The Present and Future of the Clinical Use of Physiological Traits for the Treatment of Patients with OSA: A Narrative Review.

People with obstructive sleep apnea (OSA) are a heterogeneous group. While many succeed in the treatment of their OSA, many others struggle with therapy. Herein, we discuss how anatomical and physiological factors that cause sleep apnea (OSA traits) impact treatment response and may offer an avenue for more precise care. These OSA traits, including anatomical (upper-airway collapsibility) and physiological (loop gain, airway muscle responsiveness, and arousal threshold) factors, may help determine who can succeed with continuous positive airway pressure, oral appliances, hypoglossal nerve stimulation, or pharmacotherapy. In the future, identifying OSA traits before initiating treatment may help guide the selection of the most effective and tolerable therapy modalities for each individual.

Iron Deficiency among School-Aged Adolescents in Hong Kong: Prevalence, Predictors, and Effects on Health-Related Quality of Life.

Iron deficiency (ID) is a prevalent nutritional deficiency affecting children/adolescents worldwide. We reported (1) the prevalence of ID and ID with anemia (IDA) among Chinese school-aged adolescents, (2) clinical and dietary predictors of iron status, and (3) its impact on health-related qualities of life (HRQoL). This cross-sectional study recruited 183 boys and 340 girls (mean age = 17.55) from 16 schools in Hong Kong. ID is defined as serum ferritin <15 µg/L. The participants reported their dietary habits, menstrual patterns (girls), and HRQoL using structured questionnaires. The overall prevalence of ID was 11.1%. None of the boys had ID or IDA. Among girls, the rate of ID was 17.1% and IDA was 10.9%. One-third (36.3%) reported a regular habit of skipping ≥1 meal/day. Lower ferritin was found in adolescents who skipped meals (Est = -35.1, p = 0.017). Lower ferritin is correlated with poorer school functioning (Est = 0.81, p = 0.045) and fatigue (Est = 0.92, p = 0.016). Skipping meals is associated with poorer physical (p = 0.0017) and school functioning (p = 0.027). To conclude, 1 in 10 school-aged adolescents in Hong Kong are iron-deficient. The ID rate in girls (17.1%) is similar to that in other industrialized countries (5.2-16.6%). Future work should promote awareness on the potential health consequences of poor dietary habits on ID and the well-being of adolescents.

Assessment of aPTT-based clot waveform analysis for the detection of haemostatic changes in different types of infections.

Infections cause varying degrees of haemostatic dysfunction which can be detected by clot waveform analysis (CWA), a global haemostatic marker. CWA has been shown to predict poor outcomes in severe infections with disseminated intravascular coagulopathy. The effect of less severe bacterial and viral infections on CWA has not been established. We hypothesized that different infections influence CWA distinctively. Patients admitted with bacterial infections, dengue and upper respiratory tract viral infections were recruited if they had an activated partial thromboplastin time (aPTT) measured on admission. APTT-based CWA was performed on Sysmex CS2100i automated analyser using Dade Actin FSL reagent. CWA parameters [(maximum velocity (min1), maximum acceleration (min2) and maximum deceleration (max2)] were compared against control patients. Infected patients (n = 101) had longer aPTT than controls (n = 112) (34.37 ± 7.72 s vs 27.80 ± 1.59 s, p < 0.001), with the mean (± SD) aPTT longest in dengue infection (n = 36) (37.99 ± 7.93 s), followed by bacterial infection (n = 52) (33.96 ± 7.33 s) and respiratory viral infection (n = 13) (29.98 ± 3.92 s). Compared to controls (min1; min2; max2) (5.53 ± 1.16%/s; 0.89 ± 0.19%/s2; 0.74 ± 0.16%/s2), bacterial infection has higher CWA results (6.92 ± 1.60%/s; 1.04 ± 0.28%/s2; 0.82 ± 0.24%/s2, all p < 0.05); dengue infection has significantly lower CWA values (3.93 ± 1.32%/s; 0.57 ± 0.17%/s2; 0.43 ± 0.14%/s2, all p < 0.001) whilst respiratory virus infection has similar results (6.19 ± 1.32%/s; 0.95 ± 0.21%/s2; 0.73 ± 0.18%/s2, all p > 0.05). CWA parameters demonstrated positive correlation with C-reactive protein levels (min1: r = 0.54, min2: r = 0.44, max2: r = 0.34; all p < 0.01). Different infections affect CWA distinctively. CWA could provide information on the haemostatic milieu triggered by infection and further studies are needed to better define its application in this area.

