Germany. OBJECTIVES: The aim of this article is to present an overview of the evidence of different areas of application for teledermatology. MATERIALS AND METHODS: A narrative review of national and international studies and projects on the use of teledermatology for diagnosis, monitoring of diseases, triage between primary care physicians (PCPs) and dermatologists, and its use in facilities with reduced organizational and/or geographical access to specialist care was conducted. RESULTS: Diagnostic applications allow teledermatological assessment in a large proportion of cases, with high concordance of diagnosis and patient satisfaction. For the monitoring of patients, the majority of studies demonstrated no difference in effectiveness between on-site and remote consultation, while patients are spared travel distance and waiting time. For programs enabling triage most of the patients with dermatologic conditions were able to remain with the PCP, while acute patients requiring direct referral to a dermatologist were identified. In special facilities, such as prisons, dermatological teleconsultations are successfully utilized. CONCLUSION: An adequate framework and promising evidence for the use of teledermatology exist. The areas of application are described in detail within the German S2k guideline for teledermatology. However, there is a potential risk for decreased access to telemedicine services for certain population groups.

Live interactive teledermatology compared to in-person care - a systematic review.

Teledermatology is a rapidly developing field of dermatological care, giving the opportunity to deliver more efficient healthcare to patients in remote areas. Live interactive (LI) teledermatology uses videoconferencing and, hence, allows for direct communication. A current overview on effectiveness, costs, feasibility and accuracy of LI applications compared to standard care is missing. The present systematic review provides this overview on LI teledermatology. Two databases were searched until April 2019, followed by title, abstract and full-text screening. Additionally, reference lists of the detected eligible articles were screened for further eligible studies. Studies comparing LI applications with standard care were included. Data on study design, sample size, country, objectives, main findings and characteristics of LI applications were extracted. Results on time effectiveness, costs, accuracy and feasibility of LI applications were synthesized. Additionally, the quality of included studies was assessed. Twenty-three publications were included in the final analysis: seventeen case-control studies and six randomized controlled trials. Included studies were published between 1997 and 2017. Study quality differed across studies. The studies were carried out in eight different countries. Eleven studies focused on patient consultation, three on patient organization and nine on combined applications of the aforementioned. Nine studies investigated applications facilitating patient-provider interaction. Fourteen studies evaluated applications combining patient-provider and provider-provider interaction, meaning the patient sits next to one provider while using LI applications to interact with another provider. This review reveals that LI applications can be a time effective substitute of or supplement to standard dermatological care. Results demonstrated that LI and standard care are comparable with regard to feasibility and accuracy. No clear tendencies can be reported with regard to costs. However, there is a lack of current comparative studies.

Acute pontine infarction after percutaneous coronary intervention: a very rare but devastating complication.

A 64-year-old man suffering from an acute posterior wall myocardial infarction underwent primary percutaneous coronary intervention. After several aspiration attempts, tirofiban infusion and pre- and post-dilatation, a bare-metal stent was successfully implanted in the culprit right coronary artery. While the patient did not show any neurological symptoms before or during the procedure, he exhibited hemiplegia and loss of spontaneous speech. Additional magnetic resonance imaging showed an extensive brain stem infarction. This is the first report of a brain stem infarction as a complication of percutaneous coronary intervention.

Comparative performance of intensive care mortality prediction models based on manually curated versus automatically extracted electronic health record data.

INTRODUCTION: Benchmarking intensive care units for audit and feedback is frequently based on comparing actual mortality versus predicted mortality. Traditionally, mortality prediction models rely on a limited number of input variables and significant manual data entry and curation. Using automatically extracted electronic health record data may be a promising alternative. However, adequate data on comparative performance between these approaches is currently lacking. METHODS: The AmsterdamUMCdb intensive care database was used to construct a baseline APACHE IV in-hospital mortality model based on data typically available through manual data curation. Subsequently, new in-hospital mortality models were systematically developed and evaluated. New models differed with respect to the extent of automatic variable extraction, classification method, recalibration usage and the size of collection window. RESULTS: A total of 13 models were developed based on data from 5,077 admissions divided into a train (80%) and test (20%) cohort. Adding variables or extending collection windows only marginally improved discrimination and calibration. An XGBoost model using only automatically extracted variables, and therefore no acute or chronic diagnoses, was the best performing automated model with an AUC of 0.89 and a Brier score of 0.10. DISCUSSION: Performance of intensive care mortality prediction models based on manually curated versus automatically extracted electronic health record data is similar. Importantly, our results suggest that variables typically requiring manual curation, such as diagnosis at admission and comorbidities, may not be necessary for accurate mortality prediction. These proof-of-concept results require replication using multi-centre data.

