Effectiveness of nirmatrelvir/ritonavir and molnupiravir in non-hospitalized adults with COVID-19: systematic review and meta-analysis of observational studies.

OBJECTIVE: To determine the effectiveness of nirmatrelvir/ritonavir and molnupiravir among vaccinated and unvaccinated non-hospitalized adults with COVID-19. METHODS: Observational studies of nirmatrelvir/ritonavir or molnupiravir compared to no antiviral drug treatment for COVID-19 in non-hospitalized adults with data on vaccination status were included. We searched MEDLINE, EMBASE, Scopus, Web of Science, WHO COVID-19 Research Database and medRxiv for reports published between 1 January 2022 and 8 November 2023. The primary outcome was a composite of hospitalization or mortality up to 35 days after COVID-19 diagnosis. Risk of bias was assessed with ROBINS-I. Risk ratios (RR), hazard ratios (HR) and risk differences (RD) were separately estimated using random-effects models. RESULTS: We included 30 cohort studies on adults treated with nirmatrelvir/ritonavir (n = 462 279) and molnupiravir (n = 48 008). Nirmatrelvir/ritonavir probably reduced the composite outcome (RR 0.62, 95%CI 0.55-0.70; I2 = 0%; moderate certainty) with no evidence of effect modification by vaccination status (RR Psubgroup = 0.47). In five studies, RD estimates against the composite outcome for nirmatrelvir/ritonavir were 1.21% (95%CI 0.57% to 1.84%) in vaccinated and 1.72% (95%CI 0.59% to 2.85%) in unvaccinated subgroups.Molnupiravir may slightly reduce the composite outcome (RR 0.75, 95%CI 0.67-0.85; I2 = 32%; low certainty). Evidence of effect modification by vaccination status was inconsistent among studies reporting different effect measures (RR Psubgroup = 0.78; HR Psubgroup = 0.08). In two studies, RD against the composite outcome for molnupiravir were -0.01% (95%CI -1.13% to 1.10%) in vaccinated and 1.73% (95%CI -2.08% to 5.53%) in unvaccinated subgroups. CONCLUSIONS: Among cohort studies of non-hospitalized adults with COVID-19, nirmatrelvir/ritonavir is effective against the composite outcome of severe COVID-19 independent of vaccination status. Further research and a reassessment of molnupiravir use among vaccinated adults are warranted. REGISTRATION: PROSPERO CRD42023429232.

What would have happened anyway? Population data source considerations when estimating background incident rates of adverse events following immunisation to inform vaccine safety.

INTRODUCTION: Understanding background incident rates of adverse events following immunisation (AEFI) is essential to rapidly detect, evaluate, respond to, and communicate about vaccine safety concerns, especially for new vaccines. Creating estimates based on geographic specific population level data is increasingly important, as new AEFI presentations will be subject to the same local influences of population demography, exposures, health system variations and level of health care sought. METHODS: We conducted a retrospective cohort analysis of hospital admissions, emergency department presentations and general practice consultations from 2015 to 2019-before introduction of COVID-19, Mpox or Shingrix vaccination-to estimate background incident rates for 37 conditions considered potential AEFI of special interest (AESI). Background incident rates per 100,000 population were calculated and presented as cases expected to occur coincidentally 1 day, 1 week and 6 weeks post-vaccination, by life-stage age-groups and presenting healthcare setting. We then assessed the proportional contribution of each data source to inform each AESI background rate estimate. RESULTS: 16,437,156 episodes of the 37 AESI were identified. Hospital admissions predominantly informed 19 (51%) of AESI, including exclusively ADEM and CVST; 8 AESI (22%) by primary care, and 10 (27%) a mix. Four AESI (allergic urticaria, Bell's palsy, erythema multiform and sudden death) were better informed by emergency presentations than admissions, but conversely 11 AESI (30%) were not captured in ICD-10 coded emergency presentations at all. CONCLUSIONS: Emergent safety concerns are inevitable in population-wide implementation of new vaccines, therefore understanding local background rates aids both safety signal detection as well as maintaining public confidence in vaccination. Hospital and primary care data sources can be interrogated to inform expected background incident rates of adverse events that may occur following vaccination. However, it is necessary to understand which data-source provides best intelligence according to nature of condition and presenting healthcare setting.

