Mapping end-of-life and anticipatory medications in palliative care patients using a longitudinal general practice database.

OBJECTIVE: End-of-life and anticipatory medications (AMs) have been widely used in various health care settings for people approaching end-of-life. Lack of access to medications at times of need may result in unnecessary hospital admissions and increased patient and family distress in managing palliative care at home. The study aimed to map the use of end-of-life and AM in a cohort of palliative care patients through the use of the Population Level Analysis and Reporting Data Space and to discuss the results through stakeholder consultation of the relevant organizations. METHODS: A retrospective observational cohort study of 799 palliative care patients in 25 Australian general practice health records with a palliative care referral was undertaken over a period of 10 years. This was followed by stakeholders' consultation with palliative care nurse practitioners and general practitioners who have palliative care patients. RESULTS: End-of-life and AM prescribing have been increasing over the recent years. Only a small percentage (13.5%) of palliative care patients received medications through general practice. Stakeholders' consultation on AM prescribing showed that there is confusion about identifying patients needing medications for end-of-life and mixed knowledge about palliative care referral pathways. SIGNIFICANCE OF RESULTS: Improved knowledge and information around referral pathways enabling access to palliative care services for general practice patients and their caregivers are needed. Similarly, the increased utility of screening tools to identify patients with palliative care needs may be useful for health care practitioners to ensure timely care is provided.

Evening dosing versus morning dosing of antihypertensive medications for nocturnal hypertension: a systematic review and meta-analysis of 107 randomized controlled trials.

Since the effects of once-daily antihypertensive (HT) medications are more pronounced within the first few hours of ingestion, evening administration of anti-HT medications can be a feasible treatment for nocturnal HT. However, no relevant meta-analysis has been conducted in patients with nocturnal HT. This meta-analysis included randomized controlled trials involving patients with elevated mean nocturnal blood pressure (BP) and compared evening anti-HT administration with morning administration. Multiple databases, including grey literature (e.g. clincialtrial.gov), were searched. Study selection and data extraction were conducted by two independent authors. Risk of bias assessment and overall quality of evidence were conducted using Cochrane risk-of-bias tool and GRADE by two independent authors. A total of 107 studies were included, 76 of which were investigated in China and had not been identified in previous reviews. Only one trial was ranked low risk-of-bias. Evening administration of anti-HT medications was effective in reducing nocturnal systolic BP (4.12-9.10 mmHg; I2 = 80.5-95.2%) and diastolic BP (3.38-5.87 mmHg; I2 = 87.4-95.6%). Subgroup analyses found that the effectiveness of evening administration was contributed by data from the Hermida group and China. Evening administration did not provide additional nocturnal/daytime/24-h BP reduction in non-Hermida/non-China studies (I2 = 0) and in meta-analyses that included studies with unclear or low risk of bias. The effectiveness of nocturnal BP reduction was similar across different types, doses, and half-lives of medications. Evening administration of anti-HT medications may reduce proteinuria, left ventricular hypertrophy (LVH), nondipping and morning surge. The overall quality of evidence was ranked as very low to low. Our results highlight the scarcity of low risk-of-bias studies and emphasize the need for such trials to evaluate the efficacy of evening dosing of anti-HT medications as a standard treatment for patients with nocturnal HT across diverse populations.

APSIC dental infection prevention and control (IPC) guidelines.

BACKGROUND: The Asia Pacific Society of Infection Control launched the Infection Prevention and Control Guidelines in July 2022. This document describes the guidelines and recommendations for safe practices in dental setting. It aims to highlight practical recommendations in a concise format designed to assist dental facilities at Asia Pacific region in achieving high standards in infection prevention and control practices, staff and patient safety. METHOD: The guidelines were developed by an appointed workgroup comprising experts in the Asia Pacific region, following reviews of previously published international guidelines and recommendations relevant to each section. RESULTS: It recommends standard precautions as a minimal set of preventive measures to protect staff and prevent cross transmission. Surgical aseptic technique is recommended when procedures are technically complex and longer in duration. Only trained staff are eligible to conduct reprocessing of dental instruments. The design, layout of the dental facility are important factors for successful infection prevention. The facility should also have a Pandemic Preparedness Plan. CONCLUSIONS: Dental facilities should aim for excellence in infection prevention and control practices as this is part of patient safety. The guidelines that come with a checklist help dental facilities to identify gaps for improvement to reach this goal.

Static compressive tracking.

