Outdoor light at night, genetic predisposition and type 2 diabetes mellitus: A prospective cohort study.

BACKGROUND: According to animal and human epidemiologic studies, exposure to outdoor light at night (LAN) may cause circadian disruption, which may disturb sleep quality and lead to incident type 2 diabetes mellitus (T2DM). METHODS: We followed 283,374 persons from 2006 through 2020. Outdoor LAN exposure was estimated using satellite data for individual address with 500 m2 scale buffer during follow-up. Incidence of T2DM was confirmed by hospital inpatient records. We identified potential confounders by a directed acyclic graph, including demographic, genetic, individual and regional level socioeconomic status, and environmental risk factors, and calculated hazard ratios (HRs) and 95% confidence intervals (CIs) through time-varying Cox proportional hazard model. Furthermore, we examined the association of outdoor LAN with a defined health sleep scores and moderation of genetic predisposition and shift work on the relationship of outdoor LAN and incident T2DM. RESULTS: We identified 7,775 incident T2DM cases over 3,027,505 person-years. Higher outdoor LAN exposures were significantly associated with higher risk of T2DM. The estimated HR for incident T2DM with an interquartile range (IQR: 11.22 nW/cm2/sr) increase in outdoor LAN was 1.05 (95%CI: 1.01, 1.09) in the fully adjusted model. Participants who lived in the highest quarter of outdoor LAN area were more likely to develop T2DM (HR: 1.14,95%CI: 1.02, 1.27). Besides, those who were exposed to higher levels of outdoor LAN had poorer sleep quality. No moderation role of PRS on outdoor LAN-induced T2DM observed both on the multiplicated and additive scale. The hazards of outdoor LAN were observed in those who never owned a night shift work. CONCLUSION: Although further work is required to clarify potential mechanisms, our findings indicate that exposure to residential outdoor LAN may contribute to T2DM risk and low sleep quality.

How are the processing and nutrient dimensions of foods interconnected? an issue of hierarchy based on three different food scores.

Worldwide, foods are scored with composition indices. However, processing scores are now emerging. The objective of this study was to study the interconnectedness of the degree of processing and composition for 28,747 industrially packaged foods (71.6% of ultra-processed foods, UPFs) representative of retail assortments. The Nutri-score and Traffic Light Labelling System (TLLS) were used to assess the composition, and the Siga index was used to assess the degree of processing. On average, the more nutritionally favourable Nutri-score and TLLS groups exhibited 56.5 and 50.0% UPFs, respectively. Among markers of ultra-processing non-additives mostly included added fat/sugar/fibre/vitamin, animal and/or plant protein isolates, and taste exhausters, while additives mostly included sweeteners and taste exhausters, suggesting that markers of ultra-processing (MUP) are added to foods to improve composition scores. In conclusion, both types of scores are not complementary as such but obey to a fundamental hierarchy: processing first, then composition if necessary.

Organic food retailing: to what extent are foods processed and do they contain markers of ultra-processing?

In France, around 70% of conventional industrial foods are ultra-processed, with no data for organic foods. The objectives of this study were to evaluate the percentage of ultra-processed foods (UPFs) in industrially packaged organic (n = 8554) and conventional (n = 45,791) foods, and to describe their marker of ultra-processing (MUP) profiles. The percentage of UPFs and MUP profiles were determined with the Siga methodology. UPF percentages were 53% in organic foods and 74% in conventional foods, and there was 8% more organic UPFs in conventional stores than in organic stores. The more additive MUPs are used, the greater the quantity of nonadditive MUPs. Conventional UPFs contained twice as many total MUPs as organic UPFs. Main MUPs in organic UPFs were refined oils, extracts and natural aromas, native starches, glucose syrup, lecithins and citric acid. Organic foods are, therefore, overall less ultra-processed although still containing high levels of nonadditive MUPs.

Short-term outcomes of lateral lumbar interbody fusion without decompression for the treatment of symptomatic degenerative spondylolisthesis at L4-5.

