Messenger RNA Coronavirus Disease 2019 (COVID-19) Vaccination With BNT162b2 Increased Risk of Bell's Palsy: A Nested Case-Control and Self-Controlled Case Series Study.

BACKGROUND: Observable symptoms of Bell's palsy following vaccinations arouse concern over the safety profiles of novel coronavirus disease 2019 (COVID-19) vaccines. However, there are only inconclusive findings on Bell's palsy following messenger (mRNA) COVID-19 vaccination. This study aims to update the previous analyses on the risk of Bell's palsy following mRNA (BNT162b2) COVID-19 vaccination. METHODS: This study included cases aged ≥16 years with a new diagnosis of Bell's palsy within 28 days after BNT162b2 vaccinations from the population-based electronic health records in Hong Kong. Nested case-control and self-controlled case series (SCCS) analyses were used, where the association between Bell's palsy and BNT162b2 was evaluated using conditional logistic and Poisson regression, respectively. RESULTS: Totally 54 individuals were newly diagnosed with Bell's palsy after BNT162b2 vaccinations. The incidence of Bell's palsy was 1.58 (95% confidence interval [CI], 1.19-2.07) per 100 000 doses administered. The nested case-control analysis showed significant association between BNT162b2 vaccinations and Bell's palsy (adjusted odds ratio [aOR], 1.543; 95% CI, 1.123-2.121), with up to 1.112 excess events per 100 000 people who received 2 doses of BNT162b2. An increased risk of Bell's palsy was observed during the first 14 days after the second dose of BNT162b2 in both nested case-control (aOR, 2.325; 95% CI, 1.414-3.821) and SCCS analysis (adjusted incidence rate ratio, 2.44; 95% CI, 1.32-4.50). CONCLUSIONS: There was an overall increased risk of Bell's palsy following BNT162b2 vaccination, particularly within the first 14 days after the second dose, but the absolute risk was very low.

Identification and quantification of chimeric sequencing reads in a highly multiplexed RAD-seq protocol.

Highly multiplexed approaches have become common in genomic studies. They have improved the cost-effectiveness of genotyping hundreds of individuals using combinatorially barcoded adapters. These strategies, however, can potentially misassigned reads to incorrect samples. Here, we used a modified quaddRAD protocol to analyse the occurrence of index hopping and PCR chimeras in a series of experiments with up to 100 multiplexed samples per sequencing lane (639 samples in total). We created two types of sequencing libraries: four libraries of type A, where PCRs were run on individual samples before multiplexing, and three libraries of type B, where PCRs were run on pooled samples. We used fixed pairs of inner barcodes to identify chimeric reads. Type B libraries show a higher percentage of misassigned reads (1.15%) than type A libraries (0.65%). We also quantify the commonly undetectable chimeric sequences that occur whenever multiplexed groups of samples with different outer barcodes are sequenced together on a single flow cell. Our results suggest that these types of chimeric sequences represent up to 1.56% and 1.29% of reads in type A and B libraries, respectively. We also show that increasing the number of mismatches allowed for barcode rescue to above 2 dramatically increases the number of recovered chimeric reads. We provide recommendations for developing highly multiplexed RAD-seq protocols and analysing the resulting data to minimize the generation of chimeric sequences, allowing their quantification and a finer control on the number of PCR cycles necessary to generate enough input DNA for library preparation.

Thromboembolic events and hemorrhagic stroke after mRNA (BNT162b2) and inactivated (CoronaVac) covid-19 vaccination: A self-controlled case series study.

Background: This study aims to evaluate the association between thromboembolic events and hemorrhagic stroke following BNT162b2 and CoronaVac vaccination. Methods: Patients with incident thromboembolic events or hemorrhagic stroke within 28 days of covid-19 vaccination or SARS-CoV-2 positive test during 23 February to 30 September 2021 were included. The incidence per 100,000 covid-19 vaccine doses administered and SARS-CoV-2 test positive cases were estimated. A modified self-controlled case series (SCCS) analysis using the data from the Hong Kong territory-wide electronic health and vaccination records. Seasonal effect was adjusted by month. Findings: A total of 5,526,547 doses of BNT162b2 and 3,146,741 doses of CoronaVac were administered. A total of 334 and 402 thromboembolic events, and 57 and 49 hemorrhagic stroke cases occurred within 28 days after BNT162b2 and CoronaVac vaccination, respectively. The crude incidence of thromboembolic events and hemorrhagic stroke per 100,000 doses administered for both covid-19 vaccines were smaller than that per 100,000 SARS-CoV-2 test positive cases. The modified SCCS detected an increased risk of hemorrhagic stroke in BNT162b2 14-27 days after first dose with adjusted IRR of 2.53 (95% CI 1.48-4.34), and 0-13 days after second dose with adjusted IRR 2.69 (95% CI 1.54-4.69). No statistically significant risk was observed for thromboembolic events for both vaccines. Interpretation: We detected a possible safety signal for hemorrhagic stroke following BNT162b2 vaccination. The incidence of thromboembolic event or hemorrhagic stroke following vaccination is lower than that among SARS-CoV-2 test positive cases; therefore, vaccination against covid-19 remains an important public health intervention. Funding: This study was funded by a research grant from the Food and Health Bureau, The Government of the Hong Kong Special Administrative Region (reference COVID19F01).

