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Fifty-one patients with primary myelofibrosis (PMF) received allogeneic haematopoietic stem cell transplants from related (n=33) or unrelated (n=18) donors. Twenty-seven patients, 19-54 years old, were prepared with myeloablative regimens including CY plus BU (n=4) or TBI (n=23). Twenty-four patients, 40-64 years old, received reduced-intensity conditioning (RIC) regimens. All RIC regimens contained fludarabine, combined with melphalan (n=19) or BU (n=5), and alemtuzumab or anti-thymocyte globulin (ATG) in the majority (n=19). Four patients (17%) in the RIC group had primary graft failure. Previous splenectomy reduced time to engraftment in the RIC group (13 versus 20 days; P=0.008). For MA and RIC groups, respectively, at 3 years, overall survival rates were 44 and 31% (P=0.67), progression-free survival 44 and 24% (P=0.87), and actuarial relapse rates 15 and 46% (P=0.06). Non-relapse mortality at 3 years was 41% for the myeloablative and 32% for the RIC group. Acute GVHD occurred in 29 and 38% of patients in the myeloablative and RIC groups, respectively. Extensive chronic GVHD developed in 30 and 35% of evaluable patients, respectively. [ABSTRACT FROM AUTHOR]

This study evaluated psychometric properties of the Timeline Followback interview-Children's Exposure to Partner Violence (TLFB-CEPV), an event history calendar interview designed to assess children's exposure to daily patterns of intimate partner violence. Participants were men ( N = 107) entering batterer's treatment, their female partners, and a custodial child (6-16 years). The TLFB-CEPV asked about days of partner physical aggression and children's exposure to these episodes, and was administered to partners at pretreatment, posttreatment, 6 and 12 months. At each assessment, the percentage of days of any child exposure (PAE) and of children's direct exposure (PDE) to violence were calculated. Parents completed measures of partner aggression and social desirability; parents, teachers, and children completed measures of children's adjustment. TLFB-CEPV scores had excellent temporal stability and strong evidence of concurrent, discriminant, and criterion validity. Interrater agreement for TLFB-CEPV scores was moderate at initial assessment, but high at subsequent follow-up interviews. [ABSTRACT FROM AUTHOR]

PurposeTo assess the cost-effectiveness of latanoprost or timolol in glaucoma treatment in Norway, Sweden, Denmark (Scandinavia) and the United Kingdom (UK).MethodsA Markov model was constructed to perform a cost-effectiveness analysis. Health states were ‘stable’ and ‘progressed’ glaucoma, and transition probabilities for both primary open-angle and exfoliation glaucoma were derived from the medical literature. Practice patterns were obtained from surveys completed by 54 ophthalmologists geographically dispersed throughout each country. Country specific unit costs were used for medications, patient visits, diagnostics, and therapeutic procedures.ResultsOver the life of the model latanoprost was less expensive than timolol by 5.3–7.6% (Scandinavia) and 2.1% (UK). Following adjustments, therapy in the original timolol-treated cohort was slightly more effective in each country with a difference in 0.003–0.015 years to progression of glaucoma existing between latanoprost. This may have resulted from the model design, which reflected that physicians ultimately control most patients' glaucoma over 5 years by adding or changing therapy. The associated incremental cost-effectiveness ratios for latanoprost vstimolol generated by the Scandinavian and the UK models, respectively, were: Norway 351 396 NOK; Sweden 988 985 SEK; Denmark 351 641; and the UK 4751 GBP.ConclusionsOver 5 years, in the UK timolol is the cost-effective option, whereas in Scandinavia latanoprost may be the cost-effective alternative to timolol.Eye (2009) 23, 132–140; doi:10.1038/sj.eye.6702964; published online 24 August 2007 [ABSTRACT FROM AUTHOR]

PurposeTo determine the predictive value of early Phase trials (I–II) for the ocular hypotensive efficacy observed in Phases III and IV.DesignA review of published literature.MethodsThis study evaluated 12 medicines in 65 articles in the literature with at least two phases available.ResultsFor medicines with Phase I results available (n=3), the average reduction in intraocular pressure (IOP) from untreated baseline was 16%, 26% for Phase II, 26% for Phase III, and 24% for Phase IV. For medicines with Phase II results available (n=6), the average reduction in IOP was 23%, 24% for Phase III, and 23% for Phase IV. For medicines with Phase III results available (n=11), the average reduction in IOP was 25% and 24% for Phase IV.ConclusionThis study indicates that early phase trials usually approximated the results of later regulatory studies and post-commercialization trials.Eye (2008) 22, 985–988; doi:10.1038/sj.eye.6702913; published online 22 June 2007 [ABSTRACT FROM AUTHOR]

- The Load Unload Response Ratio theory (LURR) puts forward the idea that the ratio of seismicity during times of increased tidal loading to times of decreased tidal loading takes on anomalously large values as the preparatory region of the earthquake approaches a critical state. We repeated the calculations of LURR for several earthquakes in California, for which results had been published, using estimates of the parameters which could be determined from the published work. We were unable to confirm any LURR ratio predictive significance. We test an alternative method of evaluating the influence of tidal stresses on earthquakes based on damage mechanics. As in rock mechanics experiments, it may be that anomalous activation of seismicity prior to large earthquakes occurs only during those time intervals when the applied stress exceeds values previously attained. We applied this approach to analyze the same data set used to test the LURR hypothesis, and it also failed to reveal any significant precursory indications. It may be that time-dependent failure processes such as self-driven nucleation occur on a time scale longer than the diurnal tide, thus destroying the expected synchronization. [ABSTRACT FROM AUTHOR]

