Objective
To develop and validate an international set of classification criteria for primary Sjögren's syndrome (SS) using guidelines from the American College of Rheumatology (ACR) and the European ...League Against Rheumatism (EULAR). These criteria were developed for use in individuals with signs and/or symptoms suggestive of SS.
Methods
We assigned preliminary importance weights to a consensus list of candidate criteria items, using multi‐criteria decision analysis. We tested and adapted the resulting draft criteria using existing cohort data on primary SS cases and non‐SS controls, with case/non‐case status derived from expert clinical judgment. We then validated the performance of the classification criteria in a separate cohort of patients.
Results
The final classification criteria are based on the weighted sum of 5 items: anti‐SSA/Ro antibody positivity and focal lymphocytic sialadenitis with a focus score of ≥1 foci/4 mm2, each scoring 3; an abnormal ocular staining score of ≥5 (or van Bijsterveld score of ≥4), a Schirmer's test result of ≤5 mm/5 minutes, and an unstimulated salivary flow rate of ≤0.1 ml/minute, each scoring 1. Individuals with signs and/or symptoms suggestive of SS who have a total score of ≥4 for the above items meet the criteria for primary SS. Sensitivity and specificity against clinician‐expert–derived case/non‐case status in the final validation cohort were high, i.e., 96% (95% confidence interval 95% CI 92–98%) and 95% (95% CI 92–97%), respectively.
Conclusion
Using methodology consistent with other recent ACR/EULAR‐approved classification criteria, we developed a single set of data‐driven consensus classification criteria for primary SS, which performed well in validation analyses and are well‐suited as criteria for enrollment in clinical trials.
Abstract
Background
In recent years, value-based healthcare (VBHC) has become one of the most accepted concepts for fixing the ‘broken’ healthcare systems. Numerous hospitals have embraced VBHC and ...are trying to implement value-based quality improvement (VBQI) into their practice. However, there is a lack of knowledge on how to practically implement VBHC and organizations differ in their approach. The aim of this study was to explore the main factors that were experienced as hindering and/or supporting in the implementation of VBQI teams in hospital care.
Methods
A qualitative study was performed with semi-structured interviews with 43 members of eight VBQI teams in a large Dutch top-clinical teaching hospital. Participants included physicians, physician assistants, nurses, VBHC project leaders, managers, social workers, researchers and paramedics. Interview grids were structured according to the RE-AIM model (reach, effectiveness, adoption, implementation and maintenance). A thematic content analysis with open coding was used to identify emerging (sub)themes.
Results
We identified nine main factors divided over three domains (organization, culture and practice) that determined whether the implementation of VBQI teams was successful or not: 1). Practical organization of value-based quality improvement teams, 2). Organizational structure 3). Integration of VBHC with existing quality improvement approaches and research 4). Adoption and knowledge of the VBHC concept in the hospital 5). Multidisciplinary engagement 6). Medical leadership 7). Goal setting and selecting quality improvement initiatives 8). Long-cycle benchmarking and short-cycle feedback 9). Availability of outcome data.
Conclusions
Overall, this study goes beyond the general VBHC theory and provides healthcare providers with more detailed knowledge on how to practically implement value-based quality improvement in a hospital care setting. Factors in the ‘organization’ and ‘practice’ domain were mentioned in the strategic value agenda of Porter and Lee. Though, this study provides more practical insight in these two domains. Factors in the ‘culture’ domain were not mentioned in the strategic value agenda and have not yet been thoroughly researched before.