Bell's palsy following vaccination with mRNA (BNT162b2) and inactivated (CoronaVac) SARS-CoV-2 vaccines: a case series and nested case-control study.

BACKGROUND: Bell's palsy is a rare adverse event reported in clinical trials of COVID-19 vaccines. However, to our knowledge no population-based study has assessed the association between the inactivated SARS-CoV-2 vaccines and Bell's palsy. The aim of this study was to evaluate the risk of Bell's palsy after BNT162b2 and CoronaVac vaccination. METHODS: In this case series and nested case-control study done in Hong Kong, we assessed the risk of Bell's palsy within 42 days following vaccination with BNT162b2 (Fosun-BioNTech [equivalent to Pfizer-BioNTech]) or CoronaVac (from Sinovac Biotech, Hong Kong) using data from voluntary surveillance reporting with the Hospital Authority, the COVID-19 Vaccine Adverse Event Online Reporting system for all health-care professionals, and the Hospital Authority's territory-wide electronic health records from the Clinical Data Analysis and Reporting System. We described reported cases of Bell's palsy among vaccine recipients (aged 18-110 years for CoronaVac and aged 16-110 years for BNT162b2). We compared the estimated age-standardised incidence of clinically confirmed cases among individuals who had received the CoronaVac or BNT162b2 vaccination (up to 42 days before presentation) with the background incidence in the population. A nested case-control study was also done using conditional logistic regression to estimate the odds ratio (OR) for risk of Bell's palsy and vaccination. Cases and controls were matched (1:4) by age, sex, admission setting, and admission date. FINDINGS: Between February 23 and May 4, 2021, 451 939 individuals received the first dose of CoronaVac and 537 205 individuals received the first dose of BNT162b2. 28 clinically confirmed cases of Bell's palsy were reported following CoronaVac and 16 cases were reported following BNT162b2. The age-standardised incidence of clinically confirmed Bell's palsy was 66·9 cases per 100 000 person-years (95% CI 37·2 to 96·6) following CoronaVac vaccination and 42·8 per 100 000 person-years (19·4 to 66·1) for BNT162b2 vaccination. The age-standardised difference for the incidence compared with the background population was 41·5 (95% CI 11·7 to 71·4) for CoronaVac and 17·0 (-6·6 to 40·6) for BNT162b2, equivalent to an additional 4·8 cases per 100 000 people vaccinated for CoronaVac and 2·0 cases per 100 000 people vaccinated for BNT162b2. In the nested case-control analysis, 298 cases were matched to 1181 controls, and the adjusted ORs were 2·385 (95% CI 1·415 to 4·022) for CoronaVac and 1·755 (0·886 to 3·477) for BNT162b2. INTERPRETATION: Our findings suggest an overall increased risk of Bell's palsy after CoronaVac vaccination. However, the beneficial and protective effects of the inactivated COVID-19 vaccine far outweigh the risk of this generally self-limiting adverse event. Additional studies are needed in other regions to confirm our findings. FUNDING: The Food and Health Bureau of the Government of the Hong Kong Special Administrative Region, China. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Infection control challenges in setting up community isolation and treatment facilities for patients with coronavirus disease 2019 (COVID-19): Implementation of directly observed environmental disinfection.

