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Indirect comparisons via a common comparator (anchored comparisons) are commonly used in health technology assessment. However, common comparators may not be available, or the comparison may be biased due to differences in effect modifiers between the included studies. Recently proposed population adjustment methods aim to adjust for differences between study populations in the situation where individual patient data are available from at least one study, but not all studies. They can also be used when there is no common comparator or for single-arm studies (unanchored comparisons). We aim to characterise the use of population adjustment methods in technology appraisals (TAs) submitted to the United Kingdom National Institute for Health and Care Excellence (NICE).
We reviewed NICE TAs published between 01/01/2010 and 20/04/2018.
Population adjustment methods were used in 7 percent (18/268) of TAs. Most applications used unanchored comparisons (89 percent, 16/18), and were in oncology (83 percent, 15/18). Methods used included matching-adjusted indirect comparisons (89 percent, 16/18) and simulated treatment comparisons (17 percent, 3/18). Covariates were included based on: availability, expert opinion, effective sample size, statistical significance, or cross-validation. Larger treatment networks were commonplace (56 percent, 10/18), but current methods cannot account for this. Appraisal committees received results of population-adjusted analyses with caution and typically looked for greater cost effectiveness to minimise decision risk.
Population adjustment methods are becoming increasingly common in NICE TAs, although their impact on decisions has been limited to date. Further research is needed to improve upon current methods, and to investigate their properties in simulation studies.
Background: Cerebellar atrophy is characterized by loss of cerebellar tissue, with evidence on brain imaging of enlarged interfolial spaces compared to the foliae. Genetic ataxias associated with cerebellar atrophy are a heterogeneous group of disorders. We investigated the prevalence in Canada and the diagnostic yield of whole exome sequencing (WES) for this group of conditions. Methods: Between 2011 and 2017, WES was performed in 91 participants with cerebellar atrophy as part of one of two national research programs, Finding of Rare Genetic Disease Genes (FORGE) or Enhanced Care for Rare Genetic Diseases in Canada (Care4Rare). Results: A genetic diagnosis was established in 58% of cases (53/91). Pathogenic variants were found in 24 known genes, providing a diagnosis for 46/53 participants (87%), and in four novel genes, accounting for 7/53 cases (13%). 38/91 cases (42%) remained unsolved. The most common diagnoses were channelopathies in 12/53 patients (23%) and mitochondrial disorders in 9/53 (17%). Inheritance was autosomal recessive in the majority of cases. Additional clinical findings provided useful clues to some of the diagnoses. Conclusions: This is the first report on the prevalence of genetic ataxias associated with cerebellar atrophy in Canada, and the utility of WES for this group of conditions.
Residual right ventricular outflow obstruction during Tetralogy of Fallot repair necessitates peri-operative revision often requiring trans-annular patch with its negative sequels. Bidirectional Glenn shunt in this setting reduces trans-pulmonary gradient to avoid revision.
Bidirectional Glenn shunt was added during Tetralogy repair in patients with significant residual obstruction. A total of 53 patients between January, 2011 and June, 2018 were included. Final follow-up was conducted in July, 2018.
Mean age at operation was 5.63±3.1 years. Right to left ventricular pressure ratio reduced significantly (0.91±0.09 versus 0.68±0.05; p<0.001) after bidirectional Glenn, avoiding revision in all cases. Glenn pressures at ICU admission decreased significantly by the time of ICU discharge (16.7±3.02 versus 13.5±2.19; p<0.001). Pleural drainage ≥ 7 days was seen in 14 (26.4%) patients. No side effects related to bidirectional Glenn-like facial swelling or veno-venous collaterals were noted. Mortality was 3.7%. Discharge echocardiography showed a mean trans-pulmonary gradient of 32.11±5.62 mmHg that decreased significantly to 25.64±5 (p<0.001) at the time of follow-up. Pulmonary insufficiency was none to mild in 45 (88.2%) and moderate in 6 (11.8%). Mean follow-up was 36.12±25.15 months (range 0.5–90). There was no interim intervention or death. At follow-up, all the patients were in NYHA functional class 1 with no increase in severity of pulmonary insufficiency.
