Teriparatide-associated calciphylaxis: a case series.

Calciphylaxis is a rare and potentially fatal small-vessel occlusive disease in which the tunica media becomes calcified, endothelial cells proliferate, and the tunica intima becomes thickened and fibrotic. Calciphylaxis typically occurs in the setting of end-stage renal disease with secondary hyperparathyroidism and elevated calcium-phosphorus product. The estimated incidence of calciphylaxis in dialysis or kidney transplant patients is 1 to 4%; however, the incidence of non-uremic calciphylaxis is unknown. We assessed postmarketing adverse event reports to further characterize cases of calciphylaxis associated with teriparatide. We searched for cases of teriparatide-associated calciphylaxis in the literature (EMBASE, PubMed) and those reported to FDA, including the FDA Adverse Event Reporting System, through March 31, 2021. We included calciphylaxis cases following teriparatide exposure of < 2 years. Twelve cases described teriparatide-associated calciphylaxis. The median age was 81 (range 47-86) years. Eleven cases reported confirmatory biopsy and/or imaging. The median time-to-onset of calciphylaxis following teriparatide initiation was 3.5 (range 1-20) months. Three cases reported hospitalization, of which one resulted in death due to progression of the lesions. All cases had multiple risk factors (mean (SD), 4.5 (1.0)) including concomitant medications associated with calciphylaxis (12), female sex (11), and/or underlying autoimmune disease or other inflammatory disorder (10). We believe that exposure to teriparatide, coupled with underlying risk factors, may have triggered new-onset calciphylaxis. Expedited diagnosis and management by a clinician are important because calciphylaxis may be life-threatening and early intervention may improve outcomes.

Total hip arthroplasty for femoral fractures other than capital physeal fractures in dogs: 14 cases (2012-2020).

OBJECTIVES: The goals of this retrospective study were to assess the clinical and radiographic outcomes in dogs with proximal femoral fractures, other than capital physeal fractures, treated via total hip arthroplasty. MATERIALS AND METHODS: Medical records as well as pre-operative, immediate post-operative and 2 to 3 months post-operative radiographs of 14 dogs with femoral head and neck fractures treated via total hip arthroplasty were reviewed. A Liverpool Osteoarthritis in Dogs questionnaire was completed by owners to assess long-term outcomes. RESULTS: Seven femoral head fractures, and seven femoral neck fractures were included. Four of the femoral head fractures were acute in nature, the three remaining femoral head fractures and all seven femoral neck fracture cases were chronic fractures. Malorientation of the femoral stem was more common in the chronic femoral fracture cases when compared to the acute femoral fracture cases. Two of the acute fracture cases and five chronic fracture cases experienced a change in femoral stem position post-operatively. One femoral fissure fracture occurred and was repaired intraoperatively. One case had a post-operative complication that resulted in implant removal. All dogs had good to excellent owner-perceived outcome. CLINICAL SIGNIFICANCE: Femoral head and neck fractures, and in particular the chronic cases, represented a challenging subset of cases presenting for total hip arthroplasty, resulting in suboptimal stem alignment in many cases. However, clinical outcomes were considered good to excellent in all dogs in the study, indicating that total hip arthroplasty is a viable treatment option for these types of fractures.

Generativity, hierarchical action and recursion in the technology of the Acheulean to Middle Palaeolithic transition: a perspective from Patpara, the Son Valley, India.

The Acheulean to Middle Palaeolithic transition is one of the most important technological changes that occurs over the course of human evolution. Here we examine stone artefact assemblages from Patpara and two other excavated sites in the Middle Son Valley, India, which show a mosaic of attributes associated with Acheulean and Middle Palaeolithic industries. The bifaces from these sites are very refined and generally small, but also highly variable in size. A strong relationship between flake scar density and biface size indicates extensive differential resharpening. There are relatively low proportions of bifaces at these sites, with more emphasis on small flake tools struck from recurrent Levallois cores. The eventual demise of large bifaces may be attributed to the curation of small prepared cores from which sharper, or more task-specific flakes were struck. Levallois technology appears to have arisen out of adapting aspects of handaxe knapping, including shaping of surfaces, the utilization of two inter-dependent surfaces, and the striking of invasive thinning flakes. The generativity, hierarchical organization of action, and recursion evident in recurrent Levallois technology may be attributed to improvements in working memory.

Asthma and ageing: an end user's perspective--the perception and problems with the management of asthma in the elderly.

