Social determinants of health and sepsis: a case-control study.

PURPOSE: We aimed to identify whether social determinants of health (SDoH) are associated with the development of sepsis and assess the differences between individuals living within systematically disadvantaged neighbourhoods compared with those living outside these neighbourhoods. METHODS: We conducted a single-centre case-control study including 300 randomly selected adult patients (100 patients with sepsis and 200 patients without sepsis) admitted to the emergency department of a large academic tertiary care hospital in Hamilton, ON, Canada. We collected data on demographics and a limited set of SDoH variables, including neighbourhood household income, smoking history, social support, and history of alcohol disorder. We analyzed study data using multivariate logistic regression models. RESULTS: The study included 100 patients with sepsis with a median [interquartile range (IQR)] age of 75 [58-84] yr and 200 patients without sepsis with a median [IQR] age of 72 [60-83] yr. Factors significantly associated with sepsis included arrival by ambulance, absence of a family physician, higher Hamilton Early Warning Score, and a recorded history of dyslipidemia. Important SDoH variables, such as individual or household income and race, were not available in the medical chart. In patients with SDoH available in their medical records, no SDoH was significantly associated with sepsis. Nevertheless, compared with their proportion of the Hamilton population, the rate of sepsis cases and sepsis deaths was approximately two times higher among patients living in systematically disadvantaged neighbourhoods. CONCLUSIONS: This study revealed the lack of available SDoH data in electronic health records. Despite no association between the SDoH variables available and sepsis, we found a higher rate of sepsis cases and sepsis deaths among individuals living in systematically disadvantaged neighbourhoods. Including SDoH in electronic health records is crucial to study their effect on the risk of sepsis and to provide equitable care.

RéSUMé: OBJECTIF: Nous avons cherché à déterminer si les déterminants sociaux de la santé (DSS) étaient associés à l'apparition de sepsis et à évaluer les différences entre les personnes vivant dans des quartiers systématiquement défavorisés et celles vivant à l'extérieur de ces quartiers. MéTHODE: Nous avons mené une étude cas témoins monocentrique portant sur 300 patient·es adultes sélectionné·es au hasard (100 personnes atteintes de sepsis et 200 témoins sans sepsis) admis·es au service des urgences d'un grand hôpital universitaire de soins tertiaires à Hamilton, ON, Canada. Nous avons recueilli des données démographiques et un ensemble limité de variables de DSS, y compris le revenu des ménages du quartier, les antécédents de tabagisme, le soutien social et les antécédents de troubles liés à l'alcool. Nous avons analysé les données de l'étude à l'aide de modèles de régression logistique multivariés. RéSULTATS: L'étude a inclus 100 patient·es atteint·es de sepsis avec un âge médian [écart interquartile (ÉIQ)] de 75 [58-84] ans et 200 patient·es sans sepsis avec un âge médian [ÉIQ] de 72 [60-83] ans. Les facteurs significativement associés au sepsis comprenaient l'arrivée en ambulance, l'absence de médecin de famille, un score Hamilton Early Warning Score plus élevé et des antécédents enregistrés de dyslipidémie. D'importantes variables de DSS, telles que le revenu individuel et du ménage et la race, n'étaient pas disponibles dans le dossier médical. Chez les personnes dont les DSS étaient disponibles dans leur dossier médical, aucun DSS n'était significativement associé au sepsis. Néanmoins, comparativement à leur proportion dans la population de Hamilton, le taux de cas de sepsis et de décès dus au sepsis était environ deux fois plus élevé chez les personnes vivant dans des quartiers systématiquement défavorisés. CONCLUSION: Cette étude a révélé le manque de données disponibles sur les DSS dans les dossiers de santé électroniques. Bien qu'il n'y ait pas d'association entre les variables disponibles et le sepsis, nous avons constaté un taux plus élevé de cas de sepsis et de décès dus à la septicémie chez les personnes vivant dans des quartiers systématiquement défavorisés. L'inclusion des DSS dans les dossiers de santé électroniques est cruciale pour étudier leur effet sur le risque de sepsis et pour dispenser des soins équitables.

Predicting amputation using machine learning: A systematic review.