Post-vaccination healthcare attendance rate as a proxy measure for syndromic surveillance of adverse events following immunisation.

OBJECTIVE: This study explored whether all-cause healthcare attendance rate post-vaccination could detect the two historical influenza safety episodes occurring in 2010 and 2015 using a large de-identified general practitioner (GP) consultations dataset. METHODS: A retrospective observational cohort study was conducted using GP consultation data routinely collected from 2008 to 2017 in Victoria, Australia. Post-vaccination GP consultation rates were monitored, over a 22-week surveillance period each year that aligned with each year's influenza vaccination season, using the Observed minus Expected (O-E) and the Log-Likelihood Ratio (LLR) CUSUM charts. Days 1-7 post-vaccination were considered as the risk period. The LLR CUSUM was designed to detect both a 50% and two-fold rise in the odds of the baseline post-vaccination GP consultation rates. RESULTS: Over the 10-year study period, more than 1.5 million seasonal influenza vaccines doses were administered to 295,091 persons. Overall, 1.29% had a GP consultation within one week of vaccination, but 98.53% of the consultations occurred in days 1-3 post-vaccination. The LLR CUSUM chart detected significant increases in the weekly rates of post-vaccination GP consultation in 2010 in children aged under ten years and in 2015 in adults aged 19-64 years. These increases were aligned by week, but one week earlier and by age category, with the historical adverse events following immunisation (AEFI) signals occurring in 2010 and 2015. However, in the absence of historical AEFI signals, increased rates of post-vaccination GP consultations were identified in three of the eight influenza vaccination years. CONCLUSION: The crude post-vaccination healthcare attendance rate has the potential to offer a sensitive proxy to monitor vaccine safety signal. Implications for public health: Vaccine safety monitoring using syndromic indicator has the potential to augment the existing surveillance systems as part of an integrated vaccine safety monitoring approach.

Use of telephone helpline data for syndromic surveillance of adverse events following immunization in Australia: A retrospective study, 2009 to 2017.

BACKGROUND: The increasing availability of electronic healthcare data offers an opportunity to enhance adverse events following immunisation (AEFI) signal monitoring in near real-time. AIM: To evaluate the potential use of telephone helpline data to augment the existing AEFI surveillance system in Victoria, Australia. METHODS: Anonymised telephone helpline call data were extracted between 2009 and 2017. For comparison, we included AEFI reports to the Victorian enhanced passive surveillance system, SAEFVIC-"Surveillance of Adverse Events Following Vaccination In the Community". The temporal pattern cross-correlation coefficient at different time lags was estimated as a measure of timeliness evaluation. Historically known AEFI signals in 2010 and 2015 were examined using the Farrington statistical signal detection algorithm. RESULT: During the study period, overall, the telephone helpline centre received 2,005,226 calls. Of these, 0.68% (13,719) were AEFI-related. In the same period, SAEFVIC received 10,367 AEFI related reports. Cross-correlation analysis, generally, showed that the two datasets were moderately correlated (r = 0.4) at a negative lag of 1 week. For individual years, the cross-correlation coefficient was highest (r = 0.66) in 2010 with the telephone helpline data leading by 2 weeks. Our analysis indicated the 2010 reported incidence of febrile convulsions and the 2015 reported increased allergic-related reactions following seasonal influenza vaccination three weeks and one week earlier respectively. CONCLUSION: Telephone helpline data was able to detect an increased rate of AEFI earlier than the enhanced passive AEFI surveillance system. This dataset offers a valuable and near real-time component of an integrated AEFI early signal detection system in Australia.