AIMS:To evaluate the efficacy and safety of latanoprost/timolol maleate fixed combination (LTFC) given once daily vs the concomitant therapy of brimonidine twice daily and latanoprost once daily in primary open-angle glaucoma or ocular hypertensive subjects. METHODS:A prospective, double-masked, active-controlled comparison in which qualified subjects had all glaucoma medicines discontinued for 1 month and then were randomized to either LTFC or brimonidine and latanoprost concomitant therapy for 6 weeks. They were then switched to the other treatment regimen. The intraocular pressure (IOP) was measured at 0800, 1200, and 1600?h at baseline and at the end of Periods 1 and Period 2. RESULTS:In 32 subjects, the diurnal curve of the untreated IOP of 26.0±3.4 decreased to 17.8±2.5 on LTFC and 17.2±2.8?mmHg on brimonidine and latanoprost (P=0.31). At 0800 and 1600 h, the IOPs were statistically similar between the groups (P>0.05). At 1200?h the latanoprost and brimonidine treatment IOP was statistically lower (16.2±3.2) than LTFC (18.0±2.8?mmHg). However, the reduced IOP from untreated baseline was not statistically different at each time point and for the diurnal curve for each therapy (P<0.05). Safety was similar between groups for both solicited and unsolicited side effects (P>0.05). CONCLUSION:This study suggests that LTFC and concomitant therapy of brimonidine and latanoprost provide statistically similar diurnal IOP reduction from an untreated baseline.Eye (2004) 18, 990-995. doi:10.1038/sj.eye.6701375 Published online 19 March 2004 [ABSTRACT FROM AUTHOR]

Purpose To compare ocular tolerability of dorzolamide 2%, brinzolamide 1%, and placebo given three times daily. Methods A prospective, double-masked, three-centre, crossover comparison in which 25 ocular hypertensive or primary-open angle glaucoma subjects were randomized to receive dorzolamide, brinzolamide, or placebo three times daily for 3 days. Intraocular pressure, visual acuity, a visual analogue scale, and ocular and systemic symptom queries were completed at the end of each period. Results After chronic dosing, there was a significant difference in ocular pain on the visual analogue scale among the groups at the 10-s postinstillation time point with dorzolamide having the highest level (22.5±28.9) compared to brinzolamide (5.0±8.7) or placebo (3.2±10.4) (P = 0.0006). No differences between groups were observed preinstillation nor following dosing at 3 or 10-min postinstillation. On the initial instillation, the 10-s postinstillation pain was rated as 43.3±77.1, which was significantly higher than after chronic dosing (P = 0.017). On the ocular symptom query, dorzolamide had the highest incidence of burning/stinging and redness compared to the other groups, but was generally characterized as mild. There were no significant differences in the visual acuity at any time point. Conclusions This study suggests that subjects treated with dorzolamide suffer more ocular pain upon instillation compared to brinzolamide or placebo. However, pain symptoms are fewer following chronic dosing and are generally characterized as mild. [ABSTRACT FROM AUTHOR]

The psychometric properties of the Timeline Followback Spousal Violence interview (TLFB-SV), a calendar method used to assess daily patterns and frequency of spousal violence, were evaluated. Men (N = 104) entering a spousal violence treatment program, along with their female partners, were interviewed with the TLFB-SV at pretreatment, posttreatment, and quarterly thereafter for 1 year and asked to identify days of male-to-female and female-to-male physical aggression that had occurred between them. For posttreatment and follow-up interviews, participants maintained a weekly diary, in which they catalogued the days on which acts of spousal violence occurred. The subscale scores derived from the TLFB-SV, the proportion of days of any violence, and proportion of days of severe violence for each partner were calculated for each assessment interval. The TLFB-SV subscales had excellent temporal stability and concurrent and discriminant validity. Interpartner agreement on TLFB-SV subscale scores and agreement between partners on days when spousal violence occurred was low at pretreatment, but was high for the other assessment periods. [ABSTRACT FROM AUTHOR]

Introduction: Patients with migraine have varying medical care needs. To effectively stratify patients to appropriate care, physicians should consider the frequency and intensity of attacks, and their overall impact on ability to function. The Migraine Disability Assessment Scale (MIDAS) measures headache-related disability. The MIDAS Perceptions Study investigated whether MIDAS scores reflect headache severity and the need for medical care, and assessed whether the MIDAS questionnaire is meaningful and relevant to patients, and easy to use. Design: The Perceptions Study was conducted as a follow-up to a baseline telephone interview. Upon completion of the baseline survey, 471 individuals were invited to participate in the Perceptions Study and 420 participated: 168 patients with migraine headaches and 253 with non-migraine headaches. Patients with migraine or non-migraine headaches completed the MIDAS questionnaire and the Center of Epidemiologic Studies of Depression (CES-D) questionnaire, and were then interviewed by telephone within 48 hours of receiving the questionnaires. Results: Headache frequency and pain intensity increased significantly with increasing MIDAS grade (p < 0.0001). A pattern of decreasing quality-of-life scores on the physical and mental subscales of the Short Form-12 was also seen with increasing MIDAS grade. Scores on the CES-D scale increased significantly with increasing MIDAS grade (p < 0.0001), indicating a greater likelihood of depression and more severe depression with higher grades. There were significant associations between increasing MIDAS grade and an increasing proportion of individuals who had consulted a doctor within the past year, lower use of over-the-counter medication, and greater use of prescription medications (p < 0.0001 for all three variables). Satisfaction with current therapy decreased significantly with increasing MIDAS grade, mirroring the frequency with which individuals achieved complete relief from headache. The MIDAS questionnaire was rated as easy to use by the vast majority of respondents, and ratings of its perceived value increased significantly as MIDAS grade increased. Conclusions: A low MIDAS score generally seems to indicate a low need for care, while individuals in MIDAS grades III and IV appear to have significant unmet medical care needs. The MIDAS questionnaire had increasingly perceived relevance as MIDAS grade increased, helped the majority of those in MIDAS grades III and IV to understand the impact of their headaches, and encouraged those with the greatest disability to seek medical care. The MIDAS questionnaire may facilitate communication between doctors and patients, and help physicians to identify those receiving inadequate medical care. [ABSTRACT FROM AUTHOR]

