Telemonitoring-guided ambulatory fixed CPAP titration versus ambulatory APAP titration in moderate obstructive sleep apnea: A non-inferiority randomized controlled trial.

The present study aimed to evaluate whether titration of fixed continuous positive airway pressure at home using telemonitoring produces patient outcomes equal to auto-adjusting positive airway pressure titration at home for patients with moderate obstructive sleep apnea. Patients were randomized with a 1:1 allocation ratio to receive either auto-adjusting positive airway pressure titration based on the median of the 95th percentile pressure across seven nights or fixed continuous positive airway pressure titration based on a fixed calculated pressure and specific adaptations after telemonitoring of device data after 3 and 7 nights. The results of the ambulatory titration were evaluated with in-laboratory polysomnography after 2 weeks. We hypothesized that fixed continuous positive airway pressure titration would be non-inferior to auto-adjusting positive airway pressure titration in respect to continuous positive airway pressure adherence at a 3-month follow-up. A non-inferiority margin of -0.75 hr was prespecified. One-hundred and four patients were randomly allocated to fixed continuous positive airway pressure (n = 52) and auto-adjusting positive airway pressure (n = 52) titration. The mean difference and the 95% confidence intervals in continuous positive airway pressure adherence after 3 months between the two arms were 0.80 (-0.08, 1.69) hr. The non-inferiority hypothesis was confirmed as the lower one-sided 97.5% confidence interval for the mean difference was above the prespecified margin. Patients in the fixed continuous positive airway pressure titration arm were titrated at significantly lower pressure level and had a significantly lower amount of average leaks compared with auto-adjusting positive airway pressure-titrated patients, while there was no difference in residual obstructive apnea-hypopnea index on polysomnography. Telemonitoring enables ambulatory continuous positive airway pressure titration with fixed pressure that is non-inferior to ambulatory titration with auto-adjusting pressure in patients with moderate obstructive sleep apnea.

Cardiovascular risk and kidney function profiling using conventional and novel biomarkers in young adults: the African-PREDICT study.

BACKGROUND: Low- and middle-income countries experience an increasing burden of chronic kidney disease. Cardiovascular risk factors, including advancing age, may contribute to this phenomenon. We (i) profiled cardiovascular risk factors and different biomarkers of subclinical kidney function and (ii) investigated the relationship between these variables. METHODS: We cross-sectionally analysed 956 apparently healthy adults between 20 and 30 years of age. Cardiovascular risk factors such as high adiposity, blood pressure, glucose levels, adverse lipid profiles and lifestyle factors were measured. Various biomarkers were used to assess subclinical kidney function, including estimated glomerular filtration rate (eGFR), urinary albumin, uromodulin and the CKD273 urinary proteomics classifier. These biomarkers were used to divide the total population into quartiles to compare extremes (25th percentiles) on the normal kidney function continuum. The lower 25th percentiles of eGFR and uromodulin and the upper 25th percentiles of urinary albumin and the CKD273 classifier represented the more unfavourable kidney function groups. RESULTS: In the lower 25th percentiles of eGFR and uromodulin and the upper 25th percentile of the CKD273 classifier, more adverse cardiovascular profiles were observed. In multi-variable adjusted regression analyses performed in the total group, eGFR associated negatively with HDL-C (ß= -0.44; p < 0.001) and GGT (ß= -0.24; p < 0.001), while the CKD273 classifier associated positively with age and these same risk factors (age: ß = 0.10; p = 0.021, HDL-C: ß = 0.23; p < 0.001, GGT: ß = 0.14; p = 0.002). CONCLUSION: Age, lifestyle and health measures impact kidney health even in the third decade.

Precision Mass Measurements of Neutron-Rich Scandium Isotopes Refine the Evolution of N=32 and N=34 Shell Closures.

We report high-precision mass measurements of ^{50-55}Sc isotopes performed at the LEBIT facility at NSCL and at the TITAN facility at TRIUMF. Our results provide a substantial reduction of their uncertainties and indicate significant deviations, up to 0.7 MeV, from the previously recommended mass values for ^{53-55}Sc. The results of this work provide an important update to the description of emerging closed-shell phenomena at neutron numbers N=32 and N=34 above proton-magic Z=20. In particular, they finally enable a complete and precise characterization of the trends in ground state binding energies along the N=32 isotone, confirming that the empirical neutron shell gap energies peak at the doubly magic ^{52}Ca. Moreover, our data, combined with other recent measurements, do not support the existence of a closed neutron shell in ^{55}Sc at N=34. The results were compared to predictions from both ab initio and phenomenological nuclear theories, which all had success describing N=32 neutron shell gap energies but were highly disparate in the description of the N=34 isotone.