BACKGROUND: Extensive environmental contamination by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been reported in hospitals during the coronavirus disease 2019 (COVID-19) pandemic. We report our experience with the practice of directly observed environmental disinfection (DOED) in a community isolation facility (CIF) and a community treatment facility (CTF) in Hong Kong. METHODS: The CIF, with 250 single-room bungalows in a holiday camp, opened on July 24, 2020, to receive step-down patients from hospitals. The CTF, with 500 beds in open cubicles inside a convention hall, was activated on August 1, 2020, to admit newly diagnosed COVID-19 patients from the community. Healthcare workers (HCWs) and cleaning staff received infection control training to reinforce donning and doffing of personal protective equipment and to understand the practice of DOED, in which the cleaning staff observed patient and staff activities and then performed environmental disinfection immediately thereafter. Supervisors also observed cleaning staff to ensure the quality of work. In the CTF, air and environmental samples were collected on days 7, 14, 21, and 28 for SARS-CoV-2 detection by RT-PCR. Patient compliance with mask wearing was also recorded. RESULTS: Of 291 HCWs and 54 cleaning staff who managed 243 patients in the CIF and 674 patients in the CTF from July 24 to August 29, 2020, no one acquired COVID-19. All 24 air samples and 520 environmental samples collected in the patient area of the CTF were negative for SARS-CoV-2. Patient compliance with mask wearing was 100%. CONCLUSION: With appropriate infection control measures, zero environmental contamination and nosocomial transmission of SARS-CoV-2 to HCWs and cleaning staff was achieved.

Genetic Basis of Aerobically Supported Voluntary Exercise: Results from a Selection Experiment with House Mice.

The biological basis of exercise behavior is increasingly relevant for maintaining healthy lifestyles. Various quantitative genetic studies and selection experiments have conclusively demonstrated substantial heritability for exercise behavior in both humans and laboratory rodents. In the "High Runner" selection experiment, four replicate lines of Mus domesticus were bred for high voluntary wheel running (HR), along with four nonselected control (C) lines. After 61 generations, the genomes of 79 mice (9-10 from each line) were fully sequenced and single nucleotide polymorphisms (SNPs) were identified. We used nested ANOVA with MIVQUE estimation and other approaches to compare allele frequencies between the HR and C lines for both SNPs and haplotypes. Approximately 61 genomic regions, across all somatic chromosomes, showed evidence of differentiation; 12 of these regions were differentiated by all methods of analysis. Gene function was inferred largely using Panther gene ontology terms and KO phenotypes associated with genes of interest. Some of the differentiated genes are known to be associated with behavior/motivational systems and/or athletic ability, including Sorl1, Dach1, and Cdh10 Sorl1 is a sorting protein associated with cholinergic neuron morphology, vascular wound healing, and metabolism. Dach1 is associated with limb bud development and neural differentiation. Cdh10 is a calcium ion binding protein associated with phrenic neurons. Overall, these results indicate that selective breeding for high voluntary exercise has resulted in changes in allele frequencies for multiple genes associated with both motivation and ability for endurance exercise, providing candidate genes that may explain phenotypic changes observed in previous studies.

Determination of the complexity and diversity of the TCR ß-chain CDR3 repertoire in bladder cancer using high-throughput sequencing.

The present study aimed to investigate the complexity and diversity of the T lymphocyte immune repertoire in patients with bladder cancer. To do so, the immune state of patients was assessed. The study also aimed to elucidate the aetiology and pathogenesis of bladder cancer to provide a novel theoretical basis for disease prevention, diagnosis, treatment and prognosis monitoring. Cancerous and paracancerous (control) tissue samples were collected from five patients diagnosed with muscle-invasive bladder cancer. Multiplex polymerase chain reaction and Illumina high-throughput sequencing were used to determine the characteristics and clonal diversity of the T-cell receptor (TCR) ß-chain complementarity-determining region 3 (CDR3) gene in the cancerous and paracancerous tissues of patients with bladder cancer. The degree of clonal expansion in malignant samples was significantly higher than in adjacent samples. Furthermore, ΤCRß variable (TRBV), ΤCRß diversity (TRBD) and ΤCRß joining (TRBJ) repertoires were significantly different in cancerous samples compared with adjacent samples. In addition, 13 identified V-J pairs were highly expressed in cancerous samples whereas they had low expression in control samples. In conclusion, the degree of T-cell clonal expansion in bladder cancerous tissue was higher than in paracancerous tissue, whereas the immune diversity of the tissues of patients with bladder cancer was significantly lower. The DNA sequence and amino acid sequences, and V-J combination level may be used to comprehensively understand the diversity and characteristics of TCR CDR3 in bladder cancer and paracancerous tissues, and to evaluate the immune status of bladder cancer to develop therapeutic targets and biomarkers for prognosis monitoring.