Coyotes (Canis latrans) are highly adaptable, medium-sized carnivores that now inhabit nearly every large city in the United States and Canada. To help understand how coyotes have adapted to living in urban environments, we compared two ecologically and evolutionarily important behavioral traits (i.e., bold-shy and exploration-avoidance behavior) in two contrasting environments (i.e., rural and urban). Boldness is an individual's reaction to a risky situation and exploration is an individual's willingness to explore novel situations. Our results from both tests indicate that urban coyotes are bolder and more exploratory than rural coyotes and that within both populations there are individuals that vary across both spectrums. Bolder behavior in urban coyotes emerged over several decades and we speculate on possible processes (e.g., learning and selection) and site differences that could be playing a role in this behavioral adaptation. We hypothesize that an important factor is how people treat coyotes; in the rural area coyotes were regularly persecuted whereas in the urban area coyotes were rarely persecuted and sometimes positively rewarded to be in close proximity of people. Negative consequences of this behavioral adaptation are coyotes that become bold enough to occasionally prey on pets or attack humans. [ABSTRACT FROM AUTHOR]

Medium and large carnivores coexist with people in urban areas globally, occasionally resulting in negative interactions that prompt questions about how to reduce human-wildlife conflict. Hazing, i.e., scaring wildlife, is frequently promoted as an important non-lethal means for urbanites to reduce conflict but there is limited scientific evidence for its efficacy. We used a population of captive coyotes (Canis latrans) to simulate urban human-coyote interactions and subsequent effects of hazing on coyote behavior. Past experiences with humans significantly affected the number of times a coyote approached a human to necessitate hazing. Coyotes that had been hand fed by adults had to be more frequently hazed than coyotes with other or no past experiences with adults. Past experience with children had no impact on the number of hazing events. The number of times a coyote approached an adult or child was reduced across days based on the accumulative number of times hazed, suggesting coyotes learn to avoid behaviors warranting hazing and that this could be used as a non-lethal management tool. However, prior experience and whether the interaction is with an adult or child can alter the outcomes of hazing and must be considered in determining the efficacy of hazing programs. [ABSTRACT FROM AUTHOR]

Understanding large carnivore demography on human-dominated lands is a priority to inform conservation strategies, yet few studies examine long-term trends. Jaguars (Panthera onca) are one such species whose population trends and survival rates remain unknown across working lands. We integrated nine years of camera trap data and tourist photos to estimate jaguar density, survival, abundance, and probability of tourist sightings on a working ranch and tourism destination in Colombia. We found that abundance increased from five individuals in 2014 to 28 in 2022, and density increased from 1.88 ± 0.87 per 100 km2 in 2014 to 3.80 ± 1.08 jaguars per 100 km2 in 2022. The probability of a tourist viewing a jaguar increased from 0% in 2014 to 40% in 2020 before the Covid-19 pandemic. Our results are the first robust estimates of jaguar survival and abundance on working lands. Our findings highlight the importance of productive lands for jaguar conservation and suggest that a tourism destination and working ranch can host an abundant population of jaguars when accompanied by conservation agreements and conflict interventions. Our analytical model that combines conventional data collection with tourist sightings can be applied to other species that are observed during tourism activities. Entender los patrones demográficos de los grandes carnívoros al interior de paisajes antrópicos es fundamental para el diseño de estrategias de conservación efectivas. En el Neotrópico, el jaguar (Panthera onca) es una de estas especies cuyas tendencias poblacionales y tasas de supervivencia en paisajes productivos son desconocidas. Para entender mejor estas dinámicas, integramos nueve años de fototrampeo junto a fotos de turistas para estimar la densidad, supervivencia, abundancia y probabilidad de avistamiento de esta especie en una finca ganadera y destino turístico en Colombia. Entre 2014 y 2022 encontramos que la abundancia incrementó de cinco a 28 individuos y la densidad de 1.88 ± 0.87 jaguares/ 100 km2 a 3.80 ± 1.08 jaguares/ 100 km2. La probabilidad de avistamiento por turistas aumentó de 0% en 2014 a 40% en 2020 antes de la pandemia del Covid-19. Nuestros resultados presentan las primeras estimaciones robustas de abundancia y supervivencia de este felino en paisajes antrópicos dónde el manejo de sistemas productivos combinados con turismo e intervenciones para la mitigación del conflicto puede albergar poblaciones abundantes de jaguares, demostrando su importancia para la conservación de esta especie. Nuestro modelo, al combinar datos convencionales con avistamientos, podría ser aplicado a otras especies observadas durante actividades turísticas. [ABSTRACT FROM AUTHOR]

A response by W. C. Stewart and colleagues to a letter to the editor about their article "Untreated 24-h intraocular pressures measured with Goldmann applanation tonometry vs nighttime supine pressures with Perkins applanation tonometry" in the 2010 issue is presented.

Presents a response by W.C. Stewart to a letter to the editor commenting on the article "Diurnal Intraocular Pressure Reduction With Latanoprost 0.005% Compared to Timolol Maleate 0.5% as Monotherapy in Subjects with Exfoliation Glaucoma," published in the February 27, 2004 issue of the journal "Eye."