Reliability and Agreement of 2D and 3D Measurements on MRAs for Growth Assessment of Unruptured Intracranial Aneurysms.

BACKGROUND AND PURPOSE: Reliable and reproducible measurement of unruptured intracranial aneurysm growth is important for unruptured intracranial aneurysm rupture risk assessment. This study aimed to compare the reliability and reproducibility of 2D and 3D growth measurements of unruptured intracranial aneurysms. MATERIALS AND METHODS: 2D height, width, and neck and 3D volume measurements of unruptured intracranial aneurysms on baseline and follow-up TOF-MRAs were performed by two observers. The reliability of individual 2D and 3D measurements and of change (growth) between paired scans was assessed (intraclass correlation coefficient) and stratified for aneurysm location. The smallest detectable change on 2D and 3D was determined. Proportions of growing aneurysms were compared, and Bland-Altman plots were created. RESULTS: Seventy-two patients with 84 unruptured intracranial aneurysms were included. The interobserver reliability was good-to-excellent for individual measurements (intraclass correlation coefficient > 0.70), poor for 2D change (intraclass correlation coefficient < 0.5), and good for 3D change (intraclass correlation coefficient = 0.76). For both 2D and 3D, the reliability was location-dependent and worse for irregularly shaped aneurysms. The smallest detectable changes for 2D height, width, and neck and 3D volume measurements were 1.5 , 2.0, and 1.9 mm and 0.06 mL, respectively. The proportion of growing unruptured intracranial aneurysms decreased from 10% to 2%, depending on the definition of growth (1 mm or the smallest detectable changes for 2D and 3D). CONCLUSIONS: The interobserver reliability of the size measurements of individual 2D and 3D unruptured intracranial aneurysms was good-to-excellent but lower for 2D and 3D growth measurements. For growth assessment, 3D measurements are more reliable than 2D measurements. The smallest detectable change for 2D measurements was larger than 1 mm, the current clinical definition of unruptured intracranial aneurysm growth.

Disease activity patterns in juvenile systemic lupus erythematosus and its relation to early aggressive treatment.

This study aimed to determine disease activity patterns in juvenile systemic lupus erythematosus (jSLE) and its relation to early treatment. All jSLE patients who visited the outpatient departments of three Dutch university hospitals for at least 6 months were included. Data were retrospectively collected from each patient visit and hospitalization. Patient characteristics, clinical and laboratory findings categorized in organ systems, flare rate, medication use and disease course were analysed. Included were 35 patients (female 77%; White 47%) with a total follow-up of 142 years. Median age at diagnosis was 12.8 years. Flare rate was 0.45/ patient-year. An organ system not earlier involved was affected in 34% of flares. Identifiable disease activity patterns were: chronic active (49%), relapse remitting (14%) and long quiescence (37%), with no significant difference in organ involvement at diagnosis. Positive anti-Sm and non-White ethnicity were significantly associated with a chronic active pattern. In 14 patients with severe symptoms at diagnosis, treatment with intravenous cyclophosphamide and/or biologics and/or intravenous methylprednisone in the first 6 months resulted in a long quiescence pattern in seven patients. In conclusion, distinct disease activity patterns are identifiable in children. Suppression of disease with early aggressive treatment may decrease the rate of progression.

Retention of antimicrobial activity in plaque and saliva following mouthrinse use in vivo.

The aim of this study was to determine the contribution of plaque and saliva towards the prolonged activity, also called substantivity, of three antimicrobial mouthrinses (Listerine®, Meridol®, Crest Pro Health®), used in combination with a toothpaste (Prodent Coolmint®). Volunteers brushed for 4 weeks with a toothpaste without antimicrobial claims, while during the last 2 weeks half of the volunteers used an antimicrobial mouthrinse in addition to brushing. At the end of the experimental period, plaque and saliva samples were collected 6 h after oral hygiene, and bacterial concentrations and viabilities were determined. The contribution of plaque and saliva towards substantivity was assessed by combining plaque obtained after mechanical cleaning only with plaque and saliva obtained after additional use of an antimicrobial rinse. Subsequently, resulting viabilities of the combined plaques were determined. The viabilities of plaque samples after additional rinsing with mouthrinses were lower than of plaque obtained after mechanical cleaning only, regardless of the rinse involved. Moreover, plaque collected 6 h after rinsing with antimicrobial mouthrinses contained a surplus of antimicrobial activity. Only Listerine showed decreased viability in saliva, but none of the mouthrinses showed any residual antimicrobial activity in saliva. The findings indicate that plaque left behind after mechanical cleaning contributes to the prolonged substantivity of antimicrobial mouthrinses.