Amputation is an irreversible, last-line treatment indicated for a multitude of medical problems. Delaying amputation in favor of limb-sparing treatment may lead to increased risk of morbidity and mortality. This systematic review aims to synthesize the literature on how ML is being applied to predict amputation as an outcome. OVID Embase, OVID Medline, ACM Digital Library, Scopus, Web of Science, and IEEE Xplore were searched from inception to March 5, 2023. 1376 studies were screened; 15 articles were included. In the diabetic population, models ranged from sub-optimal to excellent performance (AUC: 0.6-0.94). In trauma patients, models had strong to excellent performance (AUC: 0.88-0.95). In patients who received amputation secondary to other etiologies (e.g.: burns and peripheral vascular disease), models had similar performance (AUC: 0.81-1.0). Many studies were found to have a high PROBAST risk of bias, most often due to small sample sizes. In conclusion, multiple machine learning models have been successfully developed that have the potential to be superior to traditional modeling techniques and prospective clinical judgment in predicting amputation. Further research is needed to overcome the limitations of current studies and to bring applicability to a clinical setting.

Partial debridement is the most commonly reported treatment option for mucoid degeneration of the anterior cruciate ligament: a systematic review.

PURPOSE: To determine clinical outcomes and risks of various management strategies for mucoid degeneration of the anterior cruciate ligament (MD-ACL). METHODS: Three databases MEDLINE, PubMed and EMBASE were searched from inception to January 29th, 2023 for literature outlining clinical outcomes for various management strategies of MD-ACL. The authors adhered to the PRISMA and R-AMSTAR guidelines as well as the Cochrane Handbook for Systematic Reviews of Interventions. Data on satisfaction scores, visual analogue scale (VAS) scores, Lysholm scores, International Knee Documentation Committee (IKDC) scores, Knee Osteoarthritis and Outcome Scores (KOOS), range of motion and Lachman test were recorded. RESULTS: A total of 14 studies comprising 776 patients (782 knees) were included in this review. Partial debridement was reported in ten (71.4%) studies comprising 446 patients, showing significant improvements in VAS, Lysholm, IKDC scores and range of motion. Complete debridement was reported by two (14.2%) studies comprising 250 patients, and resulted in increases in Lysholm scores, KOOS, and range of motion. Reduction plasty was reported in two (14.2%) studies comprising 26 patients and showed improvements in VAS and Lysholm scores, and range of motion. Other methods of treatment included conservative management and ultrasound decompression. Complete debridement resulted in 10/23 (43%) patients with a positive Lachman test. This was followed by reduction plasty and partial debridement, with 5/26 (19.2%) and 45/340 (13.2%) patients respectively having positive Lachman or elevated knee arthrometer scores. Pivot shifting was only reported in studies on partial debridement and reduction plasty, with 14/93 (15.1%) and 1/21 (4.8%) patients have positive results, respectively. CONCLUSION: The most commonly reported management strategy for MD-ACL is partial debridement with complete debridement, reduction plasty and conservative management as alternative options. Current operative management strategies place individuals at risk for ACL insufficiency. Information from this review can aid surgeons and clinicians in understanding what treatment options are best for this patient population, by understanding the reported clinical benefits and risks of each strategy. LEVEL OF EVIDENCE: IV.

Posterior tibial slope, notch width index and tibial tubercle to trochlear groove distance contribute to development of mucoid degeneration of the anterior cruciate ligament: a systematic review.

