Chronic Use Of Proton Pump Inhibitors Research Articles

Effect of Chronic Proton Pump Inhibitor Use on Serum Magnesium Levels in Pediatric Patients

Effect of Chronic Proton Pump Inhibitor Use on Serum Magnesium Levels in Pediatric Patients

Consequences and Complications of Long Term Use of proton Pump Inhibitors

Proton Pump Inhibitors (PPIs) have become one of the most commonly prescribed category of drugs in both primary as well as tertiary care, commonly for gastric acid-related disorders. It is advised that no more than three 14-day treatment courses with PPIs should be used in one year. The two main indications for the long-term use of PPIs are gastro esophageal reflux disease and concomitant use with the maintenance dose of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs). PPIs block the gastric H + ,K + -ATPase, inhibiting gastric acid secretion. If the drug is discontinued, there is a potential risk for rebound hypersecretion, creating a sort of dependency on the drug because the body is acclimated to having acid suppressed. The potential adverse effects relating to PPIs are Hypochlorhydria (11%- 24%) leading to pernicious anaemia and bone fractures(elevated risk after 7 years of continuous PPI therapy) and Hypergastrinemia (20%- 25%). Review of various literatures have shown that long-term PPI use is associated with upto fourfold increase in the risk of fundic gland polyps(upto 36%). Other potential consequences of chronic PPI use are malabsorption of key minerals (calcium and magnesium) in the body, increased risk of infections, cancer (5%-12%), severe drug interactions and birth defects. The most commonly seen infections with chronic PPI use are Enteric Infections and Community Acquired Pneumonia(CAP).A case-controlled study discovered an associated 2.5-fold risk of infection with concomitant PPI therapy. A population-based case-controlled study of7642 CAP cases identified, 11% were chronic PPI users. Another study found that 50% of chronic PPI users are more likely to develop CAP.Elderly, malnourished, immune-compromised, chronically ill, and osteoporotic patients theoretically could be at increased risk from longterm therapy. In conclusion, based on the above evidences, pharmacists are poised to educate patients about the benefits and risks associated with chronic PPI use.

Long-Term Trends in Esophageal Candidiasis Prevalence and Associated Risk Factors with or without HIV Infection: Lessons from an Endoscopic Study of 80,219 Patients.

BackgroundThe prevalence of candida esophagitis (CE) might be changing in an era of highly active antiretroviral therapy (HAART) among HIV-infected patients or today’s rapidly aging society among non-HIV-infected patients. However, few studies have investigated long-term CE trends, and CE risk factors have not been studied in a large sample, case-control study. This study aimed to determine long-term trends in CE prevalence and associated risk factors for patients with or without HIV infection.MethodsTrends in CE prevalence were explored in a cohort of 80,219 patients who underwent endoscopy between 2002 and 2014. Risks for CE were examined among a subcohort of 6,011 patients. In risk analysis, we assessed lifestyles, infections, co-morbidities, immunosuppressants, and proton-pump inhibitors (PPIs). All patients were tested for HIV, hepatitis B or C virus, and syphilis infection. For HIV-infected patients, sexual behavior, CD4 cell count, history of HAART were also assessed.ResultsCE prevalence was 1.7% (1,375/80,219) in all patients, 9.8% (156/1,595) in HIV-infected patients, and 1.6% (1,219/78,624) in non-HIV-infected patients. CE prevalence from 2002-2003 to 2012-2014 tended to increase in non-HIV-infected patients (0.6% to 2.5%; P<0.01) and decrease in HIV-infected patients (13.6% to 9.0%; P=0.097). Multivariate analysis revealed increasing age (odds ratio [OR], 1.02; p=0.007), HIV infection (OR, 4.92; p<0.001), and corticosteroid use (OR, 5.90; p<0.001) were significantly associated with CE, and smoking (OR, 1.32; p=0.085) and acetaminophen use (OR, 1.70; p=0.097) were marginally associated. No significant association was found with alcohol consumption, hepatitis B or C virus, syphilis, diabetes mellitus, cardiovascular disease, cerebrovascular disease, chronic kidney disease, liver cirrhosis, anticancer, or PPIs use. In HIV-infected patients, CD4 cell count <100/μL (OR, 4.83; p<0.001) and prior HAART (OR, 0.35; p=0.006) were independently associated with CE, but sexual behavior was not. Among corticosteroid users, CE was significantly associated with higher prednisone-equivalent dose (p=0.043 for trend test).ConclusionsThis large, endoscopy-based study demonstrated that CE prevalence increased in non-HIV-infected patients but decreased in HIV-infected patients over 13 years. Risk analysis revealed that increasing age, HIV infection, and corticosteroids use, particularly at higher doses, were independently associated with CE, but alcohol, other infections, diabetes, anticancer drugs, and PPIs use were not.