A Tale of Immune-Related Adverse Events With Sequential Trials of Checkpoint Inhibitors in a Patient With Metastatic Renal Cell Carcinoma.

Immune checkpoint inhibitor (CPI) therapy is approved for the treatment of many cancers. As its use becomes more prevalent, sequential trials with different CPIs as monotherapy or combination therapy will become more common. It is thought that the increased cumulative dose of CPIs over multiple trials increases the risk of immune-related adverse events (irAEs). However, it is not known if using one CPI combination increases the risk of developing irAEs during the subsequent trial of a different CPI combination. Here, we present a patient with multiple episodes of high-grade irAEs over the course of sequential trials of combination CPIs. A 65-year-old female patient with metastatic renal cell cancer received two trials of combination CPIs. During the first trial with durvalumab and tremelimumab, she had CPI-induced grade 2 skin rashes and primary hypothyroidism with a mild elevation in lipase, normal antithyroid antibody profile, and normal blood glucose. Due to progression after the first trial, her regimen was changed to ipilimumab and nivolumab combination therapy. She subsequently presented to the emergency room with diabetic ketoacidosis on the sixth week following treatment initiation and was diagnosed with new-onset insulin-dependent type 1 diabetes mellitus (DM) with a negative antibody profile for DM. Immune CPIs cause irAEs by increasing immune activity against self-antigens. Sequential trials of CPIs may increase the risk of irAEs by increasing the cumulative CPI dose, or by organ injury inflicted by the first set of CPIs which is tipped "over the edge" by subsequent trials. We believe that the latter mechanism could be responsible for our case. Sequential CPI therapy should be planned carefully with increased surveillance for the early diagnosis and treatment of irAEs.

Accuracy of Detection and Grading of Diabetic Retinopathy and Diabetic Macular Edema Using Teleretinal Screening.

PURPOSE: To determine the accuracy of a county teleretinal screening program of detecting referable diabetic retinopathy (DR) and treatable diabetic macular edema (DME), as well as to evaluate patient compliance with clinic follow-up after referral from teleretinal screening. DESIGN: Retrospective observational study. PARTICIPANTS: Patients in the Harris Health System (HHS, Houston, TX) older than 18 years of age who underwent teleretinal screening between July 2014 and July 2016. METHODS: Teleretinal imaging (TRI) consisting of single-field 45-degree nonmydriatic color fundus photography with referral thresholds of severe nonproliferative DR, proliferative DR, and significant DME. Teleretinal imaging results for all referred subjects were obtained and cross-referenced with dilated fundus examination findings with regard to DR severity and the presence of DME. Follow-up status was also noted. Subjects underwent OCT if deemed necessary by the examining specialist. Agreement between TRI and dilated fundus examination (DFE) findings was determined by calculating the Cohen κ coefficient. MAIN OUTCOME MEASURES: The primary outcome measure is agreement between TRI results and DFE findings with regard to DR severity and the presence of DME. The secondary outcome measure is compliance with follow-up. RESULTS: Of 1767 patients who were screened and referred for clinical examination, 935 (52.9%) attended their clinic appointment. Overall agreement between DFE and TRI was moderate (weighted κ 0.45) in terms of DR severity. There was agreement within one DR severity level in 86.2% of patients. The positive predictive value for detecting referable disease was 71.3%. Of patients referred for DME, 30.4% were deemed to have treatable DME. CONCLUSIONS: The HHS teleretinal screening program demonstrates a high level of accuracy in the detection and classification of referable DR, but a lesser degree of accuracy in the detection of treatable DME. Only slightly more than half of participants were compliant with follow-up after a TRI referral. This large-scale study provides insight into the utility of teleretinal screening in a county health care system.

Cost Savings Analysis for a Diabetic Retinopathy Teleretinal Screening Program Using an Activity-Based Costing Approach.

PURPOSE: To examine the costs and cost savings associated with a large, urban teleretinal screening program for diabetic retinopathy (DR). DESIGN: Retrospective analysis. PARTICIPANTS: Eighteen thousand twenty-five patients (36 050 eyes) screened via the Harris Health System (HHS) DR teleretinal screening program between June 2013 and April 2014. METHODS: Activity-based costing applied to the operational screening pathway was implemented to determine the cost of screening. Actual costs were calculated based on retrospective chart review and figures obtained from the HHS and Centers for Medicare and Medicaid Services. Theoretical costs of in-clinic examinations and delayed intervention were compared with actual costs of screening and treatment to determine costs savings. MAIN OUTCOME MEASURES: Costs and cost savings in United States dollars were estimated. RESULTS: The per-patient cost of teleretinal screening itself was found to be $27.35, whereas the average total cost (factoring in treatment) per patient was determined to be $43.14. The physical examination-only and treatment-only models yielded cost savings estimates of $2 047 442.53 and $1 148 597.35, respectively. CONCLUSIONS: The cost savings yielded by the HHS DR teleretinal screening program compared with conventional screening are substantial and corroborate the findings of similar studies that have analyzed teleretinal screening. Additionally, it can be presumed that there are additional indirect economic benefits resulting from earlier detection and treatment of disease.

