Community acquired pneumonia incidence before and after proton pump inhibitor prescription: population based study

Objective To examine the risk of community acquired pneumonia before and after prescription of proton pump inhibitor (PPI) and assess whether unmeasured confounding explains this association. Design Cohort study and self controlled case series. Setting Clinical Practice Research Datalink (1990 to 2013) in UK. Participants Adult patients with a new prescription for a PPI individually matched with controls. Main outcome measures Association of community acquired pneumonia with PPI prescription estimated by three methods: a multivariable Cox model comparing risk in PPI exposed patients with controls, corrected for potential confounders; a self controlled case series; and a prior event rate ratio (PERR) analysis over the 12 month periods before and after the first PPI prescription. Results 160 000 new PPI users were examined. The adjusted Cox regression showed a risk of community acquired pneumonia 1.67 (95% confidence interval 1.55 to 1.79) times higher for patients exposed to PPI than for controls. In the self controlled case series, among 48 451 PPI exposed patients with a record of community acquired pneumonia, the incidence rate ratio was 1.19 (95% confidence interval 1.14 to 1.25) in the 30 days after PPI prescription but was higher in the 30 days before a PPI prescription (1.92, 1.84 to 2.00). The Cox regressions for prior event rate ratio similarly showed a greater increase in community acquired pneumonia in the year before than the year after PPI prescription, such that the analysis showed a reduced relative risk of pneumonia associated with PPI use (prior event rate ratio 0.91, 95% confidence interval 0.83 to 0.99). Conclusion The association between the use of PPIs and risk of community acquired pneumonia is likely to be due entirely to confounding factors

The risk of Clostridium difficile infection in patients with pernicious anaemia: a retrospective cohort study using primary care database.

Background: Studies have found an association between proton pump inhibitor (PPI) use and Clostridium difficile infection. The purpose of this study was to determine whether the mechanism by which PPIs induce an increased risk of C. difficile infection is supported by the same mechanism acting in another cause of achlorhydria, pernicious anaemia. Methods: Using a database of anonymised primary care records between 1990 and 2013, we selected exposed patients with a diagnosis of pernicious anaemia treated with vitamin B12 therapy. Each exposed patient was matched by age, gender and general practice to up to 10 controls. Cox regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for C. difficile infection with pernicious anaemia, adjusted for potential confounders. Results: We identified 45,467 exposed patients matched to 449,635 controls. The crude incidence rate of C. difficile infection was 1.85/1000 person-years for the exposed cohort and 1.09/1000 person-years for controls. Patients with pernicious anaemia had a greater risk of C. difficile infection than the controls (adjusted HR 1.57, 95% CI 1.40–1.76). Conclusions: Pernicious anaemia patients have an increased risk of C. difficile infection. This supports the theory that severe achlorhydria is the mechanism that increases the risk of C. difficile infection in long-term PPI users

The risk of Clostridium difficile infection in patients with pernicious anaemia: a retrospective cohort study using primary care database.

Background: Studies have found an association between proton pump inhibitor (PPI) use and Clostridium difficile infection. The purpose of this study was to determine whether the mechanism by which PPIs induce an increased risk of C. difficile infection is supported by the same mechanism acting in another cause of achlorhydria, pernicious anaemia.Methods: Using a database of anonymised primary care records between 1990 and 2013, we selected exposed patients with a diagnosis of pernicious anaemia treated with vitamin B12 therapy. Each exposed patient was matched by age, gender and general practice to up to 10 controls. Cox regression analysis was used to estimate the hazard ratio (HR) and 95% confidence interval (CI) for C. difficile infection with pernicious anaemia, adjusted for potential confounders.Results: We identified 45,467 exposed patients matched to 449,635 controls. The crude incidence rate of C. difficile infection was 1.85/1000 person-years for the exposed cohort and 1.09/1000 person-years for controls. Patients with pernicious anaemia had a greater risk of C. difficile infection than the controls (adjusted HR 1.57, 95% CI 1.40–1.76).Conclusions: Pernicious anaemia patients have an increased risk of C. difficile infection. This supports the theory that severe achlorhydria is the mechanism that increases the risk of C. difficile infection in long-term PPI users

Management of sickle cell disease patients presenting to the emergency department with vaso-occlusive crisis: a retrospective study

