Changes in COVID-19 Vaccine Acceptability among Parents with Children Aged 6-35 Months in China-Repeated Cross-Sectional Surveys in 2020 and 2021.

China is considering to offer COVID-19 vaccination for children aged 6−35 months. This study investigated the changes in COVID-19 vaccine acceptability and associated factors among parents with children aged 6−35 months in 2020 and 2021. Two rounds of cross-sectional online surveys were conducted among adult factory workers in Shenzhen, China. A subset of 208 (first round) and 229 (second round) parents with at least one child aged 6−35 months was included in the study. Parental acceptability of COVID-19 vaccination increased significantly from 66.8% in the first round to 79.5% in the second round (p = 0.01). Positive attitudes, perceived subjective norm, and perceived behavioral control were associated with higher parental acceptability in both rounds of surveys (p values ranged from <0.001 to 0.003). A negative association of negative attitudes with parental acceptability was observed in the second round (p = 0.02). No significant associations of exposure to information related to COVID-19 vaccination on social media with parental acceptability was found in either round of survey. Expanding the existing COVID-19 vaccination programs to cover children aged 6−35 months is necessary in China. Future programs should focus on modifying perceptions among parents to promote COVID-19 vaccination for children in this age group.

System dynamics modeling to understand mental model of public humiliation in medical education.

BACKGROUND: Mistreatment in medical school is a wicked or complex problem demonstrating inter-relatedness and dynamicity of factors that affect students. Many studies have outlined the causes, perceptions, and negative consequences of mistreatment; however, a comprehensive mental model of public humiliation, the most common type of mistreatment, is still incomplete. This study aims to provide insight into the reasons why public humiliation in medical school continues to be a problem despite existing for decades, and to propose a shift in paradigm that potentially improve these incidents. METHOD: A systems thinking approach is used to conceptualize related components of public humiliation and student behavior. System dynamics modeling was conducted through narrative review, developing a causal loop diagram (CLD), and validation of results with 60 medical students and 40 medical educators. RESULTS: Findings from the narrative review outlined key variables, interconnections and five emerging themes: etiology, eustress, motivation, distress, and self-esteem. The themes were conceptualized and constructed into feedback loops as a basis for the CLD. Finally, the mental model proposes three major systems underlying the consequences. The "No Pain, No Gain" illustrates the perception that stress positively drives learning, while "Stress Overload" displays the negative consequences of public humiliation. Lastly, "The Delayed Side Effect" refers to long-term side-effects on self-esteem. CONCLUSION: The mental model illustrates how public humiliation has both immediate and delayed side-effects, simultaneously succeeding and failing at motivating student growth. Therefore, public humiliation requires continuous changes in perspective along with multiple interventions to overcome the vicious cycle.

Primary care providers' role in newborn screening result notification for cystic fibrosis.

OBJECTIVE: To explore primary care providers' (PCPs') role in result notification for newborn screening (NBS) for cystic fibrosis (CF), given that expanded NBS has increased the number of positive screening test results, drawing attention to the role of PCPs in supporting families. DESIGN: Cross-sectional survey and qualitative interviews. SETTING: Ontario. PARTICIPANTS: Primary care providers (FPs, pediatricians, and midwives) who received a positive CF NBS result for an infant in their practice in the 6 months before the study. MAIN OUTCOME MEASURES: Whether the PCP notified the family of the initial positive CF screening result. RESULTS: Data from 321 PCP surveys (response rate of 51%) are reported, including 208 FPs, 68 pediatricians, and 45 midwives. Interviews were completed with 34 PCPs. Most (65%) surveyed PCPs reported notifying the infant's family of the initial positive screening result; 81% agreed that they have an important role to play in NBS; and 88% said it was important for PCPs, rather than the NBS centre, to notify families of initial positive results. With support and information from NBS centres, 68% would be extremely or very confident in doing so; this dropped to 54% when reflecting on their recent reporting experience. More than half (58%) of all PCPs said written point-of-care information from the NBS centre was the most helpful format. Adjusted for relevant factors, written educational information was associated with a lower rate of notifying families than written plus verbal information (risk ratio of 0.79; 95% CI 0.69 to 0.92). In the interviews, PCPs emphasized the challenge of balancing required content knowledge with the desire for the news to come from a familiar provider. CONCLUSION: Most PCPs notify families of NBS results and value this role. These data are relevant as NBS programs and other genomic services expand and consider ways of keeping PCPs confident and actively involved.