Despite the high prevalence of asthma in the elderly, its development, diagnosis, and treatment are under-researched. This paper provides a comprehensive review of the current state of knowledge in relation to management of asthma in the elderly - focusing on barriers to diagnosis and treatment and the central role of self-management. Asthma prevalence increases with age, as does the risk of dying from asthma, and with the ageing of the population and increasing life expectancy, the prevalence of (diagnosed and undiagnosed) asthma in older adults is expected to increase drastically, placing an increasing burden on sufferers, the community and health budgets. Asthma sufferers are more likely to be psychologically distressed and at a higher risk of anxiety and depression, more likely to experience a sense of lack of control over their health and to have lower self-reported quality of life. Asthma is under-diagnosed, and under-treated, in the elderly, further exacerbating these negative consequences. The review concludes, among other things, that there is a need to better understand the development and impact of asthma in the elderly, to increase community awareness of asthma in the elderly, to improve both 'medical management' and 'self-management' in this population and to develop more effective tools for diagnosis and treatment of asthma in the elderly. The paper concludes with key recommendations for future research and practice in this area.

Simple ostectomy to address quadriceps impingement caused by distal femoral malunion in four dogs.

Four dogs were evaluated for chronic pelvic limb lameness. Radiographs revealed distal femoral malunion with caudo-proximal displacement, resulting in impingement of the quadriceps from the distal aspect of the proximal femoral segment. All dogs presented with femoral shortening and increased femoral procurvatum when compared with the normal contralateral femur. There was minimal angular or rotational misalignment. Treatment consisted of ostectomy of the fracture segment that was causing quadriceps impingement, with debridement of proliferative fracture callus proximal to the trochlear groove in all dogs. No attempt was made to address sagittal plane deformities. Long-term orthopaedic examination with objective gait analysis in three dogs revealed minimal to no lameness in two and mild residual lameness in one dog. Long-term radiographic analysis revealed fracture-site remodelling with an increase in femoral length and a return of near-normal femoral procurvatum in all dogs. Owner-assessed long-term outcome was excellent in all dogs.

Prevalence and nature of anaemia in a prospective, population-based sample of people with diabetes: Teesside anaemia in diabetes (TAD) study.

AIMS: Anaemia occurs in 25% of people attending hospital diabetes clinics, but this may not be representative of all people with diabetes. We aimed to determine the prevalence of anaemia in a prospective population-based sample stratified by estimated glomerular filtration rate (eGFR) using the 4-point Modification of Diet in Renal Disease (MDRD) formula. METHODS: All 7331 patients on our district register were stratified by eGFR. Seven hundred and thirty were approached by letter on two occasions. Two hundred and thirty-four (32%) returned questionnaires and blood samples. Responders (R), non-responders (NR) and the whole cohort (C) were similar: mean +/- sd age R 61.7 +/- 12.7 years; NR 61.3 +/- 15.1 years; C 61.8 +/- 14.2 years; diabetes duration R 8.8 +/- 8.6 years; NR 8.2 +/- 7.9 years; C 7.5 +/- 7.8 years, Type 1 diabetes R 10.1%, NR 10.8%, C 9.4%. Anaemia was defined using World Health Organization criteria: haemoglobin < 13 g/dl for men, < 12 g/dl for women. RESULTS: Previously undiagnosed anaemia was present in 15% of the whole group, 36% with eGFR < 60 ml/min per 1.73 m(2) and 9% of those with eGFR > 60 ml/min per 1.73 m(2). Anaemia was as a result of erythropoietin deficiency in 34%, abnormal haematinics in 40% and was unexplained in 26% of patients. Five per cent of the patients had anaemia below the treatment threshold of 11 g/dl. CONCLUSIONS: The prevalence of unrecognized anaemia in population-based cohorts is lower than that in hospital-based studies. Current clinical surveillance in the UK is failing to detect anaemia in stage 3-5 chronic kidney disease (eGFR < 60 ml/min per 1.73 m(2)) and current guidelines will not detect 9% of diabetic patients with anaemia and an eGFR > 60 ml/min per 1.73 m(2).

Development of an abbreviated symptom score for the neonatal abstinence syndrome.