This paper presents the Static Computational Optical Undersampled Tracker (SCOUT), an architecture for compressive motion tracking systems. The architecture uses compressive sensing techniques to track moving targets at significantly higher resolution than the detector array, allowing for low cost, low weight design and a significant reduction in data storage and bandwidth requirements. Using two amplitude masks and a standard focal plane array, the system captures many projections simultaneously, avoiding the need for time-sequential measurements of a single scene. Scenes with few moving targets on static backgrounds have frame differences that can be reconstructed using sparse signal reconstruction techniques in order to track moving targets. Simulations demonstrate theoretical performance and help to inform the choice of design parameters. We use the coherence parameter of the system matrix as an efficient predictor of reconstruction error to avoid performing computationally intensive reconstructions over the entire design space. An experimental SCOUT system demonstrates excellent reconstruction performance with 16X compression tracking movers on scenes with zero and nonzero backgrounds.

Relation between polymorphisms of receptor for advanced glycation end products (RAGE) and cardiovascular diseases in Chinese patients with diabetic nephropathy.

BACKGROUND: Interaction of receptor for advanced glycation end products (RAGE) with advanced glycation end products (AGEs) is an important pathogenic mechanism of diabetic complications. Three mutations in the promoter region of the RAGE gene (T-429C, T-374A and a 63 bp deletion spanning from -407 to -345 nucleotides) were known to have increased transcriptional activities. We investigated the relationship between these polymorphisms and the risk of cardiovascular diseases in Chinese subjects with overt diabetic nephropathy. METHODS: A total of 219 Type 2 diabetic subjects with nephropathy were recruited. Genotyping of the three polymorphisms in the genomic DNA was done by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Patients were followed for 8 years for the development of cardiovascular events and survival. RESULTS: The T-429 C and T-374 A polymorphism had no effect on the event-free survival of the subjects. For the 63 bp deletion polymorphism, the event-free survival was 37.0% and 63.2% at 96 months for del-/- and del-/+ genotypes, respectively (log-rank test, p = 0.034). After adjusting for confounders, the 63 bp deletion polymorphism had a marginal effect on event-free survival (adjusted hazard ratio: 3.517, 95% CI: 0.852 - 14.521, p = 0.082). Subjects without any mutation of the three polymorphisms have significantly higher risk of first ischemic heart disease than those with any of the three mutations (adjusted hazard ratio: 0.218, 95% CI: 0.062 - 0.764, p = 0.017). CONCLUSION: The 63 bp del-/+ genotype of the RAGE gene has a marginal benefit on the cardiovascular event-free survival in subjects with diabetic nephropathy. Subjects with any of the three mutations have a lower risk of ischemic heart disease. The role of RAGE in the pathogenesis of cardiovascular disease in diabetic patients requires further study.

Relationship between carnosinase gene CNDP1 leucine repeat polymorphism and the clinical outcome of Chinese PD patients.

BACKGROUND: pre-clinical studies showed that carnosine may have a beneficial cardiovascular effect. We studied the effect of tri-nucleotide repeat (CTGs) polymorphisms in exon 2 of the CNDP1 gene, which codes for carnosinase and is responsible for the degradation of carnosine, on the clinical outcome of Chinese peritoneal dialysis (PD) patients. METHODS: we studied 442 PD subjects. Genotyping was done by direct sequencing of genomic DNA. Patients were followed for 43.5 ± 16.2 months. RESULTS: the prevalence of 6-6, 5-6, 5-5 and 4-6 CTGs genotypes was 80.3%, 18.6%, 0.9% and 0.2%, respectively. A total of 270 patients (61.1%) developed the primary composite end point during follow-up. The 5-year event-free survival of the 6-6 CTGs and non 6-6 group was 37.1% and 21.3%, respectively (log rank test, p = 0.3). CONCLUSION: the CTGs polymorphism of the CNDP1 gene does not affect survival of Chinese PD subjects. The role of carnosine and CNDP1 gene polymorphism in the pathogenesis of cardiovascular disease requires further study.

The Gcs1 and Age2 ArfGAP proteins provide overlapping essential function for transport from the yeast trans-Golgi network.