Influence of proton pump inhibitors on gastritis diagnosis and pathologic gastric changes.

To investigate the influence of proton pump inhibitors (PPIs) exposure on the diagnosis of Helicobacter pylori (H. pylori) gastritis and intestinal metaplasia. Chronic PPI use is associated with masking of H. pylori infection. Patients with H. pylori infection are predisposed to gastric and duodenal ulcers, and long-term infection with this organism has been associated with gastric mucosal atrophy and serious long-term complications, such as gastric lymphoma and adenocarcinoma. Three hundred patients diagnosed with gastritis between January 2008 and April 2010 were included in our study. The computerized medical database of these patients was reviewed retrospectively in order to assess whether the type of gastritis diagnosed (H. pylori vs non-H. pylori gastritis) is influenced by PPI exposure. H. pylori density was graded as low, if corresponding to mild density following the Updated Sydney System, or high, if corresponding to moderate or severe densities in the Updated Sydney System. Patients were equally distributed between males and females with a median age at the time of diagnosis of 50 years old (range: 20-87). The histological types of gastritis were classified as H. pylori gastritis (n = 156, 52%) and non-H. pylori gastritis (n = 144, 48%). All patients with non-H. pylori gastritis had inactive chronic gastritis. Patients with no previous PPI exposure were more likely to be diagnosed with H. pylori gastritis than those with previous PPI exposure (71% vs 34.2%, P < 0.001). Intestinal metaplasia was more likely to be detected in the latter patients (1.4% vs 6.5%, P = 0.023). Multivariate analysis has also demonstrated that in the presence of previous PPI exposure (OR = 0.217, 95%CI: 0.123-0.385), GERD (OR = 0.317, 95%CI: 0.132-0.763, P = 0.01), alcohol intake (OR = 0.396, 95%CI: 0.195-0.804, P = 0.01), the detection of H. pylori was less likely. Chronic use of PPIs may mask H. pylori infections promoting the diagnosis of non-H. pylori gastritis and leads to a significant drop in H. pylori densities and to an increased risk of intestinal metaplasia. The use of PPIs masks H. pylori infection, promotes the diagnosis of non-H. pylori inactive chronic gastritis diagnosis, and increases the incidence of intestinal metaplasia.

Mo1153 Gender Differences in Proton Pump Inhibitors (PPI) Dose Requirements for GERD: A Double-Blind Randomized Trial

