Tuen-Ching Chan

Immunogenicity of Intradermal Trivalent Influenza Vaccine With Topical Imiquimod: A Double Blind Randomized Controlled Trial

BACKGROUND Imiquimod, a synthetic Toll-like receptor 7 agonist enhanced immunogenicity of influenza vaccine in a mouse model. We hypothesized that topical imiquimod before intradermal influenza vaccination (TIV) would produce similar effect in human. METHODS We performed a prospective 1-year follow-up, double-blind, randomized, controlled trial with adults with comorbidities. Participants were randomized to 1 of the following 3 vaccinations: topical 5% 250 mg imiquimod ointment followed by intradermal TIV, topical aqueous-cream followed by intradermal TIV, or topical aqueous-cream followed by intramuscular TIV. Patients and investigators were blinded to the type of topical treatment applied. Hemagglutination inhibition (HI) and microneutralization antibody titers were measured. The primary outcome was the day 7 seroconversion rate. RESULTS Ninety-one recruited participants completed the study. The median age was 73 years. On day 7, 27/30 (90%) patients who received imiquimod and intradermal TIV achieved seroconversion against the H1N1 strain by HI, compared with 4/30 (13.3%) who received aqueous-cream and intramuscular TIV (P < .001), and 12/31 (38.7%) who received aqueous-cream and intradermal TIV (P < .001). The seroconversion, seroprotection, and geometric mean titer-fold increase were met in all 3 strains in the imiquimod and intradermal TIV group 2 weeks earlier, and the better seroconversion rate was sustained from day 7 to year 1 (P ≤ .001). The better immunogenicity was associated with fewer hospitalizations for influenza or pneumonia (P < .05). All adverse reactions were self-limited. CONCLUSIONS Pretreatment with topical imiquimod significantly expedited, augmented, and prolonged the immunogenicity of influenza vaccination. This strategy for influenza immunization should be considered for the elderly population.

Prevention of Mortality and Pneumonia Among Nursing Home Older Adults by Dual Pneumococcal and Seasonal Influenza Vaccination During a Pandemic Caused by Novel Pandemic Influenza A (H1N1)

OBJECTIVE To evaluate the efficacy of dual vaccination of seasonal influenza and pneumococcus in nursing home older adults during a novel pandemic of influenza A (H1N1). SETTING Nine nursing homes in Hong Kong. PARTICIPANTS A total of 532 nursing home older adults were included in the study. MEASUREMENTS Efficacy of dual vaccination of seasonal influenza and pneumococcus in nursing home older adults during a novel pandemic influenza A (H1N1). DESIGN A prospective 12-month cohort study was conducted on older residents from December 2009 to November 2010. Participants were divided into 3 groups according to their choice of vaccination: received both seasonal influenza and 23-valent pneumococcal polysaccharide vaccine (PPV-TIV group), received seasonal influenza vaccine alone (TIV group), and those who refused both vaccinations (unvaccinated group). Those who had received vaccination for influenza A (H1N1) were excluded. Outcome measures included mortality from all causes, pneumonia, and vascular causes. RESULTS There were 246 in the PPV-TIV group, 211 in the TIV group, and 75 in the unvaccinated group. Baseline characteristics were similar among the groups. The 12-month mortality rates of the PPV-TIV, TIV alone group, and unvaccinated group were 17.1%, 27.0%, and 37.3% respectively (P < .001). Multivariate analysis demonstrated that, compared with vaccination of seasonal influenza alone, dual vaccination significantly reduced all-cause mortality (hazard ratio [HR] 0.54; 95% confidence interval [CI]: 0.35-0.84; P < .01), mortality from pneumonia (HR 0.60; 95% CI: 0.35-0.99; P < .05), and mortality from vascular causes (HR 0.24; 95% CI: 0.09-0.64; P < .01). CONCLUSIONS During an influenza pandemic or when the circulating influenza strain was not matched by the trivalent seasonal influenza vaccine, dual vaccination of influenza and pneumococcus provided additional protection to nursing home older adults in reducing mortality.