OBJECTIVE Recently, authors have called into question the utility and complication index of the lateral lumbar interbody fusion procedure at the L4-5 level. Furthermore, the need for direct decompression has also been debated. Here, the authors report the clinical and radiographic outcomes of transpsoas lumbar interbody fusion, relying only on indirect decompression to treat patients with neurogenic claudication secondary to Grade 1 and 2 spondylolisthesis at the L4-5 level. METHODS The authors conducted a retrospective evaluation of 18 consecutive patients with Grade 1 or 2 spondylolisthesis from a prospectively maintained database. All patients underwent a transpsoas approach, followed by posterior percutaneous instrumentation without decompression. The Oswestry Disability Index (ODI) and SF-12 were administered during the clinical evaluations. Radiographic evaluation was also performed. The mean follow-up was 6.2 months. RESULTS Fifteen patients with Grade 1 and 3 patients with Grade 2 spondylolisthesis were identified and underwent fusion at a total of 20 levels. The mean operative time was 165 minutes for the combined anterior and posterior phases of the operation. The estimated blood loss was 113 ml. The most common cage width in the anteroposterior dimension was 22 mm (78%). Anterior thigh dysesthesia was identified on detailed sensory evaluation in 6 of 18 patients (33%); all patients experienced resolution within 6 months postoperatively. No patient had lasting sensory loss or motor deficit. The average ODI score improved 26 points by the 6-month follow-up. At the 6-month follow-up, the SF-12 mean Physical and Mental Component Summary scores improved by 11.9% and 9.6%, respectively. No patient required additional decompression postoperatively. CONCLUSIONS This study offers clinical results to establish lateral lumbar interbody fusion as an effective technique for the treatment of Grade 1 or 2 degenerative spondylolisthesis at L4-5. The use of this surgical approach provides a minimally invasive solution that offers excellent arthrodesis rates as well as favorable clinical and radiological outcomes, with low rates of postoperative complications. However, adhering to the techniques of transpsoas lateral surgery, such as minimal table break, an initial look-and-see approach to the psoas, clear identification of the plexus, minimal cranial caudal expansion of the retractor, mobilization of any traversing sensory nerves, and total psoas dilation times less than 20 minutes, ensures the lowest possible complication profile for both visceral and neural injuries even in the narrow safe zones when accessing the L4-5 disc space in patients with degenerative spondylolisthesis.

Impact of case type, length of stay, institution type, and comorbidities on Medicare diagnosis-related group reimbursement for adult spinal deformity surgery.

OBJECTIVE The aim of this study was to educate medical professionals about potential financial impacts of improper diagnosis-related group (DRG) coding in adult spinal deformity (ASD) surgery. METHODS Medicare's Inpatient Prospective Payment System PC Pricer database was used to collect 2015 reimbursement data for ASD procedures from 12 hospitals. Case type, hospital type/location, number of operative levels, proper coding, length of stay, and complications/comorbidities (CCs) were analyzed for effects on reimbursement. DRGs were used to categorize cases into 3 types: 1) anterior or posterior only fusion, 2) anterior fusion with posterior percutaneous fixation with no dorsal fusion, and 3) combined anterior and posterior fixation and fusion. RESULTS Pooling institutions, cases were reimbursed the same for single-level and multilevel ASD surgery. Longer stay, from 3 to 8 days, resulted in an additional $1400 per stay. Posterior fusion was an additional $6588, while CCs increased reimbursement by approximately $13,000. Academic institutions received higher reimbursement than private institutions, i.e., approximately $14,000 (Case Types 1 and 2) and approximately $16,000 (Case Type 3). Urban institutions received higher reimbursement than suburban institutions, i.e., approximately $3000 (Case Types 1 and 2) and approximately $3500 (Case Type 3). Longer stay, from 3 to 8 days, increased reimbursement between $208 and $494 for private institutions and between $1397 and $1879 for academic institutions per stay. CONCLUSIONS Reimbursement is based on many factors not controlled by surgeons or hospitals, but proper DRG coding can significantly impact the financial health of hospitals and availability of quality patient care.

The holistico-reductionist Siga classification according to the degree of food processing: an evaluation of ultra-processed foods in French supermarkets.

