Utilization of renal function and iron status laboratory test investigations in Eastern Health

Introduction: Healthcare spending in Canada reached 219.1 billion dollars in 2015. Unnecessary laboratory test investigations have been well documented in many countries, making it an area of interest in order to reduce costs, improve care and ultimately improve the performance of the health care system. The use of serum urea is unnecessary to evaluate kidney function in stable patients as serum creatinine has better specificity and no decrease in sensitivity. Therefore, we examined the use of serum urea in the community of a regional health authority. Ferritin is a good test of iron status and indicated in anemic patients, particularly when mean corpuscular volume/mean corpuscular hemoglobin levels are low. Therefore, we examined the use of iron status tests in the community to determine the degree of under-utilization in the patients likely to have iron deficient anemia and of over-utilization in patients with normal hemoglobin and blood indices. Methods: We performed a retrospective analysis of Eastern Health’s laboratory electronic database to investigate patterns of laboratory test utilization for two specific bundles of tests: (1) serum creatinine and serum urea; (2) hemoglobin (hgB), ferritin and iron saturation. Laboratory tests were examined for a 6-month period in 2014 (bundle 1) and a 12-month period (bundle 2) throughout 2013-2014. Test utilization is described by age, sex, patient type (inpatient/outpatient), submitting physician specialty and test result. Results: 227, 092 serum creatinine and 218, 289 serum urea tests were ordered for all patients within the Eastern Health Region during the 6-month period. 96.8 % (n=211, 279) serum urea tests were ordered in the same draw as serum creatinine. 64.6% (n=141,112) serum urea tests were ordered in the same draw as serum creatinine for outpatients. General practitioners elicited the highest rate of serum urea tests (52.5% of total), followed by the internal medicine specialty. 69.3% (n=62, 274) of coupled serum creatinine and serum urea laboratory investigations ordered by general practitioners for outpatients elicited normal results for both tests. High volumes of hemoglobin (n=450, 792) and iron status tests (ferritin; n=86,293, iron saturation; n=23,415) were ordered within the 12-month period. General practitioners elicited the highest ordering for all three tests for outpatients. 89.6% (n=55,595) of iron tests requested by general practitioners for nonanemic outpatients (first Hgb) produced a normal result in the 12-month period. 44.9% (n=136) of females (≤ 50 years of age) with anemia did not undergo iron testing within 1-year of the first documentation of the anemia by a general practitioner. Conclusion: Serum urea and iron testing may be areas of interest for the improvement of utilization of health care resources within the Eastern Health Region. Information contained in this thesis may be used as a guiding tool for decision makers in the development of interventions to improve test-ordering behaviours without compromising patient quality of care

Chalk cliff retreat in East Sussex and Kent 1870s to 2001

The retreat of chalk cliffs fringing the eastern English Channel contributes shingle to the beaches which helps to protect the cliffs and slow down erosion. Conversely, cliff retreat endangers settlements and infrastructure on the clifftop. Rates of retreat have been calculated by a variety of methods over the past century, but no attempt has been made to provide a complete coverage that allows for a true comparison of retreat rates over the entire coastline. Using historic maps and recent orthophotos, cliff retreat rates have been calculated for consecutive 50 m sections of chalk cliff along the English side of the entire eastern English Channel for a period of 125 years. The chalk cliffs of East Sussex erode at an average rate of 0.25 - 0.3 m y−1 while those in Kent at a rate of 0.1 m y−1

Pharmacological interventions for primary sclerosing cholangitis: an attempted network meta-analysis.

