Medicare's Post-Acute Care Reimbursement Models as of 2023: Past, Present, and Future.

The Centers for Medicare & Medicaid Services is continually working to mitigate unnecessary expenditures, particularly in post-acute care (PAC). Medicare reimburses for orthopaedic surgeon services in varied models, including fee-for-service, bundled payments, and merit-based incentive payment systems. The goal of these models is to improve the quality of care, reduce health-care costs, and encourage providers to adopt innovative and efficient health-care practices. This article delves into the implications of each payment model for the field of orthopaedic surgery, highlighting their unique features, incentives, and potential impact in the PAC setting. By considering the historical, current, and future Medicare reimbursement models, we hope to provide an understanding of the optimal payment model based on the specific needs of patients and providers in the PAC setting.

An atlas of gross and histologic lesions and immunohistochemical immunoreactivity during the temporal progression of aerosolized Lassa virus induced hemorrhagic fever in cynomolgus macaques.

Lassa virus (LASV) causes an acute multisystemic hemorrhagic fever in humans known as Lassa fever, which is endemic in several African countries. This manuscript focuses on the progression of disease in cynomolgus macaques challenged with aerosolized LASV and serially sampled for the development and progression of gross and histopathologic lesions. Gross lesions were first noted in tissues on day 6 and persisted throughout day 12. Viremia and histologic lesions were first noted on day 6 commencing with the pulmonary system and hemolymphatic system and progressing at later time points to include all systems. Immunoreactivity to LASV antigen was first observed in the lungs of one macaque on day 3 and appeared localized to macrophages with an increase at later time points to include immunoreactivity in all organ systems. Additionally, this manuscript will serve as a detailed atlas of histopathologic lesions and disease progression for comparison to other animal models of aerosolized Arenaviral disease.

A Single-shot ChAd3 Vaccine Provides Protection from Intramuscular and Aerosol Sudan Virus Exposure.

Infection with Sudan virus (SUDV) is characterized by an aggressive disease course with case fatality rates between 40-100% and no approved vaccines or therapeutics. SUDV causes sporadic outbreaks in sub-Saharan Africa, including a recent outbreak in Uganda which has resulted in over 100 confirmed cases in one month. Prior vaccine and therapeutic efforts have historically prioritized Ebola virus (EBOV), leading to a significant gap in available treatments. Two vaccines, Erbevo ® and Zabdeno ® /Mvabea ® , are licensed for use against EBOV but are ineffective against SUDV. Recombinant adenovirus vector vaccines have been shown to be safe and effective against filoviruses, but efficacy depends on having low seroprevalence to the vector in the target human population. For this reason, and because of an excellent safety and immunogenicity profile, ChAd3 was selected as a superior vaccine vector. Here, a ChAd3 vaccine expressing the SUDV glycoprotein (GP) was evaluated for immunogenicity and efficacy in nonhuman primates. We demonstrate that a single dose of ChAd3-SUDV confers acute and durable protection against lethal SUDV challenge with a strong correlation between the SUDV GP-specific antibody titers and survival outcome. Additionally, we show that a bivalent ChAd3 vaccine encoding the GP from both EBOV and SUDV protects against both parenteral and aerosol lethal SUDV challenge. Our data indicate that the ChAd3-SUDV vaccine is a suitable candidate for a prophylactic vaccination strategy in regions at high risk of filovirus outbreaks. One Sentence Summary: A single-dose of ChAd3 vaccine protected macaques from lethal challenge with Sudan virus (SUDV) by parenteral and aerosol routes of exposure.

Influence of sidewall retention and interference fit in total ankle replacement on implant-bone micromotion: A finite element study.