Microplastic pollution is widely detected in US municipal wastewater treatment plant effluent.

Municipal wastewater effluent has been proposed as one pathway for microplastics to enter the aquatic environment. Here we present a broad study of municipal wastewater treatment plant effluent as a pathway for microplastic pollution to enter receiving waters. A total of 90 samples were analyzed from 17 different facilities across the United States. Averaging all facilities and sampling dates, 0.05 ± 0.024 microparticles were found per liter of effluent. Though a small value on a per liter basis, even minor municipal wastewater treatment facilities process millions of liters of wastewater each day, yielding daily discharges that ranged from ∼50,000 up to nearly 15 million particles. Averaging across the 17 facilities tested, our results indicate that wastewater treatment facilities are releasing over 4 million microparticles per facility per day. Fibers and fragments were found to be the most common type of particle within the effluent; however, some fibers may be derived from non-plastic sources. Considerable inter- and intra-facility variation in discharge concentrations, as well as the relative proportions of particle types, was observed. Statistical analysis suggested facilities serving larger populations discharged more particles. Results did not suggest tertiary filtration treatments were an effective means of reducing discharge. Assuming that fragments and pellets found in the effluent arise from the 'microbeads' found in many cosmetics and personal care products, it is estimated that between 3 and 23 billion (with an average of 13 billion) of these microplastic particles are being released into US waterways every day via municipal wastewater. This estimate can be used to evaluate the contribution of microbeads to microplastic pollution relative to other sources (e.g., plastic litter and debris) and pathways (e.g., stormwater) of discharge.

Evaluation of Automated Teleretinal Screening Program for Diabetic Retinopathy.

IMPORTANCE: Diabetic retinopathy is a leading cause of blindness, but its detrimental effects are preventable with early detection and treatment. Screening for diabetic retinopathy has the potential to increase the number of cases treated early, especially in populations with limited access to care. OBJECTIVE: To determine the efficacy of an automated algorithm in interpreting screening ophthalmoscopic photographs from patients with diabetes compared with a reading center interpretation. DESIGN, SETTING, AND PARTICIPANTS: Retrospective cohort analysis of 15,015 patients with type 1 or 2 diabetes in the Harris Health System in Harris County, Texas, who had undergone a retinal screening examination and nonmydriatic fundus photography via the Intelligent Retinal Imaging System (IRIS) from June 2013 to April 2014 were included. The IRIS-based interpretations were compared with manual interpretation. The IRIS algorithm population statistics were calculated. MAIN OUTCOMES AND MEASURES: Sensitivity and false-negative rate of the IRIS computer-based algorithm compared with reading center interpretation of the same images. RESULTS: A total of 15 015 consecutive patients (aged 18-98 years); mean 54.3 years with known type 1 or 2 diabetes underwent nonmydriatic fundus photography for a diabetic retinopathy screening examination. The sensitivity of the IRIS algorithm in detecting sight-threatening diabetic eye disease compared with the reading center interpretation was 66.4% (95% CI, 62.8%-69.9%) with a false-negative rate of 2%. The specificity was 72.8% (95% CI, 72.0%-73.5%). In a population where 15.8% of people with diabetes have sight-threatening diabetic eye disease, the IRIS algorithm positive predictive value was 10.8% (95% CI, 9.6%-11.9%) and the negative predictive value was 97.8% (95% CI, 96.8%-98.6%). CONCLUSIONS AND RELEVANCE: In this large urban setting, the IRIS computer algorithm-based screening program had a high sensitivity and a low false-negative rate, suggesting that it may be an effective alternative to conventional reading center image interpretation. The IRIS algorithm shows promise as a screening program, but algorithm refinement is needed to achieve better performance. Further studies of patient safety, cost-effectiveness, and widespread applications of this type of algorithm should be pursued to better understand the role of teleretinal imaging and automated analysis in the global health care system.

Schiotz tonometry accurately measures intraocular pressure in Boston type 1 keratoprosthesis eyes.

