ABSTRACT
AIM: To evaluate the impact of recommendations from the 2019 consensus exercise conducted by radiologists and rheumatologists on the use of magnetic resonance imaging (MRI) to investigate axial spondyloarthritis (axSpA) in clinical practice. MATERIALS AND METHODS: A freedom of information (FOI) request was used to assess the use of MRI in the diagnosis of axSpA and radiologists' awareness of the 2019 guidance across all NHS Trusts and Health Boards in the UK, including England, Scotland, Northern Ireland, and Wales. RESULTS: The FOI request was sent to 150 Trusts/Health Boards, and 93 full responses were received. Of the 93 respondents (97%), 90 reported familiarity with the term axSpA and 70/93 (75%) reported familiarity with the 2019 recommendations. Awareness of recommendations regarding specific MRI features supportive of the diagnosis of axSpA was 74/93 (80%) for the sacroiliac joints (SIJs) and 66/93 (71%) for the spine. The median wait for MRI acquisition was 2-3 months. Fifty-two of the 93 (56%) reported at least some outsourcing of axSpA MRI (33%/29% for specialist/non-specialist outsourcing respectively); 32/93 (34%) reported some scans being reported in-house by non-musculoskeletal radiologists. CONCLUSION: There have been several positive developments in the understanding and use of MRI for the diagnosis of axSpA in the UK since the 2017 survey, although substantial scope for further improvement remains. Several new challenges have also emerged, including the increase in waiting times, reliance on outsourcing, and the reporting of MRI by non-musculoskeletal radiologists.
Subject(s)
Axial Spondyloarthritis , Spondylarthritis , Humans , Spondylarthritis/diagnostic imaging , Sacroiliac Joint/diagnostic imaging , Sacroiliac Joint/pathology , Magnetic Resonance Imaging , United Kingdom , FreedomABSTRACT
AIM: In a primary care population at high risk of type 2 diabetes, 24-month weight change trajectories were used to investigate the impact of weight cycling on fat mass (FM) and fat-free mass (FFM). MATERIALS AND METHODS: Cohort data from the Walking Away from Type 2 Diabetes trial was used, which recruited adults at-risk of type 2 diabetes from primary care in 2009/10. Annual weight change trajectories based on weight loss/gain of ≥5% were assessed over two 24-month periods. Body composition was measured by bioelectrical impedance analysis. Repeated measures were analysed using generalized estimating equations with participants contributing up to two 24-month observation periods. RESULTS: In total, 622 participants were included (average age = 63.6 years, body mass index = 32.0 kg/m2 , 35.4% women), contributing 1163 observations. Most observations (69.2%) were from those that maintained their body weight, with no change to FM or FFM. A minority (4.6% of observations) lost over 5% of body weight between baseline and 12 months, which was then regained between 12 and 24 months. These individuals regained FM to baseline levels, but lost 1.50 (0.66, 2.35) kg FFM, adjusted for confounders. In contrast, those that gained weight between baseline and 12 months but lost weight between 12 and 24 months (5.5% of observations) had a net gain in FM of 1.70 (0.27, 3.12) kg with no change to FFM. CONCLUSION: Weight cycling may be associated with a progressive loss in FFM and/or gain in FM in those with overweight and obesity at-risk of type 2 diabetes.
Subject(s)
Body-Weight Trajectory , Diabetes Mellitus, Type 2 , Adult , Humans , Female , Middle Aged , Male , Prospective Studies , Weight Cycling , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/metabolism , Body Composition , Body Weight , Weight Gain , Weight Loss , Body Mass Index , Cohort Studies , Electric Impedance , Adipose Tissue/metabolismABSTRACT
All laser-driven entangling operations for trapped-ion qubits have hitherto been performed without control of the optical phase of the light field, which precludes independent tuning of the carrier and motional coupling. By placing ^{88}Sr^{+} ions in a λ=674 nm standing wave, whose relative position is controlled to ≈λ/100, we suppress the carrier coupling by a factor of 18, while coherently enhancing the spin-motion coupling. We experimentally demonstrate that the off-resonant carrier coupling imposes a speed limit for conventional traveling-wave Mølmer-Sørensen gates; we use the standing wave to surpass this limit and achieve a gate duration of 15 µs, restricted by the available laser power.