The success of uncemented total ankle replacement (TAR) is linked to initial stability because bony ingrowth depends upon limited early micromotion. Tibial implant design fixation features resist micromotion aided by bony sidewall retention and interference fit. Our goal was to investigate factors influencing implant-bone micromotion in TAR. Two TAR tibial components were virtually inserted into CT-derived computer models of two distal tibias from patients with end-stage ankle arthritis. Density-based inhomogeneous material assignment was used to model bone compaction during press-fit. Finite element analysis (FEA) was used to simulate three fixation cases: (1) no sidewalls + line-to-line fit, (2) sidewalls + line-to-line fit, and (3) sidewalls + 50, 100, or 200 µm interference fit. Kinetic profiles from the stance phase of gait were simulated and micromotions computed from FEA output. Without sidewalls or interference fit, micromotions were largest in early and late stance, with largest micromotions (averaging ~150-250 µm) observed near heel strike. Micromotions decreased 39%-62% when sidewalls were retained. When interference fit was also modeled, micromotions decreased another 37%-61% to ~10 µm. Micromotion differences between patients persisted with sidewall retention but largely disappeared with interference fit. This study presents new insights into the effects of TAR fixation features on implant-bone micromotion. Stability appeared to be influenced by surrounding bone quality, but this influence was greatly diminished when interference fit was introduced. More complete understanding of TAR implant features and performance is needed, but our results show the importance of bone quality and interference fit in the stability of uncemented TAR.

Modeling delay of age at natural menopause with planned tissue cryopreservation and autologous transplantation.

BACKGROUND: Ovarian tissue cryopreservation has been proven to preserve fertility against gonadotoxic treatments. It has not been clear how this procedure would perform if planned for slowing ovarian aging. OBJECTIVE: This study aimed to determine the feasibility of cryopreserving ovarian tissue to extend reproductive life span and delay menopause by autotransplantation near menopause. STUDY DESIGN: Based on the existing biological data on follicle loss rates, a stochastic model of primordial follicle wastage was developed to determine the years of delay in menopause (denoted by D) by ovarian tissue cryopreservation and transplantation near menopause. Our model accounted for (1) age at ovarian tissue harvest (21-40 years), (2) the amount of ovarian cortex harvested, (3) transplantation of harvested tissues in single vs multiple procedures (fractionation), and (4) posttransplant follicle survival (40% [conservative] vs 80% [improved] vs 100% [ideal or hypothetical]). RESULTS: Our model predicted that, for most women aged <40 years, ovarian tissue cryopreservation and transplantation would result in a significant delay in menopause. The advantage is greater if the follicle loss after transplant can be minimized. As an example, the delay in menopause (D) for a woman with a median ovarian reserve who cryopreserves 25% of her ovarian cortex at the age of 25 years and for whom 40% of follicles survive after transplantation would be approximately 11.8 years, but this extends to 15.5 years if the survival is 80%. As another novel finding, spreading the same amount of tissue to repetitive transplants significantly extends the benefit. For example, for the same 25-year-old woman with a median ovarian reserve, 25% cortex removal, and 40% follicle survival, fractionating the transplants to 3 or 6 procedures would result in the corresponding delay in menopause (D) of 23 or 31 years. The same conditions (3 or 6 procedures) would delay menopause as much as 47 years if posttransplant follicle survival is improved to 80% with modern approaches. An interactive Web tool was created to test all variables and the feasibility of ovarian tissue freezing and transplantation to delay ovarian aging (here). CONCLUSION: Our model predicts that with harvesting at earlier adult ages and better transplant techniques, a significant menopause postponement and, potentially, fertile life span extension can be achieved by ovarian tissue cryopreservation and transplantation in healthy women.

High Risk of Readmission After THA Regardless of Functional Status in Patients Discharged to Skilled Nursing Facility.