In 2021, the American Cancer Society published its first biennial report on the status of cancer disparities in the United States. In this second report, the authors provide updated data on racial, ...ethnic, socioeconomic (educational attainment as a marker), and geographic (metropolitan status) disparities in cancer occurrence and outcomes and contributing factors to these disparities in the country. The authors also review programs that have reduced cancer disparities and provide policy recommendations to further mitigate these inequalities. There are substantial variations in risk factors, stage at diagnosis, receipt of care, survival, and mortality for many cancers by race/ethnicity, educational attainment, and metropolitan status. During 2016 through 2020, Black and American Indian/Alaska Native people continued to bear a disproportionately higher burden of cancer deaths, both overall and from major cancers. By educational attainment, overall cancer mortality rates were about 1.6–2.8 times higher in individuals with ≤12 years of education than in those with ≥16 years of education among Black and White men and women. These disparities by educational attainment within each race were considerably larger than the Black–White disparities in overall cancer mortality within each educational attainment, ranging from 1.03 to 1.5 times higher among Black people, suggesting a major role for socioeconomic status disparities in racial disparities in cancer mortality given the disproportionally larger representation of Black people in lower socioeconomic status groups. Of note, the largest Black–White disparities in overall cancer mortality were among those who had ≥16 years of education. By area of residence, mortality from all cancer and from leading causes of cancer death were substantially higher in nonmetropolitan areas than in large metropolitan areas. For colorectal cancer, for example, mortality rates in nonmetropolitan areas versus large metropolitan areas were 23% higher among males and 21% higher among females. By age group, the racial and geographic disparities in cancer mortality were greater among individuals younger than 65 years than among those aged 65 years and older. Many of the observed racial, socioeconomic, and geographic disparities in cancer mortality align with disparities in exposure to risk factors and access to cancer prevention, early detection, and treatment, which are largely rooted in fundamental inequities in social determinants of health. Equitable policies at all levels of government, broad interdisciplinary engagement to address these inequities, and equitable implementation of evidence‐based interventions, such as increasing health insurance coverage, are needed to reduce cancer disparities.
Objectives The aim of this study was to assess the validity of measuring fractional flow reserve (FFR) of the left main (LM) coronary artery in the setting of concomitant left anterior descending ...(LAD) or left circumflex (LCX) stenoses. Background The theoretical impact of a stenosis in the LAD on the FFR assessment of intermediate LM disease with the pressure wire in an unobstructed LCX is currently unknown. Methods A previously validated in vitro model of the coronary circulation was used to create a fixed intermediate stenosis of the LM and a variable downstream LAD or LCX stenosis. The true LM FFR (FFRLM true ), with no concomitant downstream disease, was compared to the apparent LM FFR (FFRLM apparent ), with concomitant downstream disease measured with different degrees of LAD or LCX disease. Additionally, an equation based on a resistors model was derived to predict the effect of downstream stenosis on LM FFR (FFRLM predicted ). Results In the setting of isolated moderate LM disease (FFR 0.72 ± 0.08), mild to moderate proximal LAD or LCX lesions did not significantly affect LM FFR. Lesions with a composite FFR (LM + downstream disease) ≥0.65 resulted in an FFRLM apparent that was not significantly different from FFRLM true (0.76 ± 0.06 vs. 0.76 ± 0.05, p = 0.124). Our equation for FFRLM predicted accurately modeled the effects of concomitant disease (r = 0.95, p < 0.001). Conclusions These data suggest that in the presence of proximal mild to moderate LAD or LCX disease, LM FFR can be reliably measured with the pressure wire placed in the uninvolved epicardial artery.
Hormone‐induced spawning of southern flounder Paralichthys lethostigma has produced substantial numbers of viable eggs, but wide variations in fertilization and hatch rates have been reported. ...Recently, sustained natural spawning of southern flounder broodstock, without hormone induction, has been achieved in our laboratory. Adults (average weight = 1.12 kg; N= 25), including 6 captured as juveniles in 1993 and 19 captured as adults during September 1998, were stocked in two 4.8‐m3 controlled‐environment tanks in October 1998 and held under natural photothermal conditions until January 1999, when an artificial winter photo‐period of 10 L:14 D was initiated and then maintained through April 1999. Sex ratio was approximately 13 females:8 males:7 unknown. Natural spawning was observed in early December 1998 and increased in frequency to a peak in March 1999, before declining in late April. Water temperature ranged from 13.9 to 24.5 C during the spawning period. Natural spawnings over 142 d produced a total of 18.3 × 106 eggs, with a mean fertilization rate of 28.0% (range = 0–100%), yielding 4.94 × 106 fertilized eggs. The mean percentage of eggs that remained buoyant in full‐strength seawater (34 ppt) was 41.3% (0–98%), while hatching rate of buoyant eggs was 37.3% (0–99%) and survival of yolksac larvae to the first‐feeding stage was 30.2% (0–100%). Gonadal biopsies in late April identified six females from both tanks as probable spawners. A preliminary comparison suggests that natural spawning produced much larger numbers of viable eggs per female, with higher egg quality (i.e., fertilization and hatching success) than hormone‐induced spawning. In contrast to natural spawning, hormone‐induced strip‐spawning enabled timing of spawnings to be more precisely controlled. These results suggest that a combination of both natural and hormone‐induced spawning of photothermally conditioned fish will help produce the large numbers of eggs required to support commercial production.
