Mortality study of 18 000 patients treated with omeprazole.

Background: The long term safety of potent gastric acid suppressive therapy has yet to be established. Method: General practice record review at a median interval of 26 months followed by retrieval of details of all deaths within four years using the UK National Health Service Central Registers in 17 936 patients prescribed omeprazole in 1993–1995. Death rates were compared with general population rates. Results: Records of 17 489 patients (97.5%) were examined. A total of 12 703 patients received further scripts for antisecretory drugs, 8097 for omeprazole only (65.6%): 3097 patients have died. All cause mortality was higher in the first year (observed/expected (O/E) 1.44 (95% confidence intervals (CI) 1.34–1.55); p<0.0001) but had fallen to population expectation by the fourth year. There were significant mortality increases in the first year, falling to or below population expectation by the fourth year, for deaths ascribed to neoplasms (1.82 (95% CI 1.58–2.08); p<0.0001), circulatory diseases (1.27 (95% CI 1.13–1.43); p<0.0001), and respiratory diseases (1.37 (95% CI 1.12–1.64); p<0.001). Increased mortality ascribed to digestive diseases (2.56 (95% CI 1.87–3.43); p<0.0001) persisted, although reduced. Increased mortality rates for cancers of the stomach (4.06 (95% CI 2.60–6.04); p<0.0001), colon and rectum (1.40 (95% CI 0.84–2.18); p=0.075), and trachea, bronchus, and lung (1.64 (95% CI 1.19–2.19); p<0.01) seen in the first year had disappeared by the fourth year but that for cancer of the oesophagus had not (O/E 7.35 (95% CI 5.20–10.09) (p<0.0001) in year 1; 2.88 (95% CI 1.62–4.79) (p<0.001) in year 4). Forty of 78 patients dying of oesophageal cancer had the disease present at registration. Twenty seven of those remaining cases had clinical evidence of Barrett’s disease, stricture, ulcer, or oesophagitis at registration (O/E 3.30 (95% CI 2.17–4.80)). Six deaths occurred in patients with hiatal hernia or reflux only (O/E 1.02 (95% CI 0.37–2.22)) and five in patients without oesophageal disease (O/E 0.77 (95% CI 0.25–1.80)). No relationships were detected with numbers of omeprazole scripts received. Conclusions: Increases in mortality associated with treatment are due to pre- existing illness, including pre-existing severe oesophageal disease. There was no evidence of an increased risk of oesophageal adenocarcinoma in those without oesophageal mucosal damage recorded at registration

High pressure mechanical seal

A relatively impervious mechanical seal is formed between the outer surface of a tube and the inside surface of a mechanical fitting of a high pressure fluid or hydraulic system by applying a very thin soft metal layer onto the outer surface of the hard metal tube and/or inner surface of the hard metal fitting, prior to swaging the fitting onto the tube. The thickness of such thin metal layer is independent of the size of the tube and/or fittings. Many metals and alloys of those metals exhibit the requisite softness, including silver, gold, nickel, tin, platinum, indium, rhodium and cadmium. Suitably, the coating is about 0.0025 millimeters (0.10 mils) in thickness. After swaging, the tube and fitting combination exhibits very low leak rates on the order or 10.sup.-8 cubic centimeters per second or less as meaured using the Helium leak test

Studies of the dynamics of nuclear clustering in human syncytiotrophoblast

Syncytial nuclear aggregates (SNAs), clusters of nuclei in the syncytiotrophoblast of the human placenta, are increased as gestation advances and in pregnancy pathologies. The origins of increased SNAs are unclear; however, a better appreciation of the mechanism may give insight into placental ageing and factors underpinning dysfunction. We developed three models to investigate whether SNA formation results from a dynamic process of nuclear movement and to generate alternative hypotheses. SNA count and size were measured in placental explants cultured over 16 days and particles released into culture medium were quantified. Primary trophoblasts were cultured for 6 days. Explants and trophoblasts were cultured with and without cytoskeletal inhibitors. An in silico model was developed to examine the effects of modulating nuclear behaviour on clustering. In explants, neither median SNA number (108 SNA/mm(2) villous area) nor size (283 μm(2)) changed over time. Subcellular particles from conditioned culture medium showed a wide range of sizes that overlapped with those of SNAs. Nuclei in primary trophoblasts did not change position relative to other nuclei; apparent movement was associated with positional changes of the syncytial cell membrane. In both models, SNAs and nuclear clusters were stable despite pharmacological disruption of cytoskeletal activity. In silico, increased nuclear movement, adhesiveness and sites of cytotrophoblast fusion were related to nuclear clustering. The prominence of SNAs in pregnancy disorders may not result from an active process involving cytoskeleton-mediated rearrangement of syncytial nuclei. Further insights into the mechanism(s) of SNA formation will aid understanding of their increased presence in pregnancy pathologies

