Corticosteroid in non-COVID-19 induced community-acquired pneumonia, a meta-analysis.

BACKGROUND: Corticosteroid treatment in non-COVID-19 induced Community-acquired pneumonia (CAP) remains inconclusive. OBJECTIVES: We aimed to assess the role of corticosteroid treatment in CAP. METHODS: We conducted a comprehensive search of online databases, including PubMed, Embase, and Cochrane, to identify articles published from January 1, 2000, to May 5, 2023. Double-blind RCTs were selected. Two authors screened studies and extracted data. The evidence was assessed using the Grading of Recommendations Assessment, Development, and Evaluation approach. RESULTS: We analyzed data from 12 RCTs, involving 2446 patients. Corticosteroids therapy may reduce short-term mortality in patients with severe CAP (sCAP) and shorten the hospital length of stay in patients with CAP. Furthermore, corticosteroids treatment can decrease the risk of requiring mechanical ventilation, developing septic shock and multiple organ dysfunction syndrome (MODS). There were no significant differences between the corticosteroid and control groups concerning gastrointestinal bleeding and nosocomial infection. The use of corticosteroids could increase the risk of hyperglycemia. CONCLUSION: Corticosteroid treatment for sCAP has the potential to provide benefits in reducing short-term mortality, but this conclusion necessitates more evidence. Besides, we found no evidence that strongly prevents us from using corticosteroids in patients with sCAP or those at risk of progressing to sCAP.

Changes in inflammatory markers and efficacy analysis of continuous subcutaneous insulin infusion in senior patients with type 2 diabetes mellitus hospitalized with community-acquired pneumonia: a randomized controlled trial.

OBJECTIVE: The purpose of this study is to analyze the changes in inflammatory markers and efficacy in the treatment of senior patients with type 2 diabetes mellitus (T2DM) and community-acquired pneumonia with continuous subcutaneous insulin infusion (CSII). METHODS: A total of 105 senior patients with T2DM and community-acquired pneumonia, were randomly divided into two groups, viz., treatment group and control group-52 patients in the treatment group were treated with CSII, and 53 patients in the control group with multiple daily insulin injections (MDI). The changes in fasting blood glucose, postprandial blood glucose, total number of white blood cells, neutrophils, percentage of neutrophils, lymphocytes, percentage of lymphocytes, C-reactive protein, serum amyloid A, procalcitonin, interleukin-6 indexes, and the improvement in clinical outcome between the two groups were compared on the 5th and the 10th day of treatment. RESULTS: In the treatment group, there were 52 patients with an average age of (73.7 ± 8.5) years, which included 28 males and 24 females. In the control group, there were 53 patients, with 27 males and 26 females, with an average age of (74.8 ± 8.8) years. On the 5th and the 10th day of the treatment, the fasting blood glucose, postprandial blood glucose, total number of white blood cells, neutrophils, percentage of neutrophils, lymphocytes, percentage of lymphocytes, C-reactive protein, serum amyloid A, procalcitonin and interleukin-6 of the treatment group were better than that of the control group (P < 0.05). The use of CSII was associated with a higher probability of a prompt recovery (P < 0.05). CONCLUSION: The administration of CSII in the treatment of senior patients with T2DM and community-acquired pneumonia can effectively control fasting and postprandial blood glucose, significantly reduce the levels of inflammatory markers, and improve infection treatment efficacy.

Effects of utilization management on health outcomes: evidence from urinary tract infections and community-acquired pneumonia.

BACKGROUND: Utilization management policies are pervasive in the Medicare Part D program. We assess the effect of utilization management restrictions in the Medicare Part D program on the quality of care in two clinical areas - community-acquired pneumonia (CAP) and urinary tract infections (UTI). METHODS: In this study, we identified new cases of CAP and UTI from Medicare claims data from 2010 to 2016. We assessed the relationship between exposure to utilization management for antibiotic medications suitable for treating these conditions and adverse health outcomes, based on the Agency for Healthcare Research and Quality prevention quality indicators. RESULTS: We identified 147,526 cases of CAP and 632,407 UTI cases in our data. In these samples, the adverse event rate varied from 3.6 to 5.7%. The probability of an adverse event increased by 0.75 (p = 0.061) percentage points for each ten percentage point increase in exposure to quantity limits (one form of utilization management) among people with CAP. There was no relationship between utilization management and adverse events in the UTI cohort. CONCLUSIONS: In some circumstances, exposure to utilization management policies-particularly quantity limits-may adversely affect health.