BACKGROUND: Primary sclerosing cholangitis is a chronic cholestatic liver disease that is associated with both hepatobiliary and colorectal malignancies, which can result in liver cirrhosis and its complications. The optimal pharmacological treatment for patients with primary sclerosing cholangitis remains controversial. OBJECTIVES: To assess the comparative benefits and harms of different pharmacological interventions in people with primary sclerosing cholangitis by performing a network meta-analysis, and to generate rankings of available pharmacological interventions according to their safety and efficacy. Given that it was not possible to assess whether potential effect modifiers were similar across comparisons, we did not perform the network meta-analysis but instead used standard Cochrane methods.When trials begin to provide an adequate description of potential effect modifiers, we will attempt to conduct network meta-analysis. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, Science Citation Index - Expanded, the WHO International Clinical Trials Registry Platform, and randomised controlled trials registers until February 2017 to identify randomised clinical trials (RCT) on pharmacological interventions for primary sclerosing cholangitis. SELECTION CRITERIA: We included only RCTs, irrespective of language, blinding, or publication status, in which participants were given a diagnosis of primary sclerosing cholangitis. We excluded trials that included previously liver-transplanted participants. We considered any of various pharmacological interventions compared with one other or with placebo. We excluded trials that compared different doses of various pharmacological interventions or that reported different treatment durations, except for ursodeoxycholic acid (UDCA). As UDCA is the drug most commonly investigated for primary sclerosing cholangitis, we performed a second analysis in which we stratified the dose of UDCA. DATA COLLECTION AND ANALYSIS: We calculated the odds ratio and the rate ratio with 95% confidence intervals (CIs) using both fixed-effect and random-effects models based on available-participant analysis with Review Manager. We assessed risk of bias according to Cochrane, controlled risk of random errors with Trial Sequential Analysis, and assessed the quality of the evidence using GRADE. MAIN RESULTS: We identified 22 RCTs in which 1211 participants were randomised to 13 different interventions. Most were placebo-controlled trials. Trials had few restrictions apart from an established diagnosis of primary sclerosing cholangitis, evidence of cholestasis, absence of decompensated liver disease, and absence of malignancy. However, some trials included symptomatic participants only, and others included both symptomatic and asymptomatic participants. A total of 11 RCTs (706 participants) provided data for one or more outcomes. The period of follow-up ranged from three months to three years in most trials. Only three trials reported follow-up longer than three years. Investigators found no evidence of differences in important clinical benefits such as reduction in mortality at maximal follow-up and improvement in health-related quality of life. Primary outcomes Mortality: Effect estimates: colchicine versus placebo: odds ratio 0.44, 95% CI 0.04 to 5.07, participants = 84, one trial; penicillamine versus placebo: odds ratio 1.18, 95% CI 0.39 to 3.58, participants = 70, one trial; steroids versus placebo: odds ratio 3.00, 95% CI 0.10 to 90.96, participants = 11, one trial; ursodeoxycholic acid versus placebo: odds ratio 1.51, 95% CI 0.63 to 3.63, participants = 348, two trials, I2 = 0%; vancomycin versus placebo: not estimable because no events in either group, participants = 29, one trial. Serious adverse events (proportion): Effect estimates: infliximab versus placebo: odds ratio not estimable (because of zero events in both arms), participants = 7, one trial; steroids versus placebo: odds ratio 20.00, 95% CI 0.93 to 429.90, participants = 11, one trial; vancomycin versus placebo: not estimable because no events in either group, participants = 29, one trial. Serious adverse events (number): Effect estimates: infliximab versus placebo: rate ratio 0.80, 95% CI 0.02 to 40.44, participants = 7, one trial; penicillamine versus placebo: rate ratio 13.60, 95% CI 0.78 to 237.83, participants = 70, one trial; steroids versus placebo: rate ratio 3.32, 95% CI 0.71 to 15.62, participants = 11, one trial. Adverse events (proportion): Effect estimates: steroids versus placebo: odds ratio 20.00, 95% CI 0.93 to 429.90, participants = 11, one trial; ursodeoxycholic acid versus placebo: odds ratio 1.22, 95% CI 0.68 to 2.17, participants = 198, one trial; vancomycin versus placebo: not estimable because no events in either group, participants = 29, one trial. Adverse events (number): Effect estimates: cyclosporin versus placebo: rate ratio 2.64, 95% CI 0.99 to 7.03, participants = 26, one trial; steroids versus placebo: rate ratio 3.32, 95% CI 0.71 to 15.62, participants = 11, one trial; ursodeoxycholic acid plus metronidazole versus ursodeoxycholic acid: rate ratio 2.36, 95% CI 0.98 to 5.71, participants = 71, one trial. Health-related quality of life: ursodeoxycholic acid versus placebo: mean difference 1.30, 95% CI -5.61 to 8.21, participants = 198, one trial (Short Form (SF)-36 General Health Scale). Secondary outcomes Studies provided no evidence of differences in clinical benefits such as a reduction in the requirement for liver transplantation or a reduction in the incidence proportion of cholangiocarcinoma. One small trial (29 participants) comparing vancomycin versus placebo reported no malignancies, no liver decompensation, and no liver transplantation in either group after a very short follow-up period of 12 weeks after treatment. None of the remaining trials clearly reported other clinical benefits such as decreased development of all malignancies, colorectal cancer, liver decompensation, time to liver decompensation, time to liver transplantation, or requirement for cholecystectomy to allow comparisons between different interventions. SOURCE OF FUNDING: Fifteen trials reported the source of funding; three were funded by parties without vested interest in results of the trial, and 12 were funded in part or in full by drug companies. AUTHORS' CONCLUSIONS: Evidence is currently insufficient to show differences in effectiveness measures such as mortality, health-related quality of life, cirrhosis, or liver transplantation between any active pharmacological intervention and no intervention. However, trials were at high risk of bias and included small numbers of participants, had short follow-up periods, and reported few clinical outcomes. An urgent need exists to identify an effective medical treatment for primary sclerosing cholangitis through well-designed RCTs with adequate follow-up that aim to identify differences in outcomes important to people with primary sclerosing cholangitis