Positive predictive value of ICD-10 codes to detect anaphylaxis due to vaccination: A validation study.

PURPOSE: To validate the use of selected International Classification of Disease Codes 10th revision (ICD-10) to predict (positive predictive value) anaphylaxis due to vaccination using emergency department (ED) data. METHODS: We conducted a retrospective study using ED encounter data from a large tertiary-care teaching hospital, Monash Medical Centre, Melbourne, Australia. We searched all ED encounters potentially due to anaphylaxis after vaccination, between 1 January 2010 and 31 December 2018, using ICD-10-CM codes T80.5, T80.6, T88.1, T88.6, and T78.2. Health records of potential cases were examined to determine if they met the Brighton Collaboration (BC) criteria for anaphylaxis. We calculated the PPV to evaluate the accuracy of the selected ICD-10-CM codes in predicting anaphylaxis due to vaccination. RESULTS: Of the 69 health records identified and reviewed, 29 (42.2%) met the criteria for anaphylaxis regardless of the cause, and 24.6% (17/69) of records were confirmed as anaphylaxis triggered by vaccination (low positive predictive value). However, of the 23 records identified using ICD-10-CM code T80.5, 22 were classified as anaphylaxis cases regardless of the cause, and 12 were anaphylaxis due to vaccination cases giving PPV of 95.7% and 52.2%, respectively. CONCLUSIONS: Given that there is no specific ICD-10-CM code for anaphylaxis due to vaccination, ICD-10-CM code T80.5 may be suitable to monitor anaphylaxis due to vaccination in the ED setting. The current study was conducted at a single centre and needs to be confirmed by future multicentre studies.

Use of routinely collected electronic healthcare data for postlicensure vaccine safety signal detection: a systematic review.

BACKGROUND: Concerns regarding adverse events following vaccination (AEFIs) are a key challenge for public confidence in vaccination. Robust postlicensure vaccine safety monitoring remains critical to detect adverse events, including those not identified in prelicensure studies, and to ensure public safety and public confidence in vaccination. We summarise the literature examined AEFI signal detection using electronic healthcare data, regarding data sources, methodological approach and statistical analysis techniques used. METHODS: We performed a systematic review using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. Five databases (PubMed/Medline, EMBASE, CINAHL, the Cochrane Library and Web of Science) were searched for studies on AEFIs monitoring published up to 25 September 2017. Studies were appraised for methodological quality, and results were synthesised narratively. RESULT: We included 47 articles describing AEFI signal detection using electronic healthcare data. All studies involved linked diagnostic healthcare data, from the emergency department, inpatient and outpatient setting and immunisation records. Statistical analysis methodologies used included non-sequential analysis in 33 studies, group sequential analysis in two studies and 12 studies used continuous sequential analysis. Partially elapsed risk window and data accrual lags were the most cited barriers to monitor AEFIs in near real-time. CONCLUSION: Routinely collected electronic healthcare data are increasingly used to detect AEFI signals in near real-time. Further research is required to check the utility of non-coded complaints and encounters, such as telephone medical helpline calls, to enhance AEFI signal detection. TRIAL REGISTRATION NUMBER: CRD42017072741.

Practice and Intention to use long acting and permanent contraceptive methods among married women in Ethiopia: Systematic meta-analysis.