BACKGROUND: The postoperative period and subsequent discharge planning are critical in our continued efforts to decrease the risk of complications after THA. Patients discharged to skilled nursing facilities (SNFs) have consistently exhibited higher readmission rates compared with those discharged to home healthcare. This elevated risk has been attributed to several factors but whether readmission is associated with patient functional status is not known. QUESTIONS/PURPOSES: After controlling for relevant confounding variables (functional status, age, gender, caregiver support available at home, diagnosis [osteoarthritis (OA) versus non-OA], Charlson comorbidity index [CCI], the Area Deprivation Index [ADI], and insurance), are the odds of 30- and 90-day hospital readmission greater among patients initially discharged to SNFs than among those treated with home healthcare after THA? METHODS: This was a retrospective, comparative study of patients undergoing THA at any of 11 hospitals in a single, large, academic healthcare system between 2017 and 2022 who were discharged to an SNF or home healthcare. During this period, 13,262 patients were included. Patients discharged to SNFs were older (73 ± 11 years versus 65 ± 11 years; p < 0.001), less independent at hospital discharge (6-click score: 16 ± 3.2 versus 22 ± 2.3; p < 0.001), more were women (71% [1279 of 1796] versus 56% [6447 of 11,466]; p < 0.001), insured by Medicare (83% [1497 of 1796] versus 52% [5974 of 11,466]; p < 0.001), living in areas with greater deprivation (30% [533 of 1796] versus 19% [2229 of 11,466]; p < 0.001), and had less assistance available from at-home caregivers (29% [527 of 1796] versus 57% [6484 of 11,466]; p < 0.001). The primary outcomes assessed in this study were 30- and 90-day hospital readmissions. Although the system automatically flags readmissions occurring within 90 days at the various facilities in the overall healthcare system, readmissions occurring outside the system would not be captured. Therefore, we were not able to account for potential differential rates of readmission to external healthcare systems between the groups. However, given the large size and broad geographic coverage of the healthcare system analyzed, we expect the readmissions data captured to be representative of the study population. The focus on a single healthcare system also ensures consistency in readmission identification and reporting across subjects. We evaluated the association between discharge disposition (home healthcare versus SNF) and readmission. Covariates evaluated included age, gender, primary payer, primary diagnosis, CCI, ADI, the availability of at-home caregivers for the patient, and the Activity Measure for Post-Acute Care (AM-PAC) 6-clicks basic mobility score in the hospital. The adjusted relative risk (ARR) of readmission within 30 and 90 days of discharge to SNF (versus home healthcare) was estimated using modified Poisson regression models. RESULTS: After adjusting for the 6-clicks mobility score, age, gender, ADI, OA versus non-OA, living environment, CCI, and insurance, patients discharged to an SNF were more likely to be readmitted within 30 and 90 days compared with home healthcare after THA (ARR 1.46 [95% CI 1.01 to 2.13]; p= 0.046 and ARR 1.57 [95% CI 1.23 to 2.01]; p < 0.001, respectively). CONCLUSION: Patients discharged to SNFs after THA had a slightly higher likelihood of hospital readmission within 30 and 90 days compared with those discharged with home healthcare. This difference persisted even after adjusting for relevant factors like functional status, home support, and social determinants of health. These results indicate that for suitable patients, direct home discharge may be a safer and more cost-effective option than SNFs. Clinicians should carefully consider these risks and benefits when making postoperative discharge plans. Policymakers could consider incentives and reforms to improve care transitions and coordination across settings. Further research using robust methods is needed to clarify the reasons for higher SNF readmission rates. Detailed analysis of patient complexity, care processes, and causes of readmission in SNFs versus home health could identify areas for quality improvement. Prospective cohorts or randomized trials would allow stronger conclusions about cause-and-effect. Importantly, no patients should be unfairly "cherry-picked" or "lemon-dropped" based only on readmission risk scores. With proper support and care coordination, even complex patients can have good outcomes. The goal should be providing excellent rehabilitation for all, while continuously improving quality, safety, and value across settings. LEVEL OF EVIDENCE: Level III, therapeutic study.

The effect of post-acute rehabilitation setting on 90-day mobility after stroke: A difference-in-difference analysis.

