Effect of COVID-19 vaccination on mortality by COVID-19 and on mortality by other causes, the Netherlands, January 2021-January 2022.

BACKGROUND: We aimed to estimate vaccine effectiveness (VE) against COVID-19 mortality, and to explore whether an increased risk of non-COVID-19 mortality exists in the weeks following a COVID-19 vaccine dose. METHODS: National registries of causes of death, COVID-19 vaccination, specialized health care and long-term care reimbursements were linked by a unique person identifier using data from 1 January 2021 to 31 January 2022. We used Cox regression with calendar time as underlying time scale to, firstly, estimate VE against COVID-19 mortality after primary and first booster vaccination, per month since vaccination and, secondly, estimate risk of non-COVID-19 mortality in the 5 or 8 weeks following a first, second or first booster dose, adjusting for birth year, sex, medical risk group and country of origin. RESULTS: VE against COVID-19 mortality was > 90 % for all age groups two months after completion of the primary series. VE gradually decreased thereafter, to around 80 % at 7-8 months post-primary series for most groups, and around 60 % for elderly receiving a high level of long-term care and for people aged 90+ years. Following a first booster dose, the VE increased to > 85 % in all groups. The risk of non-COVID-19 mortality was lower or similar in the 5 or 8 weeks following a first dose compared to no vaccination, as well as following a second dose compared to one dose and a booster compared to two doses, for all age and long-term care groups. CONCLUSION: At the population level, COVID-19 vaccination greatly reduced the risk of COVID-19 mortality and no increased risk of death from other causes was observed.

Cost-effectiveness and return-on-investment of C-reactive protein point-of-care testing in comparison with usual care to reduce antibiotic prescribing for lower respiratory tract infections in nursing homes: a cluster randomised trial.

OBJECTIVES: C-reactive protein point-of-care testing (CRP POCT) is a promising diagnostic tool to guide antibiotic prescribing for lower respiratory tract infections (LRTI) in nursing home residents. This study aimed to evaluate cost-effectiveness and return-on-investment (ROI) of CRP POCT compared with usual care for nursing home residents with suspected LRTI from a healthcare perspective. DESIGN: Economic evaluation alongside a cluster randomised, controlled trial. SETTING: 11 Dutch nursing homes. PARTICIPANTS: 241 nursing home residents with a newly suspected LRTI. INTERVENTION: Nursing home access to CRP POCT (POCT-guided care) was compared with usual care without CRP POCT (usual care). MAIN OUTCOME MEASURES: The primary outcome measure for the cost-effectiveness analysis was antibiotic prescribing at initial consultation, and the secondary outcome was full recovery at 3 weeks. ROI analyses included intervention costs, and benefits related to antibiotic prescribing. Three ROI metrics were calculated: Net Benefits, Benefit-Cost-Ratio and Return-On-Investment. RESULTS: In POCT-guided care, total costs were on average €32 higher per patient, the proportion of avoided antibiotic prescribing was higher (0.47 vs 0.18; 0.30, 95% CI 0.17 to 0.42) and the proportion of fully recovered patients statistically non-significantly lower (0.86 vs 0.91; -0.05, 95% CI -0.14 to 0.05) compared with usual care. On average, an avoided antibiotic prescription was associated with an investment of €137 in POCT-guided care compared with usual care. Sensitivity analyses showed that results were relatively robust. Taking the ROI metrics together, the probability of financial return was 0.65. CONCLUSION: POCT-guided care effectively reduces antibiotic prescribing compared with usual care without significant effects on recovery rates, but requires an investment. Future studies should take into account potential beneficial effects of POCT-guided care on costs and health outcomes related to antibiotic resistance. TRIAL REGISTRATION NUMBER: NL5054.

Implementation and Use of Point-of-Care C-Reactive Protein Testing in Nursing Homes.

OBJECTIVES: This study evaluated logistics, process data, and barriers/facilitators for the implementation and use of C-reactive protein point-of-care testing (CRP POCT) for suspected lower respiratory tract infections (LRTIs) in nursing home (NH) residents. DESIGN: This process evaluation was performed alongside a cluster randomized, controlled trial (UPCARE study) to evaluate the effect of CRP POCT on antibiotic prescribing for suspected LRTIs in NH residents. SETTING AND PARTICIPANTS: Eleven NHs in the Netherlands. METHODS: Data sources for process data regarding intervention quality included a questionnaire among NH staff, logs, reports, and CRP POCT-analyzer records. Barriers and facilitators for implementation were assessed in focus group interviews with physicians and nurses from 3 NHs. RESULTS: Correct patient selection for CRP POCT and generally continued CRP POCT use indicated good fidelity. The initial training and training of new employees seemed to fit the need, but some POCT-user group sizes had increased over time, which could have impeded frequent use. Users were generally satisfied with CRP POCT and perceived its use feasible and relevant. Facilitators for implementation were initial commitment and active initiation, followed by continued attention and enthusiasm for building routine practice and trust. Short lines of communication between staff, short distance to the POCT-analyzer, 24/7 coverage of staff, and a clear task division facilitated continued attention and routine practice. CONCLUSIONS AND IMPLICATIONS: This process evaluation showed sufficient quality of providing CRP POCT in Dutch NHs. We processed findings of intervention quality and implementation knowledge into key recommendations for CRP POCT implementation in this setting. Future research could focus on CRP POCT use in countries with different organization of care in NHs.

