Evaluation of Spending Differences Between Beneficiaries in Medicare Advantage and the Medicare Shared Savings Program.

Importance: The 2 primary efforts of Medicare to advance value-based care are Medicare Advantage (MA) and the fee-for-service-based Medicare Shared Savings Program (MSSP). It is unknown how spending differs between the 2 programs after accounting for differences in patient clinical risk. Objective: To examine how spending and utilization differ between MA and MSSP beneficiaries after accounting for differences in clinical risk using data from administrative claims and electronic health records. Design, Setting, and Participants: This retrospective economic evaluation used data from 15 763 propensity score-matched beneficiaries who were continuously enrolled in MA or MSSP from January 1, 2014, to December 31, 2018, with diabetes, congestive heart failure (CHF), chronic kidney disease (CKD), or hypertension. Participants received care at a large nonprofit academic health system in the southern United States that bears risk for Medicare beneficiaries through both the MA and MSSP programs. Differences in beneficiary risk were mitigated by propensity score matching using validated clinical criteria based on data from administrative claims and electronic health records. Data were analyzed from January 2019 to May 2022. Exposures: Enrollment in MA or attribution to an accountable care organization in the MSSP program. Main Outcomes and Measures: Per-beneficiary annual total spending and subcomponents, including inpatient hospital, outpatient hospital, skilled nursing facility, emergency department, primary care, and specialist spending. Results: The sample of 15 763 participants included 12 720 (81%) MA and 3043 (19%) MSSP beneficiaries. MA beneficiaries, compared with MSSP beneficiaries, were more likely to be older (median [IQR] age, 75.0 [69.9-81.8] years vs 73.1 [68.3-79.8] years), male (5515 [43%] vs 1119 [37%]), and White (9644 [76%] vs 2046 [69%]) and less likely to live in low-income zip codes (2338 [19%] vs 750 [25%]). The mean unadjusted per-member per-year spending difference between MSSP and MA disease-specific subcohorts was $2159 in diabetes, $4074 in CHF, $2560 in CKD, and $2330 in hypertension. After matching on clinical risk and demographic factors, MSSP spending was higher for patients with diabetes (mean per-member per-year spending difference in 2015: $2454; 95% CI, $1431-$3574), CHF ($3699; 95% CI, $1235-$6523), CKD ($2478; 95% CI, $1172-$3920), and hypertension ($2258; 95% CI, $1616-2,939). Higher MSSP spending among matched beneficiaries was consistent over time. In the matched cohort in 2018, MSSP total spending ranged from 23% (CHF) to 30% (CKD) higher than MA. Adjusting for differential trends in coding intensity did not affect these results. Higher outpatient hospital spending among MSSP beneficiaries contributed most to spending differences between MSSP and MA, representing 49% to 62% of spending differences across disease cohorts. Conclusions and Relevance: In this study, utilization and spending were consistently higher for MSSP than MA beneficiaries within the same health system even after adjusting for granular metrics of clinical risk. Nonclinical factors likely contribute to the large differences in MA vs MSSP spending, which may create challenges for health systems participating in MSSP relative to their participation in MA.

Cell-free human papillomavirus DNA kinetics after surgery for human papillomavirus-associated oropharyngeal cancer.

