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1.
NEJM Evid ; 3(1): EVIDmr2300293, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38320515

ABSTRACT

A 14-Year-Old Girl with Dyspnea and Chest PainA 14-year-old girl presented for evaluation of shortness of breath and chest pain after recent travel to the Caribbean. How do you approach the evaluation, and what is the diagnosis?


Subject(s)
Chest Pain , Dyspnea , Female , Humans , Adolescent , Thorax , Diagnosis, Differential , Caribbean Region
3.
Lancet Glob Health ; 12(1): e90-e99, 2024 Jan.
Article in English | MEDLINE | ID: mdl-37956682

ABSTRACT

BACKGROUND: Multiple studies have highlighted the inequities minority and Indigenous children face when accessing health care. Health and wellbeing are positively impacted when Indigenous children are educated and receive care in their maternal language. However, less is known about the association between minority or Indigenous language use and child development risks and outcomes. In this study, we provide global estimates of development risks and assess the associations between minority or Indigenous language status and early child development using the ten-item Early Child Development Index (ECDI), a tool widely used for global population assessments in children aged 3-4 years. METHODS: We did a secondary analysis of cross-sectional data from 65 UNICEF Multiple Indicator Cluster Surveys (MICS) containing the ECDI from 2009-19 (waves 4-6). We included individual-level data for children aged 2-4 years (23-60 months) from datasets with ECDI modules, for surveys that captured the language of the respondent, interview, or head of household. The Expanded Graded Intergenerational Disruption Scale was used to classify household languages as dominant versus minority or Indigenous at the country level. Our primary outcome was on-track overall development, defined per UNICEF's guidelines as development being on track for at least three of the four ECDI domains (literacy-numeracy, learning, physical, and socioemotional). We performed logistic regression of pooled, weighted ECDI scores, aggregated by language status and adjusting for the covariables of child sex, child nutritional status (stunting), household wealth, maternal education, developmental support by an adult caregiver, and country-level early child education proportion. Regression analyses were done for all children aged 3-4 years with ECDI results, and separately for children with functional disabilities and ECDI results. FINDINGS: 65 MICS datasets were included. 186 393 children aged 3-4 years had ECDI and language data, corresponding to an estimated represented population of 34 714 992 individuals. Estimated prevalence of on-track overall development as measured by ECDI scores was 65·7% (95% CI 64·2-67·2) for children from a minority or Indigenous language-speaking household, and 76·6% (75·7-77·4) for those from a dominant language-speaking household. After adjustment, dominant language status was associated with increased odds of on-track overall development (adjusted OR 1·54, 95% CI 1·40-1·71), which appeared to be largely driven by significantly increased odds of on-track development in the literacy-numeracy and socioemotional domains. For the represented population aged 2-4 years (n=11 465 601), the estimated prevalence of family-reported functional disability was 3·6% (95% CI 3·0-4·4). For the represented population aged 3-4 years with a functional disability (n=292 691), language status was not associated with on-track overall development (adjusted OR 1·02, 95% CI 0·43-2·45). INTERPRETATION: In a global dataset, children speaking a minority or Indigenous language were less likely to have on-track ECDI scores than those speaking a dominant language. Given the strong positive benefits of speaking an Indigenous language on the health and development of Indigenous children, this disparity is likely to reflect the sociolinguistic marginalisation faced by speakers of minority or Indigenous languages as well as differences in the performance of ECDI in these languages. Global efforts should consider performance of measures and monitor developmental data disaggregated by language status to stimulate efforts to address this disparity. FUNDING: None. TRANSLATIONS: For the Spanish, Kaqchikel and K'iche' translations of the abstract see Supplementary Materials section.