Sulfation preceding deiodination of iodothyronines in rat hepatocytes.

In man and animals iodothyronines are metabolized by deiodination and conjugation with glucuronic acid or sulfate. Until now these processes have been regarded as independent reactions. However, in the present study a close interaction of these pathways was observed in the hepatic metabolism of 3,3'-diiodothyronine and 3,3',5-triiodothyronine. Studies with rat hepatocytes and liver microsomes indicated that sulfation of the phenolic hydroxyl group facilitates the deiodination of these compounds.

Towards automated diffraction tomography. Part II--Cell parameter determination.

Automated diffraction tomography (ADT) allows the collection of three-dimensional (3d) diffraction data sets from crystals down to a size of only few nanometres. Imaging is done in STEM mode, and diffraction data are collected with quasi-parallel beam nanoelectron diffraction (NED). Here, we present a set of developed processing steps necessary for automatic unit-cell parameter determination from the collected 3d diffraction data. Cell parameter determination is done via extraction of peak positions from a recorded data set (called the data reduction path) followed by subsequent cluster analysis of difference vectors. The procedure of lattice parameter determination is presented in detail for a beam-sensitive organic material. Independently, we demonstrate a potential (called the full integration path) based on 3d reconstruction of the reciprocal space visualising special structural features of materials such as partial disorder. Furthermore, we describe new features implemented into the acquisition part.

New frontiers for health information systems using Epi Info in developing countries: structured application framework for Epi Info (SAFE).

BACKGROUND: For more than two decades, Epi Info software has been used to meet the data management, analysis, and mapping needs of public health professionals in more than 181 countries and 13 languages. Until now, most Epi Info systems have been relatively simple, mainly because of a lack of detailed and structured guidance for developing complex systems. OBJECTIVE AND RESULTS: We created the structured application framework for Epi Info (SAFE), which is a set of guidelines that allows developers to create both simple and complex information systems using accepted good programming practices. This has resulted in application code blocks that are re-useable and easy to maintain, modify, and enhance. The flexibility of SAFE allows various aggregate and case-based application modules to be rapidly created, combined, and updated to create health information systems or sub-systems enabling continuous, incremental enhancement as national and local capacity increases. CONCLUSIONS: SAFE and Epi Info are both cost-free and have low system requirements--characteristics that render this framework and software beneficial for developing countries.

Plasma acrolein levels and their association with delayed ischemic neurological deficits following aneurysmal subarachnoid haemorrhage: a pilot study.

BACKGROUND: The molecular mechanisms of cerebral vasospasm following aneurysmal subarachnoid haemorrhage (aSAH) remain unclear. Acrolein, a reactive metabolite produced in many models of mechanical and ischemic injury, has been shown to cause vasospasm in coronary artery and aorta models. These traits suggest it may play a role in post-aSAH cerebral vasospasm. This pilot study was designed as a preliminary investigation to determine if acrolein levels could be used as a clinical tool to predict the presence of vasospasm. METHODS: Eleven patients with aSAH and Hunt and Hess admission grades of III-V were prospectively enrolled. Patients were stratified according to the presence or absence of vasospasm, defined as a delayed ischaemic neurological deficit in which all other possible causes have been excluded. Soluble acrolein levels were determined at two times points: early (day 1-3 post-SAH) and late (day 8-12 post-SAH) and the change in acrolein levels over this period was computed using a Mann-Whitney test. RESULTS: The change in acrolein levels over this period between the vasospasm and non-vasospasm group trended toward but did not achieve statistical significance (means: 5.68 versus -5.54; medians: 5.27 versus -3.99; range: -8.067 to 22.904 versus -13.83 to 5.199 p=0.13). Five out of six vasospasm patients showed an increase in acrolein levels over the vasospasm period. Three out of four non-vasospasm patients showed a decrease over the vasospasm period. CONCLUSIONS: The results of this pilot study suggest that acrolein levels increase in patients undergoing vasospasm during the vasospasm window. This suggests that acrolein may play a role in the pathways leading up to or following vasospasm. There is a need for larger more definitive studies.

Towards automated diffraction tomography: part I--data acquisition.