PURPOSE: To evaluate the location of the eye and tonometry device that provides the most accurate intraocular pressure (IOP) measurements in eyes with Boston type 1 keratoprosthesis. METHODS: A single surgeon sutured a Boston keratoprosthesis into the central cornea in the usual manner in 5 eyes of deceased donors. Another investigator used a 27-gauge needle, digital manometry, and gravity infusion to set the IOP at levels of 10, 20, 30, and 40 mm Hg in random order. A second investigator masked to the level of IOP used a Schiotz tonometer (Sklar) with a 7.5-g plunger load and a Tono-pen XL tonometer (Medtronic) to determine IOP at the temporal corneoscleral limbus and temporal sclera (3 mm temporal to the corneoscleral limbus). We used generalized estimation equation models to determine an average absolute difference between the tonometer measurements compared with the "gold standard" digital manometric IOP. RESULTS: The Schiotz tonometer had a lower median absolute error compared with the Tono-pen at both temporal sclera (5.4 mm Hg vs. 39.0 mm Hg, P < 0.001) and corneoscleral limbus (4.9 vs. 15.0 mm Hg, P = 0.03). The median absolute error for Schiotz was similar at the temporal sclera and corneoscleral limbus (P = 0.44). CONCLUSIONS: The Schiotz tonometer has the highest accuracy of IOP compared with the Tono-pen and gold standard digital manometry. Clinicians could consider Schiotz tonometry when measuring IOP in patients with keratoprosthesis.

Psychometric properties of the Chinese version of the Pediatric Quality Of Life Inventory 4.0 Generic Core scales among pediatric cancer patients.

BACKGROUND: The Pediatric Quality of Life Inventory (PedsQL) 4.0 Generic Core Scales are commonly used to assess health-related quality of life of healthy children and pediatric patients. Validation of the Generic Core Scales among Chinese pediatric cancer patients has not been reported in the literature. The scales can serve to measure different quality-of-life domains that are not captured by the PedsQL Cancer Module. OBJECTIVE: Psychometric properties of the Chinese version of the PedsQL 4.0 among pediatric cancer patients and their caretakers were examined. METHODS: The Generic Core Scales were administered to 335 pairs of pediatric cancer patients (aged 8-18 years) and their caretakers in Hong Kong. RESULTS: A 5-factor structure (physical, emotional, social, school-related cognitive function, and missed school) was identified in the patient and proxy versions of the scales using confirmatory factor analysis. Both versions of the total scale reported Cronbach α's of .90 or greater, with almost all subscales reporting α's of .70 or greater. Test-retest reliability at 2 weeks was acceptable (intraclass correlations ≥0.60) for a majority of subscales. Agreement between patients' and caretakers' ratings was medium. CONCLUSIONS: The scales demonstrated acceptable psychometric properties and construct validity. IMPLICATIONS FOR PRACTICE: This study validated the Chinese version of the Generic Core Scales among pediatric cancer patients and their caretakers, which supports the future use of the scales in clinical settings. The Generic Core Scales can also be supplementary to the PedsQL Cancer Module for measuring multiple domains of quality of life in cancer population.

Humoral response to conjugate pneumococcal vaccine in paediatric oncology patients.

OBJECTIVE: Pneumococcal conjugate vaccine (PCV) is an effective way to prevent invasive pneumococcal diseases in high risk populations. The efficacy of this vaccine in paediatric oncology patients remains unknown. DESIGN AND SETTING: The authors evaluated the antibody response to seven pneumococcal serotypes in paediatric oncology patients given two doses of heptavalent PCV (PCV-7). RESULTS: Forty-four patients (20 males; 24 females) with median age 9.5 years were studied. After two doses of PCV-7, 86-100% of patients had protective antibody titres against the seven vaccine serotypes. Increases in geometric mean antibody concentrations ranged from 3.8-fold for serotype 19F to 85.8-fold for serotype 14. There was no documented invasive pneumococcal disease in our cohort during the study period. CONCLUSION: PCV can elicit protective antipneumococcal antibody responses in paediatric oncology patients.

Cranial neural crest cells on the move: their roles in craniofacial development.

The craniofacial region is assembled through the active migration of cells and the rearrangement and sculpting of facial prominences and pharyngeal arches, which consequently make it particularly susceptible to a large number of birth defects. Genetic, molecular, and cellular processes must be temporally and spatially regulated to culminate in the three-dimension structures of the face. The starting constituent for the majority of skeletal and connective tissues in the face is a pluripotent population of cells, the cranial neural crest cells (NCCs). In this review we discuss the newest scientific findings in the development of the craniofacial complex as related to NCCs. Furthermore, we present recent findings on NCC diseases called neurocristopathies and, in doing so, provide clinicians with new tools for understanding a growing number of craniofacial genetic disorders.

