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OBJECTIVE:

To estimate all cause mortality and cause specific mortality among patients taking proton pump inhibitors (PPIs).

DESIGN:

Longitudinal observational cohort study.

SETTING:

US Department of Veterans Affairs.

PARTICIPANTS:

New users of PPIs (n=157 625) or H2 blockers (n=56 842).

MAIN OUTCOME MEASURES:

All cause mortality and cause specific mortality associated with taking PPIs (values reported as number of attributable deaths per 1000 patients taking PPIs).

RESULTS:

There were 45.20 excess deaths (95% confidence interval 28.20 to 61.40) per 1000 patients taking PPIs. Circulatory system diseases (number of attributable deaths per 1000 patients taking PPIs 17.47, 95% confidence interval 5.47 to 28.80), neoplasms (12.94, 1.24 to 24.28), infectious and parasitic diseases (4.20, 1.57 to 7.02), and genitourinary system diseases (6.25, 3.22 to 9.24) were associated with taking PPIs. There was a graded relation between cumulative duration of PPI exposure and the risk of all cause mortality and death due to circulatory system diseases, neoplasms, and genitourinary system diseases. Analyses of subcauses of death suggested that taking PPIs was associated with an excess mortality due to cardiovascular disease (15.48, 5.02 to 25.19) and chronic kidney disease (4.19, 1.56 to 6.58). Among patients without documented indication for acid suppression drugs (n=116 377), taking PPIs was associated with an excess mortality due to cardiovascular disease (22.91, 11.89 to 33.57), chronic kidney disease (4.74, 1.53 to 8.05), and upper gastrointestinal cancer (3.12, 0.91 to 5.44). Formal interaction analyses suggested that the risk of death due to these subcauses was not modified by a history of cardiovascular disease, chronic kidney disease, or upper gastrointestinal cancer. Taking PPIs was not associated with an excess burden of transportation related mortality and death due to peptic ulcer disease (as negative outcome controls).

CONCLUSIONS:

Taking PPIs is associated with a small excess of cause specific mortality including death due to cardiovascular disease, chronic kidney disease, and upper gastrointestinal cancer. The burden was also observed in patients without an indication for PPI use. Heightened vigilance in the use of PPI may be warranted.

BACKGROUND:

Knee osteoarthritis (KOA) is common in elderly people, causes pain, loss of physical functioning, and disability. This was a two-arm, superiority, quasi-experimental trial. The aim of this study was to evaluate the effectiveness of a home-based exercise intervention (HBEI) to reduce KOA symptoms and improve the physical functioning of elderly patients.

METHODS:

A total of 171 elderly patients (60 years of age or older) with KOA were recruited from four community centers. Patients from two community centers were randomly assigned to the intervention group (IG) and the other two centers were randomly assigned to the control group (CG). Participants in the IG received a 12-week HBEI (including four 2-h sessions supervised by a physiotherapist and fortnightly telephone support) combined with health education, while patients in the CG only received health education. The participants and physiotherapists were aware of the group assignment and alternative treatment components, but the study's hypotheses were not disclosed to the participants. Pain intensity, joint stiffness, lower-limb muscle strength, balance, mobility, and quality of life were measured before and after the intervention by the same blinded assessor.

RESULTS:

A total of 171 patients (IG: n = 84, CG: n = 87) were enrolled. Data were obtained from 141 patients with an average age of 68 (range, 60-86 years) who completed the 12-week study (IG: n = 71, CG: n = 70). No significant group differences were found in any outcome measures at baseline. At week 12, the pretest/posttest changes 3significant between-group differences in decreases in pain intensity (- 1.60 (CI, - 2.75 to - 0.58)) and stiffness (- 0.79 (CI, - 1.37 to - 0.21)), with the IG exhibiting significantly larger improvements on both measures than the CG. The IG also showed significantly greater improvements on all the secondary outcomes than the CG did.

CONCLUSIONS:

HBEI may be effective for relieving KOA symptoms, increasing the physical functioning, and improving quality of life in community-dwelling KOA elderly patients. A large randomized controlled trial with long-term follow-up is needed to confirm these findings.