Background: Sickle cell anemia (SCA) is a hereditary disease of the hemoglobin, characterized by recurring vaso-occlusive crises (VOC) leading to severe pain. VOCs constitute the primary cause for emergency department (ED) visits among sicklers. Frequent VOC episodes are associated with greater mortality. This study aimed to evaluate pain treatment trends regarding admission, discharge, length of stay in the ED, and early ED revisits among SCA patients. Methods: A cross-sectional study was conducted from January 2020 to January 2023 at the ED of King Abdulaziz medical city in Riyadh. SCA patients who presented with VOC episodes were included in this study. Demographic and clinical data of each patient were retrieved from the electronic medical file. Results: Total of 144 patients were included in the analysis. Out of the total population, 34% were admitted to hospital. Compared to those patients who were not admitted, the number of VOC was more among patients who had been admitted. Around 34% had ED revisit within 30 days and those patients had higher frequency of VOC attacks compared to those who did not revisit the ED. Only 45% of the population received appropriate dosing, 30% received an insufficient dose, and 25% received over the appropriate dose. Receiving the correct dose of morphine reduced the likelihood of ED revisits within 30 days. Conclusions: This study explores trends in VOC among sticklers, highlighting that adequate analgesia is associated with better outcomes. Addressing these variables may lead to improved care and better outcomes for SCA patients

Seroprevalence of SARS-CoV-2 (COVID-19) among Healthcare Workers in Saudi Arabia: Comparing Case and Control Hospitals

Healthcare workers (HCWs) stand at the frontline for fighting coronavirus disease 2019 (COVID-19) pandemic. This puts them at higher risk of acquiring the infection than other individuals in the community. Defining immunity status among health care workers is therefore of interest since it helps to mitigate the exposure risk. This study was conducted between May 20th and 30th, 2020. Eighty-five hospitals across Kingdom of Saudi Arabia were divided into 2 groups: COVID-19 referral hospitals are those to which RT-PCR-confirmed COVID-19 patients were admitted or referred for management (Case-hospitals). COVID-19 nonaffected hospitals where no COVID-19 patients had been admitted or managed and no HCW outbreak (Control hospitals). Next, seroprevalence of severe acute respiratory syndrome coronavirus 2 among HCWs was evaluated; there were 12,621 HCWs from the 85 hospitals. There were 61 case-hospitals with 9379 (74.3%) observations, and 24 control-hospitals with 3242 (25.7%) observations. The overall positivity rate by the immunoassay was 299 (2.36%) with a significant difference between the case-hospital (2.9%) and the control-group (0.8%) (P value <0.001). There was a wide variation in the positivity rate between regions and/or cities in Saudi Arabia, ranging from 0% to 6.31%. Of the serology positive samples, 100 samples were further tested using the SAS2pp neutralization assay; 92 (92%) samples showed neutralization activity. The seropositivity rate in Kingdom of Saudi Arabia is low and varies across different regions with higher positivity in case-hospitals than control-hospitals. The lack of neutralizing antibodies (NAb) in 8% of the tested samples could mean that assay is a more sensitive assay or that neutralization assay has a lower detection limits; or possibly that some samples had cross-reaction to spike protein of other coronaviruses in the assay, but these were not specific to neutralize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)

Epidemiology of proton pump inhibitors therapy: an examination of the use and safety in general practice