The qualitative NOVA classification of foods according to their degree of processing is used worldwide by researchers. NOVA defines ultra-processed foods (UPFs) by the presence of processed industrial ingredients and additives to modify the sensory properties (aroma, taste, colour and texture) of reconstituted food, named 'cosmetic' compounds, i.e., modifying food appearance. Some drastic processes directly applied to food are also markers of ultra-processing. However, with the intent to develop an elaborate tool for industries and retailers, the Siga classification was developed by combining the four holistic NOVA groups with four more new reductionist subgroups considering the impact of processing on the food/ingredient matrix; the contents of added salt, sugar and fat; the nature and number of markers of ultra-processing (MUPs); and the levels of at-risk additives (groups are unprocessed, A0; minimally processed foods, A1; culinary ingredients, A2; balanced foods, B1/C0.1; high salt, sugar and/or fat level foods, B2/C0.2; processed/ultra-processed foods; and UPFs with more than one MUP, C1). The Siga algorithm was used to characterize 24 932 packaged foods in French supermarkets (baby foods and alcohol excluded), which were representative of the packaged food assortments. The main results showed that two-thirds of the products were ultra-processed. Products with more than one MUP (C1) corresponded to the most represented category, accounting for 54% of the products. Among foods with more than five ingredients, 75% were UPFs. Considering all products, the average number of ingredients, MUPs and at-risk additives were 10.1, 2.6 and 0.5, respectively. Among food categories, some contained a high percentage of UPFs: 94, 95, 95, 81, 80, and 87% for salted meats, cooked dishes, flavoured yogurts/white cheeses, energy and gourmet bars, breakfast cereals, and vegetarian dishes, respectively. Finally, the Siga algorithm presents a useful tool for improving the health potential of packaged food and for decision-making on search engine optimization (SEO) policy and assortment management in supermarkets.

Patient Selection in Cervical Disc Arthroplasty.

BACKGROUND: Patient selection for cervical disc arthroplasty (CDA) in the United States remains a topic of debate among surgeons. Many surgeons base US patient selection for CDA implantation on the Food and Drug Administration (FDA) indications/contraindications. While off-label use does occur, the frequency and extent of off-label use in the US remains largely unknown. Outside the United States, patient selection is notably less stringent; however such data also remain largely unpublished or presented/published with a low level of evidence. Here, we will review the current approved US on-label patient selection criteria for CDA and discuss the rationale and supporting evidence to expand these criteria in the United States. METHODS: A PubMed literature search was completed using the keywords "cervical disc arthroplasty" and "cervical disc replacement." The articles were evaluated by the authors for patient selection criteria. CONCLUSIONS: The current published data do not conclusively prove that the patients excluded from CDA by strict adherence to FDA indications would benefit from CDA surgery over anterior cervical discectomy and fusion. As surgeons, it is a difficult decision regarding when to expand indications to include off-label use of CDA. In our practice, generally CDA patient selection agrees with the FDA indications and contraindications, as there is a lack of level 1 evidence to confirm effectiveness of CDA outside of the current FDA indications. We will likely need more well-constructed studies to include prospective and controlled trials that specifically evaluate the "off-label" applications before US surgeons are convinced to expand indications and insurance companies agree to reimburse.

Adjacent Segment Pathology After Treatment With Cervical Disc Arthroplasty or Anterior Cervical Discectomy and Fusion, Part 1: Radiographic Results at 7-Year Follow-Up.