Effectiveness of Influenza Vaccination in Institutionalized Older Adults: A Systematic Review

INTRODUCTION Influenza infection is common among institutionalized older adults. Many nonrandomized observational studies on influenza vaccination suggested that it could reduce influenza-related hospitalizations and mortality in institutionalized older adults. Criticism regarding the effectiveness of influenza vaccine estimated by nonrandomized observational studies include the frailty selection bias and use of nonspecific outcome, such as all-cause mortality. METHODS We conducted a systematic review of studies of influenza vaccination in institutionalized older adults to determine the effects on clinical outcomes. We searched for studies from 3 databases from 1946 to June 2013 assessing effectiveness against influenza infection. We selected studies with good comparability between vaccine group and control group. We expressed vaccine effectiveness (VE) as a proportion, using the formula VE = 1-relative risk or 1-odds ratio. We focused on the following outcomes: influenza-like illness (ILI), laboratory confirmed influenza, hospitalizations due to ILI, or pneumonia and death due to influenza or pneumonia. We did not include all-cause mortality. RESULTS Eleven studies that satisfied the inclusion criteria were identified, representing 11,262 institutionalized older adults. After meta-analysis, we found a significant reduction in pneumonia (VE: 37%, 95% confidence interval [CI]: 18%-53%, P = .001) and death due to pneumonia or influenza (VE: 34%, CI: 10%-53%, P = .01). There was no significant heterogeneity between studies. There was no significant publication bias. CONCLUSION Influenza vaccination in institutionalized older adults could reduce pneumonia and death due to pneumonia or influenza. Influenza vaccination is recommended for institutionalized older adults.

Proactive infection control measures to prevent nosocomial transmission of vancomycin-resistant enterococci in Hong Kong

BACKGROUND/PURPOSE The study describes a proactive infection control approach to prevent nosocomial transmission of vancomycin-resistant enterococci (VRE) and tests if this approach is effective for controlling multiple-drug resistant organisms in a nonendemic setting. METHODS In response to the increasing prevalence of VRE in Hong Kong since 2011, we adopted a multifaceted assertive approach in our health care network. This included active surveillance culture, extensive contact tracing, directly observed hand hygiene in conscious patients before they received meals and medications, stringent hand hygiene and environmental cleanliness, and an immediate feedback antimicrobial stewardship program. We report the occurrence of VRE outbreaks in our hospital after institution of these measures and compared with the concurrent occurrence in other public hospitals in Hong Kong. RESULTS Between July 1, 2011 and November 13, 2013, VRE was identified in 0.32% (50/15,851) of admission episodes by active surveillance culture. The risk of VRE carriage was three times higher in patients with a history of hospitalization outside our hospital networks in the past 3 months (0.56% vs. 0.17%; p = 0.001) compared with those who were not. Extensive contact tracing involving 3277 patient episodes was performed in the investigation for the 25 VRE index patients upon whom implementation of contact precautions was delayed (more than 48 hours of hospitalization). One episode of VRE outbreak was identified in our hospital network, compared with the 77 VRE outbreaks reported in the other hospital networks (controls) without these proactive infection control measures. CONCLUSION Our multifaceted assertive proactive infection control approach can minimize the nosocomial transmission and outbreak of VRE in a nonendemic area.

Efficacy of dual vaccination of pandemic H1N1 2009 influenza and seasonal influenza on institutionalized elderly: A one-year prospective cohort study

BACKGROUND The influenza A (H1N1) 2009 pandemic was declared by the WHO in April 2009. In Hong Kong, the vaccination program began in December 2009 in addition to the annual seasonal trivalent influenza vaccination program. The clinical efficacy of dual vaccination was unknown. METHOD From December 2009 to November 2010, a prospective 12-month cohort study on institutionalized elderly of nine nursing homes was conducted. Elderly persons who were followed up by the Hong Kong West Community Geriatric Assessment Team and had been vaccinated by the Department of Health were included. Outcome measures included all cause mortality, all cause hospitalization, hospitalization for fever on admission and hospitalization for pneumonia based on ICD-9-CM. RESULTS 711 elderly persons were included. 274 received both seasonal influenza vaccine and (H1N1) 2009 vaccine (H1N1-TIV), 368 received seasonal influenza vaccine only (TIV alone) and 69 received no vaccination (unvaccinated). Baseline characteristics were well matched between the groups, except there were fewer females in the TIV alone. The 12-month mortality rates of the H1N1-TIV, TIV alone and unvaccinated were 10.6%, 19.8% and 29%, respectively. Multivariate analysis demonstrated that dual vaccination in the institutionalized elderly significantly reduced all cause mortality by 54% (Hazard Ratio [HR] 0.46; 95% confidence interval [CI] 0.29-0.72; p<0.001) and 74% (HR 0.26; CI 0.13-0.49; p<0.001), compared with vaccination of seasonal vaccination alone and no vaccination, respectively. Dual vaccination also reduced all cause hospitalization, hospitalization for fever on admission and hospitalization for pneumonia compared with seasonal vaccination alone and the unvaccinated group. CONCLUSION Dual vaccination with both H1N1 and seasonal vaccinations provided additional protection to institutionalized elderly in reducing mortality and hospitalization.