In utero exposure of female CD-1 mice to AZT and/or 3TC: II. Persistence of functional alterations in cardiac tissue.

To delineate temporal changes in the integrity and function of mitochondria/cardiomyocytes in hearts from mice exposed in utero to commonly used nucleoside analogs (NRTIs), CD-1 mice were exposed in utero to 80 mg AZT/kg, 40 mg 3TC/kg, 80 mg AZT/kg plus 40 mg 3TC/kg, or vehicle alone during days 12-18 of gestation and hearts from female mouse offspring were examined at 13 and 26 weeks postpartum. Alterations in cardiac mitochondrial DNA (mtDNA) content, oxidative phosphorylation (OXPHOS) enzyme activities, mtDNA mutations, and echocardiography of NRTI-exposed mice were assessed and compared with findings in vehicle-exposed control mice. A hybrid capture-chemiluminescence assay showed significant twofold increases in mtDNA levels in hearts from AZT- and AZT/3TC-exposed mice at 13 and 26 weeks postpartum, consistent with near doubling in mitochondrial numbers over time compared with vehicle-exposed mice. Echocardiographic measurements at 13 and 26 weeks postpartum indicated progressive thinning of the left ventricular posterior wall in NRTI-exposed mice, relative to controls, with differences becoming statistically significant by 26 weeks. Overall, progressive functional changes occurred in mouse mitochondria and cardiac tissue several months after in utero NRTI exposures; AZT and 3TC acted in concert to cause additive cardiotoxic effects of AZT/3TC compared with either drug alone.

Validation of the Chinese version of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module.

OBJECTIVE: The psychometric properties of the Chinese version of the Pediatric Quality of Life Inventory (PedsQL) Cancer Module were investigated. METHODS: This instrument and the Generic Core Scales were administered to 359 pediatric patients with cancer (5-18 years) and 413 parents of such patients (2-18 years old). RESULTS: Seven and eight factors were, respectively, identified for the patient and parent versions. The Cronbach's alpha coefficients were respectively .89 and .92 for the total scale, and respectively .75-.90 and .76-.93 for the subscales of the patient and parent versions. Test-retest reliability coefficients exceeded .60 for most cases. The total/subscale scores of the Cancer Module significantly correlated with those of the Generic Core Scales. Some of the subscales could distinguish between on-treatment and off-treatment patients. CONCLUSIONS: The psychometric properties of the patient and parent versions of the Chinese PedsQL Cancer Module were found acceptable.

Long-term effects of pamidronate in thalassemic patients with severe bone mineral density deficits.

Osteoporosis is a common complication in thalassemia major (TM). Our previous study demonstrated severe bone mineral density (BMD) deficits at spine and hip in 62 and 35% of TM patients. This study assessed the effects of different treatments (calcium, vitamin D and bisphosphonate) on patients' BMD, which was measured at baseline and after 3-year treatments by dual energy X-ray absorptiometry (DEXA). Twenty-one untreated patients, 11 patients on calcium/vitamin D and seven patients on additional pamidronate, were recruited. They were comparable for gender (p = 0.630) and serum ferritin levels (p = 0.412). The median BMD Z-scores at lumbar spine and left hip improved only in patients with standard plus pamidronate treatments (baseline: -3.01 and -3.05, end-of-study: -2.12 and -2.09; p = 0.018 and 0.028, respectively). In contrast, BMD Z-scores at hip worsened in untreated patients (p = 0.034). In conclusion, long-term improvement in BMD in TM patients was observed with bisphosphonate but not calcium and vitamin D treatment.

The timing of antibiotic administration in the management of infant dacryocystitis.

PURPOSE: To report (1) the prevalence of bacteremia among infants with dacryocystitis and (2) the influence of timing of antibiotic administration on the need for repeat probing in the management of these patients. METHODS: A retrospective analysis of the hospital records of 25 infants < or =6 weeks of age treated for acute dacryocystitis was conducted, including analysis of laboratory data and outcomes. RESULTS: Of 22 infants who underwent blood cultures, 5 (22.7%) were bacteremic. Twenty-one of the 25 infants underwent nasolacrimal duct probing. Infants who received preoperative antibiotics were less likely to require a repeat probing than those who did not (6% vs. 80%), and this difference was statistically significant (p = 0.004). CONCLUSIONS: The high rate of bacteremia in this series of patients and the significantly lower incidence of repeat probing among infants who received preprocedural antibiotics suggests that blood cultures and subsequent administration of intravenous antibiotics should be considered prior to probing of infants with dacryocystitis.