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1.
Am J Transplant ; 24(2S1): S119-S175, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38431358

ABSTRACT

The postpandemic recovery did not occur in pancreas transplantation as in other organs. The number of pancreas transplants in the United States decreased to 918 in 2022 from 963 in 2021. The number of simultaneous pancreas-kidney transplants decreased to 810 in 2022 from 820 in 2021, but the largest decrease was in pancreas transplant alone: 62 in 2022 compared with 92 in 2021. Pancreas-after-kidney transplants decreased to 46 in 2022 from 51 in 2021. The trend of increasing proportions of pancreas transplants in patients with type 2 diabetes seen over the past few years ended in 2022; there were 22.4% of such transplants in 2022 compared with 25.8% in 2021. The proportion of recipients older than 45 years decreased in 2022 as well. However, the proportions of candidates with type 2 diabetes and older candidates on the waiting list did not decrease. The number of pancreas donors decreased and the pancreas nonuse rate increased in 2022. Outcomes after pancreas transplant continued to improve, with an impressive 8.1% pancreas and 4.3% kidney graft failure rate for simultaneous pancreas-kidney transplant at 1 year in 2022. The proportion of pancreas transplants performed by medium-volume centers (11-24 transplants/year) returned to 37.2% in 2022 from a high of 48.3% in 2021, whereas the proportion of those done by large-volume centers (25 or more transplants/year) returned to 25.3% in 2022 from a low of 15.9% in 2021.


Subject(s)
Diabetes Mellitus, Type 2 , Tissue and Organ Procurement , Humans , United States , Graft Survival , Tissue Donors , Waiting Lists , Pancreas
2.
Am J Transplant ; 24(2S1): S457-S488, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38431364

ABSTRACT

The Scientific Registry of Transplant Recipients uses data collected by the Organ Procurement and Transplantation Network to calculate metrics such as organs recovered per donor, organs transplanted per donor, and organs recovered for transplant but not transplanted (ie, nonuse). In 2022, there were 14,905 deceased donors, a 7.5% increase from 13,863 in 2021, and this number has been increasing since 2010. The number of deceased donor organs used for transplant increased to 37,334 in 2022, a 4.6% increase from 35,687 in 2021; this number has been increasing since 2012. The increase may be due in part to the rising number of deaths of young people amid the ongoing opioid epidemic. The number of organs transplanted included 10,130 left kidneys, 10,039 right kidneys, 298 en bloc kidneys, 922 pancreata, 8,847 livers, 83 intestines, 4,169 hearts, and 2,633 lungs. Compared with 2021, transplants of all organs except pancreata and intestines increased in 2022. In 2022, 3,563 left kidneys, 3,673 right kidneys, 156 en bloc kidneys, 366 pancreata, 965 livers, 4 intestines, 54 hearts, and 219 lungs were not used. These data suggest an opportunity to increase the number of transplants by reducing the number of unused organs. Despite the COVID-19 pandemic, there was no dramatic increase in the number of unused organs and there was an increase in the total numbers of donors and transplants.


Subject(s)
Organ Transplantation , Tissue and Organ Procurement , Humans , Adolescent , Pandemics , Tissue Donors , Transplant Recipients
3.
Am J Transplant ; 24(2S1): S534-S556, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38431366

ABSTRACT

This year's chapter on vascularized composite allograft (VCA) encompasses reviews of data collected from 2014 (when VCA was included in the Final Rule) through 2022. The present Annual Data Report shows that the number of VCA recipients in the United States continues to be small and has remained consistent from the prior report. The data continue to be limited by sample size, with trends persistently demonstrating a predominance of White males in the young/middle-aged population as both donors and recipients for nonuterus VCA transplants, and White women younger than 35 years as the predominant recipients of uterus transplant. Similar to the 2021 report, there were only eight failed uterus grafts and one failed nonuterus VCA graft reported from 2014 through 2022. Standardization of definitions of success and failure as well as outcome measures for the different VCA types remain unmet needs in VCA transplantation.