Biochemical and molecular diagnosis of mitochondrial respiratory chain disorders

AbstractBiochemical diagnosis of mitochondrial respiratory chain disorders requires caution to avoid misdiagnosis of secondary enzyme defects, and can be improved by the use of conservative diagnostic criteria. Pathogenic mutations causing mitochondrial disorders have now been identified in more than 30 mitochondrial DNA (mtDNA) genes encoding respiratory chain subunits, ribosomal- and t-RNAs. mtDNA mutations appear to be responsible for most adult patients with mitochondrial disease and approximately a quarter of paediatric patients. A family history suggesting maternal inheritance is the exception rather than the norm for children with mtDNA mutations, many of whom have de novo mutations. Prenatal diagnosis and pre-implantation genetic diagnosis can be offered to some women at risk of transmitting a mtDNA mutation, particularly those at lower recurrence risk. Mutations in more than 30 nuclear genes, including those encoding for respiratory chain subunits and assembly factors, have now been shown to cause mitochondrial disorders, creating difficulties in prioritising which genes should be studied by mutation analysis in individual patients. A number of approaches offer promise to guide the choice of candidate genes, including Blue Native-PAGE immunoblotting and microarray expression analysis

Identification of H2_2CCC as a diffuse interstellar band carrier

We present strong evidence that the broad, diffuse interstellar bands (DIBs) at 4881 and 5450\,\AA are caused by the B\,^1B$_1$\,$\leftarrow$\,X\,^1A$_1$ transition of H$_2$CCC (l-C$_3$H$_2$). The large widths of the bands are due to the short lifetime of the B\,^1B$_1$ electronic state. The bands are predicted from absorption measurements in a neon matrix and observed by cavity ring-down in the gas phase and show exact matches to the profiles and wavelengths of the two broad DIBs. The strength of the 5450\,\AA DIB leads to a l-C$_3$H$_2$ column density of $\sim5\times10^{14}$ cm$^{-2}$ towards HD\,183143 and $\sim2\times10^{14}$\,cm$^{-2}$ to HD\,206267. Despite similar values of $E$($B-V$), the 4881 and 5450\,\AA DIBs in HD\,204827 are less than one third their strength in HD\,183143, while the column density of interstellar C$_3$ is unusually high for HD\,204827 but undetectable for HD\,183143. This can be understood if C$_3$ has been depleted by hydrogenation to species such as l-C$_3$H$_2$ towards HD\,183143. There are also three rotationally resolved sets of triplets of l-C$_3$H$_2$ in the 6150$-$6330\,\AA region. Simulations, based on the derived spectroscopic constants and convolved with the expected instrumental and interstellar line broadening, show credible coincidences with sharp, weak DIBs for the two observable sets of triplets. The region of the third set is too obscured by the $\alpha$-band of telluric O$_2$.Comment: 22 pages, 9 figure