BACKGROUND: New ultrasensitive methods for detecting residual disease after surgery are needed in human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC). METHODS: To determine whether the clearance kinetics of circulating tumor human papillomavirus DNA (ctHPVDNA) is associated with postoperative disease status, a prospective observational study was conducted in 33 patients with HPV+OPSCC undergoing surgery. Blood was collected before surgery, postoperative days 1 (POD 1), 7, and 30 and with follow-up. A subcohort of 12 patients underwent frequent blood collections in the first 24 hours after surgery to define early clearance kinetics. Plasma was run on custom droplet digital polymerase chain reaction (ddPCR) assays for HPV genotypes 16, 18, 33, 35, and 45. RESULTS: In patients without pathologic risk factors for recurrence who were observed after surgery, ctHPVDNA rapidly decreased to <1 copy/mL by POD 1 (n = 8/8). In patients with risk factors for macroscopic residual disease, ctHPVDNA was markedly elevated on POD 1 (>350 copies/mL) and remained elevated until adjuvant treatment (n = 3/3). Patients with intermediate POD 1 ctHPVDNA levels (1.2-58.4 copies/mL) all possessed pathologic risk factors for microscopic residual disease (n = 9/9). POD 1 ctHPVDNA levels were higher in patients with known adverse pathologic risk factors such as extranodal extension >1 mm (P = .0481) and with increasing lymph nodes involved (P = .0453) and were further associated with adjuvant treatment received (P = .0076). One of 33 patients had a recurrence that was detected by ctHPVDNA 2 months earlier than clinical detection. CONCLUSIONS: POD 1 ctHPVDNA levels are associated with the risk of residual disease in patients with HPV+OPSCC undergoing curative intent surgery and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future. LAY SUMMARY: Human papillomavirus-associated oropharyngeal squamous cell carcinoma (HPV+OPSCC) is increasing at epidemic proportions and is commonly treated with surgery. This report describes results from a study examining the clearance kinetics of circulating tumor HPV DNA (circulating tumor human papillomavirus DNA [ctHPVDNA]) following surgical treatment of HPV+OPSCC. We found that ctHPVDNA levels 1 day after surgery are associated with the risk of residual disease in patients with HPV+OPSCC and thus could be used as a personalized biomarker for selecting adjuvant treatment in the future. These findings are the first to demonstrate the potential utility of ctHPVDNA in patients with HPV+OPSCC undergoing surgery.

Cell-Free HPV DNA Provides an Accurate and Rapid Diagnosis of HPV-Associated Head and Neck Cancer.

PURPOSE: HPV-associated head and neck squamous cell carcinoma (HPV+HNSCC) is the most common HPV-associated malignancy in the United States and continues to increase in incidence. Current diagnostic approaches for HPV+HNSCC rely on tissue biopsy followed by histomorphologic assessment and detection of HPV indirectly by p16 IHC. Such approaches are invasive and have variable sensitivity. EXPERIMENTAL DESIGN: We conducted a prospective observational study in 140 subjects (70 cases and 70 controls) to test the hypothesis that a noninvasive diagnostic approach for HPV+HNSCC would have improved diagnostic accuracy, lower cost, and shorter diagnostic interval compared with standard approaches. Blood was collected, processed for circulating tumor HPV DNA (ctHPVDNA), and analyzed with custom ddPCR assays for HPV genotypes 16, 18, 33, 35, and 45. Diagnostic performance, cost, and diagnostic interval were calculated for standard clinical workup and compared with a noninvasive approach using ctHPVDNA combined with cross-sectional imaging and physical examination findings. RESULTS: Sensitivity and specificity of ctHPVDNA for detecting HPV+HNSCC were 98.4% and 98.6%, respectively. Sensitivity and specificity of a composite noninvasive diagnostic using ctHPVDNA and imaging/physical examination were 95.1% and 98.6%, respectively. Diagnostic accuracy of this noninvasive approach was significantly higher than standard of care (Youden index 0.937 vs. 0.707, P = 0.0006). Costs of noninvasive diagnostic were 36% to 38% less than standard clinical workup and the median diagnostic interval was 26 days less. CONCLUSIONS: A noninvasive diagnostic approach for HPV+HNSCC demonstrated improved accuracy, reduced cost, and a shorter time to diagnosis compared with standard clinical workup and could be a viable alternative in the future.

Assessment of Length and Readability of Informed Consent Documents for COVID-19 Vaccine Trials.