Subject(s)
Composite Tissue Allografts , Vascularized Composite Allotransplantation , Male , Middle Aged , Humans , Female , United States , Composite Tissue Allografts/transplantation , Tissue Donors
4.
Am J Transplant ; 2024 Feb 06.
Article in English | MEDLINE | ID: mdl-38331046

ABSTRACT

The Scientific Registry of Transplant Recipients has previously reported the effects of adjusting for demographic variables, including race, in the Centers for Medicare & Medicaid Services (CMS) organ procurement organization (OPO) performance metrics: donation rate and transplant rate. CMS chose not to adjust for most demographic variables other than age (for the transplant rate), arguing that there is no biological reason that these variables would affect the organ donation/utilization decision. However, organ donation is a process based on altruism and trust, not a simple biological phenomenon. Focusing only on biological impacts on health ignores other pathways through which demographic factors can influence OPO outcomes. In this study, we update analyses of demographic adjustment on the OPO metrics for 2020 with a specific focus on adjusting for race. We find that adjusting for race would lead to 8 OPOs changing their CMS tier rankings, including 2 OPOs that actually overperform the national rate among non-White donors improving from a tier 3 ranking (facing decertification without possibility of recompeting) to a tier 2 ranking (allowing the possibility of recompeting). Incorporation of stratified and risk-adjusted metrics in public reporting of OPO performance could help OPOs identify areas for improvement within specific demographic categories.

5.
Am J Transplant ; 24(2S1): S19-S118, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38431360

ABSTRACT

The year 2022 had continued successes and challenges for the field of kidney transplantation, as the community adapted to ongoing surges of the COVID-19 pandemic and broader geographic organ distribution. The total number of kidney transplants in the United States reached a record count of 26,309, driven by continued growth in deceased donor kidney transplants (DDKTs). The total number of candidates listed for DDKT rose slightly in 2022 but remained below 2019 listing levels, with 12.4% of candidates having been waiting 5 years or longer. Following the height of the COVID-19 pandemic, pretransplant mortality in 2022 declined across age, race and ethnicity, sex, and blood type groups. Pretransplant mortality continued to vary substantially by donation service area. The proportion of deceased donor kidneys recovered but not used for transplant (nonuse rate) rose to a high of 26.7% overall, with greater nonuse of biopsied kidneys (39.8%), kidneys from donors aged 55 years or older (54.7%), and kidneys with a kidney donor profile index (KDPI) of 85% or greater (71.3%). Nonuse of kidneys from donors who are hepatitis C virus (HCV) antibody positive rose to 30.2% but only slightly exceeded that of HCV antibody-negative donors. Disparities in access to living donor kidney transplant (LDKT) persist, especially for non-White and publicly insured patients. Delayed graft function continues an upward trend and occurred in 26.3% of adult kidney transplants in 2022. Five-year graft survival after LDKT compared with DDKT was 90.0% versus 81.4% for recipients aged 18-34 years and 80.8% versus 67.8% for recipients aged 65 years or older, respectively. The total number of pediatric kidney transplants performed in 2022 decreased to 705, its lowest point in the past decade; 502 (71.2%) were DDKTs and 203 (28.8%) were LDKTs. Among pediatric recipients, LDKT remains low, with continued racial disparities. The rate of DDKT among pediatric candidates has decreased by almost 25% since 2011. Congenital anomalies of the kidney and urinary tract remain the leading primary kidney disease diagnosis among pediatric candidates with a reported diagnosis. Most pediatric deceased donor recipients received a kidney from a donor with a KDPI of less than 35%. The rate of delayed graft function was 5.8% in 2022 and has been stable over the past decade. Long-term graft survival continues to improve, with superior outcomes for living donor transplant recipients.


Subject(s)
COVID-19 , Hepatitis C , Tissue and Organ Procurement , Adult , Humans , Child , United States/epidemiology , Delayed Graft Function , Pandemics , Tissue Donors , Living Donors , Graft Survival , Registries , Kidney , COVID-19/epidemiology
6.
Am J Transplant ; 24(2S1): S489-S533, 2024 Feb.
Article in English | MEDLINE | ID: mdl-38431365

ABSTRACT

This chapter updates the COVID-19 chapter from the 2021 Annual Data Report with trends through November 12, 2022, and introduces trends in recovery and use of organs from donors with a positive COVID-19 test. Posttransplant mortality and graft failure, which remained a concern in all organs at the last report due to the Omicron variant wave, have returned to lower levels in the most recent available data through November 2022. Use of organs from donors with a positive COVID-19 test has grown, particularly after the first year of the pandemic. Mortality due to COVID-19 should continue to be monitored, but most other measures have sustained their recovery and may now be responding more to changes in policy than to ongoing concerns with COVID-19.