Purpose: Current literature on the risk of fractures in patients on proton pump inhibitors (PPI) has yielded mixed results. This study evaluated the association between PPI use and incidence of osteoporotic fractures in male patients. Methods: Retrospective chart review was conducted at the Phoenix Veterans Affairs Health Care System from January 1, 1995 to July 23, 2012 for this case control study. Inclusion criteria included all male patients who were diagnosed as having a hip, wrist or spine fracture. A 3:1 sample of controls (patients without fractures) was drawn from the same period. Demographic information including age, body mass index (BMI), ethnicity, tobacco, and alcohol use were collected for all patients. Thiazides, bisphosphonates and steroid use data were also collected for patients with a fracture and PPI use. Results: A total of 246 male patients, mean age 65.3 years, suffered a hip (20%), wrist (30%) or spine (50%) fracture during the study period. Of these, 33 (13.4%) used chronic PPI's prior to the fracture. Among patients without fractures, 107 (14.1%) were using PPI's. Increasing BMI and PPI use are protective against hip fracture, (p<0.001). PPI's are protective against spine fracture and more so with increasing age, (p<0.05). For males not on PPI, incidence of spine fracture significantly increases with age. For those not taking bisphosphonate, taking PPIs reduces the risk of wrist fracture (p<0.001). Alcohol use was higher in the fracture group (74% vs 59%), and smoking rates were similar in both groups: 70% and 66% with and without fractures, respectively. Average BMI was 26 in both groups. Multivariable logistic regression modeling revealed a significant association of fracture with age and BMI, which depend on the fracture location. Conclusion: This study found no significant evidence of an association between chronic PPI use and hip, wrist or spine fracture in men over 55 years old. PPI use appears to be protective.

Endoscopic and histopathologic gastric changes in chronic users of proton-pump inhibitors.

Proton-pump inhibitors have been used for at least two decades. They are among the most commonly sold drugs in the world. However, some controversy remains about the indications for their use and the consequences of their prolonged use. To evaluate and compare the endoscopic and histopathologic gastric changes in chronic users of proton-pump inhibitors to changes in non-users. A prospective study performed at a tertiary Public Hospital involving 105 patients undergoing upper-gastrointestinal endoscopy. Subjects included 81 proton-pump inhibitor users and 24 non-users (control group). Biopsies of the antral-type mucosa, the antral-fundic transition, and the fundus were evaluated by the Sydney System. The presence of erosion or ulceration, lymphatic follicles, reactive gastropathy, and polypoid or epithelial hyperplasia was also determined. Serum levels of gastrin were measured. We found two polyps, one in each group, both of which were negative for Helicobacter pylori. There were two cases of parietal cell hyperplasia in users of proton-pump inhibitors. Gastrin was elevated in 28 users of proton-pump inhibitors and in four members of the control group. We did not find statistically significant differences in the endoscopic or histopathologic findings between the two groups. Chronic use of proton-pump inhibitors for the duration examined was not associated with significant gastric changes. An interesting finding was that the 4 chronic users of proton-pump inhibitors who had serum gastrin levels above 500 pg/mL also had positive serology for Chagas disease.

Use of proton pump inhibitors in older subjects: Risk of adverse clinical outcomes and potential mechanisms