ABSTRACT
The spectral characteristics of long-period gratings (LPGs) have been researched over the last two decades, and many sensing applications of LPGs have been proposed due to their spectral sensitivity to many surrounding environmental parameters such as the temperature, pressure, and refractive index. However, this sensitivity to many parameters can also be a curse due to cross-sensitivity and the inability to distinguish which environmental parameter is responsible for the LPG's spectral behavior. For the application proposed here-monitoring the progress of a resin flow front, its velocity, and the permeability of the reinforcement mats during the infusion stage of resin transfer molding-the multi-sensitivity of LPGs is a distinct advantage, as it provides the ability to monitor the mold environment at various stages of manufacturing.
Subject(s)
Polymers , TemperatureABSTRACT
OBJECTIVE: To investigate whether arterial stiffness (AS) differs between healthy women and women with gestational diabetes mellitus (GDM) managed by different treatment modalities. METHODS: This was a prospective longitudinal cohort study comparing AS in pregnancies complicated by GDM and low-risk controls. AS was assessed by recording aortic pulse-wave velocity (AoPWV), brachial augmentation index (BrAIx) and aortic augmentation index (AoAIx) using the Arteriograph® at four gestational-age windows: 24 + 0 to 27 + 6 weeks (W1); 28 + 0 to 31 + 6 weeks (W2); 32 + 0 to 35 + 6 weeks (W3) and ≥ 36 + 0 weeks (W4). Women with GDM were considered both as a single group and as subgroups stratified by treatment modality. Data were analyzed using a linear mixed model on each AS variable (log-transformed) with group, gestational-age window, maternal age, ethnicity, parity, body mass index, mean arterial pressure and heart rate as fixed effects and individual as a random effect. We compared the group means including relevant contrasts and adjusted the P-values using Bonferroni correction. RESULTS: The study population comprised 155 low-risk controls and 127 women with GDM, of whom 59 were treated with dietary intervention, 47 were treated with metformin only and 21 were treated with metformin + insulin. The two-way interaction term of study group and gestational age was significant for BrAIx and AoAIx (P < 0.001), but there was no evidence that mean AoPWV was different between the study groups (P = 0.729). Women in the control group demonstrated significantly lower BrAIx and AoAIx compared with the combined GDM group at W1-W3, but not at W4. The mean difference in log-transformed BrAIx was -0.37 (95% CI, -0.52 to -0.22), -0.23 (95% CI, -0.35 to -0.12) and -0.29 (95% CI, -0.40 to -0.18) at W1, W2 and W3, respectively. The mean difference in log-transformed AoAIx was -0.49 (95% CI, -0.69 to -0.30), -0.32 (95% CI, -0.47 to -0.18) and -0.38 (95% CI -0.52 to -0.24) at W1, W2 and W3, respectively. Similarly, women in the control group also demonstrated significantly lower BrAIx and AoAIx compared with each of the GDM treatment subgroups (diet, metformin only and metformin + insulin) at W1-W3. The increase in mean BrAIx and AoAIx seen between W2 and W3 in women with GDM treated with dietary management was attenuated in the metformin-only and metformin + insulin groups. However, the mean differences in BrAIx and AoAIx between these treatment groups were not statistically significant at any gestational-age window. CONCLUSIONS: Pregnancies complicated by GDM demonstrate significantly higher AS compared with low-risk pregnancies regardless of treatment modality. Our data provide the basis for further investigation into the association of metformin therapy with changes in AS and risk of placenta-mediated diseases. © 2023 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Subject(s)
Diabetes, Gestational , Metformin , Vascular Stiffness , Pregnancy , Humans , Female , Infant , Diabetes, Gestational/drug therapy , Prospective Studies , Longitudinal Studies , Metformin/therapeutic use , InsulinABSTRACT
A 9-year-old spayed female 18.8 kg mixed breed boxer dog was referred for evaluation of a 7-month history of difficulty swallowing and prehending food, regurgitation, hypersalivation, and an abnormal dorsiflexion of the tongue. Prior to referral, a barium study was performed, which revealed a mildly dilated esophagus. Treatment with sucralfate, cisapride, and prednisone was initiated. Physical examination revealed bilateral, symmetric atrophy of the temporalis muscles, dorsiflexion of the distal aspect of the tongue with concurrent muscle atrophy, and a reduced gag reflex. Electrodiagnostic examinations revealed spontaneous electrical activity in the muscles of mastication and tongue. Biopsies from the right temporalis, tongue, and biceps femoris muscles were collected. An immune-mediated myositis with fibrosis, scattered CD3, CD4, and CD8+ T-lymphocytes, and upregulation of markers for major histocompatibility antigens were observed in the tongue and temporalis muscles. The dog was treated with a tapering course of prednisone over 2 months and cyclosporine long-term. The dog was maintained on cyclosporine alone for > 2 years and clinical signs remained static, although multiple episodes of aspiration pneumonia occurred. Ultimately, euthanasia was performed due to chronic kidney disease with associated anemia, lethargy, and anorexia.