OBJECTIVE: We sought a shortened MOTHER neonatal abstinence syndrome (NAS) and Finnegan score that would retain comparable performance characteristics of the full instrument. STUDY DESIGN: Retrospective cohort. RESULTS: In total, 124,170 MOTHER NAS scores between August 2007 and May 2016 from 775 infants (≥36 weeks) were examined. Classification and regression tree model identified the most important subsets of the scored variables. A 9-element shortened scale yielded >90% sensitivity and specificity to predict clinical endpoints based on the full 19-element MOTHER NAS score. Conversion of the data sets to the Finnegan score, and applying the same procedure resulted in a nine-element score with similar performance characteristics. CONCLUSION: Shortened scoring instruments were identified with the high-predictive power for clinical endpoints based on the 19-element full MOTHER NAS score. There was no substantial variation in performance for age, supporting the current practice of utilizing a single scoring tool regardless of postnatal age.

Guidelines for the development of social marketing programmes for sun protection among adolescents and young adults.

OBJECTIVES: To formulate 'best practice' guidelines for social marketing programmes for adolescents' and young adults' sun protection. STUDY DESIGN: A Delphi consensus process. METHODS: Eleven experts in sun protection and social marketing participated in a Delphi consensus process, where they were asked to provide up to 10 key points, based on their knowledge and practical experience, which they felt were most important in developing social marketing interventions for the primary prevention of skin cancer among adolescents and young adults. After reaching consensus, the evidence base for each guideline was determined and graded via the Scottish Intercollegiate Guideline Network grading system. Participants were then asked to indicate how strongly they rated the finalized 15 recommendations based on all aspects relating to their knowledge and practical opinion, as well as the research evidence, on a visual analogue scale. RESULTS: The resultant 15 guidelines offer general principles for sun protection interventions utilizing a social marketing approach. CONCLUSIONS: This method of guideline development brought the expertise of practitioners to the forefront of guideline development, whilst still utilizing established methods of evidence confirmation. It thus offers a useful method for guideline development in a public health context.

Multiplex PCR that can distinguish between immunologically cross- reactive serovar 3, 6, and 8 Actinobacillus pleuropneumoniae strains.

We describe a highly sensitive and specific multiplex PCR, based on capsular loci and the species specific apxIV gene, that unequivocally differentiates serovar 3, 6, and 8 Actinobacillus pleuropneumoniae strains that are cross-reactive in conventional immunological tests.

PCR specific for Actinobacillus pleuropneumoniae serotype 3.

Serotypes 3 and 8 of Actinobacillus pleuropneumoniae, the aetiological agent of porcine pleuropneumonia, have been reported to predominate in the UK. Direct serotyping of isolates of the organism is typically determined by the immunological reactivity of rabbit serum to its surface polysaccharides, but the method has limitations, for example, cross-reactions between serotypes 3, 6 and 8. This study describes the development of a serotype 3-specific pcr, based on the capsule locus, which can be used in a multiplex format with the organism's specific gene apxIV. The pcr test was evaluated on 266 strains of A pleuropneumoniae and 121 strains of other organisms, including all the major respiratory bacterial pathogens of pigs. The test was highly specific and sensitive and should be useful for differentiating strains of serotypes 3, 6 and 8, and in seroprevalence and epidemiological surveys in regions where serotype 3 is prevalent, such as the UK.

Push-pull analysis of photonic Doppler velocimetry measurements.

A robust analysis method is presented for multiple-phase heterodyne velocimetry measurements. By combining information from three phase-shifted signals, it is possible to eliminate coherent intensity variations and incoherent light from the measurement. The three data signals are reduced to a pair of quadrature signals, allowing unambiguous calculation of target displacement. The analysis relies on a minimum number of adjustable parameters, and these parameters can be precisely determined from simple interferometer characterization.

Kinetic independence between red cell anion exchange and urea transport.

Urea equilibrium exchange fluxes were measured in human red cells under conditions which recruit the anion transporter into an outward-facing or an inward-facing state (with respect to the anion transport site). Regardless of these conditions, urea transport always occurred at the same rate: 41 +/- 2 mol.(kg cell solids.min)-1 with 1.5 M urea at 0 degrees C. These data suggest that the pathway on the band-3 protein which mediates anion transport is kinetically uncoupled from urea transport and is probably not involved in the transport of urea across the red cell membrane.

Liver disease knowledge and acceptability of non-invasive liver fibrosis assessment among people who inject drugs in the drug and alcohol setting: The LiveRLife Study.