Current melphalan-based intravitreal regimens for retinoblastoma (RB) vitreous seeds cause retinal toxicity. We assessed the efficacy and toxicity of topotecan monotherapy compared with melphalan in ...our rabbit model and patient cohort.
Rabbit experiments: empiric pharmacokinetics were determined following topotecan injection. For topotecan (15 μg or 30 µg), melphalan (12.5 µg) or saline, toxicity was evaluated by serial electroretinography (ERG) and histopathology, and efficacy against vitreous seed xenografts was measured by tumour cell reduction and apoptosis induction.
retrospective cohort study of 235 patients receiving 990 intravitreal injections of topotecan or melphalan.
Intravitreal topotecan 30 µg (equals 60 µg in humans) achieved the IC
across the rabbit vitreous. Three weekly topotecan injections (either 15 µg or 30 µg) caused no retinal toxicity in rabbits, whereas melphalan 12.5 µg (equals 25 µg in humans) reduced ERG amplitudes 42%-79%. Intravitreal topotecan 15 µg was equally effective to melphalan to treat WERI-Rb1 cell xenografts in rabbits (96% reduction for topotecan vs saline (p=0.004), 88% reduction for melphalan vs saline (p=0.004), topotecan vs melphalan, p=0.15). In our clinical study, patients received 881 monotherapy injections (48 topotecan, 833 melphalan). Patients receiving 20 µg or 30 µg topotecan demonstrated no significant ERG reductions; melphalan caused ERG reductions of 7.6 μV for every injection of 25 µg (p=0.03) or 30 µg (p<0.001). Most patients treated with intravitreal topotecan also received intravitreal melphalan at some point during their treatment course. Among those eyes treated exclusively with topotecan monotherapy, all eyes were salvaged.
Taken together, these experiments suggest that intravitreal topotecan monotherapy for the treatment of RB vitreous seeds is non-toxic and effective.
Expert opinion-modified Delphi study.
We used a modified Delphi approach to obtain consensus among leading spinal deformity surgeons and their neuroanesthesiology teams regarding optimal practices ...for obtaining reliable motor evoked potential (MEP) signals.
Intraoperative neurophysiological monitoring of transcranial MEPs provides the best method for assessing spinal cord integrity during complex spinal surgeries. MEPs are affected by pharmacological and physiological parameters. It is the responsibility of the spine surgeon and neuroanesthesia team to understand how they can best maintain high-quality MEP signals throughout surgery. Nevertheless, varying approaches to neuroanesthesia are seen in clinical practice.
We identified 19 international expert spinal deformity treatment teams. A modified Delphi process with two rounds of surveying was performed. Greater than 50% agreement on the final statements was considered "agreement"; >75% agreement was considered "consensus."
Anesthesia regimens and protocols were obtained from the expert centers. There was a large amount of variability among centers. Two rounds of consensus surveying were performed, and all centers participated in both rounds of surveying. Consensus was obtained for 12 of 15 statements, and majority agreement was obtained for two of the remaining statements. Total intravenous anesthesia was identified as the preferred method of maintenance, with few centers allowing for low mean alveolar concentration of inhaled anesthetic. Most centers advocated for <150 μg/kg/min of propofol with titration to the lowest dose that maintains appropriate anesthesia depth based on awareness monitoring. Use of adjuvant intravenous anesthetics, including ketamine, low-dose dexmedetomidine, and lidocaine, may help to reduce propofol requirements without negatively effecting MEP signals.