Glossite chez un chien âgé non-corgi : diagnostic et suivi à long terme. Une chienne boxer de race mixte de 18,8 kg stérilisée âgée de 9 ans a été référée pour l'évaluation d'une histoire de 7 mois de difficulté à avaler et de préhension des aliments, de régurgitation, d'hypersalivation et d'une dorsiflexion anormale de la langue. Avant la référence, un examen baryté a été réalisée et a révélé un oesophage légèrement dilaté. Un traitement par sucralfate, cisapride et prednisone a été initié. L'examen physique a révélé une atrophie bilatérale et symétrique des muscles temporaux, une flexion dorsale de la face distale de la langue avec atrophie musculaire concomitante et un réflexe nauséeux réduit. Les examens électrodiagnostiques ont révélé une activité électrique spontanée dans les muscles de la mastication et de la langue. Des biopsies des muscles temporaux droits, de la langue et du biceps fémoral ont été recueillies. Une myosite à médiation immunitaire avec fibrose, des lymphocytes T CD3, CD4 et CD8+ dispersés et une régulation positive des marqueurs des principaux antigènes d'histocompatibilité ont été observées dans la langue et les muscles temporaux. Le chien a été traité avec une posologie décroissante de prednisone sur 2 mois et de cyclosporine à long terme. Le chien a été maintenu sous cyclosporine seule pendant > 2 ans et les signes cliniques sont restés stables, bien que plusieurs épisodes de pneumonie par aspiration se soient produits. En fin de compte, l'euthanasie a été pratiquée en raison d'une maladie rénale chronique associée à une anémie, une léthargie et une anorexie.(Traduit par Dr Serge Messier).
Subject(s)
Cyclosporins , Dog Diseases , Glossitis , Tongue Diseases , Animals , Dog Diseases/diagnosis , Dog Diseases/drug therapy , Dog Diseases/pathology , Dogs , Female , Follow-Up Studies , Glossitis/diagnosis , Glossitis/pathology , Glossitis/veterinary , Prednisone/therapeutic use , Tongue/pathology , Tongue Diseases/veterinaryABSTRACT
In 2018, the giant manta ray was listed as threatened under the U.S. Endangered Species Act. We integrated decades of sightings and survey effort data from multiple sources in a comprehensive species distribution modeling (SDM) framework to evaluate the distribution of giant manta rays off the eastern United States, including the Gulf of Mexico. Manta rays were most commonly detected at productive nearshore and shelf-edge upwelling zones at surface thermal frontal boundaries within a temperature range of approximately 20-30 °C. SDMs predicted highest nearshore occurrence off northeastern Florida during April, with the distribution extending northward along the shelf-edge as temperatures warm, leading to higher occurrences north of Cape Hatteras, North Carolina from June to October, and then south of Savannah, Georgia from November to March as temperatures cool. In the Gulf of Mexico, the highest nearshore occurrence was predicted around the Mississippi River delta from April to June and again from October to November. SDM predictions will allow resource managers to more effectively protect manta rays from fisheries bycatch, boat strikes, oil and gas activities, contaminants and pollutants, and other threats.