Newborn screening for cystic fibrosis: Role of primary care providers in caring for infants with positive screening results.

OBJECTIVE: To explore primary care providers' (PCPs') preferred roles and confidence in caring for infants receiving a positive cystic fibrosis (CF) newborn screening (NBS) result, as well as management of CF family planning issues, given that expanded NBS has resulted in an increase in positive results. DESIGN: Mailed questionnaire. SETTING: Ontario. PARTICIPANTS: Ontario FPs, pediatricians, and midwives identified by Newborn Screening Ontario as having had an infant with a positive CF NBS result in their practice in the previous 6 months. MAIN OUTCOME MEASURE: Primary care providers' preferred roles in providing well-baby care for infants with positive CF screening results. RESULTS: Overall, 321 of 628 (51%) completed surveys (208 FPs, 68 pediatricians, 45 midwives). For well-baby care for infants confirmed to have CF, 77% of PCPs indicated they would not provide total care (ie, 68% would share care with other specialists and 9% would refer to specialists completely); for infants with an inconclusive CF diagnosis, 50% of PCPs would provide total care, 45% would provide shared care, and 5% would refer to a specialist; for CF carriers, 89% of PCPs would provide total care, 9% would provide shared care, and 2% would refer. Half (54%) of PCPs were extremely or very confident in providing reassurance about CF carriers' health. Only 25% knew how to order parents' CF carrier testing; 67% knew how to refer for prenatal diagnosis. Confidence in reassuring parents about the health of CF carrier children was associated with providing total well-baby care for CF carriers (risk ratio of 1.50; 95% CI 1.14 to 1.97) and infants with an inconclusive diagnosis (risk ratio of 3.30; 95% CI 1.34 to 8.16). CONCLUSION: Most PCPs indicated willingness to treat infants with a range of CF NBS results in some capacity. It is concerning that some indicated CF carriers should have specialist involvement and only half were extremely or very confident about reassuring families about carrier status. This raises issues about possible medicalization of those with carrier status, prompting the need for PCP education about genetic disorders and the meaning of genetic test results.

Non-specialist therapeutic strategies in acute respiratory distress syndrome.

INTRODUCTION: Acute respiratory distress syndrome (ARDS) is associated with significant morbidity and mortality. We undertook a meta-analysis of randomized controlled trials (RCTs) to determine the mortality benefit of non-specialist therapeutic interventions for ARDS available to general critical care units. EVIDENCE ACQUISITION: A systematic search of MEDLINE, Embase, and the Cochrane Central Register for RCTs investigating therapeutic interventions in ARDS including corticosteroids, fluid management strategy, high PEEP, low tidal volume ventilation, neuromuscular blockade, prone position ventilation, or recruitment maneuvers. Data was collected on demographic information, treatment strategy, duration and dose of treatment, and primary (28 or 30-day mortality) and secondary (PaO2:FiO2 ratio at 24-48 hours) outcomes. EVIDENCE SYNTHESIS: No improvement in 28-day mortality could be demonstrated in three RCTs investigating high PEEP (28.0% vs. 30.2% control; risk ratio [confidence interval] 0.93 [0.82-1.06]; eight assessing prone position ventilation (39.3% vs. 44.5%; RR 0.83 [0.68-1.01]; seven investigating neuromuscular blockade (37.8% vs. 42.0%; RR 0.91 [0.81-1.03]); ten investigating recruitment maneuvers (42.4% vs. 42.1%; RR 1.01 [0.91-1.12]); eight investigating steroids (34.8% vs. 41.1%; RR 0.81 [0.59-1.12]); and one investigating conservative fluid strategies (25.4% vs. 28.4%; RR 0.90 [0.73-1.10]). Three studies assessing low tidal volume ventilation (33.1% vs. 41.9%; RR 0.79 (0.68-0.91); P=0.001), and subgroup analyses within studies investigating prone position ventilation greater than 12 hours (33.1% vs. 44.4%; RR 0.75 [0.59-0.95), P=0.02) did reveal outcome benefit. CONCLUSIONS: Among non-specialist therapeutic strategies available to general critical care units, low tidal volumes and prone position ventilation for greater than 12 hours improve mortality in ARDS.