The ultimate aim of electron diffraction data collection for structure analysis is to sample the reciprocal space as accurately as possible to obtain a high-quality data set for crystal structure determination. Besides a more precise lattice parameter determination, fine sampling is expected to deliver superior data on reflection intensities, which is crucial for subsequent structure analysis. Traditionally, three-dimensional (3D) diffraction data are collected by manually tilting a crystal around a selected crystallographic axis and recording a set of diffraction patterns (a tilt series) at various crystallographic zones. In a second step, diffraction data from these zones are combined into a 3D data set and analyzed to yield the desired structure information. Data collection can also be performed automatically, with the recent advances in tomography acquisition providing a suitable basis. An experimental software module has been developed for the Tecnai microscope for such an automated diffraction pattern collection while tilting around the goniometer axis. The module combines STEM imaging with diffraction pattern acquisition in nanodiffraction mode. It allows automated recording of diffraction tilt series from nanoparticles with a size down to 5nm.

Cooling a mechanical resonator with nitrogen-vacancy centres using a room temperature excited state spin-strain interaction.

Cooling a mechanical resonator mode to a sub-thermal state has been a long-standing challenge in physics. This pursuit has recently found traction in the field of optomechanics in which a mechanical mode is coupled to an optical cavity. An alternate method is to couple the resonator to a well-controlled two-level system. Here we propose a protocol to dissipatively cool a room temperature mechanical resonator using a nitrogen-vacancy centre ensemble. The spin ensemble is coupled to the resonator through its orbitally-averaged excited state, which has a spin-strain interaction that has not been previously studied. We experimentally demonstrate that the spin-strain coupling in the excited state is 13.5±0.5 times stronger than the ground state spin-strain coupling. We then theoretically show that this interaction, combined with a high-density spin ensemble, enables the cooling of a mechanical resonator from room temperature to a fraction of its thermal phonon occupancy.

Erratum: Cooling a mechanical resonator with nitrogen-vacancy centres using a room temperature excited state spin-strain interaction.

[This corrects the article DOI: 10.1038/ncomms14358.].

Public-health impact of accelerated measles control in the WHO African Region 2000-03.

BACKGROUND: In 2000, the WHO African Region adopted a plan to accelerate efforts to lower measles mortality with the goal of decreasing the number of measles deaths to near zero. By June, 2003, 19 African countries had completed measles supplemental immunisation activities (SIA) in children aged 9 months to 14 years as part of a comprehensive measles-control strategy. We assessed the public-health impact of these control measures by use of available surveillance data. METHODS: We calculated percentage decline in reported measles cases during 1-2 years after SIA, compared with 6 years before SIA. On the basis of data from 13 of the 19 countries, we assumed that the percentage decline in measles deaths equalled that in measles cases. We also examined data on routine and SIA measles vaccine coverage, measles case-based surveillance, and suspected measles outbreaks. FINDINGS: Between 2000 and June, 2003, 82.1 million children were targeted for vaccination during initial SIA in 12 countries and follow-up SIA in seven countries. The average decline in the number of reported measles cases was 91%. In 17 of the 19 countries, measles case-based surveillance confirmed that transmission of measles virus, and therefore measles deaths, had been reduced to low or very low rates. The total estimated number of deaths averted in the year 2003 was 90,043. Between 2000 and 2003 in the African Region as a whole, we estimated that the percentage decline in annual measles deaths was around 20% (90,043 of 454,000). INTERPRETATION: The burden of measles in sub-Saharan Africa can be reduced to very low levels by means of appropriate strategies, resources, and personnel.

Isolation of a DNA polymerase alpha-associated regulatory protein from calf thymus.

A regulatory protein for DNA polymerase alpha, responsive to noncomplementary deoxyribonucleoside triphosphates, has been isolated from calf thymus. The regulatory protein was separated from DNA polymerase alpha using Affi-Gel Blue and gel filtration. The regulatory protein had a molecular weight of approximately 70,000 as determined by gel filtration, and its activity was nondialyzable, heat labile, and abolished by pronase treatment. In the presence of regulatory protein, DNA polymerase alpha activity, measured by using polydeoxyadenylate-oligodeoxythymidylate as template primer, was inhibited by 2'-deoxyguanosine 5'-triphosphate in a parabolic-competitive fashion [Ki = 15 +/- 1 (S.E.) microM] and by 2'-deoxycytidine 5'-triphosphate in a linear-competitive manner (Ki = 162 +/- 23 microM). Neither the four natural ribonucleoside triphosphates nor 2'-deoxyadenosine 5'-triphosphate inhibited the DNA polymerase-regulatory protein system to any significant extent. The regulatory protein by itself had no effect on either DNA polymerase alpha activity or the Km for template primer. These results indicate that deoxyribonucleoside triphosphate pools may be involved in the regulation of cellular DNA synthesis through a direct effect on DNA polymerization.