Background: Quality of life (QoL) is commonly impaired among people with multiple sclerosis (PwMS). The aim of this study was to evaluate via meta-analysis the efficacy of Mindfulness-based interventions (MBIs) for improving QoL in PwMS. Methods: Eligible randomized controlled trials (RCTs) were identified via searching six major electronic databases (MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, AMED, and PsycINFO) in April 2022. The primary outcome was QoL. Study quality was determined using the Cochrane Collaboration risk of bias tool. Meta-analysis using a random effects model was undertaken. Effect sizes are reported as Standardized Mean Difference (SMD). Prospero ID: 139835. Results: From a total of 1312 individual studies, 14 RCTs were eligible for inclusion in the meta-analysis, total participant n = 937. Most studies included PwMS who remained ambulatory. Cognitively impaired PwMS were largely excluded. Comorbidities were inconsistently reported. Most MBIs were delivered face-to face in group format, but five were online. Eight studies (n = 8) measured MS-specific QoL. In meta-analysis, overall effect size (SMD) for any QoL measure (n = 14) was 0.40 (0.18–0.61), p = 0.0003, I2 = 52%. SMD for MS-specific QoL measures (n = 8) was 0.39 (0.21–0.57), p < 0.0001, I2 = 0%. MBI effect was largest on subscale measures of mental QoL (n = 8), SMD 0.70 (0.33–1.06), p = 0.0002, I2 = 63%. Adverse events were infrequently reported. Conclusions: MBIs effectively improve QoL in PwMS. The greatest benefits are on mental health-related QoL. However, more research is needed to characterize optimal formatting, mechanisms of action, and effects in PwMS with more diverse social, educational, and clinical backgrounds. [ABSTRACT FROM AUTHOR]

The co-occurrence of mental and physical chronic conditions is a growing concern and a largely unaddressed challenge in low-and-middle-income countries. This study aimed to investigate the independent and multiplicative effects of depression and physical chronic conditions on health-related quality of life (HRQoL) in China, and how it varies by age and gender. We used two waves of the China Health and Retirement Longitudinal Study (2011, 2015), including 9227 participants aged ≥ 45 years, 12 physical chronic conditions and depressive symptoms. We used mixed-effects linear regression to assess the effects of depression and physical multimorbidity on HRQoL, which was measured using a proxy measure of Physical Component Scores (PCS) and Mental Component Scores (MCS) of the matched SF-36 measure. We found that each increased number of physical chronic conditions, and the presence of depression were independently associated with lower proxy PCS and MCS scores. There were multiplicative effects of depression and physical chronic conditions on PCS (− 0.83 points, 95% CI − 1.06, − 0.60) and MCS scores (− 0.50 points, 95% CI − 0.73, − 0.27). The results showed that HRQoL decreased markedly with multimorbidity and was exacerbated by the presence of co-existing physical and mental chronic conditions. [ABSTRACT FROM AUTHOR]

A response by W. C. Stewart, J. A. Stewart, and M. Mychaskiw to the letter to the editor on the article "Cost effectiveness of latanoprost and timolol maleate for the treatment of glaucoma in Scandinavia and the United Kingdom using a decision-analytic health economic model" in the previous issue is presented.

Wire arc additive manufacturing (WAAM) appears as one of the most promising technologies due to its capacity to process all types of materials used in welding, its high production rate, and capacity to process large geometries of particular interest in the aeronautical industry. Since this technology is still under investigation, it is important to determine the efficiency of the process; in this sense, the melting efficiency stands out not only as a parameter of interest in energy terms but also as a measure of the stability of the process. For calculating melting efficiency, it is necessary to use tailored colorimeters or apply models requiring specific dimensions that involve destructive testing. For this reason, in the development of this work, the melting efficiency is evaluated through machine learning algorithms. Processing parameters such as wire diameter, wire feed speed, travel speed, and net power are used to determine melting efficiency. In addition, a simplified analytical model was developed to compare the results. The average melting efficiency analytically calculated was 44.56 ± 5.48%, while the predicted value reaches a comparable value of 44.32 ± 4.79% obtained with the Gaussian process regressor, which shows the highest accuracy. Moreover, the known relationship with travel speed was verified. [ABSTRACT FROM AUTHOR]

Malignant tumours of the central nervous system (CNS) represent the second most common cancer type in the paediatric population of developed countries, and mortality caused by CNS tumours is the highest among paediatric cancers. Tumours of mesenchymal origin occurring either as primary or secondary lesions of the central nervous system are very rare in children. This paper describes the case of a 5-year-old non-immunocompromised male who presented with a right frontal primary intracranial leiomyosarcoma associated with large subdural collections. Following surgical excision and adjuvant chemoradiotherapy, the patient has remained disease-free for 18 months. The literature is reviewed and the possible association of the chronic subdurals to the later development of the leiomyosarcoma explored. [ABSTRACT FROM AUTHOR]

Presents a letter to the editor in response to the article "Chronic Myeloid Leukemia CD34+ Cells Have Elevated Levels of Phosphatidylinositol 3,4,5 Trisphosphate (PtdIns(3,4,5)P3) and Lack a PtdIns(3,4,5)P3 Response to Cytokines and Chemotactic Factors; Effects Reversed by Imatinib," previously published in the journal "Leukemia."