Subject(s)
COVID-19 , Tissue and Organ Procurement , Humans , United States/epidemiology , Graft Survival , Waiting Lists , SARS-CoV-2 , Tissue Donors
7.
J Clin Ethics ; 35(2): 107-118, 2024.
Article in English | MEDLINE | ID: mdl-38728694

ABSTRACT

AbstractEmpirical studies of pediatric clinical ethics cases are scant in the biomedical and bioethics literature. In this study, more than 100 detailed records of clinical ethics consultations spanning from 2000 to 2020 at a moderately sized U.S. Mid-Atlantic children's hospital were abstracted and analyzed. Findings of the analysis were generally consistent with other studies in pediatric clinical ethics, with additional insight into aspects of moral distress associated with cases, family engagement with consultations, and other characteristics of interest also documented. Over the 20-year time frame, ethics consults were completed on average twice a year, with a detectable upward trend. Consultations were requested across the spectrum of services and units within the hospital, with critical care environments represented most frequently and genetic and neurological conditions being the most common primary diagnoses. Ethical analysis most commonly related to questions around the principles of autonomy and beneficence.


Subject(s)
Ethics Consultation , Hospitals, Pediatric , Humans , Child , United States , Ethics, Clinical , Personal Autonomy , Ethical Analysis , Beneficence , Male , Female
8.
Am J Transplant ; 23(2 Suppl 1): S475-S522, 2023 02.
Article in English | MEDLINE | ID: mdl-37132343

ABSTRACT

This chapter updates the COVID-19 chapter from the 2020 Annual Data Report with trends through February 12, 2022, and introduces trends in COVID-19-specific cause of death on the waiting list and posttransplant. Transplant rates remain at or above prepandemic levels for all organs, indicating a sustained transplantation system recovery following the initial 3-month disruption due to the onset of the pandemic. Posttransplant mortality and graft failure remain a concern in all organs, with rates surging corresponding to waves of the pandemic. Waitlist mortality due to COVID-19 is also a concern, particularly among kidney candidates. While the recovery of the transplantation system has been sustained in the second year of the pandemic, ongoing efforts should focus on reducing posttransplant and waitlist mortality due to COVID-19, and graft failure.


Subject(s)
COVID-19 , Liver Transplantation , Lung Transplantation , Tissue and Organ Procurement , Humans , United States/epidemiology , Tissue Donors , COVID-19/epidemiology , Waiting Lists , Graft Survival
9.
Am J Transplant ; 23(2 Suppl 1): S443-S474, 2023 02.
Article in English | MEDLINE | ID: mdl-37132344

ABSTRACT

The Scientific Registry of Transplant Recipients uses data collected by the Organ Procurement and Transplantation Network to calculate metrics such as donation rate, organ yield, and rate of organs recovered for transplant but not transplanted (ie, nonuse). In 2021, there were 13,862 deceased donors, a 10.1% increase from 12,588 in 2020, and an increase from 11,870 in 2019; this number has been increasing since 2010. The number of deceased donor transplants increased to 41,346 transplants in 2021, a 5.9% increase from 39,028 in 2020; this number has been increasing since 2012. The increase may be due in part to the rising number of deaths of young people amid the ongoing opioid epidemic. The number of organs transplanted included 9,702 left kidneys, 9,509 right kidneys, 551 en bloc kidneys, 964 pancreata, 8,595 livers, 96 intestines, 3,861 hearts, and 2,443 lungs. Compared with 2019, transplants of all organs except lungs increased in 2021, which is remarkable as this occurred despite the COVID-19 pandemic. In 2021, 2,951 left kidneys, 3,149 right kidneys, 184 en bloc kidneys, 343 pancreata, 945 liver, 1 intestine, 39 hearts, and 188 lungs were not used. These numbers suggest an opportunity to increase numbers of transplants by reducing nonused organs. Despite the pandemic, there was no dramatic increase in number of nonused organs and there was an increase in total numbers of donors and transplants. The new Centers for Medicare & Medicaid Services metrics for donation rate and transplant rate have also been described and vary across organ procurement organizations; the donation rate metric varied from 5.82 to 19.14 and the transplant rate metric varied from 18.7 to 60.0.