Interactive virtual reality Wii in geriatric day hospital: A study to assess its feasibility, acceptability and efficacy

Aim:  Rehabilitation using interactive virtual reality Wii (Wii‐IVR) was shown to be feasible in patients with different medical problems, but there was no study examining its use in a geriatric day hospital (GDH). The aim of the present study was to test the feasibility, acceptability and efficacy of Wii‐IVR in GDH.

Development and validation of a prognostic index for 2‐year mortality in Chinese older residents living in nursing homes

Aim:  There is no mortality prediction index for Chinese nursing home older residents. The objective of this study was to derive and validate a 2‐year mortality prognostic index for them.

Topical imiquimod before intradermal trivalent influenza vaccine for protection against heterologous non-vaccine and antigenically drifted viruses: a single-centre, double-blind, randomised, controlled phase 2b/3 trial

BACKGROUND Pretreatment with topical imiquimod, a synthetic agonist of toll-like receptor 7, significantly improved the immunogenicity of influenza vaccination in elderly people. We aimed to clarify its effect in a younger age group. METHODS In this double-blind, randomised controlled trial, we enrolled healthy volunteers aged 18-30 years in early 2014 to receive the 2013-14 northern-hemisphere winter trivalent influenza vaccine at the Queen Mary Hospital, (Hong Kong, China). Eligible participants were randomly assigned (1:1:1:1) to one of the four vaccination groups: the study group, topical imiquimod-cream followed by intradermal trivalent influenza vaccine (INF-Q-ID), or one of three control groups, topical aqueous-cream control followed by intradermal trivalent influenza vaccine (INF-C-ID), topical aqueous-cream control followed by intramuscular trivalent influenza vaccine (INF-C-IM), and topical imiquimod-cream followed by intradermal normal-saline injection (SAL-Q-ID). Randomisation was by computer-generated lists in blocks of four. The type of topical treatment was masked from volunteers and investigators, although not from the study nurse. Serum haemagglutination-inhibition and microneutralisation-antibody titres were assayed. The primary outcome was seroconversion at day 7 after treatment for three vaccine strains of influenza (A/California/07/2009 H1N1-like virus [A/California/H1N1], A/Victoria/361/2011 H3N2-like virus [A/Victoria/H3N2], and B/Massachusetts/2/2012-like virus [B/Yamagata lineage]) and four non-vaccine strains (A/HK/485197/14 [H3N2 Switzerland-like lineage], prototype A/WSN/1933 [H1N1], A/HK/408027/09 [prepandemic seasonal H1N1], and B/HK/418078/11 [Victoria lineage]). Analysis was done on an intention-to-treat basis. This trial is registered with ClinicalTrials.gov, number NCT02103023. FINDINGS We enrolled 160 healthy volunteers between March 1 and May 31, 2014, and 40 participants were randomly assigned to each study group. For the A/California/H1N1 strain, seroconversion at day 7 occurred in 39 participants (98%) in the INF-Q-ID group, 25 (63%) in the INF-C-ID group, 18 (45%) in the INF-C-IM group, and none in the SAL-Q-ID group; for the A/Victoria/H3N2, this was 30 (75%) in the INF-Q-ID group, four (10%) in the INF-C-ID group, four (10%) in the INF-C-IM group, and none in the SAL-Q-ID group; and for the B/Massachusetts (Yamagata lineage) strain, this was 36 (90%) in the INF-Q-ID group, 27 (68%) in the INF-C-ID group, 17 (43%) in the INF-C-IM group, and one (3%) in the SAL-Q-ID group (p<0·0001 for all three vaccine strains). Adverse reactions were infrequent and self-limited and did not differ between the four groups. Furthermore, the seroconversion rate against the four non-vaccine strains was better in the INF-Q-ID group than in the control groups on days 7 and 21 (p<0·0001). The most common adverse events were grade 1 redness (five participants in the INF-Q-ID group, three in INF-C-ID, one in INF-C-IM, and one in SAL-Q-ID) and grade 1 swelling (seven participants in INF-Q-ID group, five in INF-C-ID, three in INF-C-IM, and two in SAL-Q-ID. INTERPRETATION Topical application of imiquimod before intradermal trivalent influenza vaccine significantly improved immunogenicity against the vaccine influenza strains in young healthy individuals and increased immunogenicity against the non-vaccine strains, especially the antigenically drifted H3N2 strain of 2015, which was not included in the 2013-14 recommended vaccine. Further studies should be done to establish the efficacy and safety of this approach for other injectable vaccines to augment the onset and range of protection. FUNDING The Shaw Foundation Hong Kong, Health and Medical Research Fund (Hong Kong, China), The Consultancy Service for Enhancing Laboratory Surveillance of Emerging Infectious Disease for the HKSAR (Department of Health, Hong Kong, China), The Providence Foundation, Respiratory Viral Research Foundation.