PURPOSE: To determine what knee morphological factors are associated with the development of mucoid degeneration of the anterior cruciate ligament (ACL). METHODS: Three databases MEDLINE, PubMed and EMBASE were searched from inception to January 29th, 2023 for literature outlining knee morphological factors that potentially lead to the development of mucoid degeneration of the ACL. The authors adhered to the PRISMA and R-AMSTAR guidelines as well as the Cochrane Handbook for Systematic Reviews of Interventions. Data on receiver operating characteristic (ROC) curve parameters such as area under the curve (AUC), sensitivity and specificity, odds ratios, as well as p values for comparisons of values between mucoid degeneration of the ACL and control patients were recorded. The Methodological Index for Non-Randomized Studies (MINORS) score was used for all studies to perform a quality assessment of included studies. RESULTS: A total of 7 studies comprising 1326 patients (1330 knees) were included in this review. Four studies reported a significant association between increasing posterior tibial slope angles and mucoid degeneration of the ACL presence, with one study specifying that posterolateral tibial slope had a greater association than posteromedial tibial slope. Two studies reported a significant association between lower notch width index values and mucoid degeneration of the ACL presence. One study found that the presence of trochlear dysplasia was correlated with mucoid degeneration of the ACL and two studies found that increased tibial tuberosity-trochlear groove distance (TT-TG) was associated with mucoid degeneration of the ACL. CONCLUSION: Increased posterior tibial slope, decreased notch width index, and elevated TT-TG and trochlear dysplasia were associated with the presence of mucoid degeneration of the ACL. Information from this review can aid surgeons in understanding what morphological features predispose their patients to the development of mucoid degeneration of the ACL. Identifying what features predispose patients to mucoid degeneration of the ACL can help determine if regular screening or preventative strategies are necessary. LEVEL OF EVIDENCE: Level III.

Patients with discoid menisci have similar clinical outcomes to those without discoid menisci when undergoing surgical intervention: a systematic review.

PURPOSE: To compare post-operative clinical outcomes of discoid meniscus tear procedures such as saucerization with or without repair with those of non-discoid meniscus tears such as meniscectomy or repair in skeletally mature patients with no concomitant injuries. METHODS: Three databases MEDLINE, PubMed and EMBASE were searched from inception to July 3rd, 2022 for literature describing patient-reported outcome measures after meniscus surgery in discoid or non-discoid meniscus tears. The authors adhered to the PRISMA and R-AMSTAR guidelines as well as the Cochrane Handbook for Systematic Reviews of Interventions. Clinical outcome data on Lysholm, Tegner, International Knee Documentation Committee (IKDC), revision rates, and complications were recorded, with MINORS and Detsky scores used for quality assessment. RESULTS: A total of 38 studies comprising 2213 patients were included with a mean age of 38.6 years (range: 9.0-64.4). The mean follow-up time was 54.1 months (range: 1-234) and the average percentage of female participants was 46.8% (range: 9.5-95.5). The mean change between pre-operative and post-operative Lysholm scores ranged from 21.0-39.0, 7.4-24.1, and 24.2-48.4 in the discoid, non-discoid meniscectomy, and non-discoid repair groups, respectively. The mean change in Tegner scores ranged from 0.0 to 2.3, 1.3, and 0.4-1.3 in the discoid, non-discoid meniscectomy, and non-discoid repair groups, respectively. Pre-operative IKDC scores were not reported, however mean post-operative IKDC scores ranged from 77.4 to 96.0, 46.9 to 85.7, and 63.1 to 94.0 in discoid, non-discoid meniscectomy, and non-discoid repair groups, respectively. Revision rates for discoid procedures, non-discoid meniscectomies, and non-discoid meniscus repairs ranged from 3.2 to 44.0%, 8.3 to 56.0%, and 5.9 to 28.0%, respectively. The most common reasons for revision were acute trauma and persistent pain. CONCLUSION: Discoid saucerization procedures with or without repair leads to similar Lysholm scores as non-discoid repair procedures, and similar IKDC scores and revision rates compared to non-discoid meniscectomy or repair procedures. Patients undergoing discoid procedures appeared to have slightly higher Tegner activity scores compared to patients undergoing non-discoid procedures; however this is to be considered in the context of a younger population of patients undergoing discoid procedures than non-discoid procedures. This information can help guide surgeons in the decision-making process when treating patients with discoid menisci, and should guide further investigations on this topic. LEVEL OF EVIDENCE: IV.

An Elastic Organic Crystal Enables Macroscopic Photoinduced Crystal Elongation.

Among the various types of photomechanical deformations of organic crystals, photoinduced elongation of millimeter-scale crystals has yet to be demonstrated. Here we report that the millimeter-sized crystalline rods of an anthracene-pentiptycene hybrid organic π-system (1) are highly elastic and able to elongate up to 21.6% or 0.40 mm without fragmentation upon undergoing [4 + 4] photodimerization reactions. Both the mechanical and photomechanical effects reveal a strong cohesion of the system, even at the interface of 1 and its photodimer 2 and under the conditions of randomized molecular packing, representing a new class of mechanically adaptive organic crystals.