The risk of community-acquired pneumonia in children using gastric acid suppressants.

BACKGROUND: With the increased use of acid suppressants, significant potential complications such as community-acquired pneumonia (CAP) are becoming more apparent. Paradoxically, in spite of an increased focus on potential complications, there is an increased use of acid suppressants in children and a lack of data specifically targeting the association between acid suppressants and CAP. Our main objective was to evaluate the risk of CAP in children using acid suppressants (proton pump inhibitors (PPIs) and/or histamine-2 receptor antagonists (H2RAs)). METHODS: We performed a cohort study using data from the UK Clinical Practice Research Datalink. All patients aged 1 month to 18 years with a prescription of acid suppressants were included and matched to up to four unexposed children. Time-varying Cox proportional hazards models were used to estimate the risk of CAP. The cohort consisted of 84 868 exposed and 325 329 unexposed children. RESULTS: Current use of PPIs and H2RAs was associated with an increased risk of CAP (adjusted hazard ratio 2.05 (95% CI 1.90-2.22) and 1.80 (95% CI 1.67-1.94), respectively). The risk was even greater in patients with respiratory disease. Long-term use (≥211 days) of PPIs and H2RAs led to a significantly greater risk of CAP compared with short-term use (<31 days). After cessation of therapy, the risk remained increased for the following 7 months. CONCLUSION: The use of acid suppressants in children was associated with a doubled risk of CAP. This risk increased with chronic use and respiratory disease, and remained increased after discontinuation of therapy.

Meta-analysis of proton pump inhibitors induced risk of community-acquired pneumonia.

PURPOSE: Proton pump inhibitors (PPIs), one of the most widely used medications, are commonly used to suppress several acid-related upper gastrointestinal disorders. Acid-suppressing medication use could be associated with increased risk of community-acquired pneumonia (CAP), although the results of clinical studies have been conflicting. DATA SOURCES: A comprehensive search of MEDLINE, EMBASE and Cochrane library and Database of Systematic Reviews from the earliest available online year of indexing up to October 2018. STUDY SELECTION: We performed a systematic review and meta-analysis of observational studies to evaluate the risk of PPI use on CAP outcomes. DATA EXTRACTION: Included study location, design, population, the prevalence of CAP, comparison group and other confounders. We calculated pooled odds ratio (OR) using a random-effects meta-analysis. RESULTS OF DATA SYNTHESIS: Of the 2577 studies screening, 11 papers were included in the systematic review and 7 studies with 65 590 CAP cases were included in the random-effects meta-analysis. In current PPI users, pooled OR for CAP was 1.86 (95% confidence interval (CI), 1.30-2.66), and in the case of recent users, OR for CAP was 1.66 (95% CI, 1.22-2.25). In the subgroup analysis of CAP, significance association is also observed in both high-dose and low-dose PPI therapy. When stratified by duration of exposure, 3-6 months PPIs users group was associated with increased risk of developing CAP (OR, 2.05; 95% CI, 1.22-3.45). There was a statistically significant association between the PPI users and the rate of hospitalization (OR, 2.59; 95% CI, 1.83-3.66). CONCLUSION: We found possible evidence linking PPI use to an increased risk of CAP. More randomized controlled studies are warranted to clarify an understanding of the association between PPI use and risk of CAP because observational studies cannot clarify whether the observed epidemiologic association is a causal effect or a result of unmeasured/residual confounding.

Drugs that increase the risk of community-acquired pneumonia: a narrative review.