Many intracellular vesicle transport pathways involve GTP hydrolysis by the ADP-ribosylation factor (ARF) type of monomeric G proteins, under the control of ArfGAP proteins. Here we show that the structurally related yeast proteins Gcs1 and Age2 form an essential ArfGAP pair that provides overlapping function for TGN transport. Mutant cells lacking the Age2 and Gcs1 proteins cease proliferation, accumulate membranous structures resembling Berkeley bodies, and are unable to properly process and localize the vacuolar hydrolase carboxypeptidase (CPY) and the vacuolar membrane protein alkaline phosphatase (ALP), which are transported from the TGN to the vacuole by distinct transport routes. Immunofluorescence studies localizing the proteins ALP, Kex2 (a TGN resident protein), and Vps10 (the CPY receptor for transport from the TGN to the vacuole) suggest that inadequate function of this ArfGAP pair leads to a fragmentation of TGN, with effects on secretion and endosomal transport. Our results demonstrate that the Gcs1 + Age2 ArfGAP pair provides overlapping function for transport from the TGN, and also indicate that multiple activities at the TGN can be maintained with the aid of a single ArfGAP.

Crystal structure of hemolin: a horseshoe shape with implications for homophilic adhesion.

Hemolin, an insect immunoglobulin superfamily member, is a lipopolysaccharide-binding immune protein induced during bacterial infection. The 3.1 angstrom crystal structure reveals a bound phosphate and patches of positive charge, which may represent the lipopolysaccharide binding site, and a new and unexpected arrangement of four immunoglobulin-like domains forming a horseshoe. Sequence analysis and analytical ultracentrifugation suggest that the domain arrangement is a feature of the L1 family of neural cell adhesion molecules related to hemolin. These results are relevant to interpretation of human L1 mutations in neurological diseases and suggest a domain swapping model for how L1 family proteins mediate homophilic adhesion.

Life-threatening perineal sepsis after rubber band ligation of haemorrhoids.

Rubber band ligation is a widely performed procedure in the outpatient setting for symptomatic haemorrhoids. This method is generally considered to be safe and easily performed. However, there have been reports of severe sepsis following interventions for haemorrhoids and the majority of patients had undergone rubber band ligation. We present a patient who had undergone elective rubber band ligation of haemorrhoids who presented with severe anal pain with difficulty in micturition. She deteriorated rapidly over a period of 3 days and succumbed to fulminant perineal sepsis.

The use of meiofauna as an indicator of benthic organic enrichment associated with salmonid aquaculture.

Sediment chemistry and meiofaunal samples were collected in the Broughton Archipelago, British Columbia, to examine the relationship between sediment variables and meiofauna diversity across near- and far-field gradients surrounding several finfish aquaculture operations. The sediment variables examined consisted of free sulfide concentrations, redox potential (E(NHE)), organic content, and sediment grain size. A strong trend between sediment texture and organic content was observed across all sampling locations, which reflected a wide range of sediment types (sand-silt) that exist within the Broughton Archipelago. The abundance of certain meiofaunal groups (kinorhynchs, crustaceans, polychaetes) declined in an asymptotic fashion with increasing free sulfide concentrations, an indicator of benthic organic enrichment. Within these relationships, low meiofaunal abundances occurred in fine sediments associated with higher organic contents. Although other groups (nematodes, foraminifera) showed a slight decline in abundance with increasing organic enrichment, a high amount of variability in abundance was observed at high free sulfide concentrations, rendering these groups not suitable as indicators of organic enrichment. This study reports both horizontal and vertical trends in meiofaunal distributions relative to free sulfide concentrations. The abundance of nematode and crustacean taxa decreased with sediment depth as well as increasing sulfide concentration, while polycheate abundance increased with increasing free sulfide concentration. The ratio of nematodes to copepods was also shown to represent the degree of organic loading associated with aquaculture operations and its application as an indicator of benthic impact is discussed.

Immunomodulatory effects of a traditional Chinese medicine with potential antiviral activity: a self-control study.

Traditional Chinese medicine (TCM) has been used for prevention and treatment of severe acute respiratory syndrome (SARS) in Hong Kong during the outbreak in spring 2003. We investigated the immunomodulating effects of an innovative TCM regimen derived from two herbal formulas (Sang Ju Yin and Yu Ping Feng San) for treating febrile diseases. Thirty-seven healthy volunteers were given the oral TCM regimen daily for 14 days. Peripheral venous blood samples were taken on days 0, 15 and 29 for hematology, biochemistry and immunology tests, including the measurement of blood lymphocyte subsets and plasma T-helper lymphocyte types 1 and 2 cytokines and receptor. After 3 months, 23 of the volunteers participated in a control study without TCM treatment for the same time course of blood tests. Two volunteers withdrew on day 2, due to headache and dizziness. All others remained well without any side effects. No participants showed significant changes in their blood test results, except that the T-lymphocyte CD4/CD8 ratio increased significantly from 1.31 +/- 0.50 (mean +/- SD) on day 0 to 1.41 +/- 0.63 on day 15 (p < 0.02), and reduced to 1.32 +/- 0.47 on day 29 (p < 0.05). In the control study, there were no changes in the CD4/CD8 ratio. The transient increase in CD4/CD8 ratio was likely due to the TCM intake. We postulate that the administration of the innovative TCM may have beneficial immunomodulatory effects for preventing viral infections including SARS.