Laboratory monitoring to reduce adverse drug-related events: a mixed methods study.

BACKGROUND: Therapy with angiotensinconverting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs) requires laboratory monitoring to avoid hyperkalemia and acute kidney failure. OBJECTIVE: To assess the frequency of recommended annual serum potassium and creatinine monitoring and determine potential factors associated with care gaps among adults dispensed an ACEI or ARB. METHODS: This mixed-methods study integrated findings from a retrospective cohort study and individual patient interviews. Adults aged 21 years and over within Kaiser Permanente Southern California with at least 180 treatment days of an ACEI and/or ARB in 2015 were included. Patients invited for qualitative interviews included those who did and did not complete the recommended laboratory tests. We assessed the proportion of patients completing both recommended laboratory tests, factors associated with not receiving laboratory monitoring, and patients' insights into barriers and facilitators of recommended monitoring. RESULTS: Of 437,544 patients who received an ACEI or ARB, 9.0% did not receive both a serum potassium and creatinine laboratory test during treatment (defined as a care gap). Lower risk of a care gap was observed for patients with increasing age (rate ratio [RR] per 10-year increase = 0.78, 95% CI = 0.77-0.79); diabetes mellitus (RR = 0.62, 95% CI = 0.60-0.64); hypertension (RR = 0.71, 95% CI = 0.71-0.74); Charlson Comorbidity Index score of at least 2 (RR = 0.62, 95% CI = 0.60-0.64); those who changed medication classes (RR = 0.53, 95% CI = 0.51-0.56); and patients with a cardiologist (RR = 0.81, 95% CI = 0.73-0.90) or nephrologist (RR = 0.60, 95% CI = 0.52-0.69) as their prescribing provider. Twenty-five patients completed the qualitative interviews. Patients often lacked knowledge about the need for laboratory monitoring, cited logistical barriers to accessing the laboratory, and deemed the reminders they received through an outpatient safety program as a facilitator to completing tests. CONCLUSIONS: Given the large patient population on ACEI and ARB medications, monitoring and support strategies such as electronic clinical surveillance could be important in addressing care gaps and potentially reducing adverse drug effects. DISCLOSURES: This project was supported by grant number R01HS024437 from the Agency for Healthcare Research and Quality. The funder had no role in the design of the study; collection, analyses, or interpretation of the data, or decision to submit this manuscript for publication. Harrison, Reynolds, Hahn, Munoz-Plaza, Yi, Fischer, Luong, Sim, Brettler, Handler, and Mittman are employees of the Southern California Permanente Medical Group. Danworth was employed by the Southern California Permanente Medical Group at the time of this study. Singh was partially supported by the Houston VA HSR&D Center for Innovations in Quality, Effectiveness and Safety (CIN13-413). Reynolds reports grants from Novartis, Amgen Inc., and Vital Strategies, Resolve to Save Lives, unrelated to this work. Yi reports grants from Novartis unrelated to this work. Kanter has nothing to disclose.

Disparities in Stage at Diagnosis in an Equal-access Integrated Delivery System: A Retrospective Cohort Study of 7244 Patients With Bladder Cancer.

BACKGROUND: Disparities in bladder cancer survival by race/ethnicity and gender are likely related to differences in diagnosis. We assessed disparities in stage at diagnosis and potential contributing factors within a large, integrated delivery system. PATIENTS AND METHODS: We conducted a retrospective cohort study of 7244 patients with bladder cancer age ≥ 21 years diagnosed from January 2001 to June 2015 within Kaiser Permanente Southern California. Bivariate analyses compared stage at diagnosis - as well as comorbidities, health plan membership length, and health care utilization prior to diagnosis - by race/ethnicity, gender, and age. Multivariable generalized linear mixed models with urologist as a random effect were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) for diagnosis of muscle-invasive bladder cancer (MIBC) versus non-muscle-invasive bladder cancer. RESULTS: In multivariable analyses, stage at diagnosis varied significantly by race/ethnicity (P < .001). Non-Hispanic black patients had significantly higher odds of being diagnosed with MIBC than non-Hispanic white patients (OR, 1.33; 95% CI, 1.05-1.67), whereas Asian patients had significantly lower odds (OR, 0.67; 95% CI, 0.49-0.91). Women were significantly more likely to be diagnosed with MIBC than men (OR, 1.40; 95% CI, 1.22-1.61). Non-Hispanic black women had the highest proportion (39%) of MIBC diagnoses. Among Hispanic and Asian patients, a greater proportion of diagnoses occurred at younger ages. CONCLUSIONS: Health care coverage within an equal-access system did not eliminate disparities in stage at diagnosis by race/ethnicity or gender. Studies are needed to identify etiologic factors and aspects of care delivery (eg, patient-physician interactions) that may affect the diagnostic process to inform efforts to improve health equity.