Advancement of Photospheric Radius Expansion and Clocked Type-I X-Ray Burst Models with the New

We report the first (in)elastic scattering measurement of ^{25}Al+p with the capability to select and measure in a broad energy range the proton resonances in ^{26}Si contributing to the ^{22}Mg(α,p) reaction at type I x-ray burst energies. We measured spin-parities of four resonances above the α threshold of ^{26}Si that are found to strongly impact the ^{22}Mg(α,p) rate. The new rate advances a state-of-the-art model to remarkably reproduce light curves of the GS 1826-24 clocked burster with mean deviation <9% and permits us to discover a strong correlation between the He abundance in the accreting envelope of the photospheric radius expansion burster and the dominance of ^{22}Mg(α,p) branch.

[COVID-19 in old age-The geriatric perspective]. / COVID-19 im Alter ­ Die geriatrische Perspektive.

Predominantly the older population is affected by a severe course of COVID-19. The mortality of hospitalized patients with COVID-19 above the age of 80 years is up to 54% in international studies. These observations indicate the necessity to highlight the geriatric perspective on this disease. The diagnostics and treatment of COVID-19 do not differ between younger and older patients but atypical symptoms should be expected more frequently in old age. Older subjects show an increased need for rehabilitation after COVID-19. Paradoxically, increasing rehabilitation demands go along with a reduced availability of geriatric rehabilitation options, the latter being a consequence of closure or downsizing of rehabilitation departments during the pandemic. In general, measures of isolation and quarantine should be diligently balanced as the health and emotional consequences of such measures may be severe in older persons. In light of the poor prognosis of older COVID-19 patients, advanced care planning becomes even more relevant. Caregivers and physicians should be encouraged to compose advanced care directives that also reflect the specific circumstances of COVID-19. Fortunately, current data suggest that the effectiveness of the vaccination with the mRNA-vaccines approved in Germany may be equally high in older compared to younger persons.

PROSPECT guideline for oncological breast surgery: a systematic review and procedure-specific postoperative pain management recommendations.

Analgesic protocols used to treat pain after breast surgery vary significantly. The aim of this systematic review was to evaluate the available literature on this topic and develop recommendations for optimal pain management after oncological breast surgery. A systematic review using preferred reporting items for systematic reviews and meta-analysis guidance with procedure-specific postoperative pain management (PROSPECT) methodology was undertaken. Randomised controlled trials assessing postoperative pain using analgesic, anaesthetic or surgical interventions were identified. Seven hundred and forty-nine studies were found, of which 53 randomised controlled trials and nine meta-analyses met the inclusion criteria and were included in this review. Quantitative analysis suggests that dexamethasone and gabapentin reduced postoperative pain. The use of paravertebral blocks also reduced postoperative pain scores, analgesia consumption and the incidence of postoperative nausea and vomiting. Intra-operative opioid requirements were documented to be lower when a pectoral nerves block was performed, which also reduced postoperative pain scores and opioid consumption. We recommend basic analgesics (i.e. paracetamol and non-steroidal anti-inflammatory drugs) administered pre-operatively or intra-operatively and continued postoperatively. In addition, pre-operative gabapentin and dexamethasone are also recommended. In major breast surgery, a regional anaesthetic technique such as paravertebral block or pectoral nerves block and/or local anaesthetic wound infiltration may be considered for additional pain relief. Paravertebral block may be continued postoperatively using catheter techniques. Opioids should be reserved as rescue analgesics in the postoperative period. Research is needed to evaluate the role of novel regional analgesic techniques such as erector spinae plane or retrolaminar plane blocks combined with basic analgesics in an enhanced recovery setting.

[Paraneoplastic subacute degeneration of the cerebellum in non-small cell lung cancer and positive anti-Tr3 antibodies]. / Paraneoplastische subakute Degeneration des Kleinhirns bei nichtkleinzelligem Bronchialkarzinom und positiven Anti-Tr3-Antikörpern.

Neurological disorders can occur before the diagnosis of a malignoma is set. These disorders are induced by a misguided immune response with antibodies against intracellular or cell surface antigens. One of the most common paraneoplastic diseases is the subacute degeneration of the cerebellum. In most of the cases antibodies against Anti Hu, CRMP5/CV2, Amphiphysin and Ma/Ta are found and small cell bronchial carcinoma, breast cancer and lymphoma are diagnosed. We report about a 67 years old man with cerebellar symptoms and a weight loss of 10 kg who was treated in our clinic. After our diagnostic work up we found a non small cell cancer and diagnosed a subacute degeneration of the cerebellum as a paraneoplastic disorder. We found a high positive titer for Anti-Tr3 antibodies while the rest of the paraneoplastic antibodies described as typically associated with the subacute degeneration of the cerebellum were negative. The Anti-Tr3 antibodies are usually found in patients with Hodgkin and less often Non-Hodgkin disease. After initiation of a tumor specific therapy and intravenous immunoglobulin therapy the cerebellar symptoms decreased. In future follow up examinations we will see if the anti-Tr3 antibodies were associated with the non small cell bronchial carcinoma or if a lymphoma will occur in our patient.

