Some survivors of childhood, adolescent, and young adult cancer are at increased risk of gonadal dysfunction and adverse pregnancy outcomes. We reviewed currently available literature that evaluated ...reproductive function and pregnancy outcomes of female cancer survivors diagnosed before the age of 25 years. High-dose alkylating agent chemotherapy and abdominal/pelvic radiotherapy adversely affect gonadal function in a dose-related fashion, with older age at exposure conferring greater risk as a result of the age-related decline in ovarian reserve. Gonadal injury clinically manifests as ovarian hormone insufficiency (delayed or arrested puberty, premature ovarian insufficiency, or premature menopause) and infertility. The effect of molecular-targeted agents on ovarian function has not been established. For female cancer survivors who maintain fertility, overall pregnancy (relative risk, 0.67 to 0.81) and live birth rates (hazard ratio, 0.79 to 0.82) are lower than those in the general public. Pregnancy in cancer survivors also may be associated with risks to both the mother and the fetus related to miscarriage; preterm birth; and, rarely, cardiomyopathy. Women at risk for these complications require preconception assessment and counseling from both obstetricians and oncology providers. The risk for inherited genetic disease in offspring conceived after cancer treatment exposure is not increased. The optimization of reproductive outcomes and minimization of risks of pregnancy complications in survivors requires informed, risk-based assessment and monitoring.
Cancer treatments can be damaging to the ovary, with implications for future fertility and reproductive lifespan. There is therefore a need for a biomarker than can usefully provide an assessment of ...the ovary and its potential for long-term function after cancer treatment, and ideally also be of value pre-treatment, for the prediction of post-treatment function. In this review we assess the value of anti-Müllerian hormone (AMH) in this context. Measurement of AMH at the time of cancer diagnosis has been shown to be predictive of whether or not there will remain some ovarian function post-treatment in women with breast cancer, in conjunction with age. AMH may however be reduced at the time of diagnosis in some conditions, including lymphoma, but probably not in women with breast cancer unless they are carriers of
mutations. Following chemotherapy, AMH is often much reduced compared to pretreatment levels, with recovery dependent on the chemotherapy regimen administered, the woman's age, and her pretreatment AMH. Recent data show there may be a long duration of relative stability of AMH levels over 10 to 15 years prior to decline rather than a rapid decline for many young women after cancer. Post-treatment AMH may have utility in determining that ovarian function will not recover, contributing to assessment of the need for ovarian suppression in women with hormone-sensitive breast cancer. AMH measurement provides an index of treatment gonadotoxicity, allowing comparison of different treatment regimens, although extrapolation to effects on fertility requires caution, and there are very limited data regarding the use of AMH to estimate time to menopause in the post-cancer setting.
Parkinson's disease is a neurodegenerative disorder characterized by motor and nonmotor symptoms. Psychosis is a common feature of Parkinson's disease. Parkinson's disease psychosis (PDP) encompasses ...minor phenomena (illusions, passage hallucinations and presence hallucinations), visual and nonvisual hallucinations and delusions. PDP is associated with reduced function and quality of life. The initial management approach should focus on identification and treatment of any contributory medical factors, reduction or discontinuation of medications with potential to induce or worsen psychosis, nonpharmacological strategies and consideration of acetylcholinesterase inhibitor treatment in the setting of dementia. Pimavanserin, quetiapine and clozapine may all be considered for use in PDP. In this review, we discuss the presentation, diagnosis and management of PDP.