Care Quality and Variability in the Use of Intravesical Therapy for Initial Treatment of Nonmuscle Invasive Bladder Cancer Within a Large, Diverse Integrated Delivery System.

OBJECTIVES: To examine treatment variability, disparities, and quality among newly diagnosed nonmuscle invasive bladder cancer (NMIBC) patients, and to identify factors associated with treatment use in a large, diverse integrated delivery system. METHODS: Retrospective cohort study of 5386 NMIBC patients diagnosed between January 2001 and June 2015 within Kaiser Permanente Southern California. Electronic health data were used to identify treatment outcomes and patient, provider, and tumor characteristics. Outcomes were use of (1) postoperative intravesical chemotherapy, (2) induction Bacille Calmette-Guérin (BCG) immunotherapy, and (3) any intravesical therapy. Multivariable odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using generalized linear mixed models with a binary outcome and urologist as a random effect. RESULTS: From 2001 to 2015, 41% of newly diagnosed NMIBC patients were treated with intravesical therapy. Postoperative chemotherapy use increased significantly over this period (OR per-year = 1.16, 95% CI: 1.07-1.25). BCG use was strongly associated with tumor characteristics: patients with high-grade or carcinoma in situ tumors were more likely to receive BCG (OR = 10.10, 95% CI: 8.39-12.16). Few treatment differences were found by sex or race/ethnicity, but were observed by age. Wide treatment variability across urologists was observed, with some urologists never using intravesical therapy as part of initial treatment while others almost always used it. Differences across urologists accounted for more variability in postoperative chemotherapy (intraclass correlation coefficient = 0.52) than BCG immunotherapy (intraclass correlation coefficient = 0.11) use. CONCLUSION: Substantial variability in initial treatment of NMIBC was observed across urologists, accounting for tumor, patient, and provider characteristics. Results suggest a considerable opportunity for quality improvement programs to reduce unwanted treatment variability and improve care for patients.

Factors That Influence Selectionof Urinary Diversion Among Bladder Cancer Patients in 3 Community-based Integrated Health Care Systems.

OBJECTIVE: To assess the relative contributions of patient and surgeon factors for predicting selection of ileal conduit (IC), neobladder (NB), or continent pouch (CP) urinary diversions (UD) for patients diagnosed with muscle-invasive/high-risk nonmuscle invasive bladder cancer. This information is needed to enhance research comparing cancer survivors' outcomes across different surgical treatment options. METHODS: Bladder cancer patients' age ≥21 years with cystectomy/UD performed from January 2010 to June 2015 in 3 Kaiser Permanente regions were included. All patient and surgeon data were obtained from electronic health records. A mixed effects logistic regression model was used treating surgeon as a random effect and region as a fixed effect. RESULTS: Of 991 eligible patients, 794 (80%) received IC. One hundred sixty-nine surgeons performed the surgeries and accounted for a sizeable proportion of the variability in patient receipt of UD (intraclass correlation coefficient = 0.26). The multilevel model with only patient factors showed good fit (area under the curve = 0.93, Hosmer-Lemeshow test P = .44), and older age, female sex, estimated glomerular filtration rate <45, 4+ comorbidity index score, and stage III/IV tumors were associated with higher odds of receiving an IC vs neobladder/continent pouch. However, including surgeon factors (annual cystectomy volume, specialty training, clinical tenure) had no association (P = .29). CONCLUSION: In this community setting, patient factors were major predictors of UD received. Surgeons also played a substantial role, yet clinical training and experience were not major predictors. Surgeon factors such as beliefs about UD options and outcomes should be explored.