Background In the last 2 decades, it was observed a widely increased use of proton pump inhibitors (PPIs) especially in older populations. Despite the fact that PPIs are superior to histamine receptor antagonists in treating gastroesophageal reflux disease (GERD) and peptic ulcers, the chronic use of PPIs has been associated with adverse clinical outcomes including higher risk of fractures and Clostridium difficile infections. In vitro studies have shown that PPIs negatively modulate the bioactivity of insulin-like growth factor-1 (IGF-1), anabolic hormone and nutritional marker. However, whether or not PPIs use has negative influence on survival and independence of activities of daily living (ADL) and the mechanisms underlying these hypothesized associations are still poorly known. Aims of the study The aims of the study were to test the relationship between the use of PPIs and adverse clinical outcomes (mortality and rehospitalization, loss of ADL) and the association between use of PPIs and cortical and trabecular bone mineral density, IGF-1 bioactivity in older patients of 2 different populations. Methods In 491 patients (mean age 80.1 ± 5.9 years), categorized as PPI users and non users, discharged from 11 acute care medical wards and 3 long-term care/rehabilitation units, we tested the relationship between use of PPIs and 1- year mortality or combined end-point mortality and rehospitalization and incident dependency by using time-dependent Cox proportional hazard regression models and after propensity score matching. The association between use of PPIs, IGF-1 and bone mineral density was estimated by multivariate regression model adjusted for multiple confounders in 938 subjects (413 men and 525 women) aged ≥ 65 years, from the InCHIANTI Study, with complete information on tibial pQCT, IGF-1, IGF-binding protein-1 (IGFBP-1) and medications. Results In the hospitalized population the use of PPIs was independently associated with mortality (hazard ratio, 1.51 [95% CI, 1.03–2.77]) but not with the combined end point (1.49 [0.98–2.17]). An increased risk of mortality was observed among patients exposed to high-dose PPIs vs none (hazard ratio, 2.59 [95% CI, 1.22–7.16]). Use of PPIs was significantly associated with functional decline either before (OR = 1.75; 95% CI = 1.17–2.60) and after propensity score matching (OR = 2.44; 95% CI = 1.36–4.41). In the InCHIANTI population, PPI users showed age- and sex-adjusted lower vBMDt than nonusers (180.5 ± 54.8 vs. 207.9 ± 59.4, P = 0.001). The inverse association between PPI use and vBMDt remained almost unchanged after adjustment for multiple confounders. There was no statistically significant difference in vBMDc between PPI users and nonusers. PPI users had lower IGF-1 levels (81,9 [61,1-113,8]) than non-users (110 [77,8–148,6]), P = 0.02. After further adjustment for BMI, liver function, number of medications, caloric intake and IGFBP-1, the relationship between use of PPI and IGF-1 remained statistically significant (β ± SE = –18,09 ± 9,38, P = 0,05). Conclusions In older persons discharged from acute care hospitals, the chronic use of PPIs is associated with increased 1-year mortality and functional decline. The lower trabecular bone mineral density and IGF-1 levels found in PPI users are potential mechanisms explaining this association.

Opportunistic Screening of Vitamin B12 Deficiency in IT Professionals Presenting for Routine Health Check-up.

Vitamin B12 deficiency is mainly diagnosed in symptomatic patients. However, the deficiency may also be prevalent in asymptomatic patients. Our aim was to study the prevalence of Vit B12 deficiency in IT professionals (Information Technology Professionals from Software industry) who presented for routine health screening and to correlate the deficiency to various parameters. This was single centre, observational study comprising of 84 IT professionals. The data was collected in structured format. The study was designed to identify prevalence of Vit B12 deficiency and correlate to other factors such as type of diet, income level & regular use of medication (such as Antacid & Metformin). Total 28 individuals were found to be deficient (33.34%). Prevalence of Vit B12 deficiency amongst Vegetarian and non vegetarian diet adhering subjects was 47.5% and 20.45% respectively. B12 deficiency was also prevalent in high income age group. Further chronic intake of PPI (Proton pump inhibitor) and Metformin was associated with prevalence of 37.5% and 33.34% in the present study. During health screening of IT Professionals, significant prevalence of Vit B12 deficiency was noted across all income groups & non vegetarian diet consuming subjects also. There is significant correlation between Vit B12 deficiency with chronic use of PPI and Metformin.

Proton-pump inhibitor use is associated with lower urinary magnesium excretion.

Although multiple recent studies have confirmed an association between chronic proton-pump inhibitor (PPI) use and hypomagnesaemia, the physiologic explanation for this association remains uncertain. To address this, we investigated the association of PPI use with urinary magnesium excretion. We measured 24-hour urine magnesium excretion in collections performed for nephrolithiasis evaluation in 278 consecutive ambulatory patients and determined PPI use from contemporaneous medical records. There were 50 (18%) PPI users at the time of urine collection. The mean daily urinary magnesium was 84.6 ± 42.8 mg in PPI users, compared with 101.2 ± 41.1 mg in non-PPI users (P = 0.01). In adjusted analyses, PPI use was associated with 10.54 ± 5.30 mg/day lower daily urinary magnesium excretion (P = 0.05). Diuretic use did not significantly modify the effect of PPI on urinary magnesium. As a control, PPI use was not associated with other urinary indicators of nutritional intake. Our findings suggest that PPI use is associated with lower 24-hour urine magnesium excretion. Whether this reflects decreased intestinal uptake due to PPI exposure, or residual confounding due to decreased magnesium intake, requires further study.