Subject(s)
Child Development , Indigenous Peoples , Language , Minority Groups , Humans , Cross-Sectional Studies , Socioeconomic Factors , Surveys and Questionnaires , Child, Preschool
4.
Br J Nutr ; 130(9): 1609-1624, 2023 11 14.
Article in English | MEDLINE | ID: mdl-36912073

ABSTRACT

Frequent ultra-processed food (UPF) consumption is consistently associated with poor health outcomes. Little is known about UPF intake during early childhood and its effects on growth. We assessed UPF in relation to child anthropometry, bone maturation, and their nutrition profiles in a rural Ecuadorian community. Covariate-adjusted regression models estimated relationships between UPF intake from a 24-hour Food Frequency Questionnaire and three outcomes: linear growth, weight status and bone maturation. Nutrient Profiling Models (NPM) evaluated a convenience sample of UPF (n 28) consumed by children in the community. In this cohort (n 125; mean age = 33·92 (sd 1·75) months), 92·8 % consumed some form of UPF the previous day. On average, children consuming UPF four to twelve times per day (highest tertile) had lower height-for-age z-scores than those with none or a single instance of UPF intake (lowest tertile) (ß = -0·43 [se 0·18]; P = 0·02). Adjusted stunting odds were significantly higher in the highest tertile relative to the lowest tertile (OR: 3·07, 95 % CI 1·11, 9·09). Children in the highest tertile had significantly higher bone age z-scores (BAZ) on average compared with the lowest tertile (ß = 0·58 [se 0·25]; P = 0·03). Intake of savoury UPF was negatively associated with weight-for-height z-scores (ß = -0·30 [se 0·14]; P = 0·04) but positively associated with BAZ (ß = 0·77 [se 0·23]; P < 0·001). NPM indicated the availability of unhealthy UPF to children, with excessive amounts of saturated fats, free sugars and sodium. Findings suggest that frequent UPF intake during early childhood may be linked to stunted growth (after controlling for bone age and additional covariates), despite paradoxical associations with bone maturation.


Subject(s)
Diet , Food, Processed , Humans , Child , Child, Preschool , Adult , Ecuador , Fast Foods , Food Handling , Anthropometry
6.
Telemed J E Health ; 28(7): 1044-1049, 2022 07.
Article in English | MEDLINE | ID: mdl-35012381

ABSTRACT

Introduction: Coronavirus disease 2019 (COVID-19) has widened patient care gaps and created gaps in medical student clinical training. The care gaps are often most obvious in primary care medicine clinics (PCMCs) where residents and medical students care for a vulnerable population. Materials and Methods: We designed an outpatient telehealth program to support and monitor PCMC patients who had been diagnosed or were suspected to have COVID-19 and were confined to their homes due to public health mandated isolation. To support the program, we recruited medical student volunteers. We recruited patients from our institution's primary care clinic who were recently diagnosed with COVID-19 and were currently not hospitalized. Feasibility of the home monitoring program (HMP) was assessed and mortality data for all patients were collected. Results: Over 800 monitoring phone calls were placed during the 8-month study period to 296 patients, with an average of 2.79 calls per patient. A total of 30 medical students participated. A total of four patients died during the study period. Conclusions: Our institution was able to rapidly design and implement a COVID-19 HMP integrated with our primary care clinic to ensure continued access to care during a pandemic.


Subject(s)
COVID-19 , Students, Medical , Telemedicine , COVID-19/epidemiology , Humans , Pandemics , Telephone
8.
Med Sci Educ ; 31(2): 365-369, 2021 Apr.
Article in English | MEDLINE | ID: mdl-33585072

ABSTRACT

The COVID-19 pandemic disrupted medical education worldwide, leading medical students to organize response initiatives. This paper summarizes the Washington University Medical Student COVID-19 Response (WUMS-CR) and shares lessons to guide future initiatives. We used a three-principle framework of community needs assessment, faculty mentorship, and partnership with pre-existing organizations to address needs in St. Louis, including contact tracing and childcare. In total, over 12,000 h were volunteered across 15+ projects. Overall, student response initiatives should use appropriate frameworks to guide projects and should capitalize on volunteer participation, speed and flexibility, and the diversity of student interests and skills for maximal impact.