Effect of C reactive protein point-of-care testing on antibiotic prescribing for lower respiratory tract infections in nursing home residents: cluster randomised controlled trial.

OBJECTIVE: To evaluate whether C reactive protein point-of-care testing (CRP POCT) safely reduces antibiotic prescribing for lower respiratory tract infections in nursing home residents. DESIGN: Pragmatic, cluster randomised controlled trial. SETTING: The UPCARE study included 11 nursing home organisations in the Netherlands. PARTICIPANTS: 84 physicians from 11 nursing home organisations included 241 participants with suspected lower respiratory tract infections from September 2018 to the end of March 2020. INTERVENTIONS: Nursing homes allocated to the intervention group had access to CRP POCT. The control group provided usual care without CRP POCT for patients with suspected lower respiratory tract infections. MAIN OUTCOME MEASURES: The primary outcome measure was antibiotic prescribing at initial consultation. Secondary outcome measures were full recovery at three weeks, changes in antibiotic management and additional diagnostics during follow-up at one week and three weeks, and hospital admission and all cause mortality at any point (initial consultation, one week, or three weeks). RESULTS: Antibiotics were prescribed at initial consultation for 84 (53.5%) patients in the intervention group and 65 (82.3%) in the control group. Patients in the intervention group had 4.93 higher odds (95% confidence interval 1.91 to 12.73) of not being prescribed antibiotics at initial consultation compared with the control group, irrespective of treating physician and baseline characteristics. The between group difference in antibiotic prescribing at any point from initial consultation to follow-up was 23.6%. Differences in secondary outcomes between the intervention and control groups were 4.4% in full recovery rates at three weeks (86.4% v 90.8%), 2.2% in all cause mortality rates (3.5% v 1.3%), and 0.7% in hospital admission rates (7.2% v 6.5%). The odds of full recovery at three weeks, and the odds of mortality and hospital admission at any point did not significantly differ between groups. CONCLUSIONS: CRP POCT for suspected lower respiratory tract infection safely reduced antibiotic prescribing compared with usual care in nursing home residents. The findings suggest that implementing CRP POCT in nursing homes might contribute to reduced antibiotic use in this setting and help to combat antibiotic resistance. TRIAL REGISTRATION: Netherlands Trial Register NL5054.

Using point-of-care C-reactive protein to guide antibiotic prescribing for lower respiratory tract infections in elderly nursing home residents (UPCARE): study design of a cluster randomized controlled trial.

BACKGROUND: Antibiotics are over-prescribed for lower respiratory tract infections (LRTI) in nursing home residents due to diagnostic uncertainty. Inappropriate antibiotic use is undesirable both on patient level, considering their exposure to side effects and drug interactions, and on societal level, given the development of antibiotic resistance. C-reactive protein (CRP) point-of-care testing (POCT) may be a promising diagnostic tool to reduce antibiotic prescribing for LRTI in nursing homes. The UPCARE study will evaluate whether the use of CRP POCT for suspected LRTI is (cost-) effective in reducing antibiotic prescribing in the nursing home setting. METHODS/DESIGN: A cluster randomized controlled trial will be conducted in eleven nursing homes in the Netherlands, with the nursing home as the unit of randomization. Residents with suspected LRTI who reside at a psychogeriatric, somatic, or geriatric rehabilitation ward are eligible for study participation. Nursing homes in the intervention group will provide care as usual with the possibility to use CRP POCT, and the control group will provide care as usual without CRP POCT for residents with (suspected) LRTI. Data will be collected from September 2018 for approximately 1.5 year, using case report forms that are integrated in the electronic patient record system. The primary study outcome is antibiotic prescribing for suspected LRTI at index consultation (yes/no). DISCUSSION: This is the first randomised trial to evaluate the effect of nursing home access to and training in the use of CRP POCT on antibiotic prescribing for LRTI, yielding high-level evidence and contributing to antibiotic stewardship in the nursing home setting. The relatively broad inclusion criteria and the pragmatic study design add to the applicability and generalizability of the study results. TRIAL REGISTRATION: Netherlands Trial Register, Trial NL5054. Registered 29 August 2018.

Solar ultraviolet B exposure and global variation in tuberculosis incidence: an ecological analysis.

Epidemiological evidence supports vitamin D deficiency as a risk factor for tuberculosis. Differences in solar ultraviolet B (UV-B) exposure, the major source of vitamin D, might therefore partially explain global variation in tuberculosis incidence.In a global country-based ecological study, we explored the correlation between vitamin D-proxies, such as solar UV-B exposure, and other relevant variables with tuberculosis incidence, averaged over the period 2004-2013.Across 154 countries, annual solar UV-B exposure was associated with tuberculosis incidence. Tuberculosis incidence in countries in the highest quartile of UV-B exposure was 78% (95% CI 57-88%, p<0.001) lower than that in countries in the lowest quartile, taking into account other vitamin D-proxies and covariates. Of the explained global variation in tuberculosis incidence, 6.3% could be attributed to variations in annual UV-B exposure. Exposure to UV-B had a similar, but weaker association with tuberculosis notification rates in the multilevel analysis with sub-national level data for large countries (highest versus lowest quartile 29% lower incidence; p=0.057).The potential preventive applications of vitamin D supplementation in high-risk groups for tuberculosis merits further investigation.