INTRODUCTION: Community-acquired pneumonia (CAP), a major cause of morbidity and mortality, is the leading infectious cause of death in the developed world. Population-based studies and systematic reviews have identified a large number of risk factors for the development of pneumonia in adults. In addition to age, lifestyle habits, and comorbidities, some forms of pharmacotherapy may also increase the risk for CAP. AREAS COVERED: MEDLINE, CENTRAL, and Web of Science were used in 2017 to search for case-control, cohort studies, as well as randomized controlled trials and meta-analysis that involved outpatient proton pump inhibitors (PPIs), inhaled corticosteroids (ICSs), antipsychotics, oral antidiabetics, and CAP diagnosis in patients aged >18 years. EXPERT OPINION: Our review confirmed that the use of ICSs, PPIs or antipsychotic drugs was independently associated with an increased risk for CAP. We also identified a positive association between specific oral antidiabetics and the development of pneumonia.

Adverse outcomes of long-term use of proton pump inhibitors: a systematic review and meta-analysis.

The association between the long-term use of proton pump inhibitors (PPIs) and the risks of various diseases remains controversial. Therefore, the primary objective of this study was to quantify the associations as presented in the literature and to also provide this information to healthcare professionals and patients about their potentially adverse effects. In July 2016, we searched through Medline (PubMed), Embase, and the Cochrane Library from inception using common keywords. We included observational studies that provided risk estimates on the long-term use of PPIs and their adverse effects. Overall, 43 studies were included in the systematic review, of which 28 studies were also included in the random effect meta-analysis. Odds of community-acquired pneumonia, hip fracture, and colorectal cancer were 67% [odds ratio (OR)=1.67; 95% confidence interval (CI): 1.04-2.67], 42% (OR=1.42; 95% CI: 1.33-1.53), and 55% (OR=1.55; 95% CI: 0.88-2.73) higher in patients with long-term PPIs use compared with patients who did not use PPIs. Although the use of PPIs provides short-term health benefits, their prolonged use is associated with minor and also potentially major adverse health outcomes. Hence, we strongly recommend that the prescription of PPIs should be done with caution to improve the medication's efficacy and patients' safety.

Proton-Pump Inhibitors and Long-Term Risk of Community-Acquired Pneumonia in Older Adults.

OBJECTIVES: To estimate associations between long-term use of proton pump inhibitors (PPIs) and pneumonia incidence in older adults in primary care. DESIGN: Longitudinal analyses of electronic medical records. SETTING: England PARTICIPANTS: Individuals aged 60 and older in primary care receiving PPIs for 1 year or longer (N=75,050) and age- and sex-matched controls (N=75,050). MEASUREMENTS: Net hazard ratios for pneumonia incidence in Year 2 of treatment were estimated using the prior event rate ratio (PERR), which adjusts for pneumonia incidence differences before initiation of treatment. Inverse probability weighted models adjusted for 78 demographic, disease, medication, and healthcare usage measures. RESULTS: During the second year after initiating treatment, PPIs were associated with greater hazard of incident pneumonia (PERR-adjusted hazard ratio=1.82, 95% confidence interval=1.27-2.54), accounting for pretreatment pneumonia rates. Estimates were similar across age and comorbidity subgroups. Similar results were also obtained from propensity score- and inverse probability-weighted models. CONCLUSION: In a large cohort of older adults in primary care, PPI prescription was associated with greater risk of pneumonia in the second year of treatment. Results were robust across alternative analysis approaches. Controversies about the validity of reported short-term harms of PPIs should not divert attention from potential long-term effects of PPI prescriptions on older adults.

What is the long term acid inhibitor treatment in gastroesophageal reflux disease? What are the potential problems related to long term acid inhibitor treatment in gastroesophageal reflux disease? How should these cases be followed?

The meta-analyses of observational studies (OBS) showed the risk of any fracture and hip fracture slightly increased with proton pump inhibitor (PPI) treatment depending on the dose and regardless of time. This was not observed with histamine-2 receptor antagonists (H2RA). The risk of bacterial overgrowth and spontaneous bacterial peritonitis were increased with PPI therapy, but not with H2RA. In meta-analyses of OBS, a slight increase was observed in the risk of community-acquired pneumonia (CAP) in the early stages (<1 month) of PPI use and particularly at high doses. In a five-year LOTUS study, no difference was found in vitamin B12, folic acid, vitamin D, and calcium values in terms of the initial and end of follow-up levels. No increase in the risk of premalignant gastric lesions was observed in the meta-analysis of RCTs in which PPI treatment (≥6 months) was given to Helicobacter pylori negative patients. The risk of hypomagnesemia with PPI use was increased in patients having GFR<60, using diuretics, and over 65 years of age. Quasi-experimental studies showed a reduced zinc absorption with PPI use. In the meta-analysis of OBS, long-term (>1 year) PPI use increased the risk of fundic polyps, but no risk was found in shorter use. The meta-analyses of RCTS showed no difference between PPI and surgery or placebo arms and between the arms of H2RA and placebo in terms of all side effects. No difference was found between the PPI and H2RA arms both in all and serious adverse effects.