Subject(s)
COVID-19 , Organ Transplantation , Tissue and Organ Procurement , Aged , Humans , United States , Adolescent , Pandemics , Medicare , Tissue Donors
10.
Am J Transplant ; 23(2 Suppl 1): S121-S177, 2023 02.
Article in English | MEDLINE | ID: mdl-37132349

ABSTRACT

The number of pancreas transplants in the United States was largely unchanged in 2021 at 963 transplants compared with 962 in 2020, showing that recovery from the COVID-19 pandemic was not as pronounced in pancreas transplantation as in other organs. The number of simultaneous pancreas-kidney transplants (SPKs) decreased from 827 to 820, whereas the number of pancreas-after-kidney transplants and pancreas transplants alone increased marginally to compensate. The proportion of patients with type 2 diabetes on the waiting list increased to 22.9% in 2021, compared with 20.1% in 2020. Consequently, the proportion of transplants in patients with type 2 diabetes increased from 21.3% in 2020 to 25.9% in 2021. The proportion of transplants in older recipients (aged 55 years or older) also increased to 13.5% in 2021 from 11.7% in 2020. Outcomes after SPK continue to be the best of the three categories of pancreas transplants: 1-year graft failure for kidney at 5.7% and pancreas at 10.5% for transplants performed in 2020. The proportion of pancreas transplants performed by medium-volume centers (11-24 transplants per year) increased sharply to 48.3% in 2021 from 35.1% in 2020, with a corresponding decrease in transplants in large-volume centers (25 or more transplants per year) to 15.9% in 2021 from 25.7% in 2020.


Subject(s)
COVID-19 , Diabetes Mellitus, Type 2 , Pancreas Transplantation , Tissue and Organ Procurement , Humans , United States/epidemiology , Aged , Graft Survival , COVID-19/epidemiology , Pancreas
11.
Am J Transplant ; 23(2 Suppl 1): S523-S545, 2023 02.
Article in English | MEDLINE | ID: mdl-37132342

ABSTRACT

Year 2020 marked the first OPTN/SRTR Annual Data Report that included a chapter on vascularized composite allograft (VCA), which encompassed reviews of data collected between 2014 (when VCA was included in the Final Rule) and 2020. The present Annual Data Report shows that the number of VCA recipients in the United States continues to be small and trended downward in 2021. While data continue to be limited by sample size, trends continue to show a predominance in White, young/middle-aged, male recipients. Similar to the 2020 report, eight uterus and one non-uterus VCA graft failures were reported from 2014 through 2021. Critical to advancement of VCA transplantation will be the standardization of definitions, protocols, and outcome measures for the different VCA types. Like intestinal transplants, it is likely that VCA transplants will be concentrated and performed at referral transplant centers.


Subject(s)
Composite Tissue Allografts , Transplants , Vascularized Composite Allotransplantation , Middle Aged , Male , Humans , United States , Composite Tissue Allografts/transplantation
12.
Am J Transplant ; 23(2 Suppl 1): S21-S120, 2023 02.
Article in English | MEDLINE | ID: mdl-37132350