Background: After discharged from the hospital for acute stroke, individuals typically receive rehabilitation in one of three settings: inpatient rehabilitation facilities (IRFs), skilled nursing facilities (SNFs), or home with community services (i.e., home health or outpatient clinics). The initial setting of post-acute care (i.e., discharge location) is related to mortality and hospital readmission; however, the impact of this setting on the change in functional mobility at 90-days after discharge is still poorly understood. The purpose of this work was to examine the impact of discharge location on the change in functional mobility between hospital discharge and 90-days post-discharge. Methods: In this retrospective cohort study, we used the electronic health record to identify individuals admitted to Johns Hopkins Medicine with an acute stroke and who had measurements of mobility [Activity Measure for Post Acute Care Basic Mobility (AM-PAC BM)] at discharge from the acute hospital and 90-days post-discharge. Individuals were grouped by discharge location (IRF=190 [40%], SNF=103 [22%], Home with community services=182 [(38%]). We compared the change in mobility from time of discharge to 90-days post-discharge in each group using a difference-in-differences analysis and controlling for demographics, clinical characteristics, and social determinants of health. Results: We included 475 individuals (age 64.4 [14.8] years; female: 248 [52.2%]). After adjusting for covariates, individuals who were discharged to an IRF had a significantly greater improvement in AM-PAC BM from time of discharge to 90-days post-discharge compared to individuals discharged to a SNF or home with community services (ß=-3.5 (1.4), p=0.01 and ß=-8.2 (1.3), p=<0.001, respectively). Conclusions: These findings suggest that the initial post-acute rehabilitation setting impacts the magnitude of functional recovery at 90-days after discharge from the acute hospital. These findings support the need for high-intensity rehabilitation and for policies that facilitate the delivery of high-intensity rehabilitation after stroke.

Development of a hybrid point-of-care ultrasound curriculum for first year medical students in a rural medical education program: a pilot study.

BACKGROUND: The field of point-of-care ultrasound (POCUS) has advanced in recent decades due to the benefits it holds for medical providers. However, aspiring POCUS practitioners require adequate training. Unfortunately, there remains a paucity of resources to deliver this training, particularly in rural and underserved areas. Despite these barriers, calls for POCUS training in undergraduate medical education are growing, and many medical schools now deliver some form of POCUS education. Our program lacked POCUS training; therefore, we developed and implemented a POCUS curriculum for our first-year medical students. METHODS: We developed a POCUS curriculum for first year medical students in a rural medically underserved region of the United States. To evaluate our course, we measured learning outcomes, self-reported confidence in a variety of POCUS domains, and gathered feedback on the course with a multi-modal approach: an original written pre- and post-test, survey tool, and semi-structured interview protocol, respectively. RESULTS: Student (n=24) knowledge of POCUS significantly increased (pre-test average score = 55%, post-test average score = 79%, P<0.0001), and the course was well received based on student survey and interview feedback. In addition, students reported increased confidence toward a variety of knowledge and proficiency domains in POCUS use and their future clinical education and practice. CONCLUSIONS: Despite a lack of consensus in POCUS education, existing literature describes many curricular designs across institutions. We leveraged a combination of student initiatives, online resources, remote collaborations, local volunteers, and faculty development to bring POCUS to our institution in a rural and medically underserved region. Moreover, we demonstrate positive learning and experiential outcomes that may translate to improved outcomes in students' clinical education and practice. Further research is needed to evaluate the psychomotor skills, broader learning outcomes, and clinical performance of students who take part in our POCUS course.

Mathematical recapitulation of the end stages of human ovarian aging.

Ovarian aging in women can be described as highly unpredictable within individuals but predictable across large populations. We showed previously that modeling an individual woman's ovarian reserve of primordial follicles using mathematical random walks replicates the natural pattern of growing follicles exiting the reserve. Compiling many simulations yields the observed population distribution of the age at natural menopause (ANM). Here, we have probed how stochastic control of primordial follicle loss might relate to the distribution of the preceding menopausal transition (MT), when women begin to experience menstrual cycle irregularity. We show that identical random walk model conditions produce both the reported MT distribution and the ANM distribution when thresholds are set for growing follicle availability. The MT and ANM are shown to correspond to gaps when primordial follicles fail to grow for 7 and 12 days, respectively. Modeling growing follicle supply is shown to precisely recapitulate epidemiological data and provides quantitative criteria for the MT and ANM in humans.

