Ravulizumab facilitates reduced burden of vascular access, a major benefit in paediatric atypical haemolytic uraemic syndrome.

BACKGROUND: Atypical haemolytic uraemic syndrome (aHUS) is a rare thrombotic microangiopathy resulting from dysregulation of the alternative complement pathway, leading to multi-organ dysfunction and chronic kidney disease. Eculizumab is an anti-C5 monoclonal antibody therapy that has significantly improved aHUS disease control and patient outcomes, however it requires fortnightly intravenous dosing. This often necessitates long term central access and a high hospital attendance burden. Ravulizumab is a novel, next-generation anti-C5 monoclonal antibody engineered from eculizumab to reduce endosomal degradation of the antibody, increasing the dosing interval up to 8 weeks. CASE SERIES: In this retrospective case series we present the transition of three children with aHUS from eculizumab to ravulizumab from a single tertiary paediatric nephrology service. All patients underwent genomic and immunological work up for aHUS, with no cause found. After stabilisation with eculizumab, two patients developed macrovascular thrombotic complications associated with indwelling central vascular catheters, ultimately leading to central access failure. All patients were transitioned from eculizumab to ravulizumab without relapse of aHUS. One patient successfully underwent deceased donor kidney transplantation with ravulizumab for complement inhibition. All patients have transitioned to peripheral access for infusions given the reduced frequency of dosing, maintaining good control of aHUS for 2-4 years. CONCLUSION: Ravulizumab permits sufficiently reduced frequency of infusion to allow for administration by peripheral cannulation - removing the risks of long term central vascular access often required to deliver eculizumab to paediatric patients.

Large historical growth in global terrestrial gross primary production.

Growth in terrestrial gross primary production (GPP)-the amount of carbon dioxide that is 'fixed' into organic material through the photosynthesis of land plants-may provide a negative feedback for climate change. It remains uncertain, however, to what extent biogeochemical processes can suppress global GPP growth. As a consequence, modelling estimates of terrestrial carbon storage, and of feedbacks between the carbon cycle and climate, remain poorly constrained. Here we present a global, measurement-based estimate of GPP growth during the twentieth century that is based on long-term atmospheric carbonyl sulfide (COS) records, derived from ice-core, firn and ambient air samples. We interpret these records using a model that simulates changes in COS concentration according to changes in its sources and sinks-including a large sink that is related to GPP. We find that the observation-based COS record is most consistent with simulations of climate and the carbon cycle that assume large GPP growth during the twentieth century (31% ± 5% growth; mean ± 95% confidence interval). Although this COS analysis does not directly constrain models of future GPP growth, it does provide a global-scale benchmark for historical carbon-cycle simulations.

Use of primary health care services and mortality in older patients with type 2 diabetes with or without comorbidities.

OBJECTIVE: This study aimed to examine primary health care (PHC) service utilization and mortality in older patients with type 2 diabetes (T2D) with or without comorbidities. DESIGN AND SETTING: A cohort study in PHC in the city of Vantaa, Finland. Follow-up period was set between the years 2011 and 2018. SUBJECTS: PHC patients aged 60 years or more with a T2D were included. MAIN OUTCOME MEASURES: Service utilization was defined as the number of face-to-face appointments and telephone contacts between a patient and general practitioner (GP) or nurse. The presence of comorbidities was defined using the Charlson Comorbidity Index (CCI). Mortality was assessed using hazard ratio (HR) and standardized mortality ratio (SMR). RESULTS: In total, 11,020 patients were included and followed for 71,596 person years. Mean age of the women and men in the beginning of follow-up were 71 and 69 years, respectively. The patients in the study cohort had a mean of eight appointments per person year to the GPs or nurses. Patients with T2D with comorbidities had more appointments than patients with T2D without comorbidities (incidence rate ratio (IRR) 1.44 [95% CI 1.39-1.49]). Increase in the number of all appointments reduced mortality in patients with T2D with and without comorbidities. Between patients with T2D with comorbidities and patients with T2D without comorbidities, the age and sex adjusted HR for death was 1.50 (95% CI 1.39-1.62). The SMR was higher in patients with T2D with comorbidities (1.83 [95% CI 1.74-1.92]) than in patients with T2D without comorbidities (0.91 [95% CI 0.86-0.96]). CONCLUSIONS: In older patients with T2D, the presence of comorbidities was associated with increased use of PHC services and increased mortality. Increase in the number of appointments was associated with reduced mortality in patients with T2D with or without comorbidities.Key PointsIn older patients with T2D, it has not been studied whether and to what extend multimorbidity affects use of PHC services and mortality.The presence of comorbidities according to the Charlson Comorbidity Index (CCI) was associated with increased use of PHC services.The number of appointments to GPs or nurses was associated with reduced mortality in patients with T2D with or without comorbidities according to the CCI.

Spatiotemporal analysis of lake chlorophyll-a with combined in situ and satellite data.

We estimated chlorophyll-a (Chl-a) concentration using various combinations of routine sampling, automatic station measurements, and MERIS satellite images. Our study site was the northern part of the large, shallow, mesotrophic Lake Pyhäjärvi located in southwestern Finland. Various combinations of measurements were interpolated spatiotemporally using a data fusion system (DFS) based on an ensemble Kalman filter and smoother algorithms. The estimated concentrations together with corresponding 68% confidence intervals are presented as time series at routine sampling and automated stations, as maps and as mean values over the EU Water Framework Directive monitoring period, to evaluate the efficiency of various monitoring methods. The mean Chl-a calculated with DFS in June-September was 6.5-7.5 µg/l, depending on the observations used as input. At the routine monitoring station where grab samples were used, the average uncertainty (standard deviation, SD) decreased from 2.7 to 1.6 µg/l when EO data were also included in the estimation. At the automatic station, located 0.9 km from the routine monitoring site, the SD was 0.7 µg/l. The SD of spatial mean concentration decreased from 6.7 to 2.9 µg/l when satellite observations were included in June-September, in addition to in situ monitoring data. This demonstrates the high value of the information derived from satellite observations. The conclusion is that the confidence of Chl-a monitoring could be increased by deploying spatially extensive measurements in the form of satellite imaging or transects conducted with flow-through sensors installed on a boat and spatiotemporal interpolation of the multisource data.

[Non-surgical peri-implantitis treatment with or without systemic antibiotics]. / Initiële behandeling van peri-implantitis met of zonder systemische antibiotica.

This study investigated the effect of initial nonsurgical treatment in patients with peri-implantitis with or without prescription of an antibiotic regimen consisting of amoxicillin and metronidazole. For this purpose, patients with peri-implantitis were randomized into a group of initial treatment with antibiotics and a group without antibiotics. They were re-evaluated 12 weeks after treatment. Analyses were performed at the patient level at 1 peri-implant pocket per patient. Both groups showed significant peri-implant pocket depth reductions after initial treatment. Treatment with antibiotics resulted in a higher mean reduction in peri-implant pocket depth than when no antibiotics were used, but this difference did not reach statistical significance. Only 2 implants, 1 in each group, showed a successful outcome of a peri-implant pocket depth ofunder ≤ 5 mm and with an absence of bleeding and pus after probing. Initial treatment with or without antibiotics is ultimately not sufficient to fully treat peri-implantitis; additional surgical procedures will often be required.

Pneumococcal IgG Antibody Responses to 23vPPV in Healthy Controls Using an Automated ELISA.

Measurement of pre- and post-pneumococcal antibody levels after immunization with the 23-valent capsular polysaccharide pneumococcal vaccine (23vPPV) is indicative of a T-independent antibody response. The World Health Organisation ELISA is considered gold standard yet is labor-intensive and technically difficult to perform. Interpretation criteria defining an adequate response to 23vPPV remain controversial. The diagnostic Immunology Laboratory at The Royal Children's Hospital, Melbourne (RCH), performs an in-house multi-serotype automated ELISA. The primary objective of this study was to verify RCH interpretation criteria for the laboratory's automated ELISA. Forty pneumococcal conjugate vaccine (PCV)-naïve healthy adults aged 18 to 25 years and 22 PCV-primed healthy children aged 2 to 5 years were immunized with 23vPPV. A serum sample was collected immediately prior and 28 to 42 (± 7) days post immunization. Samples were analyzed on the Tecan Freedom Evo 200 ELISA with adequate response defined as post-immunization antibody level of 1.3 µg/mL or fourfold rise from baseline in ≥ 10/15 serotypes in adult participants and ≥ 4/8 serotypes in pediatric participants. Thirty-nine (97.5%) adults and 22 (100%) children achieved an adequate response to 23vPPV. In PCV-naïve adults, serotypes contained within the conjugate vaccines were less immunogenic, with 12 (30%) adults not achieving an adequate antibody response when only PCV serotypes were used for interpretation. Our diagnostic laboratory has verified the interpretation criteria used for an automated multi-serotype pneumococcal ELISA method. Clinical Trial Registration: ANZCTR registration number ACTRN12618000822280.

[Periodontitis - infection or inflammation?] / Parodontitis; infectie of ontsteking?

Periodontitis is a complex, multifactorial disease. Multiple factors such as (epi)genetic factors, environmental factors (microbial biofilm), lifestyle (smoking, stress) and general health (diabetes mellitus) contribute to the development of periodontitis. A healthy subgingival microbiome is in balance with its host, is very stable and diverse, and keeps the host healthy. Changes, such as declining oral hygiene, lead to changes in the microbial composition in the subgingival sulcus: anaerobic and protein-degrading microorganisms with pro-inflammatory properties increase in number and disturb the proportions, leading in turn to changes in the subgingival environment and an increase in pro-inflammatory microorganisms. If the first line of the immune system is unable to restore subgingival equilibrium, microorganisms and their products invade the periodontal soft tissues, resulting in activation of osteoclasts and, ultimately, in the destruction of the periodontium and the onset of periodontitis.

Survey of microbes in industrial-scale second-generation bioethanol production for better process knowledge and operation.

The microbes present in bioethanol production processes have been previously studied in laboratory-scale experiments, but there is a lack of information on full-scale industrial processes. In this study, the microbial communities of three industrial bioethanol production processes were characterized using several methods. The samples originated from second-generation bioethanol plants that produce fuel ethanol from biowaste, food industry side streams, or sawdust. Amplicon sequencing targeting bacteria, archaea, and fungi was used to explore the microbes present in biofuel production and anaerobic digestion of wastewater and sludge. Biofilm-forming lactic acid bacteria and wild yeasts were identified in fermentation samples of a full-scale plant that uses biowaste as feedstock. During the 20-month monitoring period, the anaerobic digester adapted to the bioethanol process waste with a shift in methanogen profile indicating acclimatization to high concentrations of ammonia. Amplicon sequencing does not specifically target living microbes. The same is true for indirect parameters, such as low pH, metabolites, or genes of lactic acid bacteria. Since rapid identification of living microbes would be indispensable for process management, a commercial method was tested that detects them by measuring the rRNA of selected microbial groups. Small-scale testing indicated that the method gives results comparable with plate counts and microscopic counting, especially for bacterial quantification. The applicability of the method was verified in an industrial bioethanol plant, inspecting the clean-in-place process quality and detecting viability during yeast separation. The results supported it as a fast and promising tool for monitoring microbes throughout industrial bioethanol processes.

[The relation between halitosis and saliva]. / De relatie tussen halitose en speeksel.

Halitosis (bad breath) is caused by a number of volatiles originating, in most cases, in the oral cavity (intra-oral halitosis). These unpleasant smelling gases are volatile sulphur compounds such as hydrogen sulphide, methyl mercaptan and dimethyl sulphide secreted as a result of bacterial metabolism. Bacteria on the tongue dorsum, as well as oral pathologies such as gingivitis and periodontitis, are the main causes of intra-oral halitosis. Saliva has a number of functions that can affect intra-oral halitosis, such as mechanical cleaning, moistening of the oral cavity and antibacterial properties. Very low secretion of saliva (hyposalivation) can affect intra-oral halitosis.

[Saliva testing in the daily practice]. / Speekselonderzoek in de dagelijkse praktijk.

Saliva is a very multifaceted fluid with many different functions and it plays an essential role in oral health. With an aging population, dental professionals will increasingly be confronted with patients with reduced saliva secretion (hyposalivation) or dry mouth (xerostomia). Clinical symptoms as a result of dry mouth vary from mild to severe damage to the hard and soft tissues. Therefore it is important to establish whether a patient is suffering from hyposalivation and if so, whether the patient is able to activate the saliva secretion. Based on saliva testing, hyposalivation and dry mouth can be diagnosed in the general dental practice and be taken into account in prevention and treatment plans.

Impact of maternal income on the risk of gestational diabetes mellitus in primiparous women.

AIMS: Findings concerning the impact of socio-economic status on the risk of gestational diabetes mellitus (GDM) are inconclusive and little is known about the simultaneous impact of income and educational attainment on the risk of GDM. This study aims to assess the impact of maternal prepregnancy income in combination with traditional GDM risk factors on the incidence of GDM in primiparous women. METHODS: This is an observational cohort study including 5962 Finnish women aged ≥ 20 years from the city of Vantaa, Finland, who delivered for the first time between 2009 and 2015, excluding women with pre-existing diabetes mellitus. The Finnish Medical Birth Register, Finnish Tax Administration, Statistics Finland, Social Insurance Institution of Finland and patient healthcare records provided data for the study. We divided the study population according to five maternal income levels and four educational attainment levels. RESULTS: Incidence of GDM decreased with increasing income level in primiparous women (P < 0.001 for linearity, adjusted for smoking, age, BMI and cohabiting status). In an adjusted two-way model, the relationship was significant for both income (P = 0.007) and education (P = 0.039), but there was no interaction between income and education (P = 0.52). CONCLUSIONS: There was an inverse relationship between both maternal prepregnancy taxable income and educational attainment, and the risk of GDM in primiparous Finnish women.

[Periodontitis and proteases. Hardly a closed case]. / Parodontitis en proteasen? Geen uitgemaakte zaak.

During periodontal inflammation, a multitude of substances both from the host and of microbiological origin are released into the gingival crevicular fluid (GCV) and saliva. These substances, such as proteins and peptides, can therefore be regarded as biomarkers of the inflammatory process. With the help of sensitive and advanced laboratory technologies, the role of these biomarkers has been identified. However, the high costs, complexity and difficulty of interpretation of the results often hinder the introduction of biomarkers for diagnostic purposes in the dental practice. Certain salivary enzymes, proteases, can function as biomarkers and have interesting properties for producing rapid chairside diagnoses, because the presence of a protease or proteolytic activity can be demonstrated in a simple and rapid biochemical way, for example by colour signalling. Since other processes in the oral cavity influence the results of the test, such tests are especially useful as one element in a broader oral diagnostic investigation.

Short primiparous women are at an increased risk for gestational diabetes mellitus.

OBJECTIVES: Both short stature and adiposity are risk factors for gestational diabetes mellitus (GDM). The aim of this study was to simultaneously evaluate the importance of stature and degree of adiposity on development of GDM in primiparous women. STUDY DESIGN: Longitudinal cohort study. METHODS: In the city of Vantaa, Finland, between 2009 and 2015, all together 7750 primiparous women without previously diagnosed diabetes mellitus gave birth. Of these, 5223 women were ≥18 years of age with information on height, weight, and complete data from a 75 g 2-h oral glucose tolerance test composing the study participants of this study. RESULTS: A 155-cm tall woman with a body mass index (BMI) of 25.5 kg/m2 had a similar risk for GDM as a 175-cm tall woman with a BMI of 27.1 kg/m2. Women shorter than 159 cm had the highest prevalence of GDM, 28.7%, whereas women with height between 164 and 167 cm had the lowest prevalence of GDM, 19.9% (P < 0.001). Height was inversely and significantly associated with both 1- and 2-h glucose values (both P < 0.001). CONCLUSIONS: To avoid over diagnosis of GDM, an unbiased strategy is needed to determine and diagnose GDM in women with different stature and degree of adiposity.

Mobility and muscle strength in male former elite endurance and power athletes aged 66-91 years.

The aim of this cross-sectional study was to compare mobility and muscle strength in male former elite endurance and power athletes aged 66-91 years (n = 150; 50 men in both former elite athlete groups and in their control group). Agility, dynamic balance, walking speed, chair stand, self-rated balance confidence (ABC-scale), jumping height, and handgrip strength were assessed. Former elite power athletes had better agility performance time than the controls (age- and body mass index, BMI-adjusted mean difference -3.6 s; 95% CI -6.3, -0.8). Adjustment for current leisure time physical activity (LTPA) and prevalence of diseases made this difference non-significant (P = 0.214). The subjects in the power sports group jumped higher than the men in the control group (age- and BMI-adjusted mean differences for vertical squat jump, VSJ 4.4 cm; 95% CI 2.0, 6.8; for countermovement jump, CMJ 4.0 cm; 95% CI 1.7, 6.4). Taking current LTPA and chronic diseases for adjusting process did not improve explorative power of the model. No significant differences between the groups were found in the performances evaluating dynamic balance, walking speed, chair stand, ABC-scale, or handgrip strength. In conclusion, power athletes among the aged former elite sportsmen had greater explosive force production in their lower extremities than the men in the control group.

[Preventive dentistry 7. Getting rid of halitosis]. / Preventieve tandheelkunde 7. Halitose de mond uit helpen.

Halitosis or bad breath is a problem that affects many people and its source is generally found in the oral cavity (intra-oral halitosis). Bacteria in the oral cavity produce volatile sulphur compounds such as hydrogen sulphide and methyl mercaptan that not only emit an unpleasant odour, but may also have toxic effects on the periodontal tissues. Good oral hygiene, a healthy periodontium and healthy teeth are the basis for the prevention of intra-oral halitosis and dentists and dental hygienists therefore play an essential role in its prevention.

Population-based study of ruptured abdominal aortic aneurysm.

BACKGROUND: The incidence of abdominal aortic aneurysms (AAAs) and their rupture has been reported to be decreasing. The aim was to evaluate trends in ruptured AAA (rAAA) incidence in the hospital district of Helsinki and Uusimaa (HUS) in southern Finland. This was a population-based retrospective review of all patients with rAAA in this well defined geographical area during 2003-2013. METHODS: Data for all patients treated for rAAA at Helsinki University Hospital, the only vascular surgery centre in an area of 1·5 million inhabitants, were collected from local vascular registry. All deaths attributed to rAAA were obtained from the cause of death registry of Statistics Finland. RESULTS: The mean(s.d.) age of the 712 patients with rAAA was 76·5(9·6) years; 76·7 per cent of them were men. Only 330 patients (46·3 per cent of those with rAAA) arrived alive at Helsinki University Hospital. The turn-down rate for surgical treatment was 10·3 per cent. Of the 296 patients operated on, 199 (67·2 per cent) were alive at 30 days. Only 27·9 per cent of all patients were alive 30 days after rupture of the AAA. The incidence of rAAA was 4·3 per 100 000 inhabitants and the mortality rate was 3·2 per 100 000 inhabitants. A decreasing trend was seen in incidence and mortality during the 11-year study interval. CONCLUSION: The incidence of rAAA is decreasing in the HUS district. Mortality from rAAA remains very high, because half of the patients die before reaching the hospital.

Rupture of Abdominal Aortic Aneurysms in Patients Under Screening Age and Elective Repair Threshold.