ABSTRACT

The year 2021 marked both successes and challenges for the field of kidney transplantation, in the context of the ongoing COVID-19 pandemic and broader geographic organ distribution. The total number of kidney transplants in the United States reached a record count of 25,487, driven by growth in deceased donor kidney transplants. The total number of candidates listed for deceased donor kidney transplant rose slightly in 2021 but remained below 2019 listing levels, with nearly 10% of candidates having been waiting 5 years or longer. Pretransplant mortality declined slightly among candidates of Black, Hispanic, and other races, in parallel with increasing numbers of Black and Hispanic transplant recipients. In the context of broader organ sharing, there is growing disparity in pretransplant mortality among non-metropolitan compared with metropolitan residents. The proportion of deceased donor kidneys recovered but not used for transplant (nonuse rate) rose to a high of 24.6% overall, with greater nonuse among biopsied kidneys (35.9%), kidneys from donors aged 55 years or older (51.1%), and kidneys with kidney donor profile index (KDPI) of 85% or greater (66.6%). Nonuse of kidneys from donors who are hepatitis C virus (HCV) antibody positive only slightly exceeded that of HCV antibody-negative donors. Disparities in access to living donor kidney transplant persists, especially for non-White and publicly insured patients. Delayed graft function continues an upward trend and occurred in 24% of adult kidney transplants in 2021. Five-year graft survival after living compared with deceased donor transplant was 88.6% versus 80.7% for recipients aged 18-34 years, and 82.1% versus 68.0% for recipients aged 65 years or older. The total number of pediatric kidney transplants performed increased to 820 in 2021, the highest number since 2010. Despite numerous efforts, living donor kidney transplant remains low among pediatric recipients, with continued racial disparities. The rate of deceased donor transplants among pediatric candidates recovered in 2021 from a low in 2020. Congenital anomalies of the kidney and urinary tract remain the leading primary kidney disease diagnosis among pediatric candidates. Most pediatric deceased donor recipients receive a kidney from a donor with KDPI less than 35%. Graft survival continues to improve, with superior outcomes for living donor transplant recipients.


Subject(s)
COVID-19 , Hepatitis C , Tissue and Organ Procurement , Adult , Humans , Child , United States/epidemiology , Pandemics , COVID-19/epidemiology , Tissue Donors , Living Donors , Graft Survival , Kidney
13.
Pediatr Blood Cancer ; 68(5): e28850, 2021 05.
Article in English | MEDLINE | ID: mdl-33369068

ABSTRACT

PURPOSE: This randomized cross-over group pilot trial assessed feasibility of recruiting survivors from a long-term follow-up clinic to an exercise group and measured whether outdoor or indoor exercise sessions better supported exercise motivation and behaviors in survivors of cancer. METHODS: Sixteen adolescent and young adult survivors of any cancer completed indoor and outdoor exercise sessions in this randomized cross-over pilot trial. Measures of physical activity, motivation, and fatigue were taken 2 weeks before and 2 weeks after indoor sessions and 2 weeks before and 2 weeks after outdoor sessions. Measures of physical activity and fatigue were also taken during each exercise session. RESULTS: Initial recruiting of 19 participants met recruiting goals. Survivors who attended the most sessions lived an average of 8.7 km closer to the clinic. Objectively measured physical activity intensity was 0.63 metabolic equivalents of a task (METs) per minute greater during outdoor exercise sessions as compared to indoor exercise sessions. There were no meaningful differences in long term, habitual physical activity behavior, motivation, or fatigue in the weeks following the outdoor exercise sessions as compared to the indoor exercise sessions. CONCLUSIONS: This study shows the feasibility of recruiting survivors from a long-term follow-up clinic to community-based exercise groups. Although this brief pilot intervention did not show significant effects on habitual physical activity behavior or motivation in adolescent and young adult survivors of cancer, the greater exercise intensity during the outdoor exercise sessions indicate that holding group exercise sessions for survivors outdoors may promote greater intensity during exercise.


Subject(s)
Cancer Survivors , Exercise , Adolescent , Adult , Cross-Over Studies , Fatigue , Female , Humans , Male , Motivation , Pilot Projects , Young Adult
14.
Prog Pediatr Cardiol ; 58: 101270, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32837148

ABSTRACT

We report one of the earliest known U.S. cases of multisystem inflammatory syndrome in children associated with COVID-19 (MIS-C). This adolescent male presented prior to any known association between COVID-19 and immune mediated inflammatory syndrome in children. He presented in stable condition and without significant multisystem involvement. During hospitalization, he developed severe left ventricular dysfunction and mixed hypovolemic, distributive and cardiogenic shock. Clinical features overlapped with Kawasaki disease, acute rheumatic fever, and toxic shock syndrome. After centers in Europe began reporting a multisystem inflammatory condition in children with COVID-19, the patient's clinical course and laboratory findings were revisited. He underwent newly available antibody testing and was diagnosed as one of the first known cases of MIS-C in the United States.