9.
West J Emerg Med ; 21(6): 291-294, 2020 Sep 25.
Article in English | MEDLINE | ID: mdl-33207179

ABSTRACT

INTRODUCTION: Bull-related injuries are commonly observed in rural areas of India as result of the animal's use in sporting events as well as for agricultural purposes. These patients need early resuscitation due to complications from severe injuries. Previous work examining the epidemiology of bull-related injuries is limited, with most studies focusing on injuries in Spain and Latin America. There is scant literature examining the prevalence of such injuries in India. The objective of this study was to evaluate the demographic and clinical characteristics of bull-related injuries at a hospital in Tamil Nadu, India. METHODS: This was a prospective, observational study of patients who presented to an emergency department (ED) in Madurai, India, with a reported history of bull-related injuries between June 2017 and March 2019. We recorded information about patient demographics, location of injury, disposition, initial Injury Severity Score (ISS), and transport time. RESULTS: Our sample included a total of 42 patients. Almost a third of patients who presented were between the ages of 20-30 years (31%, n = 13), and most were male (86%, n = 36). Approximately 59% of patients (n = 25) had provoked injuries, occurring as a result of active participation during sporting activities. Injuries to the trunk were most common (55%, n = 23), followed by injuries to the perineum (19%, n = 19). The majority of patients (59.5%) had penetrating injuries (n = 25), The mean ISS was 10.1 (standard deviation 6.3). Five (12%) patients had a complication after injury including intra-abdominal abscess formation, peritonitis, and sepsis. Two patients died as a result of septicemia from peritonitis. CONCLUSION: Bull-related injuries may result in significant morbidity and mortality. Education of the population about the dangers of bull injuries from sporting events and the need for early transportation to the ED have the potential for significant reduction in morbidity and mortality.


Subject(s)
Emergency Service, Hospital/statistics & numerical data , Wounds, Penetrating/epidemiology , Adult , Animals , Cattle , Female , Humans , India/epidemiology , Injury Severity Score , Male , Prevalence , Prospective Studies , Retrospective Studies , Wounds, Penetrating/therapy , Young Adult
10.
Radiology ; 296(1): 161-169, 2020 07.
Article in English | MEDLINE | ID: mdl-32343211

ABSTRACT

Background Stunted growth and development is a serious global public health problem. A limited number of field measures exist that can be used to evaluate stunting and its underlying biologic mechanisms. Purpose To assess bone age using tablet-based US in young children living in a rural community in Ecuador, where stunting is prevalent, and to evaluate the associations between bone age, anthropometry, and diet. Materials and Methods From June through August 2017, tablet-based US was used to assess bone age in young children within their homes in rural Cotopaxi, Ecuador. Bone age z scores (BAZs) were assigned using the standards of Greulich and Pyle. Anthropometric data were collected using international protocols; z scores were generated from World Health Organization Child Growth Standards. Groups were compared using the Student t test. Univariate analyses and generalized linear regression modeling were applied to test the association between bone age and anthropometry, adjusting for covariates including age, sex, dietary intake, and morbidities. Results A total of 128 children (mean age, 33.9 months ± 1.8 [standard deviation]; 59 girls, 69 boys) were evaluated. Mean BAZ was -1.20 ± 1.16. Mean BAZ was lower in children with stunted growth (-1.42 ± 1.18) than in children without stunted growth (-0.98 ± 1.10, P = .04). In adjusted analysis, BAZ was associated with the following variables: height-for-age z score (ß coefficient, 0.26; 95% confidence interval [CI]: 0.05, 0.46; P = .01), female sex (ß coefficient, 0.51; 95% CI: 0.15, 0.88; P = .006), number of times eggs were consumed in the previous 24 hours (ß coefficient, 0.22; 95% CI: 0.05, 0.38; P = .009), number of times savory or salty snacks were consumed in the previous 24 hours (ß coefficient, 0.42; 95% CI: 0.15, 0.68; P = .002), and ownership of pig livestock, which was a binary variable (ß coefficient, -0.46; 95% CI: -0.82, -0.09; P = .01). Conclusion Bone age determined using tablet-based US was lower in children who had stunted growth and was associated with diet in a cohort of children living in rural Ecuador. © RSNA, 2020 See also the editorial by Dillman and Ayyala in this issue.