IMPORTANCE: Achieving linkage to care and viral suppression in human immunodeficiency virus (HIV)-positive patients improves their well-being and prevents new infections. Current gaps in the HIV care ...continuum substantially limit such benefits. OBJECTIVE: To evaluate the effectiveness of financial incentives on linkage to care and viral suppression in HIV-positive patients. DESIGN, SETTING, AND PARTICIPANTS: A large community-based clinical trial that randomized 37 HIV test and 39 HIV care sites in the Bronx, New York, and Washington, DC, to financial incentives or standard of care. INTERVENTIONS: Participants at financial incentive test sites who had positive test results for HIV received coupons redeemable for $125 cash-equivalent gift cards upon linkage to care. HIV-positive patients receiving antiretroviral therapy at financial incentive care sites received $70 gift cards quarterly, if virally suppressed. MAIN OUTCOMES AND MEASURES: Linkage to care: proportion of HIV-positive persons at the test site who linked to care within 3 months, as indicated by CD4+ and/or viral load test results done at a care site. Viral suppression: proportion of established patients at HIV care sites with suppressed viral load (<400 copies/mL), assessed at each calendar quarter. Outcomes assessed through laboratory test results reported to the National HIV Surveillance System. RESULTS: A total of 1061 coupons were dispensed for linkage to care at 18 financial incentive test sites and 39 359 gift cards were dispensed to 9641 HIV-positive patients eligible for gift cards at 17 financial incentive care sites. Financial incentives did not increase linkage to care (adjusted odds ratio, 1.10; 95% CI, 0.73-1.67; P = .65). However, financial incentives significantly increased viral suppression. The overall proportion of patients with viral suppression was 3.8% higher (95% CI, 0.7%-6.8%; P = .01) at financial incentive sites compared with standard of care sites. Among patients not previously consistently virally suppressed, the proportion virally suppressed was 4.9% higher (95% CI, 1.4%-8.5%; P = .007) at financial incentive sites. In addition, continuity in care was 8.7% higher (95% CI, 4.2%-13.2%; P < .001) at financial incentive sites. CONCLUSIONS AND RELEVANCE: Financial incentives, as used in this study (HPTN 065), significantly increased viral suppression and regular clinic attendance among HIV-positive patients in care. No effect was noted on linkage to care. Financial incentives offer promise for improving adherence to treatment and viral suppression among HIV-positive patients. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01152918
AbstractObjectiveTo assess the performance of rapid antigen tests with unsupervised nasal and combined oropharyngeal and nasal self-sampling during the omicron period.DesignProspective cross ...sectional diagnostic test accuracy study.SettingThree public health service covid-19 test sites in the Netherlands, 21 December 2021 to 10 February 2022.Participants6497 people with covid-19 symptoms aged ≥16 years presenting for testing.InterventionsParticipants had a swab sample taken for reverse transcription polymerase chain reaction (RT-PCR, reference test) and received one rapid antigen test to perform unsupervised using either nasal self-sampling (during the emergence of omicron, and when omicron accounted for >90% of infections, phase 1) or with combined oropharyngeal and nasal self-sampling in a subsequent (phase 2; when omicron accounted for >99% of infections). The evaluated tests were Flowflex (Acon Laboratories; phase 1 only), MPBio (MP Biomedicals), and Clinitest (Siemens-Healthineers).Main outcome measuresThe main outcomes were sensitivity, specificity, and positive and negative predictive values of each self-test, with RT-PCR testing as the reference standard.ResultsDuring phase 1, 45.0% (n=279) of participants in the Flowflex group, 29.1% (n=239) in the MPBio group, and 35.4% ((n=257) in the Clinitest group were confirmatory testers (previously tested positive by a self-test at own initiative). Overall sensitivities with nasal self-sampling were 79.0% (95% confidence interval 74.7% to 82.8%) for Flowflex, 69.9% (65.1% to 74.4%) for MPBio, and 70.2% (65.6% to 74.5%) for Clinitest. Sensitivities were substantially higher in confirmatory testers (93.6%, 83.6%, and 85.7%, respectively) than in those who tested for other reasons (52.4%, 51.5%, and 49.5%, respectively). Sensitivities decreased from 87.0% to 80.9% (P=0.16 by χ2 test), 80.0% to 73.0% (P=0.60), and 83.1% to 70.3% (P=0.03), respectively, when transitioning from omicron accounting for 29% of infections to >95% of infections. During phase 2, 53.0% (n=288) of participants in the MPBio group and 44.4% (n=290) in the Clinitest group were confirmatory testers. Overall sensitivities with combined oropharyngeal and nasal self-sampling were 83.0% (78.8% to 86.7%) for MPBio and 77.3% (72.9% to 81.2%) for Clinitest. When combined oropharyngeal and nasal self-sampling was compared with nasal self-sampling, sensitivities were found to be slightly higher in confirmatory testers (87.4% and 86.1%, respectively) and substantially higher in those testing for other reasons (69.3% and 59.9%, respectively).ConclusionsSensitivities of three rapid antigen tests with nasal self-sampling decreased during the emergence of omicron but was only statistically significant for Clinitest. Sensitivities appeared to be substantially influenced by the proportion of confirmatory testers. Sensitivities of MPBio and Clinitest improved after the addition of oropharyngeal to nasal self-sampling. A positive self-test result justifies prompt self-isolation without the need for confirmatory testing. Individuals with a negative self-test result should adhere to general preventive measures because a false negative result cannot be ruled out. Manufacturers of MPBio and Clinitest may consider extending their instructions for use to include combined oropharyngeal and nasal self-sampling, and other manufacturers of rapid antigen tests should consider evaluating this as well.
Understanding advances in the care and treatment of adults with HIV as well as remaining gaps requires comparing differences in mortality between persons entering care for HIV and the general ...population.
To assess the extent to which mortality among persons entering HIV care in the United States is elevated over mortality among matched persons in the general U.S. population and trends in this difference over time.
Observational cohort study.
Thirteen sites from the U.S. North American AIDS Cohort Collaboration on Research and Design.