15.
J Pediatr Gastroenterol Nutr ; 68(3): 389-393, 2019 03.
Article in English | MEDLINE | ID: mdl-30540708

ABSTRACT

INTRODUCTION: Acute pancreatitis (AP) is understudied in the pediatric population despite increasing incidence. Although many cases are mild and resolve with supportive care, severe acute pancreatitis (SAP) can be associated with significant morbidity and mortality. There is a lack of pediatric-specific predictive tools to help stratify risk of SAP in children. METHODS: A retrospective cohort study of patients with AP or recurrent AP at Cohen Children's Medical Center between 2011 and 2016 was performed. Lipase level and the presence of pediatric systemic inflammatory response syndrome (SIRS) on admission were examined as potential predictors of SAP and length of stay (LOS). A multivariate logistic regression or analysis of covariance was used to conduct the multivariate analysis. RESULTS: Seventy-nine pediatric patients met inclusion criteria. Approximately 37% (29/79) had SIRS on admission, 22% (17/79) developed SAP, and there were no mortalities. In both the univariate and multivariate models, SIRS was a predictor of SAP. Mean (SD) LOS for patients with SIRS compared with without SIRS was 9.6 ±â€Š8.3 compared with 6.3 ±â€Š6.9 days (P < 0.05). The mean LOS of patients with one or more comorbidity (48%, 38/79) was 10.0 ±â€Š9.5 compared with 5.2 ±â€Š4.0 days (P < 0.01) for those patients without any comorbidities. Only the presence of comorbidities predicted length of time spent nil per os (NPO; P = 0.0022). Patients with comorbidities stayed an average of 5.6 ±â€Š7.6 days NPO, whereas those without comorbidities spent 2.8 ±â€Š2.4 days NPO. Lipase was not predictive of SAP, LOS, or length of time spent NPO. CONCLUSIONS: These results support the use of SIRS as a simple screening tool on admission to identify children at risk for the development of SAP. The presence of any comorbidity was predictive of LOS and length of NPO in the multivariate model. This may reflect that comorbidities prolong pancreatitis or influence disposition planning.


Subject(s)
Length of Stay/statistics & numerical data , Lipase/blood , Pancreatitis/epidemiology , Systemic Inflammatory Response Syndrome/epidemiology , Adolescent , Case-Control Studies , Child , Comorbidity , Female , Humans , Male , Pancreatitis/diagnosis , Retrospective Studies , Sensitivity and Specificity , Systemic Inflammatory Response Syndrome/diagnosis
16.
Mol Pharm ; 14(1): 319-327, 2017 01 03.
Article in English | MEDLINE | ID: mdl-27981848

ABSTRACT

The purpose of this research was to investigate the performance of cosolvent based solubility-enabling formulations in oral delivery of lipophilic drugs, accounting for the gastrointestinal tract (GIT) luminal solubilization processes, the solubility-permeability interplay, and the overall in vivo systemic absorption. The poorly soluble antiepileptic agent carbamazepine was formulated in three cosolvent-based formulations: 20%, 60%, and 100% PEG-400, and the apparent solubility and rat permeability of the drug in these formulations were evaluated. The performance of the formulations in the dynamic GIT environment was assessed utilizing the biorelevant pH-dilution method. Then, the overall in vivo drug exposure was investigated following oral administration to rats. The three formulations showed dramatic solubility and permeability differences; the 100% PEG-400 provided the highest solubility enhancement and the 20% the poorest, while the exact opposite was evident from the permeability point of view. The dissolution results indicated that the 20% PEG-400 formulation crashes quickly following oral administration, but both the 60% and the 100% PEG-400 formulations allowed full solubilization of the dose throughout the entire GIT-like journey. The best in vivo performing formulation was the 60% PEG-400 (Fsys > 90%), followed by the 100% PEG-400 (Fsys = 76%), and the 20% PEG-400 formulation (Fsys ≈ 60%). In conclusion, this work demonstrates the in vivo solubility-permeability trade-off in oral delivery of lipophilic drugs; when a solubility-enabling formulation is developed, minimal threshold solubility should be targeted, that is just enough to allow solubilization of the drug dose throughout the GIT, while excess solubilizer should be avoided.