Multimodal Analgesic Plan for Children Undergoing Chimeric 14.18 Immunotherapy.

Immunotherapy with the chimeric 14.18 anti-GD2 antibody (ch14.18) is associated with severe neuropathic pain. Different analgesic modalities have been employed, but pain management remains challenging and side effects such as desaturation, bradycardia, and hypotension have been reported. We retrospectively analyzed the efficacy of a multimodal regimen based on gabapentin, ketamine, and morphine in controlling pain during ch14.18 chemotherapy. In our cohort, the pain was low, desaturation and hypotension were infrequent, and no episode of bradycardia was reported. Morphine consumption was similar to other studies. Our results suggest that this regimen may be a valid analgesic option in children undergoing ch14.18 infusion.

Effect of Antibiotic Discontinuation Strategies on Mortality and Infectious Complications in Critically Ill Septic Patients: A Meta-Analysis and Trial Sequential Analysis.

OBJECTIVE: To investigate methods of antibiotic duration minimization and their effect on mortality and infectious complications in critically ill patients. DATA SOURCES: A systematic search of PubMed, Embase (via Ovid), clinicaltrials.gov, and the Cochrane Central Register of Controlled Trials (via Wiley) (CENTRAL, Issue 2, 2015). STUDY SELECTION: Randomized clinical trials comparing strategies to minimize antibiotic duration (days) for patients with infections or sepsis in intensive care. DATA EXTRACTION: A systematic review with meta-analyses and trial sequential analyses of randomized clinical trials. Dichotomous data are presented as relative risk (95% CIs) and p value, and continuous data are presented as mean difference (CI) and p value. DATA SYNTHESIS: We included 22 randomized clinical trials (6,046 patients). Strategies to minimize antibiotic use included procalcitonin (14 randomized clinical trials), clinical algorithms (two randomized clinical trials), and fixed-antibiotic duration (six randomized clinical trials). Procalcitonin (-1.23 [-1.61 to -0.85]; p < 0.001), but not clinical algorithm-guided antibiotic therapy (-7.41 [-18.18 to 3.37]; p = 0.18), was associated with shorter duration of antibiotic therapy. The intended reduction in antibiotic duration ranged from 3 to 7 days in fixed-duration antibiotic therapy randomized clinical trials. Neither procalcitonin-guided antibiotic treatment (0.91 [0.82-1.01]; p = 0.09), clinical algorithm-guided antibiotic treatment (0.67 [0.30-1.54]; p = 0.35), nor fixed-duration antibiotics (1.21 [0.90-1.63]; p = 0.20) were associated with reduction in mortality. Z-curve for trial sequential analyses of mortality associated with procalcitonin-guided therapy did not reach the trial sequential monitoring boundaries for benefit, harm, or futility (adjusted CI, 0.72-1.10). Trial sequential analyses for mortality associated with clinical algorithm and fixed-duration treatment accumulated less than 5% of the required information size. Despite shorter antibiotic duration, neither procalcitonin-guided therapy (0.93 [0.84-1.03]; p = 0.15) nor fixed-duration antibiotic therapy (1.06 [0.74-1.53]; p = 0.75) was associated with treatment failure. CONCLUSIONS: Although the duration of antibiotic therapy is reduced with procalcitonin-guided therapy or prespecified limited duration, meta-analysis and trial sequential analyses are inconclusive for mortality benefit. Data on clinical algorithms to guide antibiotic cessation are limited.

Intraoperative Ketamine for Analgesia Post-Coronary Artery Bypass Surgery: A Randomized, Controlled, Double-Blind Clinical Trial.