Intramedullary spinal cord metastases from small cell carcinoma of the lung.

Four patients with intramedullary spinal cord metastases from small cell carcinoma of the lung (SCCL) are described, with emphasis on clinical presentation and treatment. All patients developed the Brown-Séquard syndrome due to intramedullary tumor in the cervical spinal cord, three within 2 mo after combined modality treatment using chemotherapy and radiotherapy. One patient presented with a Brown-Séquard syndrome and an extradural spinal cord compression from tumor. The radiological and cerebrospinal fluid findings are presented and discussed. Radiation treatment was administered to the involved segments of spinal cord in each patient. All patients responded; two for 3 and 7 mo, two for 3 and 4 wk, respectively. There was significant improvement in the quality of life for three of the four patients.

Conformation and restricted segmental flexibility of C1, the first component of human complement.

Seventy selected images of chemically crosslinked C1 are analyzed to illustrate structural details of the C1qC1r2C1s2 complex. From inspection of these images, the C1r2C1s2 tetramer can be seen to be located in the region of the C1q arms, cleanly separated from the C1q heads and from at least 90%, if not all, of the C1q stem. From measurements made upon 65 images, the semicone angles formed between the spreading arms and the symmetry axis passing through the stem of C1 may be calculated. Unlike C1q, for which a wide variety of angles is found, the C1 complex appears to possess a restricted range of angular flexibility with an average value of about 50 degrees. The volume inside the cone formed by the spreading arms of C1q is too small to contain the entire C1r2C1s2 tetramer; at least some of the tetramer must lie outside the cone when it is bound to C1q to form C1. From our knowledge of the sizes and structures of its subunits, and from symmetry considerations, a model is proposed for the configuration of the C1 complex in which the middle portion of the C1r2C1s2 tetramer is centrally located among the arms close to the stem of the C1q and with the two protruding ends of the tetramer wrapped around the outside of the cone. Functional implications of this more rigid structure are discussed with relevance to C1q-induced aggregation of latex beads and C1-induced disaggregation.

A simple method for the analysis of urinary sucralose for use in tests of intestinal permeability.

BACKGROUND: Sucralose is a unique disaccharide probe which is stable in the colon and can be used to assess permeability over the whole gut. Additional information can be gained when sucralose is administered in combination with lactulose and a monosaccharide such as L-rhamnose in the form of a 'triple sugar test.' We describe a simple assay for urinary sucralose by HPLC with refractive index detection (HPLC-RI). METHODS: Phenyl-beta-D-glucopyranoside (internal standard) was added to 10 mL of urine, which was then passed through a 0.45 microm syringe filter. Elution was with 30% methanol (1 mL/min) on a reverse-phase C18 column. Detection was by refractive index, and integration based upon peak areas. Sixty standards of sucralose in human urine were analysed in order to quantify analytical variation. RESULTS: The standard curve for urinary sucralose was linear from 25 to 500 mg/L (r>0.99). The limit of detection was 11 mg/L. Analytical recovery of sucralose at concentrations of 25, 50 and 100 mg/L was 101.5% (CV 7.59%), 102.9% (CV 5.82%) and 105.0% (CV 4.26%), respectively. CONCLUSIONS: The technique described represents a simple assay for urinary sucralose which performed with acceptable accuracy and precision and should facilitate the use of the triple sugar test in clinical research.

Chromosomal telomere shortening of kidney cells in IgA nephropathy by the measurement of DNA in urinary sediment.

BACKGROUND: The histology and function of the kidney deteriorates with age and progressive renal failure, but the mechanisms involved in renal ageing are not known. In vitro studies suggest that telomere shortening is important in replicative senescence, and is accelerated by stress factors that increase replication. We investigated whether IgA nephropathy, a prototype chronic kidney disease, is associated with localized intrarenal cellular ageing. METHODS: We studied the mean length of terminal restriction fragments (TRF), a measure of average telomere size, in the DNA of peripheral blood mononuclear cells and urinary sediment of 15 patients with IgA nephropathy. RESULTS: The mean TRF lengths in peripheral blood is 7043.8 +/- 1 182.8 base pairs, and in urinary sediment is 6 749.7 +/- 636.5 base pairs. The mean TRF lengths of urinary DNA significantly correlate with the serum creatinine (r = -0.525, p = 0.044) and estimated glomerular filtration rate (GFR) (r = 0.651, p = 0.009). The mean TRF lengths of urinary DNA had an insignificant inverse correlation with patient age (r = -0.364, p = 0.2), and do not correlate with the degree of glomerulosclerosis (r = 0.004, p = 0.9) or tubulointerstitial scarring in renal biopsy (r =-0.032, p = 0.9). After 30 months of follow-up, the rate of decline of estimated GFR has an inverse correlation with the mean TRF lengths of urinary DNA (r = -0.699, p = 0.004). The TRF lengths of peripheral blood DNA do not correlate with any clinical or histological parameter or the rate of renal function decline. CONCLUSIONS: Although this is a pilot study, our observation indicates that the TRF lengths of genomic DNA extracted from urinary sediment is related to the degree of renal impairment. However, a long telomere length of genomic DNA in urinary sediment is associated with a more rapid decline of renal function. Our findings might be relevant to the pathogenesis of progressive renal failure.

Expression and characterization of a 159 amino acid, N-terminal fragment of human complement component C1s.

A 159 residue, N-terminal fragment of the human C1s complement component, C1s alpha(159), was expressed in the baculovirus, insect cell system. The protein was abundantly produced 3 days after infection, reaching levels as high as 40 microg/ml in cell culture media. It had a molecular weight of 18,100 (+/-4.9) Da by laser desorption mass spectrometry, close to the theoretical value of 18,111 Da, confirmed by sequencing. Sedimentation equilibrium and gel filtration column chromatography showed that C1s alpha(159) was a monomer in the presence of EDTA, and a dimer in the presence of Ca2+. The C1s alpha(159)2 dimer had a sedimentation coefficient of 3.1 S. When the C1s alpha(159)2 was mixed with Clq, there was little or no interaction. Likewise, unactivated C1r2 dimer had a sedimentation coefficient of 6.8 S, and when mixed with C1q little or no interaction was observed. When C1s alpha(159)2 was mixed with the 6.8 S C1r2 in Ca2+, a 7.5 S complex was formed, presumably the C1s alpha(159) x C1r x C1r x C1s alpha(159) tetramer. When C1q, which migrated at 10.1 S was mixed with C1s alpha(159)2 and C1r2 in the presence of Ca2+, a C1-like complex, but containing C1s alpha(159) instead of C1s, was formed which migrated at 14.0 S. This C1-like molecule remained unactivated unless challenged with an ovalbumin-antiovalbumin immune complex. In the presence of immune complex, the C1r became activated. This suggested that the presence of the 159 amino acid C1s alpha domain, which held the C1r to the C1q, was sufficient to permit activation by an immune complex, even though the catalytic domains of C1s were not present.

A molecular mechanism for the activation of the first component of complement by immune complexes.

The proposed activation mechanism is based upon several key concepts, including the "S"-structure for the folding of the C1r2C1s2 tetramer among the C1q arms [Poon, et al., J. molec. Biol. 168, 563-577 (1983)]; the locations of the catalytic domains on the tetramer and the resulting functional relevance of the "S"-structure [Colomb et al., Phil. Trans. R. Soc. B306, 282-292 (1984)]; the structure of C1-inhibitor [Odermatt et al., FEBS Lett. 131, 283-289 (1981)]; and the control of C1 activation by C1-inhibitor [Ziccardi, J. Immun. 128, 2505-2508 (1982)]. The proposed activation mechanism has four main features: steric exclusion of C1-inhibitor from C1 when it binds to an immune complex; signal generation through multivalent binding of the C1q heads to an irregularly-arranged cluster of antibody Fc regions, and signal transmission through the movement of the stiff C1q arms about their semi-flexible joints, causing distortion of the symmetrical cone of C1q arms; induction of rapid activation by a shift in equilibrium favoring the autocatalytic conformation of C1r2C1s2; and release of the activated C1s from the C1q arms, so that the ends of the tetramer are free for interaction with C4 and C2 and C1-inhibitor, and the C1q subcomponent becomes more flexible, allowing access of C1-inhibitor to C1r.