Inhibition of cancer-promoting kinases is an established therapeutic strategy for the treatment of many cancers, although resistance to kinase inhibitors is common. One way to overcome resistance is to target orthogonal cancer-promoting pathways. Bromo and Extra-Terminal (BET) domain proteins, which belong to the family of epigenetic readers, have recently emerged as promising therapeutic targets in multiple cancers. The development of multitarget drugs that inhibit kinase and BET proteins therefore may be a promising strategy to overcome tumor resistance and prolong therapeutic efficacy in the clinic. We developed a general computational screening approach to identify novel dual kinase/bromodomain inhibitors from millions of commercially available small molecules. Our method integrated machine learning using big datasets of kinase inhibitors and structure-based drug design. Here we describe the computational methodology, including validation and characterization of our models and their application and integration into a scalable virtual screening pipeline. We screened over 6 million commercially available compounds and selected 24 for testing in BRD4 and EGFR biochemical assays. We identified several novel BRD4 inhibitors, among them a first in class dual EGFR-BRD4 inhibitor. Our studies suggest that this computational screening approach may be broadly applicable for identifying dual kinase/BET inhibitors with potential for treating various cancers. [ABSTRACT FROM AUTHOR]

Direct writing aims to deposit materials onto substrates in localised positions. In this paper, we demonstrate a new method for direct writing of nanoparticles at ambient-air-pressure. An electrical discharge is used to generate gold nanoparticles of the order of 10 nm diameter, which are then transported and 'focused' by an electric field in air, through the process of electric field-assisted diffusion, as opposed to normal ballistic focusing since the mean free path in air is very short. This process is novel and allows for practical normal atmospheric-pressure focused deposition of nanoparticles. The focusing mechanism is capable of producing patterned arrays of deposited nanoparticles with widths that are less than 10 % of the diameter of the focusing apparatus; in the present experimental configuration, gold spots with diameters of a few tens of micrometres were achieved, with ultimate size being limited by transverse diffusion and by charged particle mutual repulsion. In this study, the process of generating nanoparticles from bulk material, transporting and focusing these particles takes place in one operation, which is a key advantage in rapid prototyping and manufacturing techniques. [ABSTRACT FROM AUTHOR]

PurposeTo evaluate 24-h efficacy of travoprost/timolol fixed combination (TTFC) vslatanoprost/timolol fixed combination (LTFC) in exfoliative glaucoma (XFG).DesignA prospective, single-masked, crossover, active-controlled, randomized 24-h comparison.MethodsAfter up to a 6-week medicine-free period, XFG patients were randomized to either TTFC or LTFC for 3 months, dosed each evening, and then changed to the opposite treatment for another 3 months. At the end of the washout, and both treatment periods, a 24-h intraocular pressure (IOP) curve was measured.ResultsIn total, 40 patients completed the study. The TTFC group showed a lower mean absolute 24-h IOP (18.7±2.6 vs19.6±2.6 mm Hg, P<0.001), maximum IOP (20.5±2.6 vs21.5±2.6 mm Hg, P<0.001) and 24-h IOP range (3.4±1.3 vs4.1±1.6 mm Hg, P=0.01). At individual time points, TTFC showed reduced IOPs compared with LTFC, after a Bonferroni correction, at 1000, 1800, and 2200 hours (P0.04). No statistical differences existed at hours: 0600, 1400, and 0200 (P0.05) and for the minimum IOP (P=0.09).ConclusionsThis study suggests that evening-dosed TTFC may provide greater 24-h IOP reduction, primarily at the 1800 hours time point, compared with LTFC in XFG. [ABSTRACT FROM AUTHOR]

AimsTo compare supine nighttime intraocular pressure measurements with Perkins applanation tonometry to 24-h sitting intraocular pressures with Goldmann applanation tonometry.MethodsA prospective, untreated, uncontrolled, observational cohort of qualified consecutive ocular hypertensive or primary open-angle glaucoma patients. Patients underwent sitting intraocular pressure measurements over 24-h by Goldmann and patients had their supine nighttime intraocular pressure measurements by Perkins.ResultsIn 100 completed patients, the mean intraocular pressure at 1000, 2200, 0200 and 0600 hours while sitting was 22.5±3.7 mm Hg, and in the supine position, 23.5±4.3 mm Hg (P<0.001). The mean sitting Goldmann intraocular pressures across the three daytime points was 23.3±3.4 mm Hg and across three nighttime points was 21.5±4.0 mm Hg (P<0.001). In contrast, the mean daytime sitting Goldmann intraocular pressure was not different than the mean nighttime supine intraocular pressure evaluated with Perkins (22.8±4.4 mm Hg, P=0.07). However, only 70% of patients were within 1.0 mm Hg of the highest daytime reading for all nighttime supine and sitting intraocular pressures.ConclusionThis study suggests that with Perkins applanation tonometry the untreated mean supine intraocular pressures are not higher at night than daytime sitting Goldmann applanation tonometry. However, the highest daytime sitting intraocular pressure measurement does not consistently predict the highest nighttime sitting or supine intraocular pressure value. [ABSTRACT FROM AUTHOR]

A case of a tentorial meningioma with atypical histological features invading the transverse sinus and extending along the internal jugular vein up to the superior mediastinum is described. This report illustrates one of the many ways meningiomas spread beyond the cranial cavity and the difficulty in managing such a problem. [ABSTRACT FROM AUTHOR]