OBJECTIVES: To determine whether the administration of ketamine during coronary artery bypass grafting (CABG) surgery leads to a reduction in the quantity of opioids required over the first 48 hours after surgery. DESIGN: Randomized, controlled, double-blind clinical trial. SETTING: Single university academic center. PARTICIPANTS: Patients undergoing CABG surgery with a normal left ventricular ejection fraction. INTERVENTIONS: Ketamine administered intravenously as a bolus dose of 0.5 mg/kg before skin incision, followed by an infusion of 0.5 mg/kg/h until the end of surgery. MEASUREMENTS AND MAIN RESULTS: One hundred eighty-three patients were screened, and 80 patients were randomized. Baseline characteristics were similar between the 2 groups. The intervention group received 53.6 mg (95% confidence interval [CI] 47.1-60.1 mg) of morphine equivalents in the first 48 hours after surgery, whereas the placebo group received 55.7 mg (95% CI 48.4-63.1 mg) over the same time period (p = 0.66). No significant difference was noted in morphine equivalents over the first 6, 12, or 24 hours postoperatively or in maximum, minimum, or average pain scores on postoperative days 1 or 2. CONCLUSIONS: The administration of ketamine during CABG surgery did not result in reduced opioid consumption or pain scores postoperatively.

Direct Health Care Costs, Health Services Utilization, and Outcomes of Biliary Atresia: A Population-based Cohort Study.

OBJECTIVES: Biliary atresia (BA) is the most common reason for liver transplant in childhood, and outcomes worsen with older age at hepatoportoenterostomy (HPE). We determined direct health care costs in children with BA, compared to controls in a population-based cohort of children in Ontario, Canada. METHODS: We used health administrative data to identify all children diagnosed with BA between 2002 and 2016 (n = 121) and matched controls (n = 602). We determined annual direct healthcare costs, and rates of health services utilization, liver transplantation, death, portal hypertension, cirrhosis, esophageal varices, and major upper gastrointestinal bleeding requiring hospitalization. Multivariable regression models determined the association between age at HPE, risk of liver transplant, and direct costs. RESULTS: Incidence of BA was 6.07 (4.99-7.15) per 100,000 live births. The annual median (interquartile range) direct health care costs were higher in BA cases ($4210; interquartile range $1091-$16,765) compared to controls ($283; $112-$634). Compared to age at HPE <45 days, there was no significant association between direct costs and HPE ≥90 days (rate ratio 1.24, 95% confidence interval [CI] 0.78-1.97) or 45 to 90 days (rate ratio 1.05, 95% CI 0.73-1.50). Age at HPE ≥90 days was significantly associated with risk of undergoing liver transplant compared to age <45 days (hazard ratio 5.27, 95% CI 2.45-11.34). Direct costs were higher in patients with BA who underwent liver transplantation compared to those who did not ($39,476±$84,367 vs $22,579 ±â€Š$67,913). CONCLUSIONS: Direct ealth care costs were high in patients with BA, especially in those who underwent liver transplantation. Age at HPE was associated with risk of liver transplantation, but not direct health care costs, utilization, or other risk outcomes.

Psychosocial Response to Uncertain Newborn Screening Results for Cystic Fibrosis.

OBJECTIVE: To explore the psychosocial implications of diagnostic uncertainty that result from inconclusive results generated by newborn bloodspot screening (NBS) for cystic fibrosis (CF). STUDY DESIGN: Using a mixed methods prospective cohort study of children who received NBS for CF, we compared psychosocial outcomes of parents whose children who received persistently inconclusive results with those whose children received true positive or screen-negative results. RESULTS: Mothers of infants who received inconclusive results (n = 17), diagnoses of CF (n = 15), and screen-negative results (n = 411) were surveyed; 23 parent interviews were completed. Compared with mothers of infants with true positive/screen-negative results, mothers of infants with inconclusive results reported greater perceived uncertainty (P < .006) but no differences in anxiety or vulnerability (P > .05). Qualitatively, parents valued being connected to experts but struggled with the meaning of an uncertain diagnosis, worried about their infant's health-related vulnerability, and had mixed views about surveillance. CONCLUSION: Inconclusive CF NBS results were not associated with anxiety or vulnerability but led to health-related uncertainty and qualitative concerns. Findings should be considered alongside efforts to optimize protocols for CF screening and surveillance. Educational and psychosocial supports are warranted for these families.