Clinical pharmacology of alemtuzumab, an anti-CD52 immunomodulator, in multiple sclerosis.

Alemtuzumab, a humanized anti-CD52 monoclonal antibody, is approved for treatment of relapsing multiple sclerosis (MS). In the Phase II/III trials, patients received 12 or 24 mg/day of alemtuzumab in two treatment courses (5 days for course 1 and 3 days for course 2), 12 months apart. Serum concentrations of alemtuzumab peaked on the last day of dosing in each course and mostly fell below the limit of quantitation by day 30. Alemtuzumab rapidly depleted circulating T and B lymphocytes, with the lowest observed values occurring within days. Lymphocytes repopulated over time, with B cell recovery usually complete within 6 months. T lymphocytes recovered more slowly and generally did not return to baseline by 12 months post-treatment. Approximately 40 and 80% of patients had total lymphocyte counts, reaching the lower limit of normal by 6 and 12 months after each course, respectively. The clearance of alemtuzumab is dependent on circulating lymphocyte count. A majority of treated patients tested positive for anti-alemtuzumab antibodies, including inhibitory antibodies, during the 2-year studies, and a higher proportion of patients tested positive in course 2 than in course 1. The presence of anti-alemtuzumab antibody appeared to be associated with slower clearance of alemtuzumab from the circulation but had no impact on the pharmacodynamics. No effects of age, race or gender on the pharmacokinetics or pharmacodynamics were observed. Together, the pharmacokinetics, pharmacodynamics and immunogenicity results support the continued development and use of alemtuzumab for the treatment of MS, and probably explain its sustained effects beyond the dosing interval.

On the challenges and opportunities facing fish biology: a discussion of five key knowledge gaps.

Many fish species face increasing challenges associated with climate change and overfishing. At the same time, aquaculture is becoming vital for food security. Gaining a deeper understanding of the basic biology of fish is therefore more important than ever. Here we synthesize and summarize key questions, opportunities and challenges in fish biology highlighted during a round-table discussion at the 50th Anniversary Symposium of The Fisheries Society of the British Isles, held at the University of Exeter, U.K., in July 2017. We identified several knowledge gaps but also key opportunities for fish biology to inform food security, for collective behaviour, evolutionary history and trait correlations to predict responses to environmental change and for novel analytical approaches to mine existing data sets. Overall, more integrative approaches through stronger collaborations across different fields are needed to advance our understanding of the basic biology of fish.

[Altered orientation and aggressiveness in an 89-year-old woman]. / Wechselnde Vigilanz und Fremdaggressivität bei einer 89­jährigen Patientin.

An 89-year-old woman with Alzheimer's dementia was admitted because of altered orientation, aggressiveness and inability to take care of herself at home. Her patient history indicated that 14 days ago the battery of the pacemaker had be renewed. During that time the patient suffered from psychomotor alterations. Therefore, melperone had been initiated. Inspection of the urine and laboratory findings pointed towards an acute exacerbation of acute intermittent porphyria as a possible cause of the delirium. After discontinuation of melperone with additional parenteral therapy with physiological fluids, the signs of delirium significantly improved.

Topical treatments for scalp psoriasis: summary of a Cochrane Systematic Review.

People with chronic plaque psoriasis often have lesions on the scalp that are difficult to treat. This report is a summary of a Cochrane review on the efficacy and safety of topical treatments for scalp psoriasis. For quality-of-evidence assessment, we used the Grading of Recommendations Assessment, Development and Evaluation Working Group approach. Only randomized controlled trials (RCTs) were eligible for inclusion. We searched the Cochrane Skin Group Specialised Register, CENTRAL, MEDLINE, Embase and LILACS; ongoing trials; indexes of included studies and screened abstracts of six psoriasis-specific conferences up to August 2015. We included 59 RCTs, with 11 561 participants overall. Most findings were limited to short-term treatments (< 6 months). According to the clinician and patients' self-assessment, a corticosteroid-vitamin D combination (e.g. betamethasone dipropionate plus calcipotriol) and corticosteroids of high and very high potency were better than vitamin D. The two-compound combination was superior to the corticosteroid alone, but the additional benefit was small. Reporting of quality-of-life data was insufficient. The two-compound combination and corticosteroids caused fewer withdrawals due to adverse events than vitamin D. There was no difference between the two-compound combination and corticosteroid monotherapy concerning this outcome. Overall the evidence was of moderate quality. Evaluation of other topical treatments was limited. Given the comparable safety profile and only slim benefit of the two-compound combination over the corticosteroid alone, monotherapy with generic topical corticosteroids of high and very high potency may be fully acceptable for short-term therapy. More quality-of-life data and long-term assessments are needed.