BACKGROUND: The aim of this study was to assess factors associated with baseline knowledge of HCV and liver disease, acceptability of transient elastography (TE) assessment (FibroScan(®)), and willingness and intent to receive HCV treatment among persons with a history of injection drug use participating in a liver health promotion campaign. METHODS: The LiveRLife campaign involved three phases: (1) campaign resource development; (2) campaign resource testing; and (3) campaign implementation. Participants were enrolled in an observational cohort study with recruitment at four clinics - one primary health care facility, two OST clinics, and one medically supervised injecting centre - in Australia between May and October 2014. Participants received educational material, nurse clinical assessment, TE assessment, dried blood spot testing, and completed a knowledge survey. RESULTS: Of 253 participants (mean age 43 years), 68% were male, 71% had injected in the past month, and 75% self-reported as HCV positive. Median knowledge score was 16/23. In adjusted analysis, less than daily injection (AOR 5.01; 95% CI, 2.64-9.51) and no daily injection in the past month (AOR 3.54; 95% CI, 1.80-6.94) were associated with high knowledge (≥16). TE was the most preferred method both pre- (66%) and post-TE (89%) compared to liver biopsy and blood sample. Eighty-eight percent were 'definitely willing' or 'somewhat willing' to receive HCV treatment, and 56% intended to start treatment in the next 12 months. Approximately 68% had no/mild fibrosis (F0/F1, ≥2.5 to ≤7.4kPa), 13% moderate fibrosis (F2, ≥7.5 to ≤9.4kPa), 10% severe fibrosis (F3, ≥9.5 to ≤12.4kPa), and 9% had cirrhosis (F4, ≥12.5kPa). CONCLUSION: Liver disease and HCV knowledge was moderate. High acceptability of TE by PWID provides strong evidence for the inclusion of TE in HCV-related care, and could help to prioritise HCV treatment for those at greatest risk of liver disease progression.

Bone mineralization and turnover in preterm infants at 8-12 years of age: the effect of early diet.

Our previous studies raised two hypotheses: first that suboptimal early nutrition and second that human milk have enhancing effects on long-term bone mineralization. To test these hypotheses experimentally, we measured whole body and regional bone mineral content (BMC) and bone mineral density (BMD), using dual-energy X-ray absorptiometry and single-photon absorptiometry, and bone turnover at 8-12 years in 244 preterm children (128 boys) who participated in a prospective randomized study of diet during the neonatal period. Dietary randomizations studied were: banked human milk (BBM, n = 87) versus preterm formula (PTF, n = 96) as the sole diet or as a supplement to mother's expressed breast milk (EBM); PTF (n = 25) versus term formula (TF, n = 36) as sole diet. Ninety-five term children of the same age were also studied. First, preterm children were shorter and lighter than term children (height SD scores -0.49 (1.1) vs. +0.22 (0.9), weight SD scores -0.41 (1.2) vs. +0.38 (1.0)) and had significantly lower whole-body BMC than their peers; decrements were also evident at some regional sites. These differences disappeared after adjusting for bone area, body size, and pubertal status. Second, children previously randomized to BBM versus PTF or TF versus PTF showed no significant differences in anthropometry, BMC, BMD, or osteocalcin (OC). Third, there was no independent effect of the proportion of EBM on BMC, BMD, or OC and no interaction between randomized diet and the amount of EBM received. Fourth, plasma OC was significantly higher in preterm children than in term children (12.4 vs. 11.0 ng/ml, p < 0.005) and in preterm children who had received a low-nutrient (BBM/TF) as opposed to a high-nutrient diet (PTF) during the neonatal period (12. 9 vs. 11.9 ng/ml, p = 0.03). In conclusion, preterm children are shorter, lighter, and have lower bone mass than their peers at age 8-12 years. The lower BMC is, however, appropriate for the bone and body size achieved. Despite large differences in early mineral intake, early diet does not affect bone mass in preterm children, and fresh human milk has no specific effect. However, poor nutrition during the neonatal period may result in higher bone formation rates during childhood.

Evaluation of a double-tracer autoradiographic technique for the measurement of both local cerebral glucose metabolism and local cerebral blood flow.

A solvent washout technique is evaluated that could be used to remove one 14C tracer after a combined autoradiographic CMRglu and CBF study using [14C]2-deoxyglucose (2DG) and [14C]iodoantipyrine (IAP). The technique permits the simultaneous measurement of local CBF and local CMRglu in the same animal without the use of the short-lived tracers of iodine, 123I and 131I, for iodoantipyrine labeling. This report shows that brain tissue sections did not retain 14C from [14C]2DG when chloroform was used as the washout solvent. Chloroform washing removes nearly all the 14C from [14C]IAP. For this study, careful attention was given to the control, prewash measurement of 14C concentration.

Cerebral blood flow with the indicator fractionation of [14C]iodoantipyrine: effect of PaCO2 on cerebral venous appearance time.