A secondary benefit: the reproductive impact of carrier results from newborn screening for cystic fibrosis.

PURPOSE: Newborn screening (NBS) for cystic fibrosis (CF) can identify carriers, which is considered a benefit that enables reproductive planning. We examined the reproductive impact of carrier result disclosure of NBS for CF. METHODS: We surveyed mothers of carrier infants after NBS (Time 1) and 1 year later (Time 2) to ascertain intended and reported communication of their infants' carrier results to relatives, carrier testing for themselves/other children, and reproductive decisions. A sub-sample of mothers was also interviewed at Time 1 and Time 2. RESULTS: The response rate was 54%. A little more than half (55%) of mothers underwent carrier testing at Time 1; another 40% of those who intended to undergo testing at Time 1 underwent testing at Time 2. Carrier result communication to relatives was high (92%), but a majority of participants did not expect the results to influence family planning (65%). All interviewed mothers valued learning their infants' carrier results. Some underwent carrier testing and then shared results with family. Others did not use the results or used them in unintended ways. CONCLUSION: Although mothers valued learning carrier results from NBS, they reported moderate uptake of carrier testing and limited influence on family planning. Our study highlights the secondary nature of the benefit of disclosing carrier results of NBS.Genet Med 19 4, 403-411.

Parent Experience With False-Positive Newborn Screening Results for Cystic Fibrosis.

BACKGROUND: The risk of psychosocial harm in families of infants with false-positive (FP) newborn bloodspot screening (NBS) results for cystic fibrosis (CF) is a longstanding concern. Whether well designed retrieval and confirmatory testing systems can mitigate risks remains unknown. METHODS: Using a mixed-methods cohort design, we obtained prospective self-report data from mothers of infants with FP CF NBS results 2 to 3 months after confirmatory testing at Ontario's largest follow-up center, and from a randomly selected control sample of mothers of screen negative infants from the same region. Mothers completed a questionnaire assessing experience and psychosocial response. A sample of mothers of FP infants completed qualitative interviews. RESULTS: One hundred thirty-four mothers of FP infants (response rate, 55%) and 411 controls (response rate, 47%) completed questionnaires; 54 mothers of FP infants were interviewed. Selected psychosocial response measures did not detect psychosocial distress in newborns or 1 year later (P > .05). Mothers recalled distress during notification of the positive result and in the follow-up testing period related to fear of chronic illness, but valued the screening system of care in mitigating concerns. CONCLUSIONS: Although immediate distress was reported among mothers of FP infants, selected psychometric tools did not detect these concerns. The NBS center from which mothers were recruited minimizes delay between notification and confirmatory testing and ensures trained professionals are communicating results and facilitating follow-up. These factors may explain the presence of minimal psychosocial burden. The screening system reflected herein may be a model for NBS programs working to minimize FP-related psychosocial harm.

Inconclusive diagnosis of cystic fibrosis after newborn screening.

OBJECTIVES: To prospectively study infants with an inconclusive diagnosis of cystic fibrosis (CF) identified by newborn screening (NBS; "CF screen positive, inconclusive diagnosis" [CFSPID]) for disease manifestations. METHODS: Infants with CFSPID and CF based on NBS from 8 CF centers were prospectively evaluated and monitored. Genotype, phenotype, repeat sweat test, serum trypsinogen, and microbiology data were compared between subjects with CF and CFSPID and between subjects with CFSPID who did (CFSPID→CF) and did not (CFSPID→CFSPID) fulfill the criteria for CF during the first 3 years of life. RESULTS: Eighty-two subjects with CFSPID and 80 subjects with CF were enrolled. The ratio of CFSPID to CF ranged from 1:1.4 to 1:2.9 in different centers. CFTR mutation rates did not differ between groups; 96% of subjects with CFSPID and 93% of subjects with CF had 2 mutations. Subjects with CFSPID had significantly lower NBS immunoreactive trypsinogen (median [interquartile range]:77 [61-106] vs 144 [105-199] µg/L; P < .0001) than did subjects with CF. Pseudomonas aeruginosa and Stenotrophomonas maltophilia were isolated in 12% and 5%, respectively, of subjects with CFSPID. CF was diagnosed in 9 of 82 (11%) subjects with CFSPID (genotype and abnormal sweat chloride = 3; genotype alone = 4; abnormal sweat chloride only = 2). Sweat chloride was abnormal in CFSPID→CF patients at a mean (SD) age of 21.3 (13.8) months. CFSPID→CF patients had significantly higher serial sweat chloride (P < .0001) and serum trypsinogen (P = .009) levels than did CFSPID→CFSPID patients. CONCLUSIONS: A proportion of infants with CFSPID will be diagnosed with CF within the first 3 years. These findings underscore the need for clinical monitoring, repeat sweat testing at age 2 to 3 years, and extensive genotyping.

Paid caregiver motivation, work conditions, and falls among senior clients.

The purpose of this study was to determine the motivation of paid non-familial caregivers of seniors, understand more about their work conditions, and identify any links to negative outcomes among their senior clients. Ninety-eight paid caregivers (eighty-five female and thirteen male), recruited from multiple sites (i.e. senior centers, shopping malls, local parks, lobbies of senior apartments, caregiver agency meetings) completed face-to-face questionnaires and semi-structured interviews. We found that 60.7% of participants chose to become a caregiver because they enjoyed being with seniors while 31.7% were unable to obtain other work, and 8.2% stated it was a prerequisite to a different health related occupation. Caregivers stated that the most challenging conditions of their work were physical lifting (24.5%), behavioral and psychological symptoms of dementia (24.5%), senior depression/mood changes (18.4%), attachment with impending death (8.2%), missing injuries to client (5.1%), lack of sleep (4.1%), and lack of connection with outside world (3.1%). Caregivers who reported that the best part of their job was the salary, flexible hours, and ease of work were significantly more likely to have clients who fell and fractured a bone than those who enjoyed being with seniors (job characteristics, 62.5% vs. senior enjoyment, 25.6%; p<0.004). We concluded that in pursuing their occupation, paid caregivers are motivated commonly by their love of seniors and also by their lack of other job opportunities. Paid caregivers frequently face challenging work conditions. When seeking a caregiver for a senior, motivation of the caregiver should be considered when hiring.

X-linked adrenoleukodystrophy: ABCD1 de novo mutations and mosaicism.

X-linked adrenoleukodystrophy (X-ALD) is a progressive peroxisomal disorder affecting adrenal glands, testes and myelin stability that is caused by mutations in the ABCD1 (NM_000033) gene. Males with X-ALD may be diagnosed by the demonstration of elevated very long chain fatty acid (VLCFA) levels in plasma. In contrast, only 80% of female carriers have elevated plasma VLCFA; therefore targeted mutation analysis is the most effective means for carrier detection. Amongst 489 X-ALD families tested at Kennedy Krieger Institute, we identified 20 cases in which the ABCD1 mutation was de novo in the index case, indicating that the mutation arose in the maternal germ line and supporting a new mutation rate of at least 4.1% for this group. In addition, we identified 10 cases in which a de novo mutation arose in the mother or the grandmother of the index case. In two of these cases studies indicated that the mothers were low level gonosomal mosaics. In a third case biochemical, molecular and pedigree analysis indicated the mother was a gonadal mosaic. To the best of our knowledge mosaicism has not been previously reported in X-ALD. In addition, we identified one pedigree in which the maternal grandfather was mosaic for the familial ABCD1 mutation. Less than 1% of our patient population had evidence of gonadal or gonosomal mosaicism, suggesting it is a rare occurrence for this gene and its associated disorders. However, the residual maternal risk for having additional ovum carrying the mutant allele identified in an index case that appears to have a de novo mutation is at least 13%.