Use of oral antidiabetic agents and risk of community-acquired pneumonia: a nested case-control study.

AIMS: To evaluate the association between use of different oral antidiabetic agents (OAD) and the risk of community-acquired pneumonia (CAP) in patients with type-2 diabetes (T2DM). METHODS: Case-control study nested in a cohort of patients with T2DM and use of OAD between 2002 and 2013, based in a Spanish general practice research database. Cases were people diagnosed with T2DM, aged >18 years and with a validated diagnosis of CAP between 2002 and 2013. Ten controls were matched on age, sex and calendar year. Odds ratio (OR) of CAP was estimated comparing patients treated with: (1) metformin vs. other monotherapies or no antidiabetic treatment; (2) metformin + sulfonylureas vs. other antidiabetic combinations. OR of CAP was also assessed according to antidiabetic treatment duration. RESULTS: From a cohort of 76 009 T2DM patients, we identified 1803 cases of CAP. No difference in the incidence of CAP was observed when comparing any OAD in monotherapy with metformin. Compared with current use of metformin + sulfonylurea, thiazolidinediones + metformin was associated with an increased risk of CAP (adjusted OR = 2.48, 95% CI 1.40-4.38). The use of any combination with thiazolidinediones was also associated with higher risk of CAP (adjusted OR = 2.00, 95% CI 1.22-3.28). Current use of DPP-4 inhibitors was not associated with an increased risk of CAP. CONCLUSIONS: No differences in the incidence of CAP were observed between the use of OAD in monotherapy vs. metformin. Thiazolidinedione use in combination was associated with an increase in the risk of CAP when compared to metformin + sulfonylureas. The use of DPP-4 inhibitors was not associated with an increased risk of CAP.

Anticholinergic Medication Use and Risk of Pneumonia in Elderly Adults: A Nested Case-Control Study.

OBJECTIVES: To examine the risk of community-acquired pneumonia (CAP) associated with the use of anticholinergic medications in elderly adults. DESIGN: Nested case-control study. SETTING: A regional Medicare Advantage healthcare plan (2009-2010). PARTICIPANTS: Participants were Medicare Advantage Plan enrollees aged 65 and older with at least one inpatient and one outpatient claim with no history of CAP between January 1 and June 30, 2009. Cases were identified as enrollees with an incident diagnosis of CAP, between July 1, 2009, and December 31, 2010 (n = 291). Four age- and sex-matched controls (n = 1,164) were identified per case using incidence density sampling. MEASUREMENTS: Anticholinergic prescription 30 days preceding the event date was the primary exposure. Anticholinergic exposure was defined based on the Anticholinergic Drug Scale (ADS). A conditional logistic regression model stratified on matched case-control sets was used, with exposure to a Level 1, 2, or 3 anticholinergic on the ADS as the main independent variable; CAP as the main outcome variable; and risk factors for CAP as additional explanatory variables. RESULTS: After controlling for risk factors, overall use of anticholinergic medications was significantly associated with risk of pneumonia (odds ratio (OR) = 1.65, 95% confidence interval (CI) = 1.20-2.28). The risk of pneumonia remained significant across the different exposure periods, although use of higher-level (ADS Level 2 or 3) anticholinergics was not associated with pneumonia risk (OR = 1.16, 95% CI = 0.70-1.96). CONCLUSION: Overall use of anticholinergic medications, but not higher-level drugs, was associated with greater risk of CAP compared to no use after controlling for other factors. More research is needed to better understand the role of potent anticholinergic medications on pneumonia risk in elderly adults.