Evaluation of ribonucleoside and deoxyribonucleoside triphosphate pools in cultured leukemia cells during exposure to methotrexate or methotrexate plus thymidine.

Continuous exposure to inhibitory concentrations of methotrexate produces distinct rates of steady-state growth of murine leukemia L1210 and human leukemia CCRF-CEM cells in culture. Addition of thymidine to the medium produces reversal (6 to 40%) of this steady-state growth rate inhibition. This study utilized combinations of methotrexate and thymidine for an evaluation of the accompanying relationship between steady-state growth rate and changes in the ribo- and deoxyribonucleoside triphosphate pools. In L1210 cells exposed to methotrexate alone, the deoxythymidine 5'-phosphate (dTTP) pools decreased, whereas deoxyadenosine 5'-triphosphate, deoxyguanosine 5'-triphosphate, and deoxycytidine 5'-triphosphate (dCTP) remained relatively constant up to 70% inhibition of growth rate, with dCTP at a constant 112% of controls. The corresponding ribonucleoside triphosphates decreased only slightly. With the combination of methotrexate and thymidine resulting in up to 40% inhibition of growth rate, there was also a decrease in the dTTP pool while the other deoxyribonucleoside triphosphates remained relatively constant, and the corresponding ribonucleoside triphosphates again decreased only slightly. The dCTP pool was reduced to a constant 42% of control comparable to that produced by thymidine alone. With greater than 40% (with thymidine) or 70% (without thymidine) inhibition of growth rate, all pools decreased, but only dTTP was substantially reduced in proportion to the growth rate inhibition caused by methotrexate. The dTTP pool became depleted in spite of the presence of exogenous thymidine. Evaluation of CCRF-CEM cells indicated that inhibition of growth rate and nucleotide pool perturbations by methotrexate were similar to those observed in L1210 cells. However, in the presence of thymidine, inhibition of growth rate appeared related to decreased pools of dCTP, deoxyadenosine 5'-triphosphate, and deoxyguanosine 5'-triphosphate, rather than dTTP as was observed for L1210 cells. Hence, mammalian cells were capable of responding in a differential fashion to pharmacological perturbations, and this capacity may play a role in determining therapeutic selectivity. Since the ribonucleoside triphosphate decreases were slight and relatively uniform during methotrexate-induced perturbations, the deoxyribonucleoside triphosphate pools appear to be more directly related to inhibition of growth rate. The results are consistent with the concept that slight imbalances in the deoxyribonucleoside triphosphate pools dramatically inhibit DNA synthesis, as mediated through their interaction with DNA polymerase.

[5-HT3-antagonists as a substitute for metoclopramide and domperidone: a literature review]. / 5-HT3-receptorantagonisten als vervangers van metoclopramide en domperidon.

OBJECTIVE: To investigate whether the anti-emetics metoclopramide and domperidone can be replaced by 5-HT3-antagonists, as side effects restrict use of these dopamine antagonists. DESIGN: Systematic review. METHOD: We searched the Embase and PubMed databases for articles published in the period 1995-October 2015, in which the efficacy or side effects of metoclopramide or domperidone were compared with at least one of the 5-HT3-antagonists ondansetron, granisetron, tropisetron or palonosetron. These had to be randomised controlled clinical studies into the known indications for metoclopramide and domperidone for prevention and treatment of nausea and vomiting. Two reviewers independently selected articles based on the title and abstract, then assessed for eligibility based on the full texts. RESULTS: In total, 56 articles were included in this review. The conclusion in 51 studies was that the efficacy of 5-HT3-antagonists in nausea and vomiting is comparable or even superior to that of metoclopramide. Metoclopramide more often caused extrapyramidal side effects; 5-HT3-antagonists were more likely to cause headaches and constipation. The majority of the studies compared metoclopramide with ondansetron. None of the articles studied palonosetron, and only one study compared domperidone with a 5-HT3-antagonist. CONCLUSION: We found enough evidence to presume that metoclopramide can be replaced by 5-HT3-antagonists for preventing delayed chemotherapy-induced nausea and vomiting and for prophylaxis or treatment of postoperative nausea and vomiting. More research is needed into the other indications and into the substitutability of domperidone.