A latent profile analysis on patient empowerment programme in a Hong Kong primary care setting.

OBJECTIVE: This study identified the profiles of subgroups of type 2 diabetic (T2DM) patients of the Patient Empowerment Programme (PEP) by different levels of benefits gained in diabetic self-management behaviors, self-efficacy, and health literacy. METHODS: This study adopted a non-experimental repeated-measures design on T2DM patients who joined PEP, using structured questionnaires. Latent profile analysis (LPA) was used to identify patterns of participants' change on the outcome measures. RESULTS: Findings of LPA revealed that participants who were older, unemployed, weaker in diabetic self-management, and having a higher self-perception in personal disease risk were more likely to join the empowerment sessions and gained more benefits from the program. Participants with lower impairment in energy function and lower autonomy in personal health care showed more improvement in the outcomes. CONCLUSION: The study identified significant factors associated with patients' participation on and benefits gained from a service delivery model integrating health education and patient empowerment in a primary care setting. PRACTICE IMPLICATION: Findings from this study shed light on strategies to improve the PEP design in order to meet the needs of individuals with different health-related profiles.

Declining Trends of Cardiovascular-Renal Complications and Mortality in Type 2 Diabetes: The Hong Kong Diabetes Database.

OBJECTIVE: Nationwide studies on secular trends of diabetes complications are not available in Asia. We examined changes in risk factor control and incidence of complications from diabetes and death in a large longitudinal cohort of Chinese adults with type 2 diabetes in Hong Kong. RESEARCH DESIGN AND METHODS: Between 1 January 2000 and 31 December 2012, 338,908 Chinese adults with type 2 diabetes underwent metabolic and complication assessment in 16 diabetes centers operated by Hong Kong Hospital Authority that provided care to a large majority of diagnosed patients. Patients were followed for incident acute myocardial infarction (AMI), stroke, end-stage renal disease (ESRD), and death until 31 December 2012. Risk factor levels between enrollment periods were compared. Incidence of clinical events, stratified by diabetes duration, was examined over time. RESULTS: Incidence of complications from diabetes and death declined over the observation period in patients at varying disease duration. Among the high-risk group with diabetes for at least 15 years, crude incidence of AMI decreased from 8.7 to 5.8, stroke from 13.5 to 10.1, ESRD from 25.8 to 22.5, and death from 29.0 to 26.6 per 1,000 person-year between the periods 2000 to 2002 and 2010 to 2012. Improvements in levels of metabolic risk factors were detected. Proportion of patients achieving HbA1c <7.0% (53 mmol/mol) was increased from 32.9 to 50.0%, blood pressure ≤130/80 mmHg from 24.7 to 30.7%, and LDL cholesterol <2.6 mmol/L from 25.8 to 38.1%. CONCLUSIONS: From this territory-wide Hong Kong Diabetes Database, we observed decreases in incidence of cardiovascular-renal complications and death and corresponding improvements in risk factor control over a 13-year period.

Evaluation of patient-reported outcomes data in structured diabetes education intervention: 2-year follow-up data of patient empowerment programme.

To examine the effects of a structured group-based education programme, patient empowerment programme (PEP), compared with usual care on 2-year changes in patient-reported outcomes (PRO) in patients with diabetes mellitus (DM). A prospective observational study of 715 patients (PEP/non-PEP: 390/325) was conducted to complete the baseline PRO survey and followed up for 2 years. Health-related quality of life (HRQOL) was measured using the short-form 12 at baseline and annually at two follow-up assessments, which yielded physical and mental component summary and SF-6D preference-based scores. Perceived control over diabetes and general health status were measured using the patient enablement instrument (PEI) and global rating scale (GRS) at follow-ups. When compared with non-PEP, PEP participants significantly reported improvement in health condition (GRS score > 0; 24.55 % vs 10.16 %; odds ratio = 2.502; P = 0.018) in 2 years and enabled the self-perceived control over diabetes (PEI score > 0; 72.20 % vs 38.40 %; odds ratio = 3.25; P < 0.001) in 1-year follow-up but no sustained effects in year 2 (52.65 % vs 39.04 %; odds ratio = 1.366; P = 0.265). There were no significant differences between PEP and non-PEP groups in the changes in quality of life scores (all P > 0.05) at 1 year. Although HRQOL scores deteriorated over 2-year period in both groups, PEP participants reported similar changes in HRQOL scores to that of non-PEP. PEP for DM patients preserved self-perceived disease control and health condition, whereas PEP participants perceived their HRQOL similar to that of non-PEP participants. Findings of PRO should be considered alongside clinical outcomes when evaluating the overall benefits of PEP.