Background: Proton pump inhibitors (PPIs) have become the cornerstone of medical treatment for acid-related gastrointestinal disorders. To date, there is a distinct lack of understanding about the recent UK trends in PPI use and evidence about the association between the increased risk of these drugs and the potential adverse effects, in particular the risk of infection, remains questionable. The publication of contradictory findings in several research studies further compounds this situation. Aim and Objectives: This thesis aimed to examine the epidemiology of PPI use in general practices in the UK, and the side effects of PPI, mainly their proposed infective complications. The specific objectives were: • To determine the prevalence and pattern of PPI prescription, and to identify the practices employed to reduce PPI use in the UK general population. • To examine the risk of community-acquired pneumonia before and after the administration of PPI and to assess whether unmeasured confounding explains this association. • To determine whether the mechanism by which PPIs induce an increased risk of infection is supported by the same mechanism acting in another cause of achlorhydria, pernicious anaemia. Methods: This thesis describes work conducted using the UK’s Clinical Practice Research Database (CPRD) and, for some studies in this project, a subset of the CPRD linked to the hospital records from the Hospital Episodes Statistics (HES) database. Firstly, the CPRD was used to estimate the annual prevalence of PPI use during the period 1990-2013. In this study, new users of PPI therapy who had five years of follow-up data were identified to describe patterns of cessation and duration of PPI use. Secondly, cohort (analysed using Cox regression and prior event rate ratio) and self-controlled case series studies were conducted to examine the risk of community-acquired pneumonia and PPI exposure. Thirdly, a cohort of pernicious anaemia patients was used to estimate the risk of infections (community-acquired pneumonia and Clostridium difficile infection) compared to controls to examine whether a reduction in gastric acidity might be the underlying mechanism of the increased risk of these infections. Findings: 1) There was a considerable increase in the administration of PPI prescriptions in UK general practice such that both the period and point prevalence of PPI use increased between 1990 and 2012 (period prevalence increased from 0.2% to 14.8% and point prevalence from 0.03 % to 7.7%). Of new users of PPI therapy, 27% used PPI therapy over a long-term basis (≥1 year continuously), while 4% remained on PPI therapy for five years. Clear attempts to step down the dosage were identified in 41% of long-term users. 2) Among 320, 000 patients, including 160 ,000 new PPI users, the risk of community-acquired pneumonia was 1.67 (95% confidence interval (95%CI) 1.55 to 1.79) times higher for patients exposed to PPIs than it was for the controls. Among the 48,451 PPI-exposed patients with a record of community-acquired pneumonia, the relative incidence rate ratio was 1.19 (95%CI 1.14 to 1.25) in the 30 days after a PPI prescription but was higher in the 30 days before a PPI prescription (1.92, 95%CI 1.84 to 2.00). This reduction in the increased risk in PPI users after prescription was also reflected in the prior event rate of 0.91 (95%CI 0.83 to 0.99). 3) A total of 45,467 pernicious anaemia patients were identified and matched to 449,635 controls. Patients with a pernicious anaemia diagnosis had a higher risk of developing community-acquired pneumonia than the control group (adjusted hazard ratio(HR)1.24, 95%CI 1.21 to 1.26); however, this risk decreased when a stricter definition of pernicious anaemia was applied, and the data was further restricted to incident diagnosis. The findings also suggest that pernicious anaemia patients have a 57% increased risk of Clostridium difficile infection (adjusted HR 1.57, 95% CI 1.40 -1.76) and this association persisted when we limited the analysis to a subgroup with a more restrictive definition of pernicious anaemia diagnosis, or to incident cases. Conclusions: This research revealed that there was a high prevalence of PPI prescribing in the primary care setting and that there are considerable opportunities available to reduce the cost and side effects of PPI use through improving adherence to recommended withdrawal strategies. In addition, the studies investigating the proposed infective complications of PPI use on which we focussed in this thesis add important data to the development of a safety profile of PPI use

Epidemiology of proton pump inhibitors therapy: an examination of the use and safety in general practice

Background: Proton pump inhibitors (PPIs) have become the cornerstone of medical treatment for acid-related gastrointestinal disorders. To date, there is a distinct lack of understanding about the recent UK trends in PPI use and evidence about the association between the increased risk of these drugs and the potential adverse effects, in particular the risk of infection, remains questionable. The publication of contradictory findings in several research studies further compounds this situation. Aim and Objectives: This thesis aimed to examine the epidemiology of PPI use in general practices in the UK, and the side effects of PPI, mainly their proposed infective complications. The specific objectives were: • To determine the prevalence and pattern of PPI prescription, and to identify the practices employed to reduce PPI use in the UK general population. • To examine the risk of community-acquired pneumonia before and after the administration of PPI and to assess whether unmeasured confounding explains this association. • To determine whether the mechanism by which PPIs induce an increased risk of infection is supported by the same mechanism acting in another cause of achlorhydria, pernicious anaemia. Methods: This thesis describes work conducted using the UK’s Clinical Practice Research Database (CPRD) and, for some studies in this project, a subset of the CPRD linked to the hospital records from the Hospital Episodes Statistics (HES) database. Firstly, the CPRD was used to estimate the annual prevalence of PPI use during the period 1990-2013. In this study, new users of PPI therapy who had five years of follow-up data were identified to describe patterns of cessation and duration of PPI use. Secondly, cohort (analysed using Cox regression and prior event rate ratio) and self-controlled case series studies were conducted to examine the risk of community-acquired pneumonia and PPI exposure. Thirdly, a cohort of pernicious anaemia patients was used to estimate the risk of infections (community-acquired pneumonia and Clostridium difficile infection) compared to controls to examine whether a reduction in gastric acidity might be the underlying mechanism of the increased risk of these infections. Findings: 1) There was a considerable increase in the administration of PPI prescriptions in UK general practice such that both the period and point prevalence of PPI use increased between 1990 and 2012 (period prevalence increased from 0.2% to 14.8% and point prevalence from 0.03 % to 7.7%). Of new users of PPI therapy, 27% used PPI therapy over a long-term basis (≥1 year continuously), while 4% remained on PPI therapy for five years. Clear attempts to step down the dosage were identified in 41% of long-term users. 2) Among 320, 000 patients, including 160 ,000 new PPI users, the risk of community-acquired pneumonia was 1.67 (95% confidence interval (95%CI) 1.55 to 1.79) times higher for patients exposed to PPIs than it was for the controls. Among the 48,451 PPI-exposed patients with a record of community-acquired pneumonia, the relative incidence rate ratio was 1.19 (95%CI 1.14 to 1.25) in the 30 days after a PPI prescription but was higher in the 30 days before a PPI prescription (1.92, 95%CI 1.84 to 2.00). This reduction in the increased risk in PPI users after prescription was also reflected in the prior event rate of 0.91 (95%CI 0.83 to 0.99). 3) A total of 45,467 pernicious anaemia patients were identified and matched to 449,635 controls. Patients with a pernicious anaemia diagnosis had a higher risk of developing community-acquired pneumonia than the control group (adjusted hazard ratio(HR)1.24, 95%CI 1.21 to 1.26); however, this risk decreased when a stricter definition of pernicious anaemia was applied, and the data was further restricted to incident diagnosis. The findings also suggest that pernicious anaemia patients have a 57% increased risk of Clostridium difficile infection (adjusted HR 1.57, 95% CI 1.40 -1.76) and this association persisted when we limited the analysis to a subgroup with a more restrictive definition of pernicious anaemia diagnosis, or to incident cases. Conclusions: This research revealed that there was a high prevalence of PPI prescribing in the primary care setting and that there are considerable opportunities available to reduce the cost and side effects of PPI use through improving adherence to recommended withdrawal strategies. In addition, the studies investigating the proposed infective complications of PPI use on which we focussed in this thesis add important data to the development of a safety profile of PPI use