AefR, a TetR Family Transcriptional Repressor, Regulates Several Auxin Responses in Pseudomonas syringae Strain PtoDC3000.

The plant hormone indole-3-acetic acid (IAA), also known as auxin, plays important roles in plant growth and development, as well as in several plant-microbe interactions. IAA also acts as a microbial signal and in many bacteria regulates metabolism, stress responses, and virulence. In the bacterial plant pathogen Pseudomonas syringae pv. tomato strain DC3000 (PtoDC3000), exposure to IAA results in large-scale transcriptional reprogramming, including the differential expression of several known virulence genes. However, how PtoDC3000 senses and responds to IAA and what aspects of its biology are regulated by IAA is not understood. To investigate the mechanisms involved in perceiving and responding to IAA, we carried out a genetic screen for mutants with altered responses to IAA. One group of mutants of particular interest carried disruptions in the aefR gene encoding a TetR family transcriptional regulator. Gene expression analysis confirmed that the aefR mutants have altered responses to IAA. Thus, AefR is the first demonstrated auxin response regulator in PtoDC3000. We also investigated several aspects of PtoDC3000 biology that are regulated by both AefR and IAA, including antibiotic resistance, motility, and virulence. The observation that the aefR mutant has altered virulence on Arabidopsis, suggests that the sector of the IAA response regulated by aefR is important during pathogenesis. Our findings also provide evidence that AefR plays a role in coordinating changes in gene expression during the transition from early to late stages of infection. [Formula: see text] Copyright © 2024 The Author(s). This is an open access article distributed under the CC BY-NC-ND 4.0 International license.

Reducing Physical Therapy Consults for Patients With High Functional Mobility in the Acute Medical Inpatient Setting: A Difference-in-Difference Analysis.

OBJECTIVE: To evaluate the effectiveness of clinical decision support for reducing misallocation of physical therapy (PT) consults. DESIGN: A prospective quasi-experimental study. Between October 2018 and November 2021, routinely documented data on functional status and physical therapy referrals were collected from electronic medical records. SETTING: Hospital Medicine and General Internal Medicine service lines at a large quaternary academic medical center. PARTICIPANTS: 20,810 adult patients hospitalized on any of the included treatment (hospital medicine) or control (general internal medicine) service lines. MAIN OUTCOME MEASURE: The primary outcome was "change in proportion of misallocated PT consults" measured as likelihood of PT consults for patients admitted with high functional mobility scores. Changes in the primary outcome from the pre-intervention to post-intervention period were compared in the control and treatment groups using propensity score-weighted difference-in-differences multivariable logit regression adjusting for clinically relevant covariates. INTERVENTION: The intervention period was measured for 20 months and consisted of a clinical decision support tool embedded in the daily note templates for hospital medicine providers. The tool provided education on patient mobility scores and their relation to need for PT consult. The tool was rolled out without any further announcements or education. RESULTS: Our cohort included 20,810 unique admissions (mean age 58.9, 55% women, 83% Black). Post-intervention, the likelihood of PT referrals for patients with high baseline mobility (AM-PAC >18) decreased by 7.3% (P<.001) for the treatment group compared with control, adjusted for age, sex, race, ethnicity, length-of-stay, and mobility change. CONCLUSION: Mobility score-based clinical decision support can decrease unneeded PT consults in the inpatient setting. This could help allocate therapy time for at-risk patients while also having a positive effect on health care systems.

Considering Mobility Status and Home Environment in Readmission Risk After Total Knee Arthroplasty.