BACKGROUND: Adjacent segment pathology (ASP) remains a concern following treatment with cervical disc arthroplasty (CDA) and anterior cervical discectomy and fusion (ACDF). Radiographic ASP (RASP) is ASP identified on imaging, which may or may not include clinical symptoms. The risk factors for development of RASP and its clinical effects remain controversial. In part 1 of a 2-part publication we evaluate the incidence and predictors of RASP as well as determine whether any association exists between RASP and patient-reported outcomes (PROs). METHODS: Data were prospectively collected during a US Food and Drug Administration randomized, multicenter, investigational device exemption trial comparing CDA (Mobi-C; Zimmer Biomet, Westminster, CO) with ACDF. Multiple post hoc analyses were conducted on RASP as it related to demographics and patient outcomes. Kaplan-Meier estimates of time to Kellgren-Lawrence (K-L) grade 3/4 were calculated separately for all groups. Multivariate Cox proportional hazard models were used analyze whether RASP was associated with patient preoperative demographic characteristics and preoperative and postoperative radiographic characteristics. The association of RASP with PROs was analyzed using generalized estimating equations and matched, retrospective cohort analysis. RESULTS: The incidence of grade 3/4 RASP was lower for patients treated with CDA when initial treatment was at 1 level (27% vs 47%, P < .0001) and at 2 levels (14% vs 49%, P < .0001). Kaplan-Meier estimates indicated significantly lower probability of grade 3/4 RASP over time for patients receiving CDA (P < .001). Treatment with ACDF, treatment of 1 level, higher age, body mass index, higher preoperative physical components score, and a lower Cobb angle were associated with elevated risk of grade 3/4 RASP. CDA was shown to be more effective than ACDF (64.4%; 95% CI = 50.9, 74.2; P < .0001) at preventing RASP. CONCLUSIONS: The incidence and risk of RASP is decreased when patients are treated with CDA compared with ACDF. Although the mechanism of CDA that generates this protective effect is not understood, PROs remain unaffected through 7 years despite changes in RASP.

Adjacent Segment Pathology After Treatment With Cervical Disc Arthroplasty or Anterior Cervical Discectomy and Fusion, Part 2: Clinical Results at 7-Year Follow-Up.

BACKGROUND: Adjacent segment pathology (ASP) following cervical disc arthroplasty (CDA) or anterior cervical discectomy and fusion (ACDF) is identified by imaging (RASP) or clinical symptoms (CASP). Clinical symptoms of CASP have been broadly defined, but subsequent adjacent-level surgeries are clear indicators of CASP. Current literature remains inconsistent in the incidence and potential predictors of CASP. Here, we will evaluate a robust data set for the incidence of CASP resulting in subsequent surgery, attempt to identify factors that might affect CASP, and analyze the association of CASP with patient-reported outcomes (PROS) and RASP. METHODS: Data were prospectively collected during a US Food and Drug Administration randomized, multicenter, investigational device exemption trial comparing CDA (Mobi-C, Zimmer Biomet, Westminster, CO) with ACDF. CASP was defined as any adjacent-level subsequent surgical intervention. Post hoc analyses were conducted on the incidence, time to CASP diagnosis, and relationship of CASP with patient demographics. Longitudinal retrospective case-control analysis was used to assess the correlation of CASP to PROs and radiographic adjacent segment pathology (RASP). RESULTS: Kaplan-Meier estimates indicated significantly lower probability of CASP over time for 1-level (P = .002) and 2-level (P = .008) CDA patients. Treatment with ACDF and younger age were associated with higher CASP risk. CDA was more effective than ACDF (70.5%; 95% CI = 45.1, 84.2; P < .0001) at preventing CASP. Case-control analysis indicated increased probability of CASP for patients with grade 3/4 RASP, but the difference was not statistically significant. When we pooled CASP patients, the median grade of RASP at the visit prior to surgery was 1, with only 6 patients presenting with grade 3/4 RASP. CONCLUSIONS: Patients treated with CDA have a lower incidence of CASP than do patients treated with ACDF, although the mechanism remains unclear. CASP and RASP remain uncorrelated in this large data set, but other predictive variables such as treatment, age, and number of levels should be further investigated.

Synthesis and SAR of potent LXR agonists containing an indole pharmacophore.

A novel series of 1H-indol-1-yl tertiary amine LXR agonists has been designed. Compounds from this series were potent agonists with good rat pharmacokinetic parameters. In addition, the crystal structure of an LXR agonist bound to LXRalpha will be disclosed.

Cervical Disc Arthroplasty: Current Evidence and Real-World Application.