Supplementary bidirectional Glenn shunt significantly reduced residual right ventricular outflow obstruction during Tetralogy of Fallot repair avoiding revision with satisfactory early and mid-term results.
Free convective flow and heat transfer of nanofluid close to the inclined plate immersed in the porous medium under the effects of uniform magnetic field and solar radiation has been studied. Boundary-layer approach, Boussinesq approximation and two-phase nanofluid model have been used for a formulation of the governing equations taking into account convective-radiative heat exchange with an environment. The local similarity method has been adopted for the analysis of the considered phenomenon. The obtained equations have been solved numerically using MATLAB software. The effects of control characteristics on profiles of velocity, temperature and nanoparticles volume fraction as well as Nusselt number have been studied in detail.
Audience members asked questions regarding specific practices and in particular circled around the question of other ways forward—what other practices should be used to hold actors accountable for violence, especially the often still locally neglected problem of violence against women, as well as violence against people with diverse or stigmatized gender and sexual expressions and identities.
Tools applied at the point of care can provide valuable prognostic information for practitioners. In this one-year, prospective observational study, we examined the association of the short performance physical battery (SPPB) and one-year emergency department (ED) visits and hospitalizations. Overall, 191 new referrals attending an outpatient geriatric clinic in Hamilton, Ontario, were approached, and 120 were enrolled. SPPB and other assessments were completed during the routine clinical visit. ED visits and hospitalizations within one year of the baseline assessment were abstracted from electronic medical records. Logistic regression analyses were used to determine ED visits and hospitalization predictors. The mean SPPB score in the study cohort (mean age 80.6, SD 6.3 years; 53% female) was 6.3 (SD 3.2). SPPB score was associated with a one-year ED visit (OR = 0.90 [0.78–1.03]) and hospitalization (OR = 0.84 [0.72–0.97]) after adjusting for age, sex, and co-morbidities.
Use of antibiotics as feed additives has been reduced to avoid the hazard of drug residues, and consequently, the search for alternative natural additives has developed. Thus, the aim was to evaluate the influence of royal jelly (RJ) supplementation on milk composition, blood biochemical and antioxidant parameters of lactating ewes. Thirty-six Ossimi ewes were divided randomly into two groups (18 animals each). For a period of 4 weeks, the control group (CON) was fed a basal diet only, while the other group was fed the basal diet and supplemented with a single bolus of RJ (1000 mg/head). The RJ-supplemented ewes produced significantly higher milk protein, fat and total solids than the CON group. The RJ group had a significantly higher red blood cell count, haemoglobin content, haematocrit value and total leucocyte counts, but lower neutrophil to lymphocyte ratio when compared with the control treatment. The RJ group showed significantly higher concentrations of total antioxidant capacity, superoxide dismutase activity and glutathione in the serum compared with the control treatment. In conclusion, RJ supplements can improve the nutritive value of milk fat and the serum antioxidant activities in lactating ewes.
Two-photon absorption (TPA) of Au-ion irradiated glasses in the femtosecond regime has been analyzed by an open-aperture Z scan technique. Three types of glasses, namely GIL49, BK7, and Glass B were irradiated by using 1700 keV Au+ ion beams. Samples were post-annealed at 600°C for 5 h. Penetration depth and distribution of Au+ ions having 1700 keV energy within glass substrates were estimated by transport of ions in matter (TRIM) simulations. Detailed calculations with full-damage cascades were performed for each sample, taking into account the chemical composition of glass substrates. TRIM results reveal that there is no significant change in ion range, straggling, and ion distribution with the change in the substrate composition. However, Z scan results showed a difference in TPA coefficients for all three glasses. Extent of crosslinking within each of irradiated sample, owing to its chemical composition, may have affected their TPA coefficients.