Evaluation of the quality of care of a haemodialysis public-private partnership programme for patients with end-stage renal disease.

BACKGROUND: Haemodialysis (HD) is one of the life-saving options for patients with end stage renal disease but demand for this treatment exceeds capacity in publicly funded hospitals. One novel approach to addressing this problem is through a shared-care model whereby government hospitals partner with qualified private HD service providers to increase the accessibility of HD for needy patients. The aim of this study is to evaluate and enhance the quality of care (QOC) provided in such a shared-care programme in Hong Kong, the Haemodialysis Public-Private Partnership Programme (HD-PPP). METHODS/DESIGN: This is a longitudinal study based on Action Learning and Audit Spiral methodologies to measure the achievement of pre-set target standards for the HD-PPP programme over three evaluation cycles. The QOC evaluation framework is comprised of structure, process and outcome criteria with target standards in each domain developed from review of the evidence and in close collaboration with the HD-PPP working group. During each evaluation cycle, coordinators of each study site complete a questionnaire to determine adherence with structural criteria of care. Process and clinical outcomes, such as adverse events and dialysis adequacy, are extracted from the patient records of consenting study participants while face-to-face interviews are conducted to ascertain patient-reported outcomes such as self-efficacy and health-related quality of life. DISCUSSION: The study relies on the successful implementation of partnership-based action research to develop an evidence-based and pragmatic framework for evaluation of quality of care in an iterative fashion, and to use it to identify possible areas of quality enhancements in a shared-care programme for HD patients. The approach we take in this study emphasizes partnership and engagement with the clinical and administrative programme team, a robust but flexible evaluation framework, direct observation and the potential to realize positive change. The experience will be useful to inform the process of coordinating research studies involving multiple stakeholders and results will help to guide service planning and policy decision making. TRIAL REGISTRATION: US Clinical Trial Registry NCT02307903.

Macrovascular and microvascular disease in obese patients with type 2 diabetes attending structured diabetes education program: a population-based propensity-matched cohort analysis of Patient Empowerment Programme (PEP).

Patient Empowerment Programme (PEP) in primary care was effective in preventing diabetes-related complications in patients with diabetes. Nevertheless, the effect of PEP on glycaemic control, weight control, and complications was unclear in obese type 2 diabetic patients. We aimed to assess whether PEP reduced all-cause mortality, first macrovascular and microvascular disease events. A cohort of 6372 obese type 2 diabetic patients without prior occurrence of macrovascular or microvascular disease events on or before baseline study recruitment date was linked to the administrative database from 2008 to 2013. Non-PEP participants were matched one-to-one with the PEP participants using propensity score method with respect to their baseline covariates. Cox proportional hazard regressions were performed to estimate the associations of the PEP intervention with the occurrence of first macrovascular or microvascular disease events and death from any cause, controlling for demographic and clinical characteristics. During a median 31.5 months of follow-up, 350 (PEP/non-PEP: 151/199) patients suffered from a first macrovascular or microvascular disease event while 95 patients (PEP/non-PEP: 34/61) died from any cause. After adjusting for confounding variables, PEP participants had lower incidence rates of all-cause mortality [hazard ratio (HR): 0.589, 95 % confidence interval (CI) 0.380-0.915, P = 0.018] and first macrovascular or microvascular disease events (HR: 0.782, 95 % CI 0.632-0.968, P = 0.024) than those with PEP. Enrolment to PEP was an effective approach in reducing all-cause mortality and first macrovascular or microvascular disease events in obese patients with type 2 diabetes.

Increased number of structured diabetes education attendance was not associated with the improvement in patient-reported health-related quality of life: results from Patient Empowerment Programme (PEP).