Risk of community-acquired pneumonia with outpatient proton-pump inhibitor therapy: a systematic review and meta-analysis.

BACKGROUND: Proton-pump inhibitors (PPIs) are among the most frequently prescribed medications. Community-acquired pneumonia (CAP) is a common cause of morbidity, mortality and healthcare spending. Some studies suggest an increased risk of CAP among PPI users. We conducted a systematic review and meta-analysis to determine the association between outpatient PPI therapy and risk of CAP in adults. METHODS: We conducted systematic searches of MEDLINE, EMBASE, CINAHL, Cochrane Central Register of Controlled Trials, Scopus and Web of Science on February 3, 2014. Case-control studies, case-crossover, cohort studies and randomized controlled trials reporting outpatient PPI exposure and CAP diagnosis for patients ≥18 years old were eligible. Our primary outcome was the association between CAP and PPI therapy. A secondary outcome examined the risk of hospitalization for CAP and subgroup analyses evaluated the association between PPI use and CAP among patients of different age groups, by different PPI doses, and by different durations of PPI therapy. RESULTS: Systematic review of 33 studies was performed, of which 26 studies were included in the meta-analysis. These 26 studies included 226,769 cases of CAP among 6,351,656 participants. We observed a pooled risk of CAP with ambulatory PPI therapy of 1.49 (95% CI 1.16, 1.92; I2 99.2%). This risk was increased during the first month of therapy (OR 2.10; 95% CI 1.39, 3.16), regardless of PPI dose or patient age. PPI therapy also increased risk for hospitalization for CAP (OR 1.61; 95% CI: 1.12, 2.31). DISCUSSION: Outpatient PPI use is associated with a 1.5-fold increased risk of CAP, with the highest risk within the first 30 days after initiation of therapy. Providers should be aware of this risk when considering PPI use, especially in cases where alternative regimens may be available or the benefits of PPI use are uncertain.

Anticholinergic medications and risk of community-acquired pneumonia in elderly adults: a population-based case-control study.

OBJECTIVES: To determine whether use of anticholinergics is associated with risk of community-acquired pneumonia in older adults. DESIGN: Population-based case-control study. SETTING: An integrated healthcare delivery system in Washington State. PARTICIPANTS: Data from a nested case-control study of community-dwelling immunocompetent adults aged 65 to 94 were analyzed. Pneumonia cases (n=1,039) were ascertained according to International Classification of Diseases, Ninth Revision, codes from 2000 to 2003 and validated using chart review. Controls (n=2,022) were matched 2:1 to cases according to age, sex, and year. MEASUREMENTS: Anticholinergic medication exposure was ascertained using prescription data; acute use was defined as one or more prescription fills 90 days or less before the index date (date of pneumonia diagnosis), past use was defined as one or more prescription fills within the prior year but none within 90 days, and chronic use was defined as three or more prescription fills within the prior year. The reference group was those with no fills in the prior year. Conditional logistic regression was used to analyze the association between anticholinergic use and pneumonia, adjusted for comorbidities. RESULTS: Acute use of anticholinergics was observed in 59% of cases and 35% of controls (adjusted odds ratio (aOR)=2.55, 95% confidence interval (CI)=2.08-3.13) and past use in 17% of cases and 23% of controls (aOR=1.19, 95% CI=0.92-1.53). Chronic use of anticholinergics was observed in 53% of cases and 36% of controls (aOR 2.07, 95% CI=1.68-2.54). Results were not different for high- and low-potency anticholinergic medications. CONCLUSION: In older adults, anticholinergic medication use is associated with pneumonia risk, adding to substantial evidence suggesting that these medications are high risk.

Proton pump inhibitors and histamine-2 receptor antagonists in the intensive care setting: focus on therapeutic and adverse events.