Converting sunlight into audible sound by means of the photoacoustic effect: The Heliophone.

One hundred and thirty-five years after Alexander Graham Bell and his assistant Charles Sumner Tainter explored the photoacoustic effect, and about 40 years after Rosencwaig and Gersho modeled the effect in a photoacoustic cell configuration, the phenomenon is revisited in a "Heliophone" device that converts sunlight into sound. The light is focused on a carbon blackened copper coated Kapton foil in an acoustic cell by means of a compound parabolic collimator, and its intensity is modulated by a mechanical chopper. A horn is employed to make the sound audible without electronic amplification. The description of the photoacoustic effect that was introduced by Rosencwaig and Gersho is extended to a cell-horn configuration, in which the periodically heated air above the foil acts as an oscillating piston, driving acoustic waves in the horn. The pressure in the cavity-horn assembly is calculated by considering the air layer piston as an equivalent volume velocity source. The importance of the carbon black (soot) layer to enhance light absorption, but above all to enhance the photothermal excitation efficiency, is elucidated by means of an experimentally supported physical model.

Systematic review on the maintenance of response during systemic antipsoriatic therapy.

As a chronic disease psoriasis often requires long-term treatment. Successful continuation of therapy during a maintenance phase is therefore important. A systematic review was performed on the efficacy of psoriasis drugs during maintenance treatment in patients who had achieved sufficient treatment success during the induction period. Maintenance therapy is defined as treatment during the period after successful induction therapy. Inclusion criteria were prospective studies with systemic therapies recommended by the 2009 European psoriasis guidelines (plus ustekinumab), and a study population that had achieved a defined treatment response criterion after induction therapy within a period of ≥ 6 months. Maintenance studies on conventional treatments were identified for ciclosporin (CSA) only (no studies investigating acitretin, methotrexate or ustekinumab were found). Compared with placebo, CSA was shown to be effective in maintenance therapy, yet CSA 1·5 mg kg(-1) seems to be insufficient to maintain disease control. Based on the evidence, it is uncertain whether there is any difference between daily or intermittent treatment. For biologics, maintenance data were available for adalimumab, etanercept and infliximab. No differences in 75% improvement in Psoriasis Area and Severity Index (PASI 75) response were identified between adalimumab 40 mg once and twice a month. Continuous infliximab treatment was shown to be superior to as-needed treatment. For etanercept, only observational postrandomized controlled trial data were available, indicating a maintained PASI 75 response in approximately three-quarters of patients during long-term treatment. Only limited evidence is available for a conclusion on how patients with an adequate response should be optimally treated during the maintenance period. A clear ranking of the available treatments is not yet possible.

PEGylated human serum albumin (HSA) nanoparticles: preparation, characterization and quantification of the PEGylation extent.

Modification with poly(ethylene glycol) (PEG) is a widely used method for the prolongation of plasma half-life of colloidal carrier systems such as nanoparticles prepared from human serum albumin (HSA). However, the quantification of the PEGylation extent is still challenging. Moreover, the influence of different PEG derivatives, which are commonly used for nanoparticle conjugation, has not been investigated so far. The objective of the present study is to develop a method for the quantification of PEG and to monitor the influence of diverse PEG reagents on the amount of PEG linked to the surface of HSA nanoparticles. A size exclusion chromatography method with refractive index detection was established which enabled the quantification of unreacted PEG in the supernatant. The achieved results were confirmed using a fluorescent PEG derivative, which was detected by photometry and fluorimetry. Additionally, PEGylated HSA nanoparticles were enzymatically digested and the linked amount of fluorescently active PEG was directly determined. All the analytical methods confirmed that under optimized PEGylation conditions a PEGylation efficiency of up to 0.5 mg PEG per mg nanoparticle could be achieved. Model calculations made a 'brush' conformation of the PEG chains on the particle surface very likely. By incubating the nanoparticles with fetal bovine serum the reduced adsorption of serum proteins on PEGylated HSA nanoparticles compared to non-PEGylated HSA nanoparticles was demonstrated using sodium dodecylsulfate polyacrylamide gel electrophoresis. Finally, the positive effect of PEGylation on plasma half-life was demonstrated in an in vivo study in mice. Compared to unmodified nanoparticles the PEGylation led to a four times larger plasma half-life.