Cervical total disc replacement (cTDR) is still considered a developing technology, with widespread clinical use beginning in the early 2000s. Despite being relatively new to the marketplace, the literature surrounding cTDR is abundant. We conducted a thorough review of literature published in the United States (US) and outside the US to report the current global state of cTDR research and clinical use. Search criteria were restricted to publications with a clinical patient population, excluding finite element analyses, biomechanical studies, cadaver studies, surgical technique-specific papers, and case studies. US publications mostly encompass the results of the highly controlled Food and Drug Administration Investigational Device Exemption trials. The predominantly level I evidence in the US literature supports the use of cTDR at 1 and 2 surgical levels when compared to anterior cervical discectomy and fusion. In general, the outside the US studies typically have smaller patient populations, are rarely controlled, and include broader surgical indications. Though these studies are of lower levels of evidence, they serve to advance patient indications in the use of cTDR. Complications such as secondary surgery, heterotopic ossification, and adjacent segment degeneration also remain a focus of studies. Other external challenges facing cTDR technology include regulatory restrictions and health economics, both of which are beginning to be addressed. Combined, the evidence for cTDR is robust supporting a variety of clinical indications.

Heterotopic Ossification After Cervical Total Disc Replacement at 7 Years-Prevalence, Progression, Clinical Implications, and Risk Factors.

BACKGROUND: Heterotopic ossification (HO) is a known risk following cervical total disc replacement (CTDR) surgery, but the cause and effect of HO are not well understood. Reported HO rates vary, and few studies are specifically designed to report HO. The effects on outcomes, and the risk factors for the development of HO have been hypothesized and reported in small-population, retrospective analyses, using univariate statistics. METHODS: Posthoc, multiple-phase analysis of radiographic, clinical, and demographic data for CTDR as it relates to HO was performed. HO was radiographically graded for 164 one-level and 225 two-level CTDR patients using the McAfee and Mehren system. Analysis was performed to correlate HO grades to clinical outcomes and to evaluate potential risk factors for the development of HO using demographics and baseline clinical measures. RESULTS: At 7 years, 1-level clinically relevant HO grades were 17.6% grade 3 and 11.1% grade 4. Two-level clinically relevant HO grades, evaluated using the highest patient grade, were 26.6% grade 3 and 10.8% grade 4. Interaction between HO and time revealed significance for neck disability index (NDI; P = .04) and Visual Analog Scale (VAS) neck pain (P = .02). When analyzed at each time point NDI was significant at 48-84 months and VAS neck at 60 months. For predictors 2 analyses were run; odds ratios indicated follow-up visit, male sex, and preoperative VAS neck pain are related to HO development, whereas hazard ratios indicated male sex, obesity, endplate coverage, levels treated, and preoperative VAS neck pain. CONCLUSIONS: This is the largest study to report HO rates, and related outcomes and risk factors. To develop an accurate predictive model, further large-scale analyses need to be performed. Based on the results reported here, clinically relevant HO should be more accurately described as motion-restricting HO until a definitive link to outcomes has been established.

Investigation of the utility of published in vitro intrinsic clearance data for prediction of in vivo clearance.

INTRODUCTION: This study was conducted to compare and contrast published in vitro intrinsic clearance values reported for compounds from different laboratories and the predictivity of these data to project in vivo clearance. METHODS: A total of 103 compounds were selected for investigation and an exhaustive literature search was conducted to identify in vitro intrinsic clearance (CL,i) values for comparative purposes. The simple well-stirred model was used to predict in vivo clearance using these in vitro intrinsic clearance values. RESULTS: Data were available in the literature for <10% of the compounds of interest in rat, dog, monkey, or human S9, as well as <10% for dog or monkey microsomes or hepatocytes. Therefore, this comparative exercise was limited to rat and human microsomes and hepatocytes. Examination of the available CL,i values indicated a substantial (up to 100 s-fold) variation in values reported in the literature; this variability translated into substantial variation in predicted in vivo clearance. DISCUSSION: The literature paucity and variability described here demonstrate the importance of generating experimentally consistent de novo CL,i data for the purpose of method validation or in vitro-in vivo scaling.

Neurological Complications after Lateral Transpsoas Approach to Anterior Interbody Fusion with a Novel Flat-Blade Spine-Fixed Retractor.