PurposeTo determine the incidence of glaucomatous progression at mean intraocular pressure (IOP) levels in patients with ocular hypertension (OHT).MethodsA retrospective, multicentre, cohort analysis of 230 OHT patients with 5 years of follow-up evaluated for risk factors associated with progressive optic disc and visual field loss to determine the incidence of glaucomatous progression.ResultsForty percent of patients with IOPs 24 mmHg, 18% of patients with IOPs of 21–23 mmHg, 11% of patients with IOPs with 18–20 mmHg, and 3% of patients with IOPs of 17 mmHg progressed to glaucoma. The mean IOP was 19.8±2.4 mmHg in the stable group and 21.7±2.6 mmHg in the progressed group (P=0.0004). The highest average peak IOP was 23.4±4.0 mmHg in the stable group and 25.2±3.1 mmHg in the progressed group (P=0.006). Based on the pachymetry values for central corneal thickness, patients with thinner corneas more often progressed to glaucoma (P<0.0001). A multivariant regression analysis to determine risk factors for progression was positive primarily for higher peak IOPs, older age, male gender, argon laser trabeculoplasty, visual acuity 20/50, and no topical medical therapy or β-blocker therapy prior to the study.ConclusionsIOP reduction within the normal range over 5 years of follow-up reduces the chance of progression to primary open-angle glaucoma in OHT patients.Eye (2009) 23, 73–78; doi:10.1038/sj.eye.6702995; published online 5 October 2007 [ABSTRACT FROM AUTHOR]

To determine whether a process redesign could improve detection and treatment of osteoporosis, at-risk women over the age of 65 were identified using an electronic medical record and proactively contacted by letter and phone call. This resulted in a significant increase in testing for osteoporosis by DXA scan. The high-risk patients were then offered a shared medical appointment, which resulted in improved treatment outcomes compared to usual care. Our objective was to determine if redesigning care through proactive contact with women 65 at-risk of osteoporosis increased BMD testing and to determine if a shared medical appointment (SMA) improved treatment for high-risk women. Two primary care sites received the redesign intervention and two other sites served as the usual care controls. At the intervention sites, all women 65 who had not had a DXA scan performed in the prior 2 years were contacted by mail and phone calls. High-risk patients were invited to attend a SMA or follow-up visit with their primary physician. A significantly higher proportion of women at the intervention sites had a DXA (39.6% vs. 13.2%, p < 0.0001). Patients who attended the SMA were more likely to have calcium and vitamin D recommended, a vitamin D level checked, and receive a prescription medicine than those patients who had follow-up with their primary care physician. The redesigned process was highly effective in improving BMD testing for women 65. The SMA was shown to be a more effective method to make calcium and vitamin D recommendations, to evaluate secondary causes of low bone density, and to prescribe prescription medications, compared to usual care with the PCP. [ABSTRACT FROM AUTHOR]

PurposeTo evaluate the 24-h intraocular pressure (IOP) control of brimonidine/timolol fixed combination (BTFC) versusthe unfixed combination of its individual components, each dosed twice daily, in patients with primary open-angle glaucoma or ocular hypertension.MethodsAn observer-masked, randomized, crossover, active-controlled, two-centre comparison. Following a 6-week medicine-free period, patients were randomized to BTFC or to the unfixed combination of brimonidine and timolol for 3 months. Patients then were crossed over to the opposite treatment for another 3 months. At the end of the medicine-free period, and each treatment period, patients underwent 24-h IOP measurements at 0600, 1000, 1400, 1800, 2200, and 0200 hours.ResultsTwenty-eight patients completed this study. Both BTFC and the unfixed components showed a significant IOP reduction from untreated baseline (P<0.0001), and were statistically equal when compared directly, for each individual time point and for the 24-h IOP curve (P>0.05). The mean 24-h IOP was 24.6±1.9 for baseline, 19.2±1.9 for BTFC, and 19.2±1.6 mmHg for the unfixed components (P=1.0). Four patients were discontinued due to side effects. The most common ocular adverse event was ocular hyperaemia (n=3 with BTFC and n=5 with the unfixed components, P=0.7) and systemic adverse events were rare.ConclusionThis study suggests that both BTFC and the unfixed components of brimonidine and timolol provide a significant 24-h IOP reduction from untreated baseline, and statistically equal control when compared directly, at each time point and for the 24-h pressure curve.Eye (2008) 22, 1391–1397; doi:10.1038/sj.eye.6702906; published online 15 June 2007 [ABSTRACT FROM AUTHOR]

Blood pressure (BP) is known to vary by time of day and day of year. Studies differ substantially on the magnitude of the effect and there is doubt whether variation is clinically meaningful. We used more than 2 million BP measurements obtained between 1996 and 2004 from Geisinger Clinic primary care patients. General estimating equations were used to determine the effect of time of day and month of year on the probability of identifying BP values above four diagnostic cutoff points (SBP120 mm Hg, SBP140 mm Hg, DBP80 mm Hg, DBP90 mm Hg). Time of day and month of year were significantly associated with the odds of measuring elevated BP, regardless of definition. The odds ratio (OR) for SBP120 mm Hg in the evening (1900 hours) versus midday (1200 hours) was 1.32 (P<0.001). The OR for SBP120 mm Hg in winter to summer months was 1.24 (P<0.001). Similar results were found for each age/gender group. These data indicate that in clinical practice, measurement of an elevated BP may vary by 40% depending on the time of day and month of year. The magnitude of the variability in BP measurement attributable to the combined effect of these temporal factors is clinically significant. Anticipation of changes in BP attributable to temporal factors may improve accuracy of diagnosis and precision of therapy.Journal of Human Hypertension (2008) 22, 755–760; doi:10.1038/jhh.2008.44; published online 5 June 2008 [ABSTRACT FROM AUTHOR]