H2 Blockers Revisited: Any Role in Barrett’s Esophagus (BE) Management and Prevention of Esophageal Adenocarcinoma (EAC)?

Introduction: Long-term use of H2 blockers or proton pump inhibitors (PPI) was reported to be a marker for increased risk of EAC. This may be due to the underlying disease rather than the drugs per se. In fact, PPI use seems to lower the risk of dysplasia in BE. With the recent concerns raised about harmful consequences of chronic PPI use, there is renewed interest about other means of acid suppression. Henceforth, we aimed to study the effect of H2 blockers in our Barrett’s cohort. Methods: Barrett’s Registry was started in 1979 and included demographic data such as age, sex, race, endoscopic findings such as length of BE, hiatal hernia size and histological findings. We included data from BE registry of patients from 2002 to 2013. Medication use such as PPI, aspirin, H2 blockers, lipid lowering agents was obtained by chart review. Results: The cohort consisted of 2,341 patients with a mean age of 60± 13 years, of which 1756 (75%) were men and 2198 (95.8%) were Caucasians. Mean BE length was 3.2±3.5 cm and hiatal hernia size was 2±2.2 cm. Use of PPIs was observed in 825 (35.2%) and H2 blockers in 360 (15.4%). The histological findings on index biopsy are presented in table. Data from 1,034 patients was available for follow-up. There were 836 patients in no dysplasia group and 198 patients in LGD group. No dysplasia group: Median follow-up time was 47 [24, 90] months during which 22% had progression (134 to LGD, 26 to HGD and 21 to EAC). After adjusting for age, gender, BE length and hernia size, H2 blocker users had 53% lower hazard of progression to HGD/EAC than nonusers HR= 0.47(0.22, 0.97) p=0.042. LGD group: Median follow-up time was 30 [9, 56] months during which time 24% had progression (16 to HGD and 33 to adenocarcinoma). No statistically significant association was observed for progression to HGD/EAC HR=0.65 (0.32, 1.4), p=0.26.Table 1: Baseline Prevalence of DysplasiaConclusion: H2 blocker use was observed less frequently than PPI use in our Barrett’s cohort. HGD/EAC were less prevalent in H2 blocker users than non-users. In patients without dysplasia, H2 blockers had lower risk of progression to HGD/EAC. Hence, it is reasonable to conclude that H2 blockers are associated with lower risk of dysplasia and progression to HGD/EAC in patients with BE.

Nouvel effet indésirable fréquent des inhibiteurs de la pompe à protons chez le sujet âgé : l’hyponatrémie modérée

Hyponatremia is a rare side effect described in the product characteristics of proton pump inhibitors (PPIs). Hyponatremia in the elderly (>65years) was assessed in patients with exposure to PPIs for at least one year compared to controls not exposed to PPIs counterparts. Included 145 patients, twenty-four patients (16.6%) had moderate hyponatremia ([120-134] mEq/L). Forty-eight patients (33.1%) were treated with PPIs. In the end, 31.3% [18.7%-46.3%] of the treated population for more than a year by PPI suffered moderate hyponatremia against only 9.3% [14.3%-16.9%] in the rest of the population, giving an odds ratio of 4.4 ([1.8-11.1], p=0.001). The relationship between hyponatremia dose was not significant (R(2)=0.05, p=0.74). By our study, we show that the risk of moderate hyponatremia is increased by chronic use of PPI in the elderly population. We also specify a notion of prevalence between 18.7% and 46.3%.

78-jährige Patientin mit Unwohlsein, Schwindel, Apraxie und Krampