The incidence, prevalence and mortality of granulomatosis with polyangiitis in the UK Clinical Practice Research Datalink

Objectives: To estimate the incidence, prevalence and mortality of Granulomatosis with polyangiitis (GPA) in the United Kingdom. Methods: We conducted a historical cohort study using data from the Clinical Practice Research Datalink and Hospital Episode Statistics (CPRD-HES). We calculated incidence rate ratios, adjusted for age, gender and ethnicity, using Poisson regression. Results: We identified 462 cases diagnosed between 1997 and 2013. Our overall estimate of incidence was 11.8 (95% CI 10.7-12.9)/million person-years. Incidence in children (aged <16 years) was 0.88 (95% CI 0.40-1.96), and adults 14.0 (95% CI 12.8-15.4). The incidence was lower in females (adjusted IRR 0.68; 95% CI 0.56-0.81) and highest in the 55-69 year age-group (adjusted IRR 9.5, 95% CI 6.9-13.0; reference group 0-39 years). Incidence was not significantly different in the Black / Minority Ethnic population compared to the white population (adjusted odds ratio 0.78, 95% CI 0.53-1.13, p=0.13). The prevalence in 2013 was 134.9 (121.3-149.6) /million. Mortality was 13.6% at 1-year, and higher in HES than CPRD-identified cases (Hazard ratio 3.16, 95% CI 2.19-4.56, p<0.001). Conclusions: By combining primary and secondary care datasets we have found the incidence and mortality of granulomatosis with polyangiitis to be higher than previously reported. We predict that at present each year in the UK there will be approximately 700 new cases of whom 95 will die within 12 months

Re-thinking resuscitation: Leaving blood pressure cosmetics behind and moving forward to permissive hypotension and a tissue perfusion-based approach

Definitions of shock and resuscitation endpoints traditionally focus on blood pressures and cardiac output. This carries a high risk of overemphasizing systemic hemodynamics at the cost of tissue perfusion. In line with novel shock definitions and evidence of the lack of a correlation between macro- and microcirculation in shock, we recommend that macrocirculatory resuscitation endpoints, particularly arterial and central venous pressure as well as cardiac output, be reconsidered. In this viewpoint article, we propose a three-step approach of resuscitation endpoints in shock of all origins. This approach targets only a minimum individual and context-sensitive mean arterial blood pressure (for example, 45 to 50 mm Hg) to preserve heart and brain perfusion. Further resuscitation is exclusively guided by endpoints of tissue perfusion irrespectively of the presence of arterial hypotension ('permissive hypotension'). Finally, optimization of individual tissue (for example, renal) perfusion is targeted. Prospective clinical studies are necessary to confirm the postulated benefits of targeting these resuscitation endpoints

Effect of site of lactate infusion on regional lactate exchange in pigs

Background The rate of extra-hepatic lactate production and the route of influx of lactate to the liver may influence both hepatic and extra-hepatic lactate exchange. We assessed the dose-response of hepatic and extra-hepatic lactate exchange during portal and central venous lactate infusion. Methods Eighteen pigs randomly received either portal (n=5) or central venous (n=7) lactate infusion or saline (n=6). Sodium lactate was infused at 33, 66, 99, and 133 µmol kg−1 min−1 for 20 min each. Systemic and regional abdominal blood flows and plasma lactate were measured at 20 min intervals until 1 h post-infusion, and regional lactate exchange was calculated (area under lactate uptake-time curve). Results Total hepatic lactate uptake [median (95% confidence interval)] during the experimental protocol (140 min) was higher during portal [8198 (5487-12 798) µmol kg−1] than during central venous lactate infusion [4530 (3903-5514) µmol kg−1, P<0.05]. At a similar hepatic lactate delivery (∼400 µmol kg−1 min−1), hepatic lactate uptake [mean and standard deviation (sd)] was higher during portal [118 (sd 55) µmol kg−1 min−1] than during central venous lactate infusion [44 (12) µmol kg−1 min−1, P<0.05]. Time courses of arterial lactate concentrations and lactate uptake at other measured regions were similar in both groups. Conclusions Higher hepatic lactate uptake during portal compared with central venous lactate infusion at a similar total hepatic lactate influx underlines the role of portal vein lactate concentration in total hepatic lactate uptake capacity. Arterial lactate concentration does not depend on the site of lactate infusion. At higher arterial lactate concentrations, all regions participated in lactate uptak

Effects of bright light treatment on psychomotor speed in athletes

Purpose: A recent study suggests that transcranial brain targeted light treatment via ear canals may have physiological effects on brain function studied by functional magnetic resonance imaging (fMRI) techniques in humans. We tested the hypothesis that bright light treatment could improve psychomotor speed in professional ice hockey players. Methods: Psychomotor speed tests with audio and visual warning signals were administered to a Finnish National Ice Hockey League team before and after 24 days of transcranial bright light or sham treatment. The treatments were given during seasonal darkness in the Oulu region (latitude 65 degrees north) when the strain on the players was also very high (10 matches during 24 days). A daily 12-min dose of bright light or sham (n = 11 for both) treatment was given every morning between 8–12 am at home with a transcranial bright light device. Mean reaction time and motor time were analyzed separately for both psychomotor tests. Analysis of variance for repeated measures adjusted for age was performed. Results: Time x group interaction for motor time with a visual warning signal was p = 0.024 after adjustment for age. In Bonferroni post-hoc analysis, motor time with a visual warning signal decreased in the bright light treatment group from 127 ± 43 to 94 ± 26 ms (p = 0.024) but did not change significantly in the sham group 121 ± 23 vs. 110 ± 32 ms (p = 0.308). Reaction time with a visual signal did not change in either group. Reaction or motor time with an audio warning signal did not change in either the treatment or sham group. Conclusion: Psychomotor speed, particularly motor time with a visual warning signal, improves after transcranial bright light treatment in professional ice-hockey players during the competition season in the dark time of the year

Disease progression in Plasmodium knowlesi malaria is linked to variation in invasion gene family members.

Emerging pathogens undermine initiatives to control the global health impact of infectious diseases. Zoonotic malaria is no exception. Plasmodium knowlesi, a malaria parasite of Southeast Asian macaques, has entered the human population. P. knowlesi, like Plasmodium falciparum, can reach high parasitaemia in human infections, and the World Health Organization guidelines for severe malaria list hyperparasitaemia among the measures of severe malaria in both infections. Not all patients with P. knowlesi infections develop hyperparasitaemia, and it is important to determine why. Between isolate variability in erythrocyte invasion, efficiency seems key. Here we investigate the idea that particular alleles of two P. knowlesi erythrocyte invasion genes, P. knowlesi normocyte binding protein Pknbpxa and Pknbpxb, influence parasitaemia and human disease progression. Pknbpxa and Pknbpxb reference DNA sequences were generated from five geographically and temporally distinct P. knowlesi patient isolates. Polymorphic regions of each gene (approximately 800 bp) were identified by haplotyping 147 patient isolates at each locus. Parasitaemia in the study cohort was associated with markers of disease severity including liver and renal dysfunction, haemoglobin, platelets and lactate, (r = ≥ 0.34, p =  <0.0001 for all). Seventy-five and 51 Pknbpxa and Pknbpxb haplotypes were resolved in 138 (94%) and 134 (92%) patient isolates respectively. The haplotypes formed twelve Pknbpxa and two Pknbpxb allelic groups. Patients infected with parasites with particular Pknbpxa and Pknbpxb alleles within the groups had significantly higher parasitaemia and other markers of disease severity. Our study strongly suggests that P. knowlesi invasion gene variants contribute to parasite virulence. We focused on two invasion genes, and we anticipate that additional virulent loci will be identified in pathogen genome-wide studies. The multiple sustained entries of this diverse pathogen into the human population must give cause for concern to malaria elimination strategists in the Southeast Asian region

Dexmedetomidine versus propofol/midazolam for long-term sedation during mechanical ventilation

Purpose: To compare dexmedetomidine (DEX) with standard care (SC, either propofol or midazolam) for long-term sedation in terms of maintaining target sedation and length of intensive care unit (ICU) stay. Methods: A pilot, phase III, double-blind multicenter study in randomized medical and surgical patients (n=85) within the first 72h of ICU stay with an expected ICU stay of ≥48h and sedation need for ≥24h after randomization. Patients were assigned to either DEX (≤1.4μgkg−1h−1; n=41) or SC (n=44), with daily sedation stops. Results: Non-inferiority of DEX versus SC was not confirmed. Target Richmond agitation-sedation score (RASS) was reached a median of 64% (DEX) and 63% (SC) of the sedation time (ns). The length of ICU stay was similar in DEX and SC. Patients with RASS target 0-3 (DEX 78%, SC 80%) were at target sedation 74% (DEX) and 64% (SC) of the time (ns), whereas those with RASS target −4 or less reached the target 42% (DEX) and 62% (SC) of the time (P=.006). Post hoc analyses suggested shorter duration of mechanical ventilation for DEX (P=0.025). Conclusions: This pilot study suggests that in long-term sedation, DEX is comparable to SC in maintaining sedation targets of RASS 0 to −3 but not suitable for deep sedation (RASS −4 or less). DEX had no effect on length of ICU stay. Its effects on other relevant clinical outcomes, such as duration of mechanical ventilation, should be tested furthe

Penglibatan wanita yang mengikuti Technical Vocational Education and Training (TVET) dalam industri Oil & Gas

Persediaan wanita yang mengikuti TVET untuk menceburkan diri dalam industri oil & gas merupakan suatu masalah yang sering diperkatakan dikalangan wanita ketika ini. Permasalahan ini menjadi suatu persoalan dalam kalangan wanita tentang apakah persediaan yang perlu mereka lakukan dalam merencana kerjaya dalam industri oil & gas ini. Secara umumnya kajian ini adalah bertujuan mengenalpasti faktor-faktor yang mempengaruhi pemilihan kerja dalam industri oil & gas, kesediaan diri wanita dari segi fizikal dan mental serta cabaran yang dihadapi dalam merealisasikan kerjaya mereka dalam industri oil & gas ini. Kajian ini telah dilakukan ke atas pekerja wanita yang telah berkhidmat dalam industri ini bagi zon selatan dan zon tengah. Seramai 110 sampel kajian yang terlibat dalam penyelidikan ini melalui pengedaran borang kaji selidik sebagai instrumen kajian. Data daripada 86 sampel kajian yang diperolehi dari soal selidik kemudiannya dianalisis dengan menggunakan perisian Statistical Package for the Social Science (SPSS) versi 20.0. Hasil dapatan kajian menunjukkan faktor yang mempengaruhi wanita untuk menceburkan diri dalam industri oil & gas ini adalah faktor gaji iaitu skor min sebanyak 4.41 dan diikuti dengan kesediaan dari segi mental dengan nilai skor min pada tahap yang tinggi iaitu 4.392. Dapatan kajian juga mendapati cabaran semasa mendapatkan pekerjaan adalah perkara paling mencabar yang perlu dihadapi oleh wanita iaitu dengan dapatan skor min sebanyak 4.242. Ini membuktikan bahawa wanita perlu mempersiapkan diri dengan sebaiknya sebelum menceburi industri ini. Terdapat hubungan yang signifikan di antara faktor pemilihan kerja dan kesediaan diri wanita. Kesimpulannya, wanita perlu mempersiapkan diri bukan sekadar dengan memperolehi keputusan yang baik dalam akademik, tetapi kecenderungan dan minat dalam meletakkan diri untuk bersaing dengan lelaki bagi membuktikan wanita turut berkemahiran dan mempunyai jati diri yang tinggi untuk berkerja dalam bidang yang sungguh mencabar

Comparison of continuous and intermittent renal replacement therapy for acute renal failure

Background. Mortality rates of critically ill patients with acute renal failure (ARF) requiring renal replacement therapy (RRT) are high. Intermittent and continuous RRT are available for these patients on the intensive care units (ICUs). It is unknown which technique is superior with respect to patient outcome. Methods. We randomized 125 patients to treatment with either continuous venovenous haemodiafiltration (CVVHDF) or intermittent haemodialysis (IHD) from a total of 191 patients with ARF in a tertiary-care university hospital ICU. The primary end-point was ICU and in-hospital mortality, while recovery of renal function and hospital length of stay were secondary end-points. Results. During 30 months, no patient escaped randomization for medical reasons. Sixty-six patients were not randomized for non-medical reasons. Of the 125 randomized patients, 70 were treated with CVVHDF and 55 with IHD. The two groups were comparable at the start of RRT with respect to age (62±15 vs 62±15 years, CVVHDF vs IHD), gender (66 vs 73% male sex), number of failed organ systems (2.4±1.5 vs 2.5±1.6), Simplified Acute Physiology Scores (57±17 vs 58±23), septicaemia (43 vs 51%), shock (59 vs 58%) or previous surgery (53 vs 45%). Mortality rates in the hospital (47 vs 51%, CVVHDF vs IHD, P = 0.72) or in the ICU (34 vs 38%, P = 0.71) were independent of the technique of RRT applied. Hospital length of stay in the survivors was comparable in patients on CVVHDF [median (range) 20 (6-71) days, n = 36] and in those on IHD [30 (2-89) days, n = 27, P = 0.25]. The duration of RRT required was the same in both groups. Conclusion. The present investigation provides no evidence for a survival benefit of continuous vs intermittent RRT in ICU patients with AR