BACKGROUND: The long acting and permanent contraceptive methods (LAPCMs) has not used unlike that of short-acting methods in Ethiopia. Ethiopia is the second most populous country in Sub Saharan Africa with a high total fertility rate, and high maternal and child mortality rates. This study summarized the evidence of practice and intention to use long acting and permanent family planning methods among women in Ethiopia using systemic review and meta-analysis. METHODS: A systematic review and meta-analysis of the published and unpublished observational studies were conducted. Original studies were identified using databases of Medline/Pubmed, and Google Scholar. Heterogeneity across studies was checked using Cochrane Q test statistic and I(2)test. The pooled proportion of intention to use and the practice of long acting and permanent contraceptive methods were computed using a/the random effect model. RESULTS: Based on the ten observational studies included in the meta-analysis, the pooled prevalence of intention to use long acting and permanent contraceptive methods among married women according to the random effect model was 42.98 % (95 % CI 32.53, 53.27 %). On the other hand, the pooled practice of long acting and permanent methods of contraceptive among the study participants was 16.64 % (95 % CI 12.4 to 20.87 %). CONCLUSION: This meta-analysis revealed that women's intention to use LAPCMs is generally good but their utilization is low. It is recommended, therefore, that LAPMCs must be made more readily available and accessible to women at the lower level of health service delivery who are in need of it.

Is protease inhibitors based antiretroviral therapy during pregnancy associated with an increased risk of preterm birth? Systematic review and a meta-analysis.

BACKGROUND: Antiretroviral therapy is recommended during pregnancy to decrease the risk of perinatal transmission of HIV-1 infection and to improve maternal health. However, some studies have reported that antiretroviral treatment (ART) containing protease inhibitors (PI) is associated with an increased risk of preterm birth. In contrast, other studies have reported no increased risk. This meta-analysis was conducted to derive a more reliable estimate of the association between the prenatal use of PI based ART regimen and preterm birth. METHODS: A systemic review and meta-analysis was conducted using published studies which were identified through a computerized search using the Medline/PubMed database, Google Scholar and Health Inter Network Access to Research Initiative (HINARI). The analysis was undertaken using STATA version 11.0 software and studies were described by forest plot. Heterogeneity across studies was checked using Cochran Q test and I2 test. An adjusted odd ratio with 95% confidence intervals [95% CI] was pooled using a random effects model. RESULTS: The Cochrane Q test (Q test p = 0.051) showed a good homogeneity among studies. However, medium heterogeneity was observed in up to 46% of the sample using the I2 test (I2 = 46.5%). The Egger weighted regression method (p = 0.04) showed evidence of publication bias, but Begg rank correlation statistics (p = 0.47) did not show evidence of publication bias. The pooled analysis of 10 studies showed that protease based ART exposure during pregnancy was associated with an increased risk of preterm birth (pooled odds ratio 1.32 (95% CI, 1.04 to 1.59). CONCLUSIONS: This meta-analysis revealed that the PI based ART exposure during pregnancy is significantly associated with an increased risk of preterm birth. There should be strong cautions against initiating ART during pregnancy and PI based ARV should be replaced by others drug regime. Protease inhibitor ART drugs should not be included as part of therapy during pregnancy.

Prevalence of hypertension in Ethiopia: a systematic meta-analysis.

BACKGROUND: Hypertension has been increasing in developing countries including Ethiopia. Other than smaller studies, there is no national prevalence study on hypertension in Ethiopia. These smaller studies reported varied prevalence of hypertension. This study is intended to summarize and pool the results of smaller region based studies to provide a national level estimate of the prevalence of hypertension. METHODS: The studies were identified through internet search using the data base of MEDLINE/PubMed, Google scholar, EMBASE, HINARI, Cochrane library and reference lists of previous prevalence studies. We also made manual searches to identify relevant articles. Descriptive information for the original studies is presented in a table and the quantitative results were presented in forest plots. The Cochrane Q test and I2 test statistic were used to test heterogeneity across studies. The Pooled estimate of prevalence of hypertension was computed by a random effects model. RESULTS: One hundred eight titles were identified through electronic searching using keywords. Of these, nine studies were meet the inclusion criteria. A random effect meta-analysis of the results from these 9 studies was conducted to provide an estimate of the prevalence of hypertension in the Ethiopian population. The analysis showed that the prevalence of hypertension among Ethiopian population was estimated to be 19.6 % (95 % CI: 13.7 %, 25.5 %). Subgroup analyses indicated that the prevalence of hypertension is higher in the urban population (23.7 %) than rural and urban combined (14.7 %). The prevalence of hypertension among males (20.6 %) and females (19.2 %) was similar. CONCLUSION: This study found that the prevalence of hypertension in Ethiopia is increasing. This evidence suggests that attention has to be given to primary prevention of hypertension in the Ethiopian adult population, especially in the urban population by integrating it with health extension programs.