Candyflipping and Other Combinations: Identifying Drug-Drug Combinations from an Online Forum.

Novel psychoactive substances (NPS) refer to synthetic compounds or derivatives of more widely known substances of abuse that have emerged over the last two decades. Case reports suggest that users combine substances to achieve desired psychotropic experiences while reducing dysphoria and unpleasant somatic effects. However, the pattern of combining NPS has not been studied on a large scale. Here, we show that posts discussing NPS describe combining nootropics with sedative-hypnotics and stimulants with plant hallucinogens or psychiatric medications. Discussions that mention sedative-hypnotics most commonly also mention hallucinogens and stimulants. We analyzed 20 years of publicly available posts from Lycaeum, an Internet forum dedicated to sharing information about psychoactive substance use. We used techniques from natural language processing and machine learning to identify NPS and correlate patterns of co-mentions of substances across posts. We found that conversations mentioning synthetic hallucinogens tended to divide into those mentioning hallucinogens derived from amphetamine and those derived from ergot. Conversations that mentioned synthetic hallucinogens tended not to mention plant hallucinogens. Conversations that mention bath salts commonly mention sedative-hypnotics or nootropics while more canonical stimulants are discussed with plant hallucinogens and psychiatric medications. All types of substances are frequently compared to MDMA, DMT, cocaine, or atropine when trying to describe their effects. Our results provide the largest analysis to date of online descriptions of patterns of polysubstance use and further demonstrate the utility of social media in learning about trends in substance use. We anticipate this work to lead to a more detailed analysis of the knowledge contained online about the patterns of usage and effects of novel psychoactive substances.

Impact of colorectal surgeon case volume on outcomes and applications to quality improvement.

PURPOSE: To evaluate the impact of surgeon case volumes on procedural, financial, and clinical outcomes in colorectal surgery and apply findings to improve hospital care quality. METHODS: A retrospective review was performed using 2013-2014 administrative data from a large hospital system in Southeast U.S. region; univariate and multivariable regression analyses were used to explore the impact of surgeon case volume on outcomes. RESULTS: One thousand one hundred ninety patients were included in this 2-year study. When compared with low-volume surgeons (LVS) (< 14 cases in 2 years), the high-volume surgeons (HVS) (> 34 cases) were estimated per case to have shorter cut-to-close time in the operation room by 79 min, ([95% CI 58 to 99]), lower total hospitalization cost by $4314, ([95% CI $2261 to $6367]), and shorter post-surgery and overall length of stay by 0.92 days, ([95% CI 0.50 to 1.35]) and 1.27 days ([95% CI 0.56 to 1.98]), respectively. The HVS also showed a higher tendency to choose a laparoscopic approach over an open approach, with an odds ratio of 3.16 ([95% CI 1.23 to 8.07]). When compared with medium-volume surgeons (MVS) (14-34 cases), the HVS were estimated per case to have shorter cut-to-close time in the operation room by 62 min ([95% CI 37 to 87]). Surgeon case volumes had no statistically significant impact on outcomes including in-hospital mortality, 30-day readmission, blood utilization, and surgical site infection (SSI). CONCLUSIONS: Surgeon case volume had positive impacts on procedural, financial, and clinical outcomes and this finding may be used to improve hospital's quality of care.

Impact of Inpatient Harms on Hospital Finances and Patient Clinical Outcomes.