Subject(s)
Anthropometry/methods , Bone and Bones/diagnostic imaging , Growth Disorders/diagnostic imaging , Nutritional Status , Rural Population/statistics & numerical data , Ultrasonography/methods , Child, Preschool , Ecuador , Female , Humans , Male , Prospective Studies
11.
PDA J Pharm Sci Technol ; 74(2): 213-228, 2020.
Article in English | MEDLINE | ID: mdl-31519784

ABSTRACT

Trumenba (MenB-FHbp; bivalent rLP2086), the first meningococcal serogroup B vaccine approved in the United States and subsequently approved in Europe, Canada, and Australia, is well-characterized. Pfizer devised a control strategy approach by using a simplified control strategy wheel for Trumenba based on International Council for Harmonisation (ICH) Q8 (R2), Q9, Q10, and Q11 guidelines, which provide complementary guidance on pharmaceutical development, quality risk management, quality systems, and development and manufacture of drug substances, respectively. These guidelines ensure product quality using a scientific and risk-based approach. Trumenba contains two factor H binding proteins (FHbps), one from each of the two FHbp subfamilies (A and B), adsorbed onto aluminum phosphate. Trumenba manufacturing processes are complicated by the recombinant protein expression of Subfamily A and B proteins and the nature of the drug product (suspension in syringes); the latter also introduces challenges in controlling product critical quality attributes during the development process. In such complex systems, the control strategy is critical to ensuring consistent desired product quality; it also supports the regulatory requirement of continued improvement through continuous process verification and aids regulatory filing. This article describes Pfizer's approach toward robust control strategy development, built on product and process understanding, and links control strategy to regulatory document sections and flow of controls. Specifically, an approach is presented on product quality attribute criticality determination based on safety and efficacy and on an understanding of process parameter criticality. This was achieved by studying the impact of the approach on product quality attributes to define process parameter and in-process controls. This approach is further explained through Trumenba case studies, highlighting specific quality attributes and the associated controls implemented, and provides a holistic view of controls employed for both drug substance and drug product.


Subject(s)
Drug Development/trends , Drug Industry/trends , Meningitis, Meningococcal/prevention & control , Meningococcal Vaccines/administration & dosage , Meningococcal Vaccines/chemical synthesis , Neisseria meningitidis, Serogroup B/drug effects , Drug Development/methods , Drug Development/standards , Drug Industry/methods , Drug Industry/standards , Humans , Meningitis, Meningococcal/epidemiology , Meningococcal Vaccines/standards , Neisseria meningitidis, Serogroup B/physiology
12.
Matern Child Nutr ; 16(2): e12925, 2020 04.
Article in English | MEDLINE | ID: mdl-31849201

ABSTRACT

The Lulun Project, a randomized controlled trial conducted in 2015, found that one egg per day for 6 months during early complementary feeding reduced stunting by 47% and increased linear growth by 0.63 length-for-age Z (LAZ). This follow-up cohort study (Lulun Project II) aimed to test whether the growth effect remained in the egg intervention group compared with the control group after approximately 2 years. Mothers or caregivers from the Lulun Project were recontacted and recruited for this study. Enumerators collected data on socio-economic and demographic factors, 24-hr frequency of dietary intakes, morbidities, and anthropometric measures of height, weight, and head circumference using World Health Organization protocols. Statistical analyses followed the same analytical plan as Lulun Project, applying generalized linear models and regression modelling to test group differences in height-for-age z (HAZ) from LAZ at Lulun Project endline, and structural equation modelling for mediation. One hundred thirty-five mother-child dyads were included in Lulun II, with 11% losses to follow-up from endline Lulun Project. Growth faltering across all children was evident with HAZ -2.07 ± 0.91 and a stunting prevelance of 50%. Regression modelling showed no difference between egg and control groups for the HAZ outcome and other anthropometric outcomes, and significant declines in HAZ from endline Lulun Project in the egg intervention are compared with control groups. Current dietary egg intake, however, was associated with reduced growth faltering in HAZ from Lulun Project endline to Lulun Project II, independent of group assignment and through mediation, explaining 8.8% of the total effect. Findings suggest the need for a longer intervention period and ongoing nutrition support to young children during early childhood.