INTRODUCTION: Histamine-2 receptor antagonists (H2RA) and proton pump inhibitors (PPI) are frequently used to prevent stress-related mucosal bleeding (SRMB). A paucity of data implicates these agents with pneumonia and Clostridium difficile infection (CDI). AREAS COVERED: This review comparatively evaluates the effectiveness of H2RAs and PPIs and delineates their associations with these infectious complications. A literature review through 30 September 2014 was performed. EXPERT OPINION: The rate of SRMB is declining, likely due better resuscitation strategies and the early provision of enteral nutrition. Therefore, gastric acid-suppressing therapies arguably reduce SRMB. However, they may contribute to pneumonia and CDI. The risks of these infectious complications depend on the extent of acid suppression and may vary by patient population. PPIs are associated with the greatest hazard for these infections, likely because they provide stronger acid suppression. Intermittent administration of H2RAs has theoretical advantages over continuous H2RA or PPI therapies as this dosing strategy does not fully suppress gastric acid and may limit infection risk. Placebo-controlled studies are warranted because clinical equipoise exists as the detrimental outcomes of these infections may outweigh the benefit of preventing SRMB given the infrequent occurrence of SRMB.

Proton pump inhibitors and the risk of hospitalisation for community-acquired pneumonia: replicated cohort studies with meta-analysis.

OBJECTIVE: Previous observational studies suggest that the use of proton pump inhibitors (PPIs) may increase the risk of hospitalisation for community-acquired pneumonia (HCAP). However, the potential presence of confounding and protopathic biases limits the conclusions that can be drawn from these studies. Our objective was, therefore, to examine the risk of HCAP with PPIs prescribed prophylactically in new users of non-steroidal anti-inflammatory drugs (NSAIDs). DESIGN: We formed eight restricted cohorts of new users of NSAIDs, aged ≥40 years, using a common protocol in eight databases (Alberta, Saskatchewan, Manitoba, Ontario, Quebec, Nova Scotia, US MarketScan and the UK's General Practice Research Database (GPRD)). This specific patient population was studied to minimise bias due to unmeasured confounders. High-dimensional propensity scores were used to estimate site-specific adjusted ORs (aORs) for HCAP at 6 months in PPI patients compared with unexposed patients. Fixed-effects meta-analytic models were used to estimate overall effects across databases. RESULTS: Of the 4,238,504 new users of NSAIDs, 2.3% also started a PPI. The cumulative 6-month incidence of HCAP was 0.17% among patients prescribed PPIs and 0.12% in unexposed patients. After adjustment, PPIs were not associated with an increased risk of HCAP (aOR=1.05; 95% CI 0.89 to 1.25). Histamine-2 receptor antagonists yielded similar results (aOR=0.95, 95% CI 0.75 to 1.21). CONCLUSIONS: Our study does not support the proposition of a pharmacological effect of gastric acid suppressors on the risk of HCAP.

Inhaled corticosteroids and risk of recurrent pneumonia: a population-based, nested case-control study.

BACKGROUND: Studies have suggested an increased risk of pneumonia with inhaled corticosteroid (ICS) use, although this association is inconsistent. We evaluated the risk of recurrent pneumonia associated with ICS use in a high-risk population of individuals who survived an episode of pneumonia. METHODS: Clinical and 5-year follow-up data were collected on all adults aged ≥ 65 years with pneumonia over a period of 2 years. Using a nested case-control design, first cases (patients with recurrent pneumonia ≥ 30 days after initial episode) and then controls (free of pneumonia and matched on age, sex, and chronic obstructive pulmonary disease [COPD]) were identified. ICS use was classified as never, past (remote, only before initial pneumonia), or current. Our primary outcome measure was recurrent pneumonia assessed using conditional multivariate logistic regression after adjustment of demographics and clinical data. RESULTS: During 5 years of follow-up, 653 recurrent pneumonia cases were matched with 6244 controls; mean age was 79 (SD, 8) years, 3577 (52%) were male, 2652 (38%) had COPD, and 2294 (33%) ever used ICS. Overall, 123 of 870 (14%) current ICS users had recurrent pneumonia compared to 395 of 4603 (9%) never-users (adjusted odds ratio, 1.90; 95% confidence interval, 1.45-2.50; P < .001; number need to harm = 20). Conversely, there was no association between past (remote) use of ICS and pneumonia: 9% of past users versus 9% never-users (P = .36). CONCLUSIONS: ICS use was associated with a 90% relative increase in the risk of recurrent pneumonia among high-risk pneumonia survivors. This should be considered when prescribing ICS and when deciding which patients might need more intensive follow-up.