Subject(s)
Elasmobranchii , Skates, Fish , Animals , Atlantic Ocean , Endangered Species , Fisheries , Georgia , United StatesABSTRACT
OBJECTIVE: Normal pregnancy is characterized by significant changes in maternal hemodynamics that are associated with fetal growth. Pregnancies complicated by gestational diabetes mellitus (GDM) are associated with large-for-gestational age and macrosomia, but the relationship between maternal hemodynamic parameters and birth weight (BW) among women with GDM has not been established. Our objective was to investigate the influence of maternal hemodynamics on neonatal BW in healthy pregnancies and in those complicated by GDM. METHODS: This was a prospective, cross-sectional case-control study of women aged ≥ 16 years with a singleton viable pregnancy, recruited between January 2016 and February 2021 at Leicester Royal Infirmary, Leicester, UK. GDM was defined as a fasting glucose level ≥ 5.3 mmol/L and/or serum glucose level ≥ 7.8 mmol/L, 2 h following a 75-g oral glucose load. We collected data on maternal characteristics and pregnancy outcome, including body mass index (BMI) at booking and BW centile adjusted for gestational age at delivery. Maternal hemodynamic parameters were assessed at 34-42 weeks' gestation using the Arteriograph® and bioreactance techniques. Graphical causal inference methodology was used to identify causal effects of the measured variables on neonatal BW centile. RESULTS: Included in the analysis were 141 women with GDM and 136 normotensive non-diabetic pregnant controls. 62% of the women with GDM were managed pharmacologically, with metformin and/or insulin. Variables included in the final model were cardiac output (CO), mean arterial pressure (MAP), total peripheral resistance (TPR), aortic augmentation index (AIx), aortic pulse wave velocity (PWV) and BMI at booking. Among the controls, maternal BMI, CO and aortic PWV were significantly associated with neonatal BW. Each SD increase in booking BMI produced an increase of 8.4 BW centiles (P = 0.002), in CO produced an increase of 9.4 BW centiles (P = 0.008) and in aortic PWV produced an increase of 7.1 BW centiles (P = 0.017). We found no significant relationship between MAP, TPR or aortic AIx and neonatal BW. Maternal hemodynamics influenced neonatal BW among the women with GDM in a similar manner to that in the control group, but only the relationship between maternal BMI and neonatal BW reached statistical significance, with a 1-SD increase in BMI producing an increase of 6.1 BW centiles (P = 0.019). CONCLUSIONS: Maternal BMI, CO and PWV were determinants of BW in our control group. The relationship between maternal hemodynamics and neonatal BW was similar between women with GDM and healthy controls. Our findings therefore suggest that fetal growth restriction in pregnancies complicated by GDM may indicate maternal cardiovascular dysfunction. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology.
Subject(s)
Diabetes, Gestational , Birth Weight , Case-Control Studies , Cross-Sectional Studies , Female , Glucose , Hemodynamics , Humans , Infant, Newborn , Pregnancy , Pregnancy Outcome , Prospective Studies , Pulse Wave AnalysisABSTRACT
BACKGROUND: Understanding factors impacting deaths from COVID-19 is of the highest priority. Seasonal variation in environmental meteorological conditions affects the incidence of many infectious diseases and may also affect COVID-19. Ultraviolet (UV) A (UVA) radiation induces release of cutaneous photolabile nitric oxide (NO) impacting the cardiovascular system and metabolic syndrome, both COVID-19 risk factors. NO also inhibits the replication of SARS-CoV2. OBJECTIVES: To investigate the relationship between ambient UVA radiation and COVID-19 deaths. METHODS: COVID-19 deaths at the county level, across the USA, were modelled in a zero-inflated negative-binomial model with a random effect for states adjusting for confounding by demographic, socioeconomic and long-term environmental variables. Only those areas where UVB was too low to induce significant cutaneous vitamin D3 synthesis were modelled. We used satellite-derived estimates of UVA, UVB and temperature and relative humidity. Replication models were undertaken using comparable data for England and Italy. RESULTS: The mortality rate ratio (MRR) in the USA falls by 29% [95% confidence interval (CI) 40% to 15%) per 100 kJ m-2 increase in mean daily UVA. We replicated this in independent studies in Italy and England and estimate a pooled decline in MRR of 32% (95% CI 48% to 12%) per 100 kJ m-2 across the three studies. CONCLUSIONS: Our analysis suggests that higher ambient UVA exposure is associated with lower COVID-19-specific mortality. Further research on the mechanism may indicate novel treatments. Optimized UVA exposure may have population health benefits.