Importance: Informed consent is a fundamental element of research ethics. The COVID-19 vaccine trials are high profile trials that have enrolled more than 100 000 participants. Consent documents must be succinct and understandable to ensure informed voluntary participation. Objective: To assess how well informed consent documents of the COVID-19 vaccine trials achieve the ideal of being succinct and understandable, and to create a shorter, more readable document. Design, Setting, and Participants: This quality improvement study collected and analyzed the informed consent documents used in 4 COVID-19 vaccine phase III randomized clinical trials to quantitatively assess readability and length and, based on this analysis, created a measurably more accessible informed consent document. Analysis was conducted from October 2020 to January 2021. Main Outcomes and Measures: The main outcomes were number of words (measured as word count), time-to-read (measured at reading speeds of 175-300 words per minute), language complexity (measured using Flesch-Kincaid Grade Level assessment), and readability (measured using Flesch Reading Ease Score). Secondary outcomes included clarity of how the placebo group could access the vaccine if it is proven safe and effective. The study also examined the length and readability of an improved consent document. Results: The 4 informed consent documents were a mean (range) of 8333 (7821 to 9340) words long, with a mean (range) 35 (32.6 to 38.9) minutes to read at 240 words per minute. All documents exceeded grade 9 language complexity and scored lower than 60 in the formal reading ease metric, which constitutes difficult. Only 1 document specified that participants in the placebo group might receive vaccine. It was possible to write a document in fewer than 3000 words with a grade 7 to 8 reading level and a formal readability score that was not difficult. Conclusions and Relevance: These findings suggest that existing COVID-19 vaccine informed consent documents were too long, difficult to read, and exceeded grade 9 in language complexity. It was possible to create a shorter, more readable informed consent document for these trials.

Oropharyngeal Squamous Cell Carcinoma Morphology and Subtypes by Human Papillomavirus Type and by 16 Lineages and Sublineages.

Oropharyngeal squamous cell carcinoma (SCC) is increasing in incidence and, in Western countries, strongly associated with transcriptionally-active high-risk human papillomavirus (HPV). Within HPV-positive tumors, there is wide morphologic diversity with numerous histologic subtypes of SCC. There are also variable degrees of keratinization, anaplasia, stromal fibrosis, and maturing squamous differentiation. Unlike in the uterine cervix, where associations between HPV types and lineages/sublineages within types have been investigated with some clear correlations identified, little to no data exists for oropharyngeal SCC. In this study, for a large cohort of oropharyngeal SCC patients, we performed RTPCR for high-risk HPV. For the HPV positive patients, we sequenced the DNA of the entire HPV16 genome and determined lineages and sublineages, correlating HPV status, genotype, and HPV16 lineages/sublineages with SCC subtype and various histologic features. Of the 259 patients, 224 (86.5%) were high-risk HPV positive, of which 210/224 (93.8%) were HPV type 16 and 6/224 (2.7%) HPV type 33. Of the four HPV16 lineages, A was the most frequent (192/214 or 89.8%) and of the HPV16 A sublineages, A1 was the most frequent (112/210 or 53.3%). Patients with HPV negative tumors were more often keratinizing vs other types (23/35 or 65.7%) and thus more likely to have more maturing squamous differentiation and stromal desmoplasia. There was no significant correlation between HPV type (16 versus other), between HPV16 lineage (A versus others), or HPV16 A sublineages (A1 or A2 versus others) and morphologic type of SCC nor the various morphologic features of anaplasia/multinucleation, degree of keratinization, nor amount of stromal desmoplasia. In summary, in our cohort, there was no correlation between the type of HPV, the HPV 16 lineage or sublineage, and any of the histologic features or morphologic SCC subtypes.

Full Thermoelectric Characterization of Stoichiometric Electrodeposited Thin Film Tin Selenide (SnSe).

Tin selenide (SnSe) has attracted much attention in the thermoelectric community since the discovery of the record figure of merit (ZT) of 2.6 in single crystal tin selenide in 2014. There have been many reports since of the thermoelectric characterization of SnSe synthesized or manufactured by several methods, but so far none of these have concerned the electrodeposition of SnSe. In this work, stoichiometric SnSe was successfully electrodeposited at -0.50 V vs SCE as shown by EDX, XPS, UPS, and XRD. The full ZT of the electrodeposits were then measured. This was done by both a delamination technique to measure the Seebeck coefficient and electrical conductivity which showed a peak power factor of 4.2 and 5.8 µW m-1 K-2 for the as deposited and heat-treated films, respectively. A novel modified transient 3ω method was used to measure the thermal conductivity of the deposited films on the deposition substrate. This revealed the thermal conductivity to be similar to the ultralow thermal conductivity of single crystal SnSe, with a value of 0.34 W m-1 K-1 being observed at 313 K.