Outcomes associated with introduction of a shoulder dystocia protocol.

The objective of this study was to assess outcomes that are associated with the implementation of a shoulder dystocia protocol that is focused on team response. We identified women who had a shoulder dystocia during 3 time periods: 6 months before (period A), 6 months during (period B), and 6 months after (period C) the institution of a shoulder dystocia protocol. Documentation and health outcomes were compared among the time periods. During the study period, 254 women (77, 100, and 77 in periods A, B, and C, respectively) had a shoulder dystocia. There were no differences among study periods in patient characteristics. However, complete and consistent documentation increased (14% to 50% to 92%; P < .001), and brachial plexus palsy that was diagnosed at delivery (10.1% to 4.0% to 2.6%; P = .03) and at neonatal discharge (7.6% to 3.0% to 1.3%; P = .04) declined.

Inadequate health literacy among paid caregivers of seniors.

BACKGROUND: Many seniors rely on paid non-familial caregivers to maintain their independence at home. Caregivers often assist with medication reminding and activities of daily living. No prior studies have examined the health literacy levels among paid non-familial caregivers. OBJECTIVES: To determine health literacy levels and the health-related responsibilities of paid non-familial caregivers of seniors. DESIGN: One-on-one face-to-face surveys. The Test for Functional Health Literacy (TOFHLA) was administered to identify health literacy levels. Caregivers were asked to demonstrate their skill in medication use by following directions on pill bottles and sorting medications into pill boxes. PARTICIPANTS: Ninety-eight paid unrelated caregivers of seniors recruited at physician offices, caregiver agencies, senior shopping areas, and independent living facilities. RESULTS: Average age of caregivers was 49.5 years, and 86.7% were female. Inadequate health literacy was found in 35.7% of caregivers; 60.2% of all caregivers made errors with the pillbox test medications, showing difficulty in following label directions. Health-related tasks (i.e., medication reminding, sorting, dispensing, and accompanying seniors to physician appointments) were performed by 85.7% of caregivers. The mean age of their seniors was 83.9 years (range 65-99 years), and 82.1% were female. CONCLUSION: Paid non-familial caregivers are essential for many seniors to remain independent and maintain their health. Many caregivers perform health-related duties, but over 1/3 have inadequate health literacy and have difficulties following medication-related instructions. Educating caregivers and ascertaining their health literacy levels prior to assigning health-related tasks may be an important process in providing optimal care to seniors.

Characterization of SNARE cleavage products generated by formulated botulinum neurotoxin type-a drug products.

The study evaluated substrate cleavage product(s) generated by three botulinum neurotoxin serotype A (BoNT/A) medicinal drug products utilizing a novel and highly specific, light-chain activity, high-performance liquid chromatography (LCA-HPLC) method. Samples were reacted with a commercially available BoNT/A fluorescent substrate derived from the SNAP-25 sequence. Reaction products were separated by reversed-phase HPLC. The method detected an atypical cleavage pattern by one of the formulated drug products. IncobotulinumtoxinA produced two cleavage fragments rather than the single fragment typically generated by BoNT/A. Identification confirmed the secondary cleavage at a position corresponding to SNAP-25 Arg198-Ala199 (normal BoNT/A cleavage is Gln197-Arg198). Arg198-Ala199 is also the cleavage site for trypsin and serotype C toxin. Normal cleavage was observed for all other BoNT/A drug product samples, as well as 900-kD and 150-kD bulk toxin BoNT/A. The reason for this unexpected secondary cleavage pattern by one formulated BoNT/A drug product is unknown. Possible explanations include a contaminating protease and/or damage to the 150-kD type-A toxin causing nonspecific substrate recognition and subsequent cleavage uncharacteristic of type-A toxin. The BoNT/A drug products were also analyzed via the LCA-HPLC assay using a commercial BoNT/C fluorescent substrate derived from the syntaxin sequence. Cleavage of the serotype C substrate by incobotulinumtoxinA was also confirmed whilst neither of the other drug products cleaved the syntaxin substrate.