Subject(s)
Anthropometry/methods , Body Height , Child Development , Diet/methods , Eggs , Growth Disorders/epidemiology , Body Weight , Child, Preschool , Ecuador/epidemiology , Female , Follow-Up Studies , Growth Disorders/prevention & control , Humans , Longitudinal Studies , Male
13.
Nutr J ; 18(1): 57, 2019 09 10.
Article in English | MEDLINE | ID: mdl-31506077

ABSTRACT

BACKGROUND: Dietary preferences vary depending on cancer type. The purpose of this study was to report dietary intervention preferences and a study program evaluation from post-treatment head and neck cancer survivors participating in a dietary intervention. METHODS: Between January 2015 and August 2016, 24 head and neck cancer survivors participated in a 12-week randomized clinical dietary intervention trial that promoted weekly consumption of 2.5 cups of cruciferous vegetables and 3.5 cups of green leafy vegetables. At study completion, survivors completed a preferences survey and a study program evaluation to probe interests and improvement aspects for planning future dietary intervention trials. Descriptive statistics (means and frequencies) were generated for multiple choice question responses. Responses to open-ended questions were recorded and grouped based on themes, and verified by quality assurance checks by a second study team member. RESULTS: Twenty-three survivors completed the preferences and evaluation surveys (response rate 96%). Overall, most participants reported a preference for one-on-one telephone counseling from a registered dietitian nutritionist before beginning treatment. Ninety-six percent of participants ranked the overall study program as "very good" to "excellent," and all agreed the objectives of the study were clear, the study staff was helpful and easy to contact, and the registered dietitian nutritionist was knowledgeable. CONCLUSIONS: Future research and dietary intervention planning for head and neck cancer survivors should focus on strategies to promote one-on-one telephone or other distance-based counseling combined with face-to-face visits, according to survivor preference.


Subject(s)
Cancer Survivors/statistics & numerical data , Diet/methods , Head and Neck Neoplasms/complications , Malnutrition/diet therapy , Malnutrition/etiology , Program Evaluation/methods , Adult , Aged , Counseling/methods , Feasibility Studies , Female , Food Preferences , Humans , Male , Middle Aged , Patient Satisfaction/statistics & numerical data , Pilot Projects , Vegetables
14.
Curr Nutr Rep ; 8(3): 230-239, 2019 09.
Article in English | MEDLINE | ID: mdl-30895469

ABSTRACT

PURPOSE OF REVIEW: This review summarizes a selection of epidemiologic research assessing the associations between carbohydrate intake and cancer incidence and survival. Evidence for plausible biological mechanisms is also considered. RECENT FINDINGS: The mechanistic paradigm explaining the relationship between carbohydrates and cancer risk has been contested by numerous observational studies. Carbohydrates have conventionally been ascribed a deleterious role in the field of cancer research due to previous preclinical findings. A breadth of studies suggests that complex carbohydrate intake is inversely associated with risk of a number of cancer types. Data from studies assessing simple carbohydrates and cancer risk are mixed. Furthermore, recommendations for subsequent studies are framed.


Subject(s)
Dietary Carbohydrates/adverse effects , Neoplasms/epidemiology , Neoplasms/etiology , Dietary Fiber , Glucose/metabolism , Glycemic Index , Humans , Incidence , Neoplasms/prevention & control , Risk Factors
15.
J Acad Nutr Diet ; 119(4): 659-671, 2019 04.
Article in English | MEDLINE | ID: mdl-30661935