Laser-induced breakdown spectroscopy has been exploited to investigate the laser-produced lead plasma with and without external magnetic field. Plasma on the lead surface was generated by focusing a beam of a Nd:YAG laser (532 nm). An external magnetic field was applied across the laser-produced plasma; its value was varied from 0.3 to 0.7 T and the time-integrated spectra were captured at different time delays. Maximum enhancement in the neutral and ionic line intensities have been observed at 130 mJ laser energy. The neutral line of Pb at 368.34 nm reveals an enhancement factor of nearly 1.3, 1.6, and 2.3 at 0.3, 0.5, and 0.7 T, whereas the Pb ionic line at 424.49 nm shows enhancement factor of approximately 2.8 and 4.2 at 0.3 and 0.7 T. The magnetic field effects on various plasma parameters such as plasma temperature, electron number density, and emission line intensities have also been investigated. The plasma parameter “β” is found to be <1 in all the experimental conditions which signifies that the enhancement in the signal intensity is due to the plasma confinement. The increase in the emission signal intensity, number density as well as plasma temperature is observed with increasing laser energy and magnetic field. The spatial and temporal behavior reveals that the plasma temperature and electron number density decrease slowly in the applied magnetic field due to the deceleration of the plasma plume. The optimized conditions for the maximum plasma confinement and the emission intensity enhancement are observed at 130 mJ laser energy at 0.7 T magnetic field.
Objective: To summarize the findings of randomized controlled trials (RCTs) on the efficacy and safety of vitamins and minerals for migraine prophylaxis. Methods: We systematically searched bibliographic databases and relevant websites for parallel and crossover RCTs reporting efficacy and/or safety of vitamins and/or minerals for migraine prophylaxis. Our primary outcomes were migraine frequency (number of attacks) and duration (hours). Secondary outcomes were severity (intensity), days with migraine, and adverse events. Meta-analysis was conducted when analyzable data were available from at least two trials. Results: Eighteen placebo-controlled trials met our eligibility criteria. Only coenzyme Q10 and magnesium contributed to meta-analyses. In adults, compared with placebo, coenzyme Q10 did not significantly decrease migraine frequency (mean difference (MD) −0.44 (−2.14 to 1.26); I2 53%; 2 trials; 97 participants; moderate strength of the evidence), duration (MD −1.97 (−4.82 to 0.87); I2 0%; 2 trials; 97 participants; moderate strength of the evidence), or severity (ratio of means (RoM) −0.05 (−0.20 to 0.11); I2 0%; 2 trials; 97 participants). In adults, compared with placebo, magnesium did not significantly decrease migraine severity (RoM −0.17 (−0.36 to 0.02); I2 48%; 3 trials; 226 participants; low strength of the evidence). Meta-analysis of other vitamins and minerals, and other outcomes were not feasible due to a lack of sufficiently reported data. Conclusions: Based on insufficient evidence, it is unknown if coenzyme Q10 and magnesium are effective for migraine prophylaxis in adults. High-quality, adequately powered RCTs are needed to fully evaluate the efficacy and safety of vitamins and minerals for migraine prophylaxis.
Beyond medical schools’ historical focus on pillar missions including clinical care, education, and research, several medical schools now include community engagement (CE) as a mission. However, most academic health systems (AHSs) lack the tools to provide metrics, evaluation, and standardization for quantifying progress and contributions of the CE mission. Several nationwide initiatives, such as that driven by the Institute of Medicine recommending advances in CE metrics at institutions receiving Clinical and Translational Science Awards, have encouraged the research and development of systematic metrics for CE, but more progress is needed. The CE components practical model provides a foundation for analyzing and evaluating different types of CE activities at AHSs through five components: research, education, community outreach and community service, policy and advocacy, and clinical care. At the Medical College of Wisconsin (MCW), an annual survey administered to faculty and staff assessed the types and number of CE activities from the prior year. Survey results were combined to create a CE report for departments across the institution and inform MCW leadership. Insights gathered from the survey have contributed to next steps in CE tracking and evaluation, including the development of a CE dashboard to track CE activities in real time. The dashboard provides resources for how individuals can advance the CE mission through their work and guide CE at the institutional level.