The indicator fractionation technique using a diffusible indicator as a tracer for the determination of CBF has been used for numerous investigations of the cerebral circulation and its pathophysiology. The diffusible tracer is "trapped" in the brain based on the proper delay between tracer injection and cessation of the cerebral circulation by decapitation before the appearance of the tracer in the cerebral venous circulation. If this delay is too long, the quantitative assumption of the indicator fractionation technique will not be met, and CBF values will be underestimated. In 13 Sprague-Dawley rats anesthetized with pentobarbital, the appearance of [14C]iodoantipyrine at the torcular was assessed as a function of PaCO2. An inverse linear relationship between PaCO2 (in millimeters of mercury) and cerebral venous appearance, Ta (in seconds), was established with the regression equation Ta = -0.0842.PaCO2 + 12.3 (R2 = 0.70, slope significantly different from zero, p less than 0.001). Ta varied between 5 and 12 s and PaCO2 varied between 84 and 18 mm Hg, respectively. Thus, in low-flow states, the decapitation time may be lengthened to 12 s, whereas in high-flow states, the time must be 5 s to eliminate the possibility of backflux of tracer out of the brain.

Validation of continuous thermal measurement of cerebral blood flow by arterial pressure change.

A thermal measurement system to monitor cerebral blood flow (CBF) continuously from the cortical surface is evaluated in vivo. It has a temperature resolution of better than 0.001 degrees C (1 m degrees C) and can compensate for baseline temperature fluctuations in the brain tissue. A new approach has been developed to test the capability of monitoring dynamic CBF response. Transient CBF changes associated with changes in mean arterial blood pressure (MABP) caused by repeated bolus norepinephrine injections are used to examine the response of the measurement system in both the heated mode, sensitive to flow, and the unheated mode, sensitive only to temperature. Experiments on 13 rats demonstrate that changes in the MABP are closely correlated with those of temperature difference in the heated mode. Regression analysis shows a mean slope of 0.9 m degrees C/mm Hg in the heated mode, which is significantly different from zero (p < 0.002) and from the mean slope in the unheated mode (p < 0.002). This indicates that flow signal in the system output can be distinguished from the baseline thermal fluctuations. Thus, the system can be used to detect and study dynamic perfusion changes from the brain surface with minimal tissue damage. Furthermore, analysis of the data shows that the transient flow signal before autoregulation is linearly correlated with changes in MABP.

Effect of iodoacetate on local cerebral blood flow and glucose metabolism in cats: a double-radionuclide autoradiographic study.

The effect of iodoacetate (IAA), an inhibitor of glycolysis, on local CBF (LCBF) and local CMRglu (LCMRglu) was studied in cats by means of a double-radionuclide autoradiographic method. Artificial CSF containing 5 mM IAA was superfused on the left parietal cortex under a cranial window for 30 min. [14C]2-Deoxyglucose and [123I]iodoantipyrine were injected for the determination of LCMRglu and LCBF, respectively. A marked increase in LCBF, accompanied by a moderate to severe depression of LCMRglu, was observed in the IAA-superfused cortex. This result suggests that LCBF may be closely regulated by the cellular energy state associated with glycolytic activity in brain tissue.

Use of 2-deoxy-D[1-11C]glucose for the determination of local cerebral glucose metabolism in humans: variation within and between subjects.

The deoxyglucose technique for the measurement of local cerebral glucose metabolism (LCMRgl) has been widely applied in animals utilizing 14C-deoxyglucose and in humans employing 18F-fluorodeoxyglucose. Repeat studies in humans over a relatively brief period of time have not been possible because of the 110-min half-life of fluorine-18. With the synthesis of 11C-deoxyglucose it has now become possible to utilize this short-lived (20 min) tracer for the measurement of LCMRgl and to determine its variability within subjects over a 2-h period. The kinetic rate constants for 11C-deoxyglucose were determined for gray and white matter and found to be very similar to those for 18F-fluorodeoxyglucose, suggesting that these two analogues of glucose have similar affinities for the facilitated transport system and are similar substrates for hexokinase in the brain. The coefficient of variation of repeated measurements of LCMRgl in a series of six normal subjects was 5.5% to 8.7% for various gray matter structures and 9.7% and 14.0% for white matter structures. The pattern of cerebral metabolic rates is relatively constant in a given individual when the conditions of the study are unchanged. The ability to make repeat measurements in the same subject reduces the variance due to between-subject differences, allowing smaller changes in LCMRgl to be detected with confidence.