ABSTRACT

BACKGROUND: Higher intakes of cruciferous vegetables (CVs) and green leafy vegetables (GLVs) in observational studies are associated with improvements in survival and cancer-related biomarkers in patients diagnosed with head and neck cancer (HNC). These results have yet to be corroborated in a randomized clinical trial (RCT). OBJECTIVE: Determine the feasibility of implementing a 12-week RCT to increase CV and GLV intake in posttreatment HNC survivors. DESIGN AND PARTICIPANTS: This was a two-arm RCT conducted among 24 posttreatment HNC survivors. Survivors were recruited from a southeastern, National Cancer Institute-designated Comprehensive Cancer Center between January 2015 and September 2016. INTERVENTION: There were two groups: (1) an experimental group (n=12) receiving weekly 15- to 30-minute telephone dietary counseling from a registered dietitian nutritionist stressing 2.5 cups per week CVs and 3.5 cups per week GLVs, and (2) an attention control group (n=12) receiving weekly 15- to 30-minute telephone dietary counseling from a registered dietitian nutritionist focusing on general healthy eating for cancer survivors. Participants completed a baseline survey, three 24-hour dietary recalls, phlebotomy, and anthropometric measures prior to randomization and at the end of the 12-week study period. The experimental group also completed weekly vegetable record recalls. MAIN OUTCOME MEASURES: Primary outcomes included feasibility, recruitment, retention, adherence, and safety. Secondary outcomes included inflammatory markers and carotenoids. STATISTICAL ANALYSES PERFORMED: Descriptive statistics were generated for demographic, epidemiological, and clinical variables as well as the primary feasibility outcomes. Between- and within-group comparisons of mean serum cytokine and carotenoid levels were performed using appropriate statistical tests depending on their respective distributions for the purpose of generating preliminary effect sizes. RESULTS: Overall, 350 incident HNC cases were screened for eligibility, and 98 were eligible for study participation. Reasons for ineligibility and exclusion included deceased (n=93); wrong or inactive telephone numbers, or unable to be reached, or lost to follow-up (n=93); not meeting inclusion criteria (n=39); and too ill to participate (n=27). Of the 98 eligible HNC cases, 24 agreed to participate, for an enrollment rate of 25%. The most common reason for nonparticipation was distance (n=48), as participants were asked to report for two on-site assignments. The retention rate was 96%. Mean intervention adherence rates for weekly goals were 67% CV, 74% GLV, and 71% overall. Completion rate of weekly counseling calls was 90%. The experimental group reported an overall mean increase of 5.5 cups GLV and 3.5 cups CV per week from baseline intake, respectively. No significant between- or within-arm differences were observed for inflammatory markers or carotenoids. CONCLUSION: A posttreatment intervention aimed at increasing CV and GLV intake in HNC survivors is feasible. A larger RCT is needed to assess the efficacy of this intervention on disease outcomes.


Subject(s)
Cancer Survivors/psychology , Diet/methods , Head and Neck Neoplasms/diet therapy , Vegetables , Adult , Carotenoids/blood , Counseling , Diet/psychology , Feasibility Studies , Female , Head and Neck Neoplasms/blood , Head and Neck Neoplasms/psychology , Humans , Inflammation Mediators/blood , Male , Middle Aged , Patient Compliance , Pilot Projects , Telephone
16.
J Cancer Surviv ; 12(4): 479-494, 2018 08.
Article in English | MEDLINE | ID: mdl-29556926