Analysis of energy savings potentials for integrated room automation

The energy savings potential of selected low-cost measures related to the simultaneous control of blinds, electric lighting, heating, cooling and ventilation in a single building zone (Integrated Room Automation) was investigated. The analysis was based on a factorial study comprising several thousands, whole-year hourly time step simulations. The largest energy savings potential was found for the use of CO2-controlled ventilation as opposed to non-air quality controlled ventilation (average savings of 13%–28%, depending on the building zone characteristics and the choice of technical building system), followed by a widening of the thermal comfort range by ~1.5 oC (6%–16%), and the allowance for night/weekend room temperature set-back (0%–18%). Substantial energy savings potentials were also detected for advanced control: readily realizable energy savings thanks to improved non-predictive control amounted to 1%–15%, and theoretical savings potentials for predictive control to 16%–41%. The found, large case-to-case variability surrounding these average numbers un- derlines the importance of simulation-based assessments on a per case basis

A unique bacteriohopanetetrol stereoisomer of marine anammox

Anaerobic ammonium oxidation (anammox) is a major process of bioavailable nitrogen removal from marine systems. Previously, a bacteriohopanetetrol (BHT) isomer, with unknown stereochemistry, eluting later than BHT using high performance liquid chromatography (HPLC), was detected in ‘Ca. Scalindua profunda’ and proposed as a biomarker for anammox in marine paleo-environments. However, the utility of this BHT isomer as an anammox biomarker is hindered by the fact that four other, non-anammox bacteria are also known to produce a late-eluting BHT stereoisomer. The stereochemistry in Acetobacter pasteurianus, Komagataeibacter xylinus and Frankia sp. was known to be 17β, 21β(H), 22R, 32R, 33R, 34R (BHT-34R). The stereochemistry of the late-eluting BHT in Methylocella palustris was unknown. To determine if marine anammox bacteria produce a unique BHT isomer, we studied the BHT distributions and stereochemistry of known BHT isomer producers and of previously unscreened marine (‘Ca. Scalindua brodeae’) and freshwater (‘Ca. Brocadia sp.’) anammox bacteria using HPLC and gas chromatographic (GC) analysis of acetylated BHTs and ultra high performance liquid chromatography (UHPLC)-high resolution mass spectrometry (HRMS) analysis of non-acetylated BHTs. The 34R stereochemistry was confirmed for the BHT isomers in Ca. Brocadia sp. and Methylocella palustris. However, ‘Ca. Scalindua sp.’ synthesise a stereochemically distinct BHT isomer, with still unconfirmed stereochemistry (BHT-x). Only GC analysis of acetylated BHT and UHPLC analysis of non-acetylated BHT distinguished between late-eluting BHT isomers. Acetylated BHT-x and BHT-34R co-elute by HPLC. As BHT-x is currently only known to be produced by ‘Ca. Scalindua spp.’, it may be a biomarker for marine anammox

UK export performance research - review and implications

Previous research on export performance has been criticized for being a mosaic of autonomous endeavours and for a lack of theoretical development. Building upon extant models of export performance, and a review and analysis of research on export performance in the UK for the period 1990-2005, an integrated model of export performance is developed and theoretical explanations of export performance are put forward. It is suggested that a multi-theory approach to explaining export performance is viable. Management and policy implications for the UK emerging from the review and synthesis of the literature and the integrated model are discussed