Association between HIV/AIDS and multi-drug resistance tuberculosis: a systematic review and meta-analysis.

BACKGROUND: Human immunodeficiency virus (HIV), multi-drug resistant tuberculosis (MDR) is emerging as major challenge facing tuberculosis control programs worldwide particularly in Asia and Africa. Findings from different studies on associations of HIV co-infection and drug resistance among patients with TB have been contradictory (discordant). Some institution based studies found strongly increased risks for multi-drug resistant TB (MDR TB) among patients co-infected with TB and HIV, whereas other studies found no increased risk (it remains less clear in community based studies. The aim was to conduct a systematic review and meta-analysis of the association between multi-drug resistant tuberculosis and HIV infection. METHODS AND FINDINGS: Systematic review of the published literature of observational studies was conducted. Original studies were identified using databases of Medline/Pubmed, Google Scholar and HINARI. The descriptions of original studies were made using frequency and forest plot. Publication bias was assessed using Funnel plot graphically and Egger weighted and Begg rank regression tests statistically. Heterogeneity across studies was checked using Cochrane Q test statistic and I(2). Pool risk estimates of MDR-TB and sub-grouping analysis were computed to analyze associations with HIV. Random effects of the meta-analysis of all 24 observational studies showed that HIV is associated with a marginal increased risk of multi-drug resistant tuberculosis (estimated Pooled OR 1.24; 95%, 1.04-1.43). Subgroup analyses showed that effect estimates were higher (Pooled OR 2.28; 95%, 1.52-3.04) for primary multi-drug resistance tuberculosis and moderate association between HIV/AIDS and MDR-TB among population based studies and no significant association in institution settings. CONCLUSIONS: This study demonstrated that there is association between MDR-TB and HIV. Capacity for diagnosis of MDR-TB and initiating and scale up of antiretroviral treatment, and collaborations between HIV and TB control programs need to be considered and strengthened.

Assessment of knowledge and practice towards hepatitis B among medical and health science students in Haramaya University, Ethiopia.

INTRODUCTION: Hepatitis B (HB) is a serious infection that affects liver and caused by hepatitis B virus (HBV). HB is a serious global public health problem and the health professionals are most at risk. It is contagious and easy to be transmitted from one infected individual to another by blood to blood contact, mother to child, unprotected sexual intercourse, sharing of eating utensils and other barber shop and beauty salon equipment. The aim of this study was to assess knowledge and practices about transmissions and prevention of hepatitis B among medical and health science students on clinical attachment in Haramaya University. METHODS AND FINDINGS: A cross sectional study was conducted among 322 health science and medical students who are starting clinical attachment (year II, III, IV, V and IV) from February 1-15, 2013. Self-administered structured questionnaire was used to collect information. Out of 322 distributed questionnaires, 322 were returned with a response rate of 100.0%. Majority of the students (91%) were in the age group 20-24 and 232 (72%) of the respondents were male. Majorities (95.3%) of students were not fully vaccinated against Hepatitis B and 48.4% of the students were not aware about the availability of post exposure prophylaxis for HB. Mean scores for knowledge and practice were 11.52±2.37 and 2.76±1.1 respectively. Significant and positive linear correlations between knowledge-practice (r = 0.173, p = 0.002) was observed. Study department was significantly associated with mean knowledge and practice of study respondents. CONCLUSION: This study indicates that lack of awareness about Hepatitis B, its route of transmission and modes of prevention among the medical students entering into the profession. Similarly, 95.3% the students were not fully vaccinated against Hepatitis B, which makes them vulnerable to the disease.