ABSTRACT

PURPOSE: It is estimated that more than 90% of head and neck cancer (HNC) survivors who underwent chemoradiotherapy experience one or more nutrition impact symptoms (NIS) in the months or years thereafter. Despite the high prevalence, there is limited research addressing long-term impact of NIS on outcomes such as nutrition and quality of life in HNC survivors treated with chemoradiotherapy. OBJECTIVE: To conduct a systematic review of the literature pertaining to the presence of nutrition impact symptoms and their associated outcomes in post-chemoradiotherapy head and neck cancer survivors. EVIDENCE REVIEW: A systematic review was conducted across three databases according to PRISMA guidelines and used to identify current literature regarding NIS in HNC survivors. A keyword search was conducted in PubMed, Scopus, and Web of Science from 2007 to 2017. Studies that met all of the following criteria were included in the review: (1) studies must include human subjects with a HNC diagnosis; (2) study participants must have received chemoradiotherapy; (3) study participants must have been post-treatment for a minimum of 3 months at the time of data collection; (4) full-text articles must have appeared in peer-reviewed journals; (5) papers must have been published in English; (6) studies must be quantitative in nature; (7) studies must have reported at least one NIS; and (8) studies must address at least one of the following outcomes: nutrition, functional status, or quality of life. Two independent reviewers assessed study quality using a predefined set of criteria. FINDINGS: A systematic search yielded 1119 papers, of which 15 met the inclusion criteria. The study reviewed existing evidence of NIS in a variety of HNC survivors ranging from 3 months to greater than 10 years post-chemoradiotherapy treatment. Eight hundred forty-nine study participants were included in the review. Of the 15 studies, 10 were designed as prospective cohort studies, 4 were cross-sectional studies, and 1 was a retrospective cohort study. Functional impairments as a result of chemoradiotherapy to the head and neck are prevalent in research and include dysphagia, xerostomia, trismus, salivary issues, mucositis, and oral pain. CONCLUSIONS: NIS negatively influence HNC survivors beyond the acute phase of treatment. These symptoms are associated with decreased nutrition and quality of life. Interventions are necessary to improve survivors' eating challenges beyond the completion of treatment. If practitioners do not follow patients long term, patients may suffer consequences of NIS including malnutrition risk, weight loss, and decreased food intake and quality of life. IMPLICATIONS FOR CANCER SURVIVORS: The prevalence and consequences of nutrition impact symptoms are substantial among head and neck cancer survivors beyond the acute phase of cancer treatment. Oncology clinicians should continuously monitor and manage these symptoms throughout the cancer continuum.


Subject(s)
Cancer Survivors , Chemoradiotherapy , Head and Neck Neoplasms/therapy , Nutritional Status/physiology , Quality of Life , Activities of Daily Living , Adult , Aged , Aged, 80 and over , Cancer Survivors/psychology , Cancer Survivors/statistics & numerical data , Chemoradiotherapy/adverse effects , Chemoradiotherapy/statistics & numerical data , Cross-Sectional Studies , Deglutition Disorders/epidemiology , Deglutition Disorders/etiology , Drug-Related Side Effects and Adverse Reactions/epidemiology , Female , Head and Neck Neoplasms/rehabilitation , Humans , Male , Middle Aged , Radiation Injuries/epidemiology , Retrospective Studies , Taste Disorders/epidemiology , Taste Disorders/etiology , Treatment Outcome , Weight Loss/physiology , Xerostomia/epidemiology , Xerostomia/etiology
17.
Vaccine ; 36(22): 3180-3189, 2018 05 24.
Article in English | MEDLINE | ID: mdl-28433330

ABSTRACT

The phrase "Process is the Product" is often applied to biologics, including multicomponent vaccines composed of complex components that evade complete characterization. Vaccine production processes must be defined and locked early in the development cycle to ensure consistent quality of the vaccine throughout scale-up, clinical studies, and commercialization. This approach of front-loading the development work helped facilitate the accelerated approval of the Biologic License Application for the well-characterized vaccine bivalent rLP2086 (Trumenba®, Pfizer Inc) in 2014 under Breakthrough Therapy Designation. Bivalent rLP2086 contains two rLP2086 antigens and is licensed for the prevention of meningococcal meningitis disease caused by Neisseria meningitidis serogroup B in individuals 10-25years of age in the United States. This paper discusses the development of the manufacturing process of the two antigens for the purpose of making it amenable to any manufacturing facility. For the journey to commercialization, the operating model used to manage this highly accelerated program led to a framework that ensured "right the first time" execution, robust process characterization, and proactive process monitoring. This framework enabled quick problem identification and proactive resolutions, resulting in a robust control strategy for the commercial process.