Patient Information on Benign Colorectal Disease: An Assessment of the Value and Effectiveness of Traditional Methods.

Health literacy is the best predictor of health status, with patient information leaflets (PILs) commonly used to improve information access. However, they can often be inconsistent. Benign colorectal disease can be challenging for patients and ensuring they are accurate and understandable is important. Available PILs in a tertiary unit were assessed. The Flesch reading ease and Flesch-Kincaid Grade level scores were used to calculate objective readability. Subjective assessment of readability, understandability, and patient opinion was assessed using a questionnaire. All PILs had objective readability scores at age 14 or older, above recommended advice. Three hundred sixty patient questionnaires were collected. The relationship between subjective readability and understandability was significant (P < .05); the easier a patient was able to read the information the more likely they were to understand it. There was no link between objective and subjective readability-a more difficult calculated reading score didn't correspond to the patient finding it harder to read. Patients preferring paper information were significantly older than patients who preferred online information (P = .01). Patient information leaflets remain valued by patients, and PILs that patients find easier to read are then better understood; however, ease of reading is not related to objective readability scoring and there was no consensus that a shift to online information is merited.

Tuning charge transport dynamics via clustering of doping in organic semiconductor thin films.

A significant challenge in the rational design of organic thermoelectric materials is to realize simultaneously high electrical conductivity and high induced-voltage in response to a thermal gradient, which is represented by the Seebeck coefficient. Conventional wisdom posits that the polymer alone dictates thermoelectric efficiency. Herein, we show that doping - in particular, clustering of dopants within conjugated polymer films - has a profound and predictable influence on their thermoelectric properties. We correlate Seebeck coefficient and electrical conductivity of iodine-doped poly(3-hexylthiophene) and poly[2,5-bis(2-octyldodecyl)pyrrolo[3,4-c]pyrrole-1,4(2H,5H)-dione-3,6-diyl)-alt-(2,2';5',2'';5'',2'''-quaterthiophen-5,5'''-diyl)] films with Kelvin probe force microscopy to highlight the role of the spatial distribution of dopants in determining overall charge transport. We fit the experimental data to a phonon-assisted hopping model and found that the distribution of dopants alters the distribution of the density of states and the Kang-Snyder transport parameter. These results highlight the importance of controlling dopant distribution within conjugated polymer films for thermoelectric and other electronic applications.

Effects of Disorder on Thermoelectric Properties of Semiconducting Polymers.

Organic materials have attracted recent interest as thermoelectric (TE) converters due to their low cost and ease of fabrication. We examine the effects of disorder on the TE properties of semiconducting polymers based on the Gaussian disorder model (GDM) for site energies while employing Pauli's master equation approach to model hopping between localized sites. Our model is in good agreement with experimental results and a useful tool to study hopping transport. We show that stronger overlap between sites can improve the electrical conductivity without adversely affecting the Seebeck coefficient. We find that positional disorder aids the formation of new conduction paths with an increased probability of carriers in high energy sites, leading to an increase in electrical conductivity while leaving the Seebeck unchanged. On the other hand, energetic disorder leads to increased energy gaps between sites, hindering transport. This adversely affects conductivity while only slightly increasing Seebeck and results in lower TE power factors. Furthermore, positional correlation primarily affects conductivity, while correlation in site energies has no effect on TE properties of polymers. Our results also show that the Lorenz number increases with Seebeck coefficient, largely deviating from the Sommerfeld value, in agreement with experiments and in contrast to band conductors. We conclude that reducing energetic disorder and positional correlation, while increasing positional disorder can lead to higher TE power factors.

Revision ACL reconstruction with autograft: long-term functional outcomes and influencing factors.