OBJECTIVE: The aim of this study was to determine the impact of all-cause inpatient harms on hospital finances and patient clinical outcomes. RESEARCH DESIGN: A retrospective analysis of inpatient harm from 24 hospitals in a large multistate health system was conducted during 2009 to 2012 using the Institute of Healthcare Improvement Global Trigger Tool for Measuring Adverse Events. Inpatient harms were detected and categorized into harm (F-I), temporary harm (E), and no harm. RESULTS: Of the 21,007 inpatients in this study, 15,610 (74.3%) experienced no harm, 2818 (13.4%) experienced temporary harm, and 2579 (12.3%) experienced harm. A patient with harm was estimated to have higher total cost ($4617 [95% confidence interval (CI), $4364 to 4871]), higher variable cost ($1774 [95% CI, $1648 to $1900]), lower contribution margin (-$1112 [95% CI, -$1378 to -$847]), longer length of stay (2.6 d [95% CI, 2.5 to 2.8]), higher mortality probability (59%; odds ratio, 1.4 [95% CI, 1.0 to 2.0]), and higher 30-day readmission probability (74.4%; odds ratio, 2.9 [95% CI, 2.6 to 3.2]). A patient with temporary harm was estimated to have higher total cost ($2187 [95% CI, $2008 to $2366]), higher variable cost ($800 [95% CI, $709 to $892]), lower contribution margin (-$669 [95% CI, -$891 to -$446]), longer length of stay (1.3 d [95% CI, 1.2 to 1.4]), mortality probability not statistically different, and higher 30-day readmission probability (54.6%; odds ratio, 1.2 [95% CI, 1.1 to 1.4]). Total health system reduction of harm was associated with a decrease of $108 million in total cost, $48 million in variable cost, an increase of contribution margin by $18 million, and savings of 60,000 inpatient care days. CONCLUSIONS: This all-cause harm safety study indicates that inpatient harm has negative financial outcomes for hospitals and negative clinical outcomes for patients.

Dynamic, heterogeneous endothelial Tie2 expression and capillary blood flow during microvascular remodeling.

Microvascular endothelial cell heterogeneity and its relationship to hemodynamics remains poorly understood due to a lack of sufficient methods to examine these parameters in vivo at high resolution throughout an angiogenic network. The availability of surrogate markers for functional vascular proteins, such as green fluorescent protein, enables expression in individual cells to be followed over time using confocal microscopy, while photoacoustic microscopy enables dynamic measurement of blood flow across the network with capillary-level resolution. We combined these two non-invasive imaging modalities in order to spatially and temporally analyze biochemical and biomechanical drivers of angiogenesis in murine corneal neovessels. By stimulating corneal angiogenesis with an alkali burn in Tie2-GFP fluorescent-reporter mice, we evaluated how onset of blood flow and surgically-altered blood flow affects Tie2-GFP expression. Our study establishes a novel platform for analyzing heterogeneous blood flow and fluorescent reporter protein expression across a dynamic microvascular network in an adult mammal.

Predicting Adherence and Persistence with Oral Bisphosphonate Therapy in an Integrated Health Care Delivery System.