Subject(s)
Meningococcal Vaccines/biosynthesis , Antigens, Bacterial/chemistry , Antigens, Bacterial/immunology , Drug Industry , Humans , Meningitis, Meningococcal/prevention & control , Neisseria meningitidis, Serogroup B/immunology , United States
18.
Org Biomol Chem ; 14(48): 11473-11479, 2016 Dec 28.
Article in English | MEDLINE | ID: mdl-27883144

ABSTRACT

A protocol is established for the high-yielding synthesis of F-BODIPYs involving non-anhydrous reagents and not requiring precautions to exclude moisture. This simple and robust strategy simply requires a second addition of NEt3 and BF3·OEt2, midway through the reaction period. The ratio and amounts of NEt3 and BF3·OEt2 used in each aliquot are critical to success (6 : 9 for each aliquot). The protocol can be completed using bench-dry apparatus, without need to achieve and maintain anhydrous conditions or solvents.

19.
Biologicals ; 44(3): 178-81, 2016 May.
Article in English | MEDLINE | ID: mdl-26996102

ABSTRACT

The United States Food and Drug Administration recently removed the requirement for a General Safety Test (GST) for biologics in the Code of Federal Regulations (21 CFR 610.11). The GST, as well as abnormal toxicity (European Pharmacopeia) and innocuity tests (World Health Organization), were designed to test for extraneous toxic contaminants on each product lot intended for human use. Tests require one-week observations for general health and weight following injection of specified volumes of product batches into guinea pigs and mice. At the volumes specified, dose-related toxicity may result when the product is pharmacologically active in rodents. With vaccines, required doses may be > 3 logs higher than intended human dose on a weight-adjusted basis and if an immune modulatory adjuvant is included, systemic immune hyperactivation may cause toxicity. Herein, using the CpG/alum adjuvant combination we evaluated the different test protocols and showed their unsuitability for this adjuvant combination.


Subject(s)
Biological Products/standards , Consumer Product Safety/legislation & jurisprudence , Consumer Product Safety/standards , Drug Approval/legislation & jurisprudence , Licensure/legislation & jurisprudence , Animals , Guinea Pigs , Humans , Mice , Toxicity Tests/methods , United States , United States Food and Drug Administration , World Health Organization
20.
Pediatr Crit Care Med ; 16(9): 828-36, 2015 Nov.
Article in English | MEDLINE | ID: mdl-26218259

ABSTRACT

OBJECTIVE: We aimed to review gastric dysmotility in critically ill children: 1) its pathophysiology, with a focus on critical care diseases and therapies that affect gastric motility, 2) diagnostic methodologies, and 3) current and future potential therapies. DATA SOURCES: Eligible studies were identified from PubMed and MEDLINE. STUDY SELECTION: Literature search included the following key terms: "gastric emptying," "gastric motility/dysmotility," "gastrointestinal motility/dysmotility," "nutrition intolerance," and "gastric residual volume." DATA EXTRACTION: Studies since 1995 were extracted and reviewed for inclusion by the authors related to the physiology, pathophysiology, diagnostic methodologies, and available therapies for gastric emptying. DATA SYNTHESIS: Delayed gastric emptying, a common presentation of gastric dysmotility, is present in up to 50% of critically ill children. It is associated with the potential for aspiration, ventilator-associated pneumonia, and inadequate delivery of enteral nutrition and may affect the efficacy of enteral medications, all of which may be result in poor patient outcomes. Gastric motility is affected by critical illness and its associated therapies. Currently available diagnostic tools to identify gastric emptying at the bedside have not been systematically studied and applied in this cohort. Gastric residual volume measurement, used as an indirect marker of delayed gastric emptying in PICUs around the world, may be inaccurate. CONCLUSIONS: Gastric dysmotility is common in critically ill children and impacts patient safety and outcomes. However, it is poorly understood, inadequately defined, and current therapies are limited and based on scant evidence. Understanding gastric motility and developing accurate bedside measures and novel therapies for gastric emptying are highly desirable and need to be further investigated.


Subject(s)
Gastric Emptying/physiology , Stomach Diseases/diagnosis , Stomach Diseases/physiopathology , Stomach/physiopathology , Blood Glucose/physiology , Child , Critical Care , Critical Illness , Gastric Emptying/drug effects , Humans , Hyperglycemia/physiopathology , Inflammation/physiopathology , Respiration, Artificial/adverse effects , Stomach Diseases/therapy
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