PURPOSE: To present the long-term functional outcomes of revision anterior cruciate ligament (ACL) reconstruction with autograft and factors that influence the outcomes. METHODS: Retrospective study of 51 consecutive revision ACL reconstructions performed using autograft under the care of a single surgeon with interference screw fixation. Bone-patellar tendon-bone graft was used in 35 (69%) and hamstring tendons in 16 (31%). The subjective IKDC activity level and Lysholm Knee functional scores were collected at mean follow-up of 9.0 years (range 5.17-14.75 years). RESULTS: Five (9.8%) had re-ruptured and one patient had a total knee replacement. Functional scores were available for 43 patients (84.3%). Twenty-eight had IKDC activity level I or II (65%), level III in 12 (28%) and level IV in 3 (7%). The average Lysholm score was 86.2 ± 12.88, and there is a statistically significant relationship with age (95% CI: - 0.88, - 0.60) (P < 0.05). For each additional 10 years of age, there is a reduction of 5.18 points. No statistically significant effect of sex has been detected. The mean Lysholm score was lower in patients who had partial medial meniscectomy (77.33), although this was not statistically significant (P = 0.06). Regression analysis of the Lysholm score means by chondral damage category adjusted for age, showed that the Grade 3 or 4 group shows a reduction of about 25 points for every 10 years increase in age (95% CI; P = 0.05). CONCLUSION: Revision ACL reconstruction with autograft affords satisfactory long-term outcomes. Expectations should be carefully managed in patients with increasing age associated with severe chondral damage and previous medial meniscectomy.

Mumps presenting with unilateral, synchronous parotid and submandibular gland swelling.

A previously healthy 22-year-old woman presented with acute, unilateral facial and neck swelling, associated with fever and malaise. She was initially treated with intravenous antibiotics; however, CT imaging showed unilateral, synchronous swelling and inflammation of the parotid and submandibular glands, and a PCR swab from the parotid duct was positive for mumps. She was fully immunised and had no contact in the preceding period with anyone diagnosed with mumps. She responded to supportive management and her symptoms resolved over the course of her admission. Unilateral, synchronous swelling and severe inflammation of both the parotid and submandibular glands in mumps is a very unusual presentation, and not one previously reported in the literature.

Primary meningococcal septic arthritis with multiple native joint involvement.

A previously healthy 18-year-old woman presented with an acutely painful, swollen right ankle joint, with similar symptoms subsequently developing in the right hip and right wrist. Microbiological samples from the ankle aspirate grew Neisseria meningitidis She had had no preceding clinical symptoms of meningitis or previous contact with a patient with meningitis. She was treated with intravenous antibiotics and surgical drainage.On follow-up, her symptoms had resolved, inflammatory markers had returned to normal and she has no long-term sequelae of septic arthritis. Primary meningococcal septic arthritis in the adult population is extremely uncommon, and makes up approximately 1% of all cases of primary septic arthritis.

Persistent radical anion polymers based on naphthalenediimide and a vinylene spacer.

Persistent n-doped conjugated polymers were achieved by doping the electron accepting PDNDIV and PFNDIV polymers with ionic (TBACN) or neutral (TDAE) dopants. The great electron affinities, as indicated by the low LUMO levels of PDNDIV (-4.09 eV) and PFNDIV (-4.27 eV), facilitated the chemical reduction from either TBACN or TDAE. The low-lying LUMOs of the neutral polymers PDNDIV and PFNDIV were achieved by incorporation of vinylene spacers between the electron poor NDI units to increase the conjugation length without the use of an electron donor, and this was lowered further by an electron-withdrawing fluorinated N-substituent on the NDI moiety. The polymer radical anions were found to persist for several days under ambient conditions by EPR spectroscopy. A distinguishing and noteworthy feature of these polymers is that they can be consecutively reduced by up to four electrons in acetonitrile. Conductivity measurements demonstrate the prospective impact of PDNDIV and PFNDIV for organic electronics.

High Energy Density in Azobenzene-based Materials for Photo-Thermal Batteries via Controlled Polymer Architecture and Polymer-Solvent Interactions.

Energy densities of ~510 J/g (max: 698 J/g) have been achieved in azobenzene-based syndiotactic-rich poly(methacrylate) polymers. The processing solvent and polymer-solvent interactions are important to achieve morphologically optimal structures for high-energy density materials. This work shows that morphological changes of solid-state syndiotactic polymers, driven by different solvent processings play an important role in controlling the activation energy of Z-E isomerization as well as the shape of the DSC exotherm. Thus, this study shows the crucial role of processing solvents and thin film structure in achieving higher energy densities.