PurposeTo provide initial validation of the Treatment Satisfaction Survey-Intraocular Pressure (TSS-IOP) quality-of-life survey that analyses specific issues related to side effects, patient satisfaction, and compliance.MethodsA prospective, observational cohort of 250 consecutive patients with primary open-angle glaucoma or ocular hypertension was administered the TSS-IOP survey.ResultsFactors that correlated with patient satisfaction included perceived effectiveness of the medicine (F=7.47, P<0.001), ocular irritation (F=6.06, P<0.001), conjunctival hyperaemia (F=4.40, P<0.001), ease of use (F=8.52, P<0.001), and convenience of use (F=6.90, P<0.001). Patient compliance, acceptance of their illness, and knowledge of glaucoma were also related to perceived effectiveness of the medicine (P<0.001), ease of use (P<0.05) and convenience (P<0.001). Physician ratings of patient pressure control, side effects, and instillation problems also were significantly correlated to patient satisfaction (R=0.13–0.26, P=0.05–0.001). The physician ratings of patient compliance, however, were not significantly related to any dimension of patient satisfaction (P>0.05). Among monotherapy prostaglandin treatments, latanoprost demonstrated statistically greater satisfaction than bimatoprost or travoprost regarding conjunctival hyperaemia (P<0.05) and eye irritation (P<0.01).ConclusionsThis study provides initial evidence that patient satisfaction may be related to compliance, perceived effectiveness of treatment, adverse side effects, ease and convenience of use, acceptance of illness, and knowledge of glaucoma.Eye (2006) 20, 583–590. doi:10.1038/sj.eye.6701932; published online 3 June 2005 [ABSTRACT FROM AUTHOR]

Purpose: To compare the efficacy and safety of brimonidine 0.2% vs unoprostone 0.15%, both added to timolol maleate 0.5% each given twice daily.Methods: In this prospective, multi-centred, double-masked, crossover comparison, patients were randomized to one treatment group for a 6-week treatment period, and then crossed over to the opposite treatment. Measurements were performed at 0800, 1000, 1600, 1800, and 2000 h at baseline and at the end of each treatment period.Results: In all, 33 patients entered this trial and 29 completed. The baseline trough intraocular pressure (IOP) was 23.3+/-2.4 and the diurnal curve IOP was 22.0+/-1.3 mmHg. For the brimonidine and timolol maleate treatment group, the trough IOP was 21.6+/-3.3 and the diurnal curve IOP was 19.8+/-2.1 mmHg, while the timolol and unoprostone treatment showed a trough IOP of 20.9+/-3.8 and a diurnal curve IOP of 19.3+/-2.4 mmHg. There was no significant difference between treatment groups at any time point for the diurnal curve, or in the reduction from baseline (P>0.05). Both treatments failed to statistically reduce the IOP from baseline at 1800 h. There was no difference between treatment groups regarding ocular and systemic unsolicited adverse events, but patients admitted to more dryness (P=0.02) and burning upon instillation (P<0.0001) with unoprostone by survey.Conclusion: Brimonidine 0.2% or unoprostone 0.15% added to timolol maleate 0.5% provide similar efficacy and safety throughout the daytime diurnal curve. [ABSTRACT FROM AUTHOR]

PURPOSE:The diurnal efficacy and safety of the fixed combinations of latanoprost/timolol given once daily vs dorzolamide/timolol given twice daily in primary open-angle glaucoma or ocular hypertensive patients. DESIGN:A double-masked, two-centre, crossover comparison. RESULTS:In 33 patients, the mean diurnal IOP (0800-2000, measured every 2?h) for latanoprost/timolol fixed combination was 17.3±2.2?mmHg and for dorzolamide/timolol, the fixed combination was 17.0±2.0?mmHg (P=0.36). Additionally, there was no statistical difference for individual time points following a Bonferroni correction. A bitter taste was found more frequently with the dorzolamide/timolol fixed combination (n=6) than the latanoprost/timolol fixed combination (n=0) (P=0.040), while the latanoprost/timolol fixed combination demonstrated more conjunctival hyperaemia (n=9) than the dorzolamide/timolol fixed combination (n=2) (P=0.045). One patient was discontinued early from the dorzolamide/timolol fixed combination due to elevated IOP. CONCLUSION:This study suggests that the daytime diurnal IOP is not statistically different between the dorzolamide/timolol fixed combination and latanoprost/timolol fixed combination in primary open-angle glaucoma and ocular hypertensive patients.Eye (2004) 18, 1264-1269. doi:10.1038/sj.eye.6701446 Published online 25 June 2004 [ABSTRACT FROM AUTHOR]

Aims To compare the diurnal intraocular pressure (IOP) efficacy and safety of timolol vs latanoprost in subjects with exfoliation glaucoma (XFG). Methods A 3-month prospective, single- masked, active-controlled, parallel comparison performed in six centres in Greece that randomized subjects in a 1:1 ratio to either latanoprost in the evening (2000 hours) and placebo in the morning (0800 hours), or timolol twice daily (0800 and 2000 hours). Results In all, 103 subjects completed the study. After 3 months of chronic dosing, the latanoprost group exhibited a trend to a greater diurnal IOP reduction from an untreated baseline (24.9±3.2–17.4±2.9) compared with timolol (24.7±2.8–18.3±1.9 mmHg) (P=0.07). Latanoprost showed a significantly greater IOP reduction at 0800 hours (-8.5 vs -6.0 mm Hg for timolol, P<0.0001) whereas no difference was observed between the two medications at 1000, 1400, and 2000 hours after a Bonferroni Correction. In addition, latanoprost demonstrated a narrower range of diurnal IOP (2.4) than timolol (3.2 mmHg)(P=0.0017). Safety was similar between groups, except there was more conjunctival hyperaemia with latanoprost (n=8) than timolol (n = 1)(P=0.01). Conclusions This study suggests that latanoprost provides a statistically lower 08:00-hour IOP and better range of IOP than timolol in the treatment of XFG glaucoma. Eye (2004) 18, 893–899. [ABSTRACT FROM AUTHOR]