Adenoid hypertrophy is a common cause of upper airway obstruction, and adenoidectomy is one of the most frequently performed operations in children. Topical nasal steroids can act directly on nasopharyngeal lymphoid tissue to decrease its reactive inflammatory changes and potentially reduce its size.
To study the light microscopic changes in adenoidal lymphoid tissue after one month of topical steroid use.
Twenty-six children with adenoid hypertrophy grade 3 scheduled for adenoidectomy were randomly divided into two equal groups: one group received mometasone furoate aqueous nasal spray (Nasonex) 100 mcg/day for four weeks, and a control group received nasal normal saline 0.9 per cent for four weeks. The removed adenoids were examined histopathologically.
Adenoidal tissue from the mometasone group had less reactive germinal centres and less spongiosis compared to the control group. The latter showed proliferating, reactive, variable sized and shaped lymphoid follicles, with congested blood vessels in the interfollicular areas.
The use of intranasal mometasone furoate aqueous nasal spray (Nasonex) for one month reduced adenoidal tissue reactive cellular changes and its vascularity. This is, however, a pilot study; a longer treatment period is needed to assess the effect of treatment on adenoidal size.
To investigate a Middle East respiratory syndrome coronavirus (MERS-CoV) outbreak event involving multiple healthcare facilities in Riyadh, Saudi Arabia; to characterize transmission; and to explore infection control implications.
Cases presented in 4 healthcare facilities in Riyadh, Saudi Arabia: a tertiary-care hospital, a specialty pulmonary hospital, an outpatient clinic, and an outpatient dialysis unit.
Contact tracing and testing were performed following reports of cases at 2 hospitals. Laboratory results were confirmed by real-time reverse transcription polymerase chain reaction (rRT-PCR) and/or genome sequencing. We assessed exposures and determined seropositivity among available healthcare personnel (HCP) cases and HCP contacts of cases.
In total, 48 cases were identified, involving patients, HCP, and family members across 2 hospitals, an outpatient clinic, and a dialysis clinic. At each hospital, transmission was linked to a unique index case. Moreover, 4 cases were associated with superspreading events (any interaction where a case patient transmitted to ≥5 subsequent case patients). All 4 of these patients were severely ill, were initially not recognized as MERS-CoV cases, and subsequently died. Genomic sequences clustered separately, suggesting 2 distinct outbreaks. Overall, 4 (24%) of 17 HCP cases and 3 (3%) of 114 HCP contacts of cases were seropositive.
We describe 2 distinct healthcare-associated outbreaks, each initiated by a unique index case and characterized by multiple superspreading events. Delays in recognition and in subsequent implementation of control measures contributed to secondary transmission. Prompt contact tracing, repeated testing, HCP furloughing, and implementation of recommended transmission-based precautions for suspected cases ultimately halted transmission.
The relative velocity and extra pressure drop of a single vesicle flowing through a square microchannel are quantified via boundary element simulations, lubrication theory and microfluidic experiments. The vesicle is modelled as a fluid sac enclosed by an inextensible, fluidic membrane with a negligible bending stiffness. All results are parametrized in terms of the vesicle sphericity (i.e. the reduced volume) and flow confinement (i.e. the ratio of the vesicle radius to the channel hydraulic radius). Direct comparison is made to previous studies of vesicle flow through circular tubes, revealing several distinct features of the square-channel geometry. Firstly, fluid in the suspending medium bypasses the vesicle through the corners of the channel, which in turn reduces the dissipation created by the vesicle. Secondly, the absence of rotational symmetry about the channel axis permits surface circulation in the membrane (tank treading), which in turn reduces the vesicle’s speed. At very high confinement, both theory and experiment indicate that the vesicle’s speed can be reduced below the mean speed of the suspending fluid through this mechanism. Finally, the contact area for lubrication is greatly reduced in the square-duct geometry, which in turn weakens the stress singularity predicted by lubrication theory. This fact directly leads to a breakdown of the lubrication approximation at low flow confinement, as verified by comparison to boundary element simulations. Since the only distinct property assumed of the membrane is its ability to preserve surface area locally, it is expected that the results of this study are applicable to other types of soft particles with immobilized surfaces (e.g. Pickering droplets, gel beads and biological cells).