AIMS: To assess the effect of a structured education intervention, Patient Empowerment Programme (PEP) patient-reported health-related quality of life (HRQOL) among type 2 diabetes mellitus (T2DM) patients, and if positive effect is confirmed, to further explore any association between frequency of sessions attendance and HRQOL. METHODS: A total of 298 T2DM patients were recruited when they attended the first session of PEP, between March and September 2010, and were followed over a one-year period from baseline. HRQOL data were assessed using Short Form-12 Health Survey version 2 (SF-12) and Short Form-6 Dimension (SF-6D) at baseline and one-year follow-up. Individuals' anthropometric and biomedical data were extracted from an administrative database in Hong Kong. Unadjusted and adjusted analyses of linear regression models were performed to examine the impact of PEP session attendance on the change in the HRQOL scores, accounting for the socio-demographic and clinical characteristics at baseline. RESULTS: Of the 298 eligible patients, 257 (86.2%) participated in the baseline assessment and 179 (60.1%) patients completed the follow-up assessment, respectively. Overall, PEP resulted in a significant improvement in SF-12 bodily pain and role emotional subscales and SF-6D utility scores. These positive changes were not associated with the level of participation as shown in both unadjusted and adjusted analyses. CONCLUSIONS: The PEP made significant improvement in bodily pain, role emotional and overall aspects of HRQOL. Higher number of session attendance was not associated with improvement in HRQOL in primary care real-world setting. Key Messages ● Participants with type 2 diabetes mellitus who participated in structured diabetes education programme made significant improvement in bodily pain and role emotional subscales and SF-6D scores. ● There was no association between the number of sessions attended and any aspect of HRQOL.

How much do elders with chronic conditions know about their medications?

BACKGROUND: Patients with chronic diseases often undertake multiple medication regimes to manage their condition, prevent complications and to maintain their quality of life. A patient's medication knowledge has been defined as the awareness of drug name, purpose, administration schedule, adverse effects or side-effects and special administration instructions. Poor medication knowledge can have a negative impact on medication adherence and patient safety and, in increasing the use of medical resources. The objective of the study is to assess the medication knowledge of elderly patients with chronic disease conditions and the factors affecting this knowledge. METHODS: A cross-sectional survey was conducted in patients aged ≥ 60 with chronic disease conditions or their caregivers were recruited from two general outpatient clinics and two medical outpatient clinics in the public sector. Participants were approached by trained interviewers to complete a semi-structured questionnaire to assess their understanding of the instructions and information relating to their regular medications, which included medication name, regimen, purpose and common side-effects and precautions. RESULTS: A total of 412 patients were recruited with the mean age of 72.86 ± 7.70. Of those, 221 (54.2%) were male and 226 (55.4%) were of primary school educational level or below. The mean number of medications taken per patient was 3.75 ± 1.93. Overall, 52.7% of patients felt that healthcare staff or clinic pharmacists had very clearly explained the administration instruction of the prescribed medications whilst 47.9% had very clear explanations of drug purpose but only 11.4% felt they had very clear explanations of side-effects. 396 patients (96.1%) failed to recall any side effects or precautions of each of their prescribed medications, although 232 patients (58.4%) would consult a doctor if they encountered problems with their medications. Logistic regression analysis showed that for every additional medication prescribed, the likeliness of patients to recall side-effects of all the medications prescribed was significantly lowered by 35% (OR = 0.65; 95% CI = 0.44-0.94; P = 0.023). In addition, those who finished secondary school or higher education were likely to possess more knowledge of side-effects (OR = 9.88; 95% CI = 2.11-46.25; P = 0.004). CONCLUSIONS: Patients who take medications for their chronic diseases generally lack knowledge on side-effects of their medications which could potentially affect medication compliance and medication safety.

Effects of misalignment on static torsional strength of anterior cervical plate systems.

BACKGROUND CONTEXT: There is little understanding of cervical plate misalignment as a risk factor for plate failure at the plate-screw-bone interface. PURPOSE: To assess the torsional strength and mode of failure of cervical plates misaligned relative to the midsagittal vertical axis. STUDY DESIGN: Plastic and foam model spine segments were tested using static compression and torsion to assess effects of misaligned and various lengths anterior cervical plate (ACPs). METHODS: Different length ACPs and cancellous fixed angle screws underwent axial torsional testing on a servo-hydraulic test frame at a rate of 0.5°/s. A construct consisted of one ACP, four screws, one ultrahigh-molecular weight polyethylene inferior block, and one polyurethane foam superior block. Group 1 had ACPs aligned in the midsagittal vertical axis, group 2 plates were positioned 20° offset from the midline, and group 3 had the ACP shifted 5 mm away and 20° offset from midline. Torques versus angle data were recorded. The failure criterion was the first sign of pullout determined visually and graphically. RESULTS: Group 1 had a more direct screw pullout during failure. For the misaligned plates, failure was a combination of the screws elongating the holes and shear forces acting between the plate and block. The misaligned plates needed more torque to failure. The failure torque was 50% reduced for the longer versus the shorter plates in the neutral position. Graphically shown initial screw slippage inside the block preceded visual identification of slippage in some cases. CONCLUSIONS: We observed different failure mechanisms for neutral versus misaligned plates. Clinically, misalignment may have the benefit of needing more torque to fail. Misalignment was a risk factor for failure of the screw-bone interface, especially in longer plate constructs. These comparisons of angulations may be a solid platform for expansion toward a more applicable in vivo model.