Evidence- and consensus-based (S3) Guidelines for the Treatment of Actinic Keratosis - International League of Dermatological Societies in cooperation with the European Dermatology Forum - Short version.

BACKGROUND: Actinic keratosis (AK) is a frequent health condition attributable to chronic exposure to ultraviolet radiation. Several treatment options are available and evidence based guidelines are missing. OBJECTIVES: The goal of these evidence- and consensus-based guidelines was the development of treatment recommendations appropriate for different subgroups of patients presenting with AK. A secondary aim of these guidelines was the implementation of knowledge relating to the clinical background of AK, including consensus-based recommendations for the histopathological definition, diagnosis and the assessment of patients. METHODS: The guidelines development followed a pre-defined and structured process. For the underlying systematic literature review of interventions for AK, the methodology suggested by the Cochrane Handbook for Systematic Reviews of Interventions, the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement and Grading of Recommendations Assessment, Development and Evaluation (GRADE) methodology was adapted. All recommendations were consented during a consensus conference using a formal consensus methodology. Strength of recommendations was expressed based on the GRADE approach. If expert opinion without external evidence was incorporated into the reasoning for making a certain recommendation, the rationale was provided. The Guidelines underwent open public review and approval by the commissioning societies. RESULTS: Various interventions for the treatment of AK have been assessed for their efficacy. The consenting procedure led to a treatment algorithm as shown in the guidelines document. Based on expert consensus, the present guidelines present recommendations on the classification of patients, diagnosis and histopathological definition of AK. Details on the methods and results of the systematic literature review and guideline development process have been published separately. CONCLUSIONS: International guidelines are intended to be adapted to national or regional circumstances (regulatory approval, availability and reimbursement of treatments).

[Sarcopenia and frailty in neurology]. / Sarkopenie und Frailty in der Neurologie.

Sarcopenia and frailty are common geriatric syndromes and are associated with adverse health outcome and impaired health-related quality of life. Co-occurrences of these two syndromes with age-related neurological diseases are potentially high but not well investigated. Moreover, it is not well understood how these syndromes interact with neurological diseases, such as Parkinson's disease, Alzheimer's disease and stroke. This article introduces the currently most accepted concepts of sarcopenia and frailty, discusses the potential relevance of the syndromes for geriatric patients and presents examples of studies that investigated potential interactions between these geriatric and neurological syndromes and conditions. First results indicate that (i) the co-occurrence of these geriatric syndromes and age-related neurological diseases is high, (ii) sarcopenia and frailty can influence the clinical state of neurological diseases to a relevant extent and (iii) at least some common causes and pathophysiological processes confer the geriatric and neurological conditions. In conclusion, profound knowledge about the interaction of sarcopenia, frailty and age-associated neurological conditions is currently not available. Such knowledge would have an enormous potential for improved therapy of these neurological conditions.

Systematic review on the rapidity of the onset of action of topical treatments in the therapy of mild-to-moderate acne vulgaris.

The time until a patient achieves a relevant improvement during the treatment of a skin disease is important for selecting a therapy, but has been largely neglected in reviews and guidelines. The aim of this systematic review was to determine the time until the onset of action (TOA) of topical acne treatments. The primary outcome was the TOA defined as the time until a 25% reduction in the mean number of inflammatory lesions had been achieved. A systematic literature search in Medline and Embase was carried out. Clinical trials that evaluated head-to-head comparisons of treatments in patients suffering from mild-to-moderate papulopustular acne were included. Abstract and full-text screening and data extraction were done independently by two investigators. With respect to inflammatory lesions, different concentrations of benzoyl peroxide (BPO) or adapalene did not seem to influence the TOA. BPO seemed to act more quickly than isotretinoin and tretinoin. Adapalene showed a shorter TOA than isotretinoin. Conflicting results were seen when comparing adapalene with tretinoin, with a tendency for adapalene to be faster. Clindamycin/BPO seemed to act more quickly than adapalene. Inconsistent results were seen for the comparison of clindamycin/BPO and BPO alone with a slight indication of a shorter TOA for clindamycin/BPO. Adapalene/BPO and clindamycin/BPO showed comparable TOA. When interpreting the data, the different study designs and the limited study quality need to be taken into account. Further research is needed to identify treatments that offer an early onset of action and possibly help to optimize patients' adherence. TOA should be considered as an additional outcome in acne trials.