BACKGROUND: Discharge disposition following total knee arthroplasty (TKA) offers varying levels of post-acute care monitoring depending on the medical status of the patient and his or her ability to function independently. Discharge disposition following TKA is associated with 30-day and 90-day hospital readmission, but prior studies have not consistently considered confounding due to mobility status after TKA, available caregiver support, and measures of home area deprivation. The purpose of this study was to examine 30-day and 90-day readmission risk for patients discharged to a skilled nursing facility (SNF) following TKA after controlling specifically for these factors, among other covariates. METHODS: This was a retrospective cohort study of patients undergoing TKA at any of 11 hospitals in a single, large, academic health-care system between January 2, 2017, and August 31, 2022, who were discharged to an SNF or home health care (HHC). The adjusted relative risk of readmission within 30 and 90 days of discharge to an SNF compared with HHC was estimated using modified Poisson regression models. RESULTS: There were 15,212 patients discharged to HHC and 1,721 patients discharged to SNFs. Readmission within 30 days was 7.1% among patients discharged to SNFs and 2.4% among patients discharged to HHC; readmission within 90 days was 12.1% for the SNF group and 4.8% for the HHC group. The adjusted relative risk after discharge to an SNF was 1.07 (95% confidence interval [CI], 0.79 to 1.46; p = 0.65) for 30-day readmission and 1.45 (95% CI, 1.16 to 1.82; p < 0.01) for 90-day readmission. CONCLUSIONS: Discharge to an SNF compared with HHC was independently associated with 90-day readmission, but not with 30-day readmission, after controlling for mobility status after TKA, available caregiver support, and home Area Deprivation Index, among other covariates. LEVEL OF EVIDENCE: Therapeutic Level III . See Instructions for Authors for a complete description of levels of evidence.

An mpox virus mRNA-lipid nanoparticle vaccine confers protection against lethal orthopoxviral challenge.

Mpox virus (MPXV) caused a global outbreak in 2022. Although smallpox vaccines were rapidly deployed to curb spread and disease among those at highest risk, breakthrough disease was noted after complete immunization. Given the threat of additional zoonotic events and the virus's evolving ability to drive human-to-human transmission, there is an urgent need for an MPXV-specific vaccine that confers protection against evolving MPXV strains and related orthopoxviruses. Here, we demonstrate that an mRNA-lipid nanoparticle vaccine encoding a set of four highly conserved MPXV surface proteins involved in virus attachment, entry, and transmission can induce MPXV-specific immunity and heterologous protection against a lethal vaccinia virus (VACV) challenge. Compared with modified vaccinia virus Ankara (MVA), which forms the basis for the current MPXV vaccine, immunization with an mRNA-based MPXV vaccine generated superior neutralizing activity against MPXV and VACV and more efficiently inhibited spread between cells. We also observed greater Fc effector TH1-biased humoral immunity to the four MPXV antigens encoded by the vaccine, as well as to the four VACV homologs. Single MPXV antigen-encoding mRNA vaccines provided partial protection against VACV challenge, whereas multivalent vaccines combining mRNAs encoding two, three, or four MPXV antigens protected against disease-related weight loss and death equal or superior to MVA vaccination. These data demonstrate that an mRNA-based MPXV vaccine confers robust protection against VACV.

Physical therapy provision for patients with pneumonia in US hospitals.

BACKGROUND: Physical therapy (PT) appears beneficial for hospitalized patients. Little is known about PT practice patterns and costs across hospitals. OBJECTIVE: To examine whether receiving PT is associated with specific patient and hospital characteristics for patients with pneumonia. We also explored the variability in PT service provision and costs between hospitals. METHODS: We included administrative claims from 2010 to 2015 in the Premier Healthcare Database, inclusive of 644 US hospitals. We examined associations between receiving at least one PT visit and patient (age, race, insurance, intensive care utilization, comorbidity status, and length of stay) and hospital (academic status, rurality, size, and location) characteristics. Exploratory measures included timing and proportion of days with PT visits, and per-visit and per-admission costs. RESULTS: Of 768,010 patients, 49% had PT. After adjustment, older age most significantly increased the probability of receiving PT (+38.0% if >80 vs. ≤50 years). Higher comorbidity burden, longer length of stay, and hospitalization in an urban setting were also associated with higher probability. Hospitalization in the South most significantly decreased the probability (-9.1% vs. Midwest). Patients without Medicare and Non-White patients also had lower probability. Median (interquartile range) days to first visit was 2 (1-4). Mean proportion of days with a visit was 35% ± 20%. Median per-visit cost was $88.90 [$56.70-$130.90] and per-admission was $224.00 [$137.80-$369.20]. CONCLUSION: Both clinical (intensive care utilization and comorbidity status) and non-clinical (age, race, rurality, location) factors were associated with receiving PT. Within and between hospitals, there was high variability in the number and frequency of visits, and costs.