Chronic psychosocial stress: does it modulate immunity to the influenza vaccine in Hong Kong Chinese elderly caregivers?

Previous studies evaluated the effects of psychosocial stress on influenza vaccine responses. However, there were methodological limitations. This study aims to determine whether chronic stress is associated with poorer influenza-specific immune responses to influenza vaccines in Hong Kong Chinese elderly people. This is a prospective study with a 12-week follow-up. Subjects were recruited from government general out-patient clinics, non-government organizations, and public housing estates in Hong Kong. Participants include 55 caregivers of spouses with chronic conditions that impaired their activities of daily living and 61 age- and sex-matched non-caregivers. A single-dose trivalent influenza vaccine was given to all subjects by intramuscular ingestion. Blood samples were collected before vaccination, at 6 weeks, and at 12 weeks after vaccination. Influenza vaccine strain-specific antibody titers were measured by the hemagglutination inhibition method. Lymphocyte subsets were analyzed for ratios and absolute counts, and cytokine concentration were measured by flow cytometry. Validated scales were used to assess psychological (depressive symptoms, perceived stress, and caregiver strain), social (multidimensional social support scale), and lifestyle factors (physical exercise, cigarette smoking, and alcohol consumption) at baseline prior to vaccination. Demographic and socioeconomic variables were also collected. Albumin levels were measured as an indicator for nutritional status in subjects. Caregivers had statistically significant (p < 0.05) lower cell-mediated immune responses to influenza vaccination at 12 weeks when compared with those of the controls. No differences in humoral immune response to vaccination were observed between caregivers and controls. Hong Kong Chinese elderly who experience chronic stress have a significantly lower cell-mediated immune response to influenza vaccination when compared with non-caregivers.

Framework and components for effective discharge planning system: a Delphi methodology.

BACKGROUND: To reduce avoidable hospital readmissions, effective discharge planning and appropriate post discharge support care are key requirements. This study is a 3-staged process to develop, pretest and pilot a framework for an effective discharge planning system in Hong Kong. This paper reports on the methodology of Delphi approach and findings of the second stage on pre-testing the framework developed so as to validate and attest to its applicability and practicability in which consensus was sought on the key components of discharge planning. METHODS: Delphi methodology was adopted to engage a group of experienced healthcare professionals to rate and discuss the framework and components of an effective discharge planning. The framework was consisted 36 statements under 5 major themes: initial screening, discharge planning process, coordination of discharge, implementation of discharge, and post discharge follow-up. Each statement was rated independently based on 3 aspects including clarity, validity and applicability on a 5-point Likert-scale. Statement with 75% or above of participants scoring 4-5 on all 3 aspects would be included in the discharge planning framework. For those statements not reaching 75% of consensus in any one of the aspect, it would be revised or discarded following the group discussion, and be re-rated in another round. RESULTS: A total of 24 participants participated in the consensus-building process. In round one rating, consensus was achieved in 25 out of 36 statements. Among those 11 statements not reaching consensus, the major concern was related to the "applicability" of the statements. The participants expressed a lack of manpower, skills and time in particular during weekends and long holidays in carrying out assessment and care plans within 24 h after admission. There were also timeliness and availability issue in providing transportation and necessary equipment to the patients. To make the statements more applicable, the wordings of some of the statements were revised to provide greater flexibility. Due to the lack of a statement in clarifying the role of the members of the healthcare professional team, one additional statement on the role and responsibility of the multidisciplinary team members was added. The first theme on "initial screening" was further revised to "initial screening and assessment" to better reflect the first stage of discharge planning process. After two rounds of rating process, all the 36 statements and the newly added statement reached consensus CONCLUSIONS: A structured, systematic and coordinated system of hospital discharge system is required to facilitate the discharge process to ensure a smooth patient transition from the hospital to the community and improve patient health outcome in both clinical and social aspect. The findings of this paper provide a reference framework helping policymakers and hospital managers to facilitate the development of a coherent and systematized discharge planning process. Adopting a Delphi approach also demonstrates the values of the method as a pre-test (before the clinical run) of the components and requirements of a discharge planning system taking into account of the local context and system constraints, which would lead to improvements to its applicability and practicability. To confirm the applicability and practicability of this consensus framework for discharge planning system, the third stage of process of development of the discharge planning framework is to apply and pilot the framework in a hospital setting to evaluate its feasibility, applicability and impact in hospital including satisfaction from both the perspectives of staff and patients.