Subject(s)
Carbamazepine/blood , Carbamazepine/chemistry , Pharmaceutical Preparations/blood , Pharmaceutical Preparations/chemistry , Administration, Oral , Animals , Chemistry, Pharmaceutical/methods , Male , Permeability , Polyethylene Glycols/chemistry , Rats , Rats, Wistar , Solubility
17.
Mol Pharm ; 14(6): 2138-2146, 2017 06 05.
Article in English | MEDLINE | ID: mdl-28505451

ABSTRACT

The purpose of this work was to investigate key factors dictating the success/failure of cyclodextrin-based solubility-enabling formulations for oral delivery of low-solubility drugs. We have studied the solubility, the permeability, and the solubility-permeability interplay, of the highly lipophilic drug danazol, formulated with different levels (8.5, 10, 20, and 30%) of the commonly used hydroxypropyl-ß-cyclodextrin (HPßCD), accounting for the biorelevant solubilization of the drug along the gastrointestinal tract (GIT), the unstirred water layer (UWL) adjacent to the GI membrane, and the overall absorption. HPßCD significantly increased danazol solubility, and decreased the drugs' permeability, in a concentration-dependent manner. These Peff results were in good correlation (R2 = 0.977) to literature rat AUC data of the same formulations. Unlike vehicle without HPßCD, formulations containing 8.5% HPßCD and above were shown to successfully dissolve the drug dose during the entire biorelevant dissolution experiment. We conclude that CD-based solubility-enabling formulations should contain the minimal amount of CD sufficient to dissolve the drug dose throughout the GIT, and not more than that; excess CD does not provide solubility gain but causes further permeability loss, and the overall absorption is then impaired. Moreover, a significant UWL effect was revealed in danazol intestinal permeability, and accounting for this effect allowed an excellent prediction of the solubility-permeability trade-off vs % HPßCD. Overall, this work assessed the contribution of each individual step of the absorption cascade to the success/failure of HPßCD-based formulation, allowing a more mechanistic development process of better solubility-enabling formulations.


Subject(s)
Cyclodextrins/chemistry , Administration, Oral , Chemistry, Pharmaceutical , Danazol/chemistry , Excipients/chemistry , Intestinal Absorption , Solubility , beta-Cyclodextrins
18.
Appetite ; 112: 23-34, 2017 05 01.
Article in English | MEDLINE | ID: mdl-28082196

ABSTRACT

Frequent consumption of energy-dense, nutrient-poor snack foods is an eating behavior of public health concern. This study was designed to inform strategies for reducing adolescent intake of energy-dense snack foods by identifying individual and environmental influences. Surveys were completed in 2009-2010 by 2540 adolescents (54% females, mean age = 14.5 ± 2.0, 80% nonwhite) in Minneapolis-St. Paul, Minnesota schools. Daily servings of energy-dense snack food was assessed using a food frequency questionnaire that asked about consumption of 21 common snack food items, such as potato chips, cookies, and candy. Data representing characteristics of adolescents' environments were collected from parents/caregivers, friends, school personnel, Geographic Information System sources, and a content analysis of favorite television shows. Linear regression was used to examine relationships between each individual or environmental characteristic and snack food consumption in separate models and also to examine relationships in a model including all of the characteristics simultaneously. The factors found to be significantly associated with higher energy-dense snack food intake represented individual attitudes/behaviors (e.g., snacking while watching television) and characteristics of home/family (e.g., home unhealthy food availability), peer (friends' energy-dense snack food consumption), and school (e.g., student snack consumption norms) environments. In total, 25.5% of the variance in adolescents' energy-dense snack food consumption was explained when factors from within each context were examined together. The results suggest that the design of interventions targeting improvement in the dietary quality of adolescents' snack food choices should address relevant individual factors (e.g., eating while watching television) along with characteristics of their home/family (e.g., limiting the availability of unhealthy foods), peer (e.g., guiding the efforts of a peer leader in making healthy choices), and school environments (e.g., establishing student norms for selecting nutrient-dense snack foods).