Proton pump inhibitor prescribing patterns in the UK: a primary care database study

Purpose: To determine the prevalence and pattern of proton pump inhibitor (PPI) prescription and the practices employed to reduce PPI use in the UK general population. Methods: The UK's Clinical Practice Research Database was used to identify individuals who were issued with ≥1 PPI prescription during the period 1990–2014. Point and period prevalence of PPI use were estimated annually. Additionally, new users of PPI therapy who had 5 years of follow-up data were included in a cohort analysis to describe patterns of cessation and duration of PPI use. Results: Both the period and point prevalence of PPI use increased between 1990 and 2014 (period prevalence increased from 0.2 to 15.0% and point from 0.03 to 7.7%). A total of 596 334 new users of PPI therapy in the cohort study received 8 784 272 prescriptions. Of these, 26.7% used PPI therapy long term (≥1 year continuously), while 3.9% remained on PPI therapy for 5 years. Clear attempts to step down dose were identified in 39.9% of long-term users, while this was 47% in patients whose initial indication did not mandate long-term use. Conclusion: A considerable increase in PPI use was observed in UK general practice. Of long-term PPI users, 60% did not have an attempt to discontinue or step down. Considerable opportunities may therefore exist to reduce the cost and side effects of PPI use through improving adherence to recommended withdrawal strategies

Symptomatic MERS-CoV infection reduces the risk of future COVID-19 disease; a retrospective cohort study

Abstract Background The general human immune responses similarity against different coronaviruses may reflect some degree of cross-immunity, whereby exposure to one coronavirus may confer partial immunity to another. The aim was to determine whether previous MERS-CoV infection was associated with a lower risk of subsequent COVID-19 disease and its related outcomes. Methods We conducted a retrospective cohort study among all patients screened for MERS-CoV at a tertiary care hospital in Saudi Arabia between 2012 and early 2020. Both MERS-CoV positive and negative patients were followed up from early 2020 to September 2021 for developing COVID-19 infection confirmed by RT-PCR testing. Results A total of 397 participants followed for an average 15 months during COVID-19 pandemic (4.9 years from MERS-CoV infection). Of the 397 participants, 93 (23.4%) were positive for MERS-CoV at baseline; 61 (65.6%) of the positive cases were symptomatic. Out of 397, 48 (12.1%) participants developed COVID-19 by the end of the follow-up period. Cox regression analysis adjusted for age, gender, and major comorbidity showed a marginally significant lower risk of COVID-19 disease (hazard ratio = 0.533, p = 0.085) and hospital admission (hazard ratio = 0.411, p = 0.061) in patients with positive MERS-CoV. Additionally, the risk of COVID-19 disease was further reduced and became significant in patients with symptomatic MERS-CoV infection (hazard ratio = 0.324, p = 0.034) and hospital admission (hazard ratio = 0.317, p = 0.042). Conclusions The current findings may indicate a partial cross-immunity, where patients with symptomatic MERS-CoV have a lower risk of future COVID-19 infection and related hospitalization. The present results may need further examination nationally using immunity markers