Quantifying subtle but persistent peri-spine inflammation in vivo to submicron cobalt-chromium alloy particles.

PURPOSE: We evaluated the consequences of cobalt-chromium alloy (CoCr) wear debris challenge in the peri-spine region to determine the inflammation and toxicity associated with submicron particulates of CoCr-alloy and nickel on the peri-spine. METHODS: The lumbar epidural spaces of (n = 50) New Zealand white rabbits were challenged with: 2.5 mg CoCr, 5.0 mg CoCr, 10.0 mg CoCr, a positive control (20.0 mg of nickel) and a negative control (ISOVUE-M-300). The CoCr-alloy and Ni particles had a mean diameter of 0.2 and 0.6 µm, respectively. Five rabbits per dose group were studied at 12 and 24 weeks. Local and distant tissues were analyzed histologically and quantitatively analyzed immunohistochemically (TNF-α and IL-6). RESULTS: Histologically, wear particles were observed in all animals. There was no evidence of toxicity or local irritation noted during macroscopic observations in any CoCr-dosed animals. However, Ni-treated control animals experienced bilateral hind leg paralysis and were euthanized at Day 2. Histopathology of the Ni particle-treated group revealed severe neuropathy. Quantitative immunohistochemistry demonstrated a CoCr-alloy dose-dependent increase in cytokines (IL-6, TNF-α, p < 0.05) at 12 and 24 weeks. CONCLUSIONS: Subtle peri-spine inflammation associated with CoCr-alloy implant particles was dose dependent and persistent. Neuropathy can be induced by highly reactive Ni particles. This suggests peri-spine challenge with CoCr-alloy implant debris (e.g., TDA) is consistent with past reports using titanium alloy particles, i.e., mild persistent inflammation.

Comparison of in vivo and simulator-retrieved metal-on-metal cervical disc replacements.

BACKGROUND: Cervical disc arthroplasty is regarded as a promising treatment for myelopathy and radiculopathy as an alternative to cervical spine fusion. On the basis of 2-year clinical data for the PRESTIGE(®) Cervical Disc (Medtronic, Memphis, Tennessee), the Food and Drug Administration recommended conditional approval in September 2006 and final approval in July 2007; however, relatively little is known about its wear and damage modes in vivo. The main objective was to analyze the tribological findings of the PRESTIGE(®) Cervical Disc. This study characterized the in vivo wear patterns of retrieved cervical discs and tested the hypothesis that the total disc replacements exhibited similar surface morphology and wear patterns in vitro as in vivo. METHODS: Ten explanted total disc replacements (PRESTIGE(®), PRESTIGE(®) I, and PRESTIGE(®) II) from 10 patients retrieved after a mean of 1.8 years (range, 0.3-4.1 years) were analyzed. Wear testing included coupled lateral bending ( ±4.7°) and axial rotation ( ±3.8°) with a 49 N axial load for 5 million cycles followed by 10 million cycles of flexion-extension ( ±9.7°) with 148 N. Implant surfaces were characterized by the use of white-light interferometry, scanning electron microscopy, and energy dispersive spectroscopy. RESULTS: The explants generally exhibited a slightly discolored, elliptic wear region of varying dimension centered in the bearing center, with the long axis oriented in the medial-lateral direction. Abrasive wear was the dominant in vivo wear mechanism, with microscopic scratches generally oriented in the medial-lateral direction. Wear testing resulted in severe abrasive wear in a curvilinear fashion oriented primarily in the medial-lateral direction. All retrievals showed evidence of an abrasive wear mechanism. CONCLUSIONS: This study documented important similarity between the wear mechanisms of components tested in vitro and explanted PRESTIGE(®) Cervical Discs; however, the severity of wear was much greater during the in vitro test compared with the retrievals.