The current research paper addresses the hypothesis that management system (grazing vs. stabling) and/or stage of lactation (early- to late-lactation) can influence the lactation performance and milk fatty acid (MFA) profile in dromedary camels. The results obtained revealed that milk and protein yields of stabled camels were higher, while milk fat content was lower compared to grazing camels. In addition, stabled camels produced milk richer in short- and medium-chains fatty acids but lower in long-chain fatty acids and fatty acids linked with possible health benefits such as oleic acid, vaccenic acid (VA) and rumenic acid (RA), when compared to grazing camels. Moreover, atherogenicity index was higher, while overall Δ9-desaturase and health-promoting indices were lower in stabled camels. In a similar way, results demonstrated an increase in milk fat and protein contents as lactation advanced. In fact, camels at mid-lactation produced milk richer in short- and medium-chain fatty acids as well as total saturated fatty acids but poorer in oleic acid, VA, RA, long-chain fatty acids and total unsaturated fatty acids, when compared to milk samples collected at early stage of lactation. Moreover, compared to early- and late-lactations, atherogenicity index was higher while overall-Δ9-desaturase and health promoting indexes were lower at mid-lactation. In conclusion, the intensive stabling system and mid-lactation stage can alter lactation performance and MFA profile in dairy dromedary camels.
The elastic polymer composite embedded with carbon nanotubes (CNTs) is an ideal candidate for stretchable and flexible sensor fabrication due to the perfect combination between the excellent properties of CNTs and the high stretchability of the elastomer. A cube model of nanotube/polymer composite is constructed to comprehensively and theoretically analyze its electrical behavior, which is dominantly governed by the CNT network. The aspect ratio and alignment of CNTs significantly influence both the percolation threshold range and the electrical conductivity; however, the electrical conductivity of CNTs has little impact on the percolation threshold. The piezoresistivity of the composite is not only governed by the property of CNTs but also by the mechanical property of the polymer matrix, including the Poisson’s ratio and alignment of CNTs. The specific reasons why the composite resistance rises when it is stretched are investigated. Finally, one optimizing suggestion is given for making the CNTs/polymer composite with high sensitivity.
Objectives: The Addenbrooke’s Cognitive Examination (ACE) is a common cognitive screening test for dementia. Here, we examined the relationship between the most recent version (ACE-III) and its predecessor (ACE-R), determined ACE-III cutoff scores for the detection of dementia, and explored its relationship with functional ability. Methods: Study 1 included 199 dementia patients and 52 healthy controls who completed the ACE-III and ACE-R. ACE-III total and domain scores were regressed on their corresponding ACE-R values to obtain conversion formulae. Study 2 included 331 mixed dementia patients and 87 controls to establish the optimal ACE-III cutoff scores for the detection of dementia using receiver operator curve analysis. Study 3 included 194 dementia patients and their carers to investigate the relationship between ACE-III total score and functional ability. Results: Study 1: ACE-III and ACE-R scores differed by ≤1 point overall, the magnitude varying according to dementia type. Study 2: a new lower bound cutoff ACE-III score of 84/100 to detect dementia was identified (compared with 82 for the ACE-R). The upper bound cutoff score of 88/100 was retained. Study 3: ACE-III scores were significantly related to functional ability on the Clinical Dementia Rating Scale across all dementia syndromes, except for semantic dementia. Conclusions: This study represents one of the largest and most clinically diverse investigations of the ACE-III. Our results demonstrate that the ACE-III is an acceptable alternative to the ACE-R. In addition, ACE-III performance has broader clinical implications in that it relates to carer reports of functional impairment in most common dementias. (JINS, 2018, 24, 854–863)