Prehospital Systolic Blood Pressure Thresholds: A Community‐based Outcomes Study

Objectives Emergency medical services (EMS) personnel commonly use systolic blood pressure ( sBP ) to triage and treat acutely ill patients. The definition of prehospital hypotension and its associated outcomes are poorly defined. The authors sought to determine the discrimination of prehospital sBP thresholds for 30‐day mortality and to compare patient classification by best‐performing thresholds to traditional cutoffs. Methods In a community‐based cohort of adult, nontrauma, noncardiac arrest patients transported by EMS between 2002 and 2006, entries to state hospital discharge data and death certificates were linked. Prehospital sBP thresholds between 40 and 140 mm Hg in derivation ( n =  132,624) and validation ( n =  22,020) cohorts and their discrimination for 30‐day mortality, were examined. Cutoffs were evaluated using the 0/1 distance, Youden index, and adjusted Z‐statistics from multivariable logistic regression models. Results In the derivation cohort, 1,594 (1.2%) died within 24 hours, 7,404 (6%) were critically ill during hospitalization, and 6,888 (5%) died within 30 days. The area under the receiver operating characteristic (ROC) curve for sBP was 0.60 (95% confidence interval [CI] = 0.59, 0.61) for 30‐day mortality and 0.64 (95% CI = 0.62 0.66) for 24‐hour mortality. The 0/1 distance, Youden index, and adjusted Z‐statistics found best‐performing sBP thresholds between 110 and 120 mm Hg. When compared to an sBP ≤ 90 mm Hg, a cutoff of 110 mm Hg would identify 17% ( n =  137) more deaths at 30 days, while overtriaging four times as many survivors. Conclusions Prehospital sBP is a modest discriminator of clinical outcomes, yet no threshold avoids substantial misclassification of 30‐day mortality among noninjured patients. Resumen Los Umbrales de la Presión Arterial Sistólica Prehospitalaria: Un Estudio de Base Comunitaria Acerca de la Evolución de los Pacientes Objetivos El personal de los sistemas de emergencias médicas ( SEM ) usa frecuentemente la presión arterial sistólica ( PAS ) para clasificar y tratar a los pacientes agudos. Las definiciones de hipotensión prehospitalaria y sus resultados asociados están pobremente definidos. Se determinó la discriminación de los umbrales de PAS prehospitalaria para la mortalidad a los 30 días, y se comparó la clasificación del paciente por los mejores umbrales con los puntos de corte tradicionales. Metodología Estudio de cohorte de base comunitaria de pacientes adultos no traumatológicos ni con paradas cardiorrespiratorias transportados por los SEM entre 2002 y 2006, cuyas historias estaban vinculadas con los datos de alta hospitalaria y los certificados de mortalidad. Se examinaron los umbrales de PAS prehospitalaria entre 40 mm Hg y 140 mm Hg en las cohortes de derivación ( n =  132.624), y validación ( n =  22,020), y su discriminación para la mortalidad a los 30 días. Los puntos de corte se evaluaron usando la distancia 0/1, el índice de Youden y los estadísticos Z ajustados de los modelos de regresión logística multivariable. Resultados: En la cohorte de derivación, 1.594 (1,2%) fallecieron en las primeras 24 horas, 7.404 (6%) estuvieron críticamente enfermos durante el ingreso y 6.888 (5%) fallecieron en los 30 primeros días. El área bajo la curva de la ROC para PAS fue 0,60 ( IC 95% = 0,59–0,61) para la mortalidad a los 30 días y 0,64 ( IC 95% = 0,62–0,66) para la mortalidad a las 24 horas. La distancia 0/1, el índice de Youden y las estadísticas Z ajustadas hallaronque los mejores umbrales de PAS estaban entre 110 y 120 mm Hg. Cuando se comparó con una PAS ≤ 90 mm Hg, un punto de corte de 110 mm Hg identificaría un 17% ( n =  137) más de muertes a los 30 días, mientras que sobreclasificaría cuatro veces más a los supervivientes. Conclusiones La presión arterial sistólica es un discriminador modesto de resultados clínicos. No obstante, ningún umbral evita una mala clasificación de la mortalidad a los 30 días entre los pacientes no traumatológicos.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/1/acem12142-sup-0002-DataSupplementS2_FigS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/2/acem12142-sup-0007-DataSupplementS7_FigS4.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/3/acem12142-sup-0006-DataSupplementS6_FigS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/4/acem12142-sup-0009-DataSupplementS9_TableS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/5/acem12142-sup-0003-DataSupplementS3.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/6/acem12142-sup-0008-DataSupplementS8_TableS2.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/7/acem12142-sup-0004-DataSupplementS4_TableS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/8/acem12142-sup-0001-DataSupplementS1.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/98303/9/acem12142.pd

Is diabetic retinopathy screening worthwhile among people first diagnosed with diabetes at older ages? A cohort study of Norfolk diabetic retinopathy screening programme

Aims: England's Diabetic Eye Disease Screening Programme offers screening to every resident over age 12 with diabetes, starting as soon as possible after diagnosis and repeated annually. People first diagnosed with diabetes at older ages have shorter life expectancy and therefore may be less likely to benefit from screening and treatment. To inform decisions about whether diabetic eye screening policy should be stratified by age, we investigated the probability of receiving treatment according to age at first screening episode. Methods: This was a cohort study of participants in the Norfolk Diabetic Retinopathy Screening Programme from 2006 to 2017, with individuals' programme data linked to hospital treatment and death data recorded up to 2021. We estimated and compared the probability, annual incidence and screening costs of receiving retinal laser photocoagulation or intravitreal injection and of death, in age groups defined by age at first screening episode. Results: The probability of death increased with increasing age at diagnosis, while the probability of receiving either treatment decreased with increasing age. The estimated cost of screening per person who received either or both treatments was £18,608 among all participants, increasing with age up to £21,721 in those aged 70–79 and £26,214 in those aged 80–89. Conclusions: Diabetic retinopathy screening is less effective and less cost-effective with increasing age at diagnosis of diabetes, because of the increasing probability of death before participants develop sight-threatening diabetic retinopathy and can benefit from treatment. Upper age limits on entry into screening programmes or risk stratification in older age groups may, therefore, be justifiable

When data drive health: an archaeology of medical records technology

Medicine is often thought of as a science of the body, but it is also a science of data. In some contexts, it can even be asserted that data drive health. This article focuses on a key piece of data technology central to contemporary practices of medicine: the medical record. By situating the medical record in the perspective of its history, we inquire into how the kinds of data that are kept at sites of clinical encounter often depend on informational requirements that originate well outside of the clinic, in particular in health insurance records systems. Although this dependency of today's electronic medical records on billing requirements is widely lamented by clinical providers, its history remains little studied. Following the archaeology of medicine developed by Michel Foucault in The Birth of the Clinic and expanding his methodology in light of more recent contributions to the field of media archaeology, this article excavates some of the underexplored technological conditions that help constitute today's electronic medical record. If in some contexts, it is true that data drive health, then an archaeology of medical records helps reveal how health insurance records often impact clinical care and, by extension, health and disease