Prevalence and Associated Comorbidities of Moderate to Severe Chronic Renal Impairment in Chinese Nursing Home Older Adults

OBJECTIVE To investigate the prevalence and associated comorbidities of Stage 3 (GFR 30-59 mL/min/1.73m(2)) and Stages 4 and 5 (GFR <30 mL/min/1.73m(2)) chronic kidney disease (CKD) among Chinese nursing home older adults. DESIGN Retrospective cross-sectional study. Glomerular filtration rate (GFR) was estimated by Modification of Diet in Renal Disease Study (Chinese-adjusted) equation and The Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations. SETTING Nine nursing homes in Hong Kong PARTICIPANTS Participants included 812 nursing home older adults (271 men and 571 women), mean age 86.0 ± 7.6. MEASUREMENTS Prevalence of Stage 3 (GFR 30-59 mL/min/1.73m(2)) and Stages 4 and 5 (GFR <30 mL/min/1.73m(2)) CKD. The comorbidities associated with renal impairment were also assessed. RESULTS There were 18.4% of nursing home older adults who had elevated serum creatinine levels above the normal limits. Using Modification of Diet in Renal Disease Study and CKD-EPI equations, 26.4% and 21.2% of them had Stage 3 CKD, whereas 6.8% and 4.4% had Stage 4-5 CKD, respectively. Diabetes mellitus, hypertension, congestive heart failure, and ischemic heart disease correlated significantly with moderate to severe renal impairment in Chinese nursing home older adults. CONCLUSION Stages 3 to 5 CKD are prevalent in Chinese nursing home older adults. Early identification of these patients facilitates drug prescription, renal management, and advance care planning.

Continuous use of antipsychotics and its association with mortality and hospitalization in institutionalized Chinese older adults: an 18-month prospective cohort study.

BACKGROUND Previous meta-analyses have suggested that antipsychotics are associated with increased mortality in dementia patients with behavioral and psychological symptoms (BPSD). Subsequent observational studies, however, have produced conflicting results. In view of this controversy and the lack of any suitable pharmacological alternative for BPSD, this study aimed to investigate the relationship between continuous use of antipsychotics and mortality as well as hospitalizations in Chinese older adults with BPSD residing in nursing homes. METHODS This was a prospective cohort study conducted in nursing homes in the Central & Western and Southern Districts of Hong Kong from July 2009 to December 2010. Older adults were stratified into the exposed group (current users of antipsychotics) and control group (non-users). Demographics, comorbidity according to the Charlson Comorbidity Index (CCI), Barthel Index (BI(20)), Abbreviated Mental Test (AMT), and vaccination status for pandemic Influenza A (H1N1) 2009, seasonal influenza and pneumococcus were collected at baseline. Subjects were followed up at 18 months. All-cause mortality and all-cause hospitalizations were recorded. RESULTS 599 older adults with dementia from nine nursing homes were recruited. The 18-month mortality rate for the exposed group was 24.1% while that for control group was 27.5% (P = 0.38). The exposed group also had a lower median rate of hospitalizations (56 (0-111) per 1000 person-months vs 111 (0-222) per 1000 person-months, median (interquartile range), p<0.001). CONCLUSIONS The continuous use of antipsychotics for BPSD does not increase mortality among Chinese older adults with dementia living in nursing homes. Furthermore, our results show that the use of antipsychotics can lead to decreased hospitalizations.