OBJECTIVES: The objective of this study was to identify the proportion of abdominal aortic aneurysm ruptures that occur before the screening age or threshold diameter for operative repair is reached. METHODS: The study was a retrospective analysis of RAAA patients including all RAAA patients admitted to Helsinki (HUH) and Tampere University Hospitals (TaUH) during 2002-2013. The data for age, gender, and comorbidities were collected from vascular registry and patient records. Computed tomography images taken at the time of admission were used for the measurement of maximum anteroposterior (AP) aneurysm diameter at the time of rupture. Age and diameter data were compared with risk factors. RESULTS: A total of 585 patients diagnosed with RAAA were admitted to the two hospitals during the 12 year period. The mean age at the time of rupture was 73.6 years (SD 9.5, range 42-96 years). 18.3% of patients were under 65: 21.4% of men and 3.0% of women. Men were on average 8 years younger than women. The odds ratio (OR) for rupture before 65 years of age for smokers was 2.1 compared with non-smokers, and 28.4% of smokers were under 65 at the time of rupture. Of all RAAA patients, 327 had a computed tomography scan confirming rupture. The mean AP diameter of the aneurysm was 75.6 mm (SD 15.8, range 32-155 mm). The mean size was significantly lower in women than in men (70.5 vs. 76.8, p = .005). CONCLUSIONS: The data from this study show that a fifth of men would not make it to the screening age of 65 before AAA rupture, the proportion being even larger in active smokers. The data from this study also supports the previous finding that aneurysm size at the time of rupture is significantly smaller in women.

Former male elite athletes have better metabolic health in late life than their controls.

Elite-class athletes have longer life expectancy and lower risk for chronic noncommunicable diseases possibly because of physically active and healthier lifestyle. In this study, we assessed former male Finnish elite-class athletes' (n = 392) and their matched controls' (n = 207) body composition, and risk for the metabolic syndrome (MS) and nonalcoholic fatty liver disease (NAFLD) in later life. Compared with the controls, the former athletes had lower body fat percentage (24.8% vs 26.0%, P = 0.021), lower risk for MS [odds ratio (OR) 0.57, 95% confidence interval (CI) 0.40-0.81], and NAFLD (OR 0.61, 95% CI 0.42-0.88). High volume of current leisure-time physical activity (LTPA) was associated with lower body fat percentage (P for trend < 0.001). When current volume of LTPA increased 1 MET h/week, the risk of MS and NAFLD decreased (OR 0.99, 95% CI 0.98-0.99 and OR 0.97, 95% CI 0.96-0.98, respectively). Although a career as an elite-class athlete during young adulthood may help to protect from developing metabolic syndrome, present exercise levels and volume of LTPA seem equally important as well.

Peripheral nervous system involvement in primary burning mouth syndrome--results of a pilot study.

OBJECTIVE: The pathophysiology of primary burning mouth syndrome (BMS) has remained enigmatic, but recent studies suggest pathology within the nervous system at multiple levels. This study aimed to investigate in detail the contribution of either focal or generalized alterations within the peripheral nervous system (PNS) in the etiopathogenesis of BMS. SUBJECTS AND METHODS: Intraepithelial nerve fiber density (IENFD) of tongue mucosa was assessed in 10 carefully characterized BMS, and the results were compared to 19 age- and gender-matched cadaver controls, 6 with lifetime diabetes. Extensive neurophysiologic and psychophysical examinations of the trigeminal system and distal extremities were performed to profile PNS function in BMS. RESULTS: Patients with BMS had significantly fewer intraepithelial nerve fibers (0,27, s.e. 0,18 mm(-1); P = 0.0253) than non-diabetic controls (0,92, s.e. 0,15 mm(-1)). In the subepithelial space, the amount of nerve fibers did not differ between the groups. The majority (9/10) of patients with BMS showed neurophysiologic or psychophysical signs of a more generalized PNS dysfunction. CONCLUSIONS: Our results in neurophysiologically optimally characterized BMS patients confirm that pure focal small fiber neuropathy of the oral mucosa has a role in the pathophysiology of primary BMS. Furthermore, BMS may be related to a more generalized, yet subclinical peripheral neuropathy.