Introduction. The lateral lumbar interbody fusion (LLIF) surgical approach has potential advantages over other approaches but is associated with some unique neurologic risks due to the proximity of the lumbosacral plexus. The present study analyzed complications following LLIF surgical approach using a novel single flat-blade retractor system. Methods. A retrospective data collection of patients receiving LLIF using a novel single flat-blade retractor system at two institutions in the US. Inclusion criteria were all patients receiving an LLIF procedure with the RAVINE® Lateral Access System (K2M, Inc., Leesburg, VA, USA). There was no restriction on preoperative diagnosis or number of levels treated. Approach-related neurologic complications were collected and analyzed postoperatively through a minimum of one year. Results. Analysis included 253 patients with one to four treated lateral levels. Immediate postoperative neurologic complications were present in 11.1% (28/253) of patients. At one-year follow-up the approach-related neurologic complications resolved in all except 5 patients (2.0%). Conclusion. We observed an 11.1% neurologic complication rate in LLIF procedures. There was resolution of symptoms for most patients by 12-month follow-up, with only 2% of patients with residual symptoms. This supports the hypothesis that the vast majority of approach-related neurologic symptoms are transient.

Preliminary Results of Bioactive Amniotic Suspension with Allograft for Achieving One and Two-Level Lumbar Interbody Fusion.

BACKGROUND: Bone graft material for lumbar fusion was historically autologous bone graft (ABG). In recent years alternatives such as allograft, demineralized bone matrix (DBM), ceramics, and bone morphogenetic protein (BMP) have gained favor, although the complications of these are not fully understood. Bioactive amniotic suspension (BAS) with allograft is a new class of material derived from human amniotic tissue. METHODS: Eligible patients receiving a one or two level lumbar interbody fusion with Nucel, a BAS with allograft, were contacted and scheduled for a mininmim 12 month follow-up visit. Patients were evaluated for fusion using CT's and plain radiographs. Clincal outcomes, including ODI, VAS back and leg were collected, as well as comorbidities including BMI, smoking status, diabetes and previous lumbar surgery. RESULTS: One-level patients (N=38) were 71.1% female with mean age of 58.4 ± 12.7 and mean BMI of 30.6 ± 6.08. Two-level patients (N=34) were 58.8% female with mean age of 49.3 ±10.9 and mean BMI of 30.1 ± 5.82. Kinematic fusion was achieved in 97.4% of one-level patients and 100% of two-level patients. Baseline comorbidities were present in 89.5% of one-level patients and 88.2% of two-level patients. No adverse events related to BAS were reported in this study. CONCLUSION: Fusion status is evaluated with many different biologics and varying methods in the literature. BAS with allograft in this study demonstrated high fusion rates with no complications within a largely comorbid population. Although a small population, BAS with allograft results were encouraging for one and two-level lumbar interbody fusion in this study. Further prospective studies should be conducted to investigate safety and efficacy in a larger population.

Variation in infection prevention practices in dialysis facilities: results from the national opportunity to improve infection control in ESRD (End-Stage Renal Disease) project.

OBJECTIVE To observe patient care across hemodialysis facilities enrolled in the National Opportunity to Improve Infection Control in ESRD (end-stage renal disease) (NOTICE) project in order to evaluate adherence to evidence-based practices aimed at prevention of infection. SETTING AND PARTICIPANTS Thirty-four hemodialysis facilities were randomly selected from among 772 facilities in 4 end-stage renal disease participating networks. Facility selection was stratified on dialysis organization affiliation, size, socioeconomic status, and urban/rural status. MEASUREMENTS Trained infection control evaluators used an infection control worksheet to observe 73 distinct infection control practices at the hemodialysis facilities, from October 1, 2011, through January 31, 2012. RESULTS There was considerable variation in infection control practices across enrolled facilities. Overall adherence to recommended practices was 68% (range, 45%-92%) across all facilities. Overall adherence to expected hand hygiene practice was 72% (range, 10%-100%). Compliance to hand hygiene before and after procedures was high; however, during procedures hand hygiene compliance averaged 58%. Use of chlorhexidine as the specific agent for exit site care was 19% overall but varied from 0% to 35% by facility type. The 8 checklists varied in the frequency of perfect performance from 0% for meeting every item on the checklist for disinfection practices to 22% on the arteriovenous access practices at initiation. CONCLUSIONS Our findings suggest that there are many areas for improvement in hand hygiene and other infection prevention practices in end-stage renal disease. These NOTICE project findings will help inform the development of a larger quality improvement initiative at dialysis facilities.