BACKGROUND: Examining drug exposure is essential to pharmacovigilance, especially for bisphosphonate (BP) therapy. OBJECTIVE: To examine differences in 4 measures of oral BP exposure: treatment discontinuation, adherence, persistence, and nonpersistence. METHODS: Among women aged ≥ 50 years who initiated oral BP therapy during 2002-2007 with at least 3 years of health plan membership follow-up, discontinuation was defined by evidence of no further treatment during the study observation period. Among those with at least 2 filled BP prescriptions during the study period, adherence was calculated for each year of follow-up using the (modified) proportion of days covered (mPDC) metric that allows for stockpiling of prescription/refills overlap ≤ 30 days supply. Persistence was quantified by treatment duration, allowing a gap of up to 60 days between prescription/refill days covered. Nonpersistence was quantified by the periods without drugs outside this allowable gap. Multivariable logistic regression was used to compare age and race groups and the relationships of early adherence (adherence during the first year) with subsequent adherence. RESULTS: Among 48,390 women initiating oral BP therapy and followed for 3 years, 26.7% discontinued in year 1, and 14.7% of the remaining 35,456 women discontinued in year 2. Discontinuation rates were slightly higher (29.4%, P < 0.001) for women aged ≥ 75 years and somewhat lower (21.1%, P < 0.001) for Asian women. During the first year, 60.4% of the women achieved an mPDC of ≥ 75%, with demographic differences in adherence similar to that seen for treatment discontinuation. Over the 3 years, the median mPDC levels for BP therapy were 86%, 84%, and 85% in years 1, 2, and 3, respectively, for those receiving treatment. Cumulative persistence was 2.3 years (median, IQR = 1.0-3.0) overall and slightly greater for Asian versus white women and lower for older women. There were 18,174 (42.9%) women with at least 1 period of nonpersistence during 3 years follow-up in excess of the 60-day allowable gap between prescription/refills (median cumulative nonpersistence = 0.65, IQR = 0.30-1.25 years). Women with mPDC ≥ 75% during the first year had a 12-fold and 6-fold increased odds of mPDC ≥ 75% during year 2 and year 3, respectively. CONCLUSIONS: BP discontinuation rates are highest for women during the first year. Among those continuing treatment in subsequent years, adherence rates were relatively stable. Persistence and adherence varied slightly by age and was somewhat higher in Asians, contributing to differences in cumulative BP exposure. We also found evidence that optimal adherence in the first year was highly predictive of optimal adherence in the subsequent 1-2 years. Hence, subgroups of patients receiving oral BP drugs may require different levels of support and monitoring to maximize treatment benefit, especially based on early patterns of use. DISCLOSURES: This study was supported by grants from the Kaiser Permanente Northern California Community Benefit Program and the National Institutes of Health, 1R01AG047230-01A1. The opinions expressed in this publication are solely the responsibility of the authors and do not represent the official views of Kaiser Permanente or the National Institutes of Health. Hui, Yi, and Chandra have received past research funding from Amgen not related to the current study. Adams has received research funding from Amgen, Merck, and Otsuka not related to the current study. Niu has received research funding from Bristol-Myers Squibb not related to the current study. Ettinger has received past legal fees in litigation involving Fosamax. Lo has received past research funding from Amgen and current research funding from Sanofi not related to the current study. The data from this study were presented at the Academy of Managed Care Pharmacy Annual Meeting; April 19-22, 2016; San Francisco, California. Study concept and design were contributed primarily by Hui and Lo, along with Adams, Niu, Yi, and Ettinger. Hui took the lead in data collection, along with Chandra, and data interpretation was performed by Niu, Yi, and Lo, along with the other authors. The manuscript was written by Hui, Adams, and Lo, along with Niu, Yi, and Ettinger, and revised by Ettinger, Hui, Lo, and Niu, along with the other authors.

New preventative approach for negative dysphotopsia.

PURPOSE: To evaluate whether positioning the intraocular lens (IOL) to decrease the entry of inferotemporal light would decrease the incidence of negative dysphotopsia. SETTING: Private practices, Boston and Chelmsford, Massachusetts, USA. DESIGN: Prospective randomized case study. METHODS: Patients had cataract surgery with implantation of either a silicone IOL inferotemporally or vertically (randomly assigned) or a 1-piece acrylic IOL with the optic-haptic junction inferotemporally or vertically (randomly assigned). Other patients received acrylic IOLs bilaterally and inferotemporally without randomization. Patients were asked about negative dysphotopsia symptoms postoperatively. Data were analyzed using the z test and a chi-square test for comparing the incidence of negative dysphotopsia between the 3 groups. RESULTS: The study comprised 305 patients (418 eyes). A silicone IOL was implanted inferotemporally in 39 eyes and vertically in 60 eyes. An acrylic IOL was implanted with the optic-haptic junction inferotemporally in 163 eyes and with the junction vertical in 114 eyes. Forty-two eyes had bilateral inferotemporal implantation of an acrylic IOL. For the acrylic IOL on the first postoperative day, the incidence of negative dysphotopsia was smaller for the inferotemporal IOL orientation (6%) than in the control group (14%) (P = .026). The rate of persistent negative dysphotopsia decreased in both groups over time, and the difference 1 month after surgery was no longer statistically significant. The negative dysphotopsia rate for the silicone IOL was 0%. CONCLUSIONS: Positioning the optic-haptic junction of an acrylic IOL inferotemporally resulted in a 2.3-fold decrease in the incidence of negative dysphotopsia after cataract surgery. When implanted in the vertical position, Acrylic IOLs seemed to lead to a higher incidence of negative dysphotopsia than silicone IOLs. FINANCIAL DISCLOSURE: Dr. Henderson is a consultant to Abbott Medical Optics, Inc., Alcon Laboratories, Inc., and Bausch & Lomb, Inc. None of the other authors has a financial or proprietary interest in any material or method mentioned.