Subject(s)
Adolescent Behavior , Attitude , Energy Intake , Feeding Behavior , Snacks , Social Environment , Adolescent , Cross-Sectional Studies , Diet , Diet Surveys , Eating , Family , Female , Food Supply , Friends , Humans , Male , Minnesota , Models, Biological , Obesity/prevention & control , Peer Group , Schools
19.
J Nutr ; 146(7): 1348-55, 2016 07.
Article in English | MEDLINE | ID: mdl-27281807

ABSTRACT

BACKGROUND: Most adolescents consume ≥1 snack/d; exploring the relevance of snacking patterns for overall diet and weight status is important to guide dietary counseling and public health strategies for obesity prevention. OBJECTIVE: This study examined intake of common energy-dense snack foods, total number of snacks consumed, frequency of consuming snacks prepared away from home, and frequency of snacking while watching television in adolescents and how these behaviors may be linked to diet and weight status. Relations were examined with attention to potential confounders that may help explain the mixed findings of previous research. METHODS: Survey measures of snacking behavior, a food-frequency questionnaire, and anthropometric measurements were completed by 2793 adolescents (53.2% girls, mean age = 14.4 y) in Minneapolis-St. Paul school classrooms in 2009-2010. Linear regression was used to examine associations with adjustment for sociodemographic characteristics and other potential confounding factors, such as meal skipping, underreporting energy intake, dieting to lose weight, and physical activity. RESULTS: Adolescents reported consuming a mean of 2.2 energy-dense snack food servings/d and 4.3 snacks/d and purchasing snacks prepared away from home on 3.2 occasions/wk. More than two-thirds of adolescents reported that they sometimes, usually, or always consumed a snack while watching television. The measures of snacking were directly associated (P < 0.01) with higher energy, lower fruit/vegetable, higher sugar-sweetened beverage, and more frequent fast-food intakes in all models except for one: energy-dense snack food servings were not related to sugar-sweetened beverage intake. A direct relation between daily servings of energy-dense snack foods and body mass index (BMI) z score was found; however, the snacking behaviors were inversely related to BMI z score (P < 0.01). CONCLUSIONS: The observed cross-sectional associations suggest that snack consumption is a risk factor for poor diet, but unless energy-dense foods are consumed, snacking does not consistently contribute to overweight in US adolescents.


Subject(s)
Body Weight , Eating , Adolescent , Adolescent Behavior , Adolescent Nutritional Physiological Phenomena , Diet Surveys , Female , Food Preferences , Humans , Male , Snacks
20.
Pediatr Qual Saf ; 9(3): e728, 2024.
Article in English | MEDLINE | ID: mdl-38751897

ABSTRACT

Background: Despite limited evidence, a high-flow nasal cannula (HFNC) is often used to treat mild to moderate (m/m) bronchiolitis. We aimed to decrease the rate of HFNC use in the pediatric emergency department (PED) for m/m bronchiolitis from a baseline of 37% to less than 18.5%. Methods: A multidisciplinary team created a bronchiolitis pathway and implemented it in December 2019. A respiratory score (RS) in the electronic medical record objectively classified bronchiolitis severity as mild, moderate, or severe. We tracked HFNC utilization in the PED among patients with m/m bronchiolitis as our primary outcome measure between December 2019 and December 2021. We monitored the percentage of patients with an RS as a process measure. Interventions through four plan-do-study-act cycles included updating the hospital oxygen therapy policy, applying the RS to all patients in respiratory distress, modifying the bronchiolitis order set, and developing a bronchiolitis-specific HFNC order. Results: Three hundred twenty-five patients were admitted from the PED with m/m bronchiolitis during the 11-month baseline period and 600 patients during the 25-month intervention period. The mean rate of HFNC utilization decreased from 37% to 17%. Despite a decrease in bronchiolitis encounters after the pandemic, in the spring of 2021, when volumes returned, we had a sustained HFNC utilization rate of 17%. RS entry increased from 60% to 73% in the intervention period. Conclusions: A clinical pathway for bronchiolitis can lead to decreased use of HFNC for m/m bronchiolitis. Consistent RS, order set development with decision support, and education led to sustained improvement despite pandemic-related volumes.

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