82 766 adults entering HIV clinical care between 1999 and 2017 and a subset of the U.S. population matched on calendar time, age, sex, race/ethnicity, and county using U.S. mortality and population data compiled by the National Center for Health Statistics.
Five-year all-cause mortality, estimated using the Kaplan-Meier estimator of the survival function.
Overall 5-year mortality among persons entering HIV care was 10.6%, and mortality among the matched U.S. population was 2.9%, for a difference of 7.7 (95% CI, 7.4 to 7.9) percentage points. This difference decreased over time, from 11.1 percentage points among those entering care between 1999 and 2004 to 2.7 percentage points among those entering care between 2011 and 2017.
Matching on available covariates may have failed to account for differences in mortality that were due to sociodemographic factors rather than consequences of HIV infection and other modifiable factors.
Mortality among persons entering HIV care decreased dramatically between 1999 and 2017, although those entering care remained at modestly higher risk for death in the years after starting care than comparable persons in the general U.S. population.
National Institutes of Health.
To determine the effect of a Best Practice Advisory (BPA) on the ordering and administration of contraindicated dopamine blocking agents (DBA) to hospitalized patients with Parkinson's disease (PD) ...and related disorders.
Patients with PD are more likely to require hospitalization and are at increased risk of complications. Administration of contraindicated DBA contributes to worsened outcomes in this patient population. Electronic medical record (EMR) warnings (also referred to as BPA) have been proposed as a way to prevent the administration of contraindicated medications.
A BPA was launched in January 2020 within the University of Rochester EMR system, which alerts the provider when a contraindicated DBA is ordered in hospitalized patients with PD and related disorders. Patients with PD and related disorders hospitalized at two hospitals affiliated to the University of Rochester during a time period before (
: 1/1/2019-1/1/2020) and after (
: 1/8/2020-1/8/2021) the implementation of the BPA were included in this study. Epic SliderDicer was used to collect the data from the University of Rochester EMR. The number of patients who had contraindicated DBA orders and administrations in both time periods, and the number of patients who had the BPA triggered during
were obtained. We compared the results before and after the implementation of the BPA.
306 patients with PD and related disorders were hospitalized during
and 273 during
. There was significantly less percentage of patients who had contraindicated DBA orders (41.5% in
vs. 17.6% in
) and patients who had contraindicated DBA administrations (16% in
vs. 8.8% in
) during
(
< 0.05 for both comparisons). There was no significant difference between the percentage of patients who had contraindicated DBA orders in
and patients with attempted orders (BPA triggered) in
(
= 0.27).
The results of this study increase the evidence of the potential benefit of EMR warnings for the optimization of inpatient medication management in patients with PD and related disorders. In particular, our results suggest that EMR warnings help reduce the administration of contraindicated medications, which is a known contributing factor for hospital complications in this patient population.
To examine complications and outcomes of hospitalizations for common indications for hospitalization among patients with Parkinson disease (PD).
We identified and selected the ten most common ...indications for hospitalization among individuals ≥65 years of age using principal diagnoses from the California State Inpatient Database, 2018-2020. Patients with comorbid PD were identified using secondary diagnosis codes and matched one-to-one to patients without PD based on principal diagnosis (exact matching), age, gender, race and ethnicity, and Elixhauser comorbidity index (coarsened exact matching). We identified potentially preventable complications based on the absence of present on admission indicators among secondary diagnoses. In the matched cohort, we compared inpatient complications, early Do-Not-Resuscitate (DNR) orders (placed within 24 h of admission), use of life-sustaining therapies, new nursing facility requirement on discharge, and death or hospice discharge for patients with and without PD.
We identified 35,457 patients with PD among the ten leading indications for hospitalization in older adults who were matched one-to-one to patients without PD (
= 70,914 in total). Comorbid PD was associated with an increased odds of developing aspiration pneumonia (OR 1.17 95% CI 1.02-1.35) and delirium (OR 1.11 95% CI 1.02-1.22) during admission. Patients with PD had greater odds of early DNR orders placed within 24 h of admission (OR 1.34 95% CI 1.29-1.39). While there was no difference in the odds of mechanical ventilation (OR 1.04 95% CI 0.98-1.11), patients with PD demonstrated greater odds of tracheostomy (OR 1.41 95% CI 1.12-1.77) and gastrostomy placement (OR 2.00 95% CI 1.82-2.20). PD was associated with greater odds of new nursing facility requirement upon discharge (OR 1.58 95% CI 1.53-1.64). Patients with PD were more likely to die as a result of their hospitalization (OR 1.11 95% CI 1.06-1.16).
Patients with PD are at greater risk of developing aspiration pneumonia and delirium as a complication of their hospitalization. While patients with PD more often have early DNR orders, they have greater utilization of life-sustaining therapies and experience worse outcomes of their hospitalization including new nursing facility requirement upon discharge and greater mortality.