Purpose To evaluate the safety and efficacy of the timolol/dorzolamide fixed combination vs latanoprost 0.005% in exfoliation glaucoma patients. Methods We randomized in an observer-masked fashion 65 newly diagnosed exfoliation glaucoma patients to either the timolol/dorzolamide twice daily or latanoprost daily treatment for 2 months and then crossed these over to the other treatment. Results A total of fifty-four patients completed the study. After 2 months of chronic dosing, the morning intraocular pressure (IOP) (10:00) was reduced from a baseline of 31.2 ± 6.5 mmHg to 18.1 ± 3.0 with the fixed combination and to 18.9 ± 4.1 mmHg with latanoprost (P = 0.21). Six patients were discontinued early from both treatment periods owing to inadequate IOP control and two others were discontinued from latanoprost treatment only. The fixed combination showed a significantly greater incidence of taste perversion (P < 0.001) and stinging upon instillation (P = 0.036), while latanoprost showed a trend for increased conjunctival injection (P = 0.056). However, five patients demonstrated either bradycardia or asthmatic symptoms with initiation of the fixed combination therapy. One patient on latanoprost complained of dizziness. Patient preference was generally given to latanoprost (63 vs 20.3%) mainly because of its once daily dosing (P < 0001). Conclusions This study suggests that both latanoprost and the timolol/dorzolamide fixed combination are efficacious in the treatment of newly diagnosed exfoliation glaucoma. [ABSTRACT FROM AUTHOR]

Alcohol and tobacco consumption are closely correlated and published results on their association with breast cancer have not always allowed adequately for confounding between these exposures. Over 80% of the relevant information worldwide on alcohol and tobacco consumption and breast cancer were collated, checked and analysed centrally. Analyses included 58,515 women with invasive breast cancer and 95,067 controls from 53 studies. Relative risks of breast cancer were estimated, after stratifying by study, age, parity and, where appropriate, women's age when their first child was born and consumption of alcohol and tobacco. The average consumption of alcohol reported by controls from developed countries was 6.0 g per day, i.e. about half a unit/drink of alcohol per day, and was greater in ever-smokers than never-smokers, (8.4 g per day and 5.0 g per day, respectively). Compared with women who reported drinking no alcohol, the relative risk of breast cancer was 1.32 (1.19-1.45, P<0.00001) for an intake of 35-44 g per day alcohol, and 1.46 (1.33-1.61, P<0.00001) for >/=45 g per day alcohol. The relative risk of breast cancer increased by 7.1% (95% CI 5.5-8.7%; P<0.00001) for each additional 10 g per day intake of alcohol, i.e. for each extra unit or drink of alcohol consumed on a daily basis. This increase was the same in ever-smokers and never-smokers (7.1% per 10 g per day, P<0.00001, in each group). By contrast, the relationship between smoking and breast cancer was substantially confounded by the effect of alcohol. When analyses were restricted to 22 255 women with breast cancer and 40 832 controls who reported drinking no alcohol, smoking was not associated with breast cancer (compared to never-smokers, relative risk for ever-smokers=1.03, 95% CI 0.98-1.07, and for current smokers=0.99, 0.92-1.05). The results for alcohol and for tobacco did not vary substantially across studies, study designs, or according to 15 personal characteristics of the women; nor were the findings materially confounded by any of these factors. If the observed relationship for alcohol is causal, these results suggest that about 4% of the breast cancers in developed countries are attributable to alcohol. In developing countries, where alcohol consumption among controls averaged only 0.4 g per day, alcohol would have a negligible effect on the incidence of breast cancer. In conclusion, smoking has little or no independent effect on the risk of developing breast cancer; the effect of alcohol on breast cancer needs to be interpreted in the context of its beneficial effects, in moderation, on cardiovascular disease and its harmful effects on cirrhosis and cancers of the mouth, larynx, oesophagus and liver. [ABSTRACT FROM AUTHOR]

Objective: Overactive bladder (OAB) is characterized by symptoms of urinary frequency and urgency, with and without incontinence, and has been shown to have significant impact on health-related quality of life (HRQL). Currently, no OAB-specific questionnaires exist to evaluate all symptoms of OAB; thus we sought to evaluate the psychometric properties of a newly developed OAB HRQL questionnaire.Methods: The 33-item, self-administered OAB-q contains a symptom bother and HRQL scale. Both the OAB-q and SF-36 were completed by participants from two sources: (1) a community sample who screened positive for OAB in a random-digit dial telephone survey and participated in a clinical validation study (n = 254); and (2) a clinical study of patients' seeking treatment for OAB symptoms (baseline assessment) (n = 736). Item and exploratory factor analysis were performed to assess the subscale structure of the questionnaire. Psychometric evaluation was conducted to assess reliability and validity.Results: Seventy-four percent of the sample were women with mean age of 58.5. Participants with continent and incontinent symptoms reported significantly greater symptom bother and HRQL impact than normal participants. Significant differences were present among all patient groups in all OAB-q subscales (p < 0.0001) except sleep where the impact of continent and incontinent OAB was similar, but significantly worse than normal participants (p < 0.0001). Internal consistency was high with the subscale Cronbach alpha-values ranging from 0.86 to 0.94.Conclusion: The OAB-q is a reliable and valid instrument that discriminates between normal and clinically diagnosed continent and incontinent OAB participants. The OAB-q demonstrates that both continent and incontinent OAB symptoms cause significant symptom bother and have a negative impact on HRQL. [ABSTRACT FROM AUTHOR]