Spine surgeons and neuroanesthesia teams should be familiar with methods for optimizing MEPs during deformity and complex spinal cases. Although variability in practices exists, there is consensus among international spinal deformity treatment centers regarding best practices.
5.
Atrial fibrillation (AF) affects more than 33 million individuals worldwide
and has a complex heritability
. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to ...date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF.
Little is known about the metabolic outcomes of adolescent bariatric surgery. We report changes in weight, metabolic profile, and types of complications seen in a multicenter cohort.
One-year ...outcomes were included. For weight loss comparisons, a nonsurgical cohort (n = 12) was used. The primary outcome was weight change (n = 30) and secondary outcomes were metabolic variables (n = 24) and complications (n = 36). Data were analyzed using signed rank or paired
t tests.
Mean body mass index fell 37% (from 56.5 preoperatively to 35.8 kg/m
2;
P < .001) in surgical patients and 3% (from 47.2 to 46 kg/m
2;
P = NS) in nonsurgical patients. Surgical patients showed significant improvements in triglycerides (−65 mg/dL), total cholesterol (−28 mg/dL), fasting blood glucose (−12 mg/dL), and fasting insulin (−21
μM/mL). Improvement in high-density lipoprotein cholesterol (−3.9 mg/dL) and low-density lipoprotein cholesterol (−8.8 mg/dL) was not statistically significant. Sixty-one percent of surgical patients had no complications. Of 15 patients with complications, 9 had minor complications with no long-term sequelae, 4 had at least 1 moderate complication with sequelae for at least 1 month and 2 had at least 1 severe medical complication with long-term consequences (including beriberi and death). There were no perioperative deaths or other severe surgical complications in this series.
Postoperatively, adolescents lose significant weight and realize major metabolic improvements. The complication profile compares favorably to severely obese (body mass index >40 kg/m
2) adults; however, small sample size precludes calculation of complication rates. Although there are considerable risks of bariatric surgery, early experience suggests that risks are offset by health benefits.
Objectives
To assess the cost‐effectiveness of progesterone compared with placebo in preventing pregnancy loss in women with early pregnancy vaginal bleeding.
Design
Economic evaluation alongside a ...large multi‐centre randomised placebo‐controlled trial.
Setting
Forty‐eight UK NHS early pregnancy units.
Population
Four thousand one hundred and fifty‐three women aged 16–39 years with bleeding in early pregnancy and ultrasound evidence of an intrauterine sac.
Methods
An incremental cost‐effectiveness analysis was performed from National Health Service (NHS) and NHS and Personal Social Services perspectives. Subgroup analyses were carried out on women with one or more and three or more previous miscarriages.
Main outcome measures
Cost per additional live birth at ≥34 weeks of gestation.
Results
Progesterone intervention led to an effect difference of 0.022 (95% CI −0.004 to 0.050) in the trial. The mean cost per woman in the progesterone group was £76 (95% CI −£559 to £711) more than the mean cost in the placebo group. The incremental cost‐effectiveness ratio for progesterone compared with placebo was £3305 per additional live birth. For women with at least one previous miscarriage, progesterone was more effective than placebo with an effect difference of 0.055 (95% CI 0.014–0.096) and this was associated with a cost saving of £322 (95% CI −£1318 to £673).
Conclusions
The results suggest that progesterone is associated with a small positive impact and a small additional cost. Both subgroup analyses were more favourable, especially for women who had one or more previous miscarriages. Given available evidence, progesterone is likely to be a cost‐effective intervention, particularly for women with previous miscarriage(s).
Tweetable
Progesterone treatment is likely to be cost‐effective in women with early pregnancy bleeding and a history of miscarriage.
Tweetable
Progesterone treatment is likely to be cost‐effective in women with early pregnancy bleeding and a history of miscarriage.
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