Subject(s)
COVID-19 , Humans , Italy , RNA, Viral , SARS-CoV-2 , Ultraviolet Rays/adverse effects , United States/epidemiologyABSTRACT
AIM: To quantify how differences in metrics characterizing physical activity and sedentary behaviour in type 2 diabetes are associated with physical function. METHODS: This analysis included participants' data from the Chronotype of Patients with Type 2 Diabetes and Effect on Glycaemic Control (CODEC) cross-sectional study. Data were stratified into two groups according to their short physical performance battery (SPPB) score (impaired physical function = SPPB < 10 and normal physical function = SPPB ≥ 10). Hand-grip strength, sit-to-stand 60 (STS-60) and the Duke Activity Status Index (DASI) score were used to assess functional capacity, while physical activity metrics were measured with a wrist-worn accelerometer. The associations between physical activity metrics and measures of functional capacity were analysed using generalized linear modelling. RESULTS: Some 635 adults (median age 66 years, 34% female) were included in this analysis. Overall, 29% of the cohort scored < 10 in the SPPB test indicating impaired physical function. This group spent more time in prolonged sedentary behaviour (600.7 vs. 572.5 min) and undertook less-intense physical activity. Each sd increase in physical activity volume and intensity gradients for those with impaired physical function was associated with 17% more repetitions for STS-60 with similar associations seen for DASI score. Each sd in sedentary time was associated with 15% fewer repetitions in STS-60 and 16% lower DASI score in those with impaired physical function, whereas in normal physical function group it was 2% and 1%, respectively. CONCLUSIONS: The strength of the associations for physical activity measures and functional capacity were modified by physical function status, with the strongest association seen in those with impaired physical function.
Subject(s)
Diabetes Mellitus, Type 2/physiopathology , Exercise Test/instrumentation , Exercise/physiology , Hand Strength/physiology , Sedentary Behavior , Adolescent , Adult , Aged , Cross-Sectional Studies , Diabetes Mellitus, Type 2/diagnosis , Equipment Design , Female , Humans , Male , Middle Aged , Young AdultABSTRACT
PURPOSE: To review the existing available information regarding urolithiasis management and the impact of COVID-19 on this, and propose recommendations for management of emergency urolithiasis presentations in the COVID-19 era. METHODS: Review of published guidelines produced by Urological Governing Bodies, followed by the literature review regarding urolithiasis management during the COVID-19 pandemic. RESULTS: Consistent recommendations across guidelines and literature were that urolithiasis with concurrent sepsis or renal failure remains a urological emergency warranting urgent intervention within the pandemic environment. Ureteric stenting and percutaneous nephrostomy are considered equivalent for decompression in this setting, with both ideally to be performed under local anaesthesia where possible to spare ventilators and reduce aerosol-generating procedures. Greater utilization of medical expulsive therapy and dissolution chemolysis may occur during the pandemic, and longer indwelling stent times may be accepted while definite stone clearance is deferred. CONCLUSIONS: Urolithiasis will continue to be a source of emergency presentations requiring urgent intervention during the COVID-19 pandemic. However, it is possible to limit these interventions to decompression of the collecting system in the setting of concurrent obstruction or infection, performed under local anaesthesia to limit use of resources and minimise aerosol-generating procedures, with deferral of definitive management.
Subject(s)
COVID-19 , Emergency Medical Services , Nephrostomy, Percutaneous , Practice Patterns, Physicians' , Urolithiasis , COVID-19/epidemiology , COVID-19/prevention & control , Emergency Medical Services/methods , Emergency Medical Services/organization & administration , Humans , Infection Control/methods , Nephrostomy, Percutaneous/methods , Nephrostomy, Percutaneous/trends , Organizational Innovation , Practice Guidelines as Topic , Practice Patterns, Physicians'/organization & administration , Practice Patterns, Physicians'/trends , SARS-CoV-2 , Urolithiasis/diagnosis , Urolithiasis/physiopathology , Urolithiasis/surgeryABSTRACT
AIMS: To present the longer-term impact of multifactorial treatment of type 2 diabetes on self-reported health status, diabetes-specific quality of life, and diabetes treatment satisfaction at 10-year follow up of the ADDITION-Europe trial. METHODS: The ADDITION-Europe trial enrolled 3057 individuals with screen-detected type 2 diabetes from four centres [Denmark, the UK (Cambridge and Leicester) and the Netherlands], between 2001 and 2006. Participants were randomized at general practice level to intensive treatment or to routine care . The trial ended in 2009 and a 10-year follow-up was performed at the end of 2014. We measured self-reported health status (36-item Short-Form Health Survey and EQ-5D), diabetes-specific quality of life (Audit of Diabetes-Dependent Quality of Life questionnaire), and diabetes treatment satisfaction (Diabetes Treatment Satisfaction Questionnaire) at different time points during the study period. A mixed-effects model was applied to estimate the effect of intensive treatment (intention-to-treat analyses) on patient-reported outcome measures for each centre. Centre-specific estimates were pooled using a fixed effects meta-analysis. RESULTS: There was no difference in patient-reported outcome measures between the routine care and intensive treatment arms in this 10-year follow-up study [EQ-5D: -0.01 (95% CI -0.03, 0.01); Physical Composite Score (36-item Short-Form Health Survey): -0.27 (95% CI -1.11, 0.57), Audit of Diabetes-Dependent Quality of Life questionnaire: -0.01 (95% CI -0.11, 0.10); and Diabetes Treatment Satisfaction Questionnaire: -0.20 (95% CI -0.70, 0.29)]. CONCLUSIONS: Intensive, multifactorial treatment of individuals with screen-detected type 2 diabetes did not affect self-reported health status, diabetes-specific quality of life, or diabetes treatment satisfaction at 10-year follow-up compared to routine care.
Subject(s)
Diabetes Mellitus, Type 2/therapy , Hypoglycemic Agents/therapeutic use , Patient Reported Outcome Measures , Patient Satisfaction , Quality of Life , Aged , Blood Pressure , Cholesterol/blood , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/metabolism , Female , Follow-Up Studies , Glycated Hemoglobin/metabolism , Health Status , Humans , Male , Mass Screening , Mental Health , Middle Aged , Patient Care PlanningABSTRACT
Whale sharks (Rhincodon typus) - the largest extant fish species - reside in tropical environments, making them an exception to the general rule that animal size increases with latitude. How this largest fish thrives in tropical environments that promote high metabolism but support less robust zooplankton communities has not been sufficiently explained. We used open-source inertial measurement units (IMU) to log 397â h of whale shark behavior in Yucatán, Mexico, at a site of both active feeding and intense wildlife tourism. Here we show that the strategies employed by whale sharks to compensate for the increased drag of an open mouth are similar to ram feeders five orders of magnitude smaller and one order of magnitude larger. Presumed feeding constituted 20% of the total time budget of four sharks, with individual feeding bouts lasting up to 11 consecutive hours. Compared with normal, sub-surface swimming, three sharks increased their stroke rate and amplitude while surface feeding, while one shark that fed at depth did not demonstrate a greatly increased energetic cost. Additionally, based on time-depth budgets, we estimate that aerial surveys of shark populations should consider including a correction factor of 3 to account for the proportion of daylight hours that sharks are not visible at the surface. With foraging bouts generally lasting several hours, interruptions to foraging during critical feeding periods may represent substantial energetic costs to these endangered species, and this study presents baseline data from which management decisions affecting tourist interactions with whale sharks may be made.
Subject(s)
Sharks , Swimming , Animals , Endangered Species , Male , MexicoABSTRACT
Introduction To examine efficacy and tolerability of Levetiracetam monotherapy as a first line agent in a national cohort of children with epilepsy, naïve to anti-epileptic medication. Methods A retrospective analysis of children with epilepsy who attended 4 Irish tertiary Paediatric Neurology Clinics (2009-2015) started on Levetiracetam as a first line monotherapy. Results 182 children were identified aged one month to 16 years (mean 6.2 years (SD=5.1) Retention at 6 and 12 months was 88% (n=161) and 83% (n=145) respectively. 75% (n=104) achieved seizure freedom or > 50% improvement in seizure control at 12 months. 30% (n=55) experienced ≥1 adverse effect with aggression (12%; n=21) the most frequent. Treatment was discontinued in 16% (n=29) because of intolerance. Underlying conditions and epilepsy type were not found to influence efficacy or tolerability. Conclusion Levetiracetam monotherapy was observed as effective and safe for children with epilepsy although side effects limit tolerance in a sizeable minority.
Subject(s)
Drug Tolerance , Epilepsy/drug therapy , Levetiracetam/therapeutic use , Adolescent , Child , Child, Preschool , Female , Humans , Infant , Ireland , Levetiracetam/adverse effects , Male , Retrospective Studies , Safety , Treatment OutcomeSubject(s)
Caloric Restriction , Clinical Decision Rules , Diabetes Mellitus, Type 2/diet therapy , Primary Health Care , Antihypertensive Agents/therapeutic use , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/metabolism , Glycated Hemoglobin/metabolism , Humans , Hypoglycemic Agents/therapeutic use , Hypolipidemic Agents/therapeutic use , Time FactorsABSTRACT
BACKGROUND AND AIMS: The association of beta-blockers and their selectivity with mortality and cardiovascular events in patients with and without hypoglycaemia is unknown. METHODS AND RESULTS: Insulin-treated patients with diabetes were identified within the UK CPRD database. All-cause deaths, cardiovascular events, and hypoglycaemic episodes were captured to assess the interaction between beta-blocker therapy and selectivity with hypoglycaemia. 13,682 patients, of which 2036 (14.9%) with at least one hypoglycaemic episode, were included; 3148 deaths and 1235 cardiovascular events were recorded during a median of 2.3 and 4.7 years in patients with and without incident hypoglycaemia, respectively. Treatment with any beta-blocker was not associated with risk of death in both patients with and without hypoglycaemia, without significant interaction. Compared to no therapy, non-selective beta-blockers were associated with higher risk of death in patients without hypoglycaemia (hazard ratio (HR) 2.93 [1.26-6.83] in the fully adjusted model) but not in those with hypoglycaemia; interactions was not significant. For beta1-selective beta-blockers, there was no association with mortality in both patients with and without hypoglycaemia, without significant interaction. After missing data imputation, results were consistent for non-selective beta-blockers (HR in patients without hypoglycaemia 1.59 [1.22-2.08]) while indicated a reduced risk of death for beta1-selective beta-blockers in patients with hypoglycaemia (HR 0.76 [0.61-0.94]). Due to few cardiovascular events, complete-case analysis compared only any vs no beta-blocker therapy and indicated no associations with therapy or interaction by hypoglycaemia. CONCLUSION: In patients with hypoglycaemic episodes, treatment with beta1-selective beta-blockers may potentially reduce the risk of death. These explorative findings and the potential role of confounding by indication need to be evaluated in other studies.
Subject(s)
Adrenergic beta-Antagonists/therapeutic use , Cardiovascular Diseases/drug therapy , Diabetes Mellitus/drug therapy , Hypoglycemia/mortality , Hypoglycemic Agents/adverse effects , Insulin/adverse effects , Adrenergic beta-Antagonists/adverse effects , Aged , Cardiovascular Diseases/mortality , Cause of Death , Databases, Factual , Diabetes Mellitus/mortality , Female , Humans , Hypoglycemia/chemically induced , Male , Middle Aged , Risk Assessment , Risk Factors , Time Factors , Treatment Outcome , United Kingdom/epidemiologyABSTRACT
We investigate a nano-patterning process which creates reproducible periodic surface topological features that range in size from â¼100 µm to â¼20 µm. Specifically, we have fabricated multi-layered thin films consisting of germanium/silicon strata on a planar substrate, with each layer having nanometers thickness. The material processing exploits focused 244 nm ultra-violet laser light and an opto-mechanical setup typically applied to the inscription of fiber gratings, and is based upon the well-known material compaction interaction of ultra-violet light with germanium oxides. We show this process can be extended to create arrays of metal nano-antennas by adding a metal overlay to the thin film. This results in arrays with dimensions that span nanometer- to centimeter-length scales. Also, each nano-antenna consists of "nano-blocks." Experimental data are presented that show the UV irradiance dosage used to create these metal nanostructures on D-shaped optical fibers has a direct relationship to their transmission spectral characteristics as plasmonic devices.
ABSTRACT
Aims Physical activity has been proposed to be an effective non-pharmacological method of reducing systemic inflammation and therefore may prove particularly efficacious for women with polycystic ovary syndrome (PCOS) who have been shown to have high levels of inflammation and an increased risk of type 2 diabetes (T2DM) and cardiovascular disease (CVD). Therefore, the aim of the present study was to assess whether modest changes in daily step count could significantly reduce levels of inflammatory markers in women with PCOS. Subjects and Methods Sixty-five women with PCOS were assessed at baseline and again at 6 months. All had been provided with an accelerometer and encouraged to increase activity levels. Multivariate linear regression analyses (adjusted for age, ethnicity, baseline step count, change in BMI and change in accelerometer wear-time) were used to assess changes in daily step count against clinical and research biomarkers of inflammation, CVD and T2DM. Results Mean step count/day at baseline was 6337 (±270). An increase in step count (by 1000 steps) was associated with a 13% reduction in IL6 (ß: -0.81 ng/L; 95% CI, -1.37, -0.25, P = 0.005) and a 13% reduction in CRP (ß: -0.68 mg/L; 95% CI, -1.30, -0.06, P = 0.033). Additionally, there was a modest decrease in BMI (ß: 0.20 kg/m2; 95% CI, -0.38, -0.01, P = 0.038). Clinical markers of T2DM and CVD were not affected by increased step count. Conclusions Modest increases in step count/day can reduce levels of inflammatory markers in women with PCOS, which may reduce the future risk of T2DM and CVD.
ABSTRACT
South Africa (SA) is home to a heterogeneous population with a wide range of cardiovascular risk factors. Cholesterol reduction in combination with aggressive management of modifiable risk factors, including nutrition, physical activity, blood pressure and smoking, can help to reduce and prevent morbidity and mortality in individuals who are at increased risk of cardiovascular events. This updated consensus guide to management of dyslipidaemia in SA is based on the updated European Society of Cardiology and European Atherosclerosis Society dyslipidaemia guidelines published in 2016. For individuals who are not considered to be at high or very high cardiovascular risk, the decision whether to treat and which interventional strategy to use is based on a cardiovascular risk score calculated using total cholesterol, high-density lipoprotein cholesterol (HDL-C), gender, age and smoking status. The cardiovascular risk score refers to the 10-year risk of any cardiovascular event and includes 4 categories of risk (low, moderate, high and very high). People with established cardiovascular disease, diabetes mellitus, chronic kidney disease and genetic or severe dyslipidaemias are considered to already be at high or very high risk and do not require risk scoring. Therapeutic lifestyle change is the mainstay of management for all patients. The need for and intensity of drug therapy is determined according to baseline low-density lipoprotein (LDL-C) levels and the target LDL-C concentration appropriate to the individual. LDL-C treatment targets are based on pre-treatment risk and are as follows: <3 mmol/L in low- and moderate risk cases; <2.5 mmol/L and a reduction of at least 50% if the baseline concentration is 2.5 - 5.2 mmol/L in high-risk cases; and <1.8 mmol/L and a reduction of at least 50% if the baseline concentration is 1.8 - 3.5 mmol/L in very high-risk cases. A statin is usually recommended first-line; the specific agent is based on the required degree of cholesterol reduction, comorbidities and co-prescribed medication. Special attention should be paid to children with a family history of genetic or severe dyslipidaemia, who should be screened for dyslipidaemia from 8 years of age. In SA, HIV infection is not considered to be a significant cardiovascular risk factor and treatment recommendations for HIV-positive individuals are the same as for the general population, with careful choice of pharmacotherapy to avoid potential adverse drug-drug interactions. The benefit of statins in individuals older than 70 years is uncertain and clinical judgement should be used to guide treatment decisions and to avoid side-effects and overmedication in this group.
Subject(s)
Cardiovascular Diseases , Dyslipidemias , Hydroxymethylglutaryl-CoA Reductase Inhibitors , Mass Screening/methods , Patient Care Management , Risk Reduction Behavior , Cardiovascular Diseases/epidemiology , Cardiovascular Diseases/prevention & control , Cardiovascular Diseases/psychology , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Consensus , Dyslipidemias/blood , Dyslipidemias/epidemiology , Dyslipidemias/therapy , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects , Patient Care Management/methods , Patient Care Management/standards , Risk Assessment/methods , Risk Factors , South AfricaABSTRACT
PURPOSE: Circulating microRNAs represent a reservoir for biomarker discovery. Our objective was to profile the change in human circulating microRNA associated with recreational use of alcohol at a social event. MATERIAL AND METHODS: Blood was collected from healthy volunteers (N = 16) before and after recreational consumption of alcohol (ethanol). Biochemistry, hematology and ethanol measurements were performed. The change in the serum small RNA fraction was quantified by RNA sequencing. RESULTS: Blood ethanol was undetectable at study entry in all subjects [<10 mg/dL]. After consuming alcohol the median concentration was 89 mg/dL [IQR: 71-138. Min-max 20-175]. There were no changes in biochemistry and hematology parameters. Serum RNA sequencing identified 1371 small RNA species (1305 microRNAs). There were significant increases [adjusted p-value <0.05, fold increase 2 or more] in 265 microRNAs, around a fifth of the total [median fold increase 2.3 [IQR: 2.1-2.5; Max: 3.7]]. miR-185-5p decreased following alcohol exposure [adjusted p-value <0.05, fold decrease 2 or more]. CONCLUSIONS: The microRNA composition of human serum is dynamic and environmental factors may have a significant impact. Within its context of use the fold change 'signal' of a microRNA must be large enough to negate the risk of false results due to background 'noise'.