Association between physical therapy frequency and postacute care for a national cohort of patients hospitalized with pneumonia.

BACKGROUND: Annually more than 300,000 patients hospitalized for pneumonia need postacute care. Patients and systems prefer home discharge, but physical limitations often necessitate postacute care. It is unknown whether frequency of physical therapy in the hospital affects postacute care discharges. OBJECTIVE: Examine the relationship between physical therapy visit frequency and disposition among a national sample of patients hospitalized with pneumonia. DESIGNS: Observational cohort study. SETTING: Acute care hospital. PARTICIPANTS: Adult patients with primary diagnosis of pneumonia in the Premier Data Set who received physical therapy in the hospital during a 5-day window, with therapy on at least days 1 and 5. INTERVENTION: Physical therapy visit frequency. MAIN OUTCOME AND MEASURES: Discharge disposition (home or postacute care). RESULTS: We included 18,886 patients from 595 hospitals. Just over half were discharged home (n = 9638; 51.0%) and 558 (2.95%) died. Patients getting more frequent therapy were older, non-Hispanic white, treated in small non-teaching rural hospitals in the West, Midwest, or South, and had fewer severe illness indicators. In adjusted models, patients who received physical therapy on 100% of days were 7% [(95% confidence interval, 4.3-9.7), p < .0001] more likely to go home than patients who received physical therapy on 40% of days. As a falsification test, we found that there was no relationship between physical therapy frequency and all-cause mortality. Physical therapy visit frequency was positively associated with discharge to home. Increasing visit frequency of physical therapy in hospitals might reduce the need for postacute care, but randomized controlled trials are needed to confirm the effect.

The Aging Ovary and the Tales Learned Since Fetal Development.

BACKGROUND: While the term "aging" implies a process typically associated with later life, the consequences of ovarian aging are evident by the time a woman reaches her forties, and sometimes earlier. This is due to a gradual decline in the quantity and quality of oocytes which occurs over a woman's reproductive lifespan. Indeed, the reproductive potential of the ovary is established even before birth, as the proper formation and assembly of the ovarian germ cell population during fetal life determines the lifetime endowment of oocytes and follicles. In the ovary, sophisticated molecular processes have been identified that regulate the timing of ovarian aging and these are critical to ensuring follicular maintenance. SUMMARY: The mechanisms thought to contribute to overall aging have been summarized under the term the "hallmarks of aging" and include such processes as DNA damage, mitochondrial dysfunction, telomere attrition, genomic instability, and stem cell exhaustion, among others. Similarly, in the ovary, molecular processes have been identified that regulate the timing of ovarian aging and these are critical to ensuring follicular maintenance. In this review, we outline critical processes involved in ovarian aging, highlight major achievements for treatment of ovarian aging, and discuss ongoing questions and areas of debate. KEY MESSAGES: Ovarian aging is recognized as what may be a complex process in which age, genetics, environment, and many other factors contribute to the size and depletion of the follicle pool. The putative hallmarks of reproductive aging outlined herein include a diversity of plausible processes contributing to the depletion of the ovarian reserve. More research is needed to clarify if and to what extent these putative regulators do in fact govern follicle and oocyte behavior, and how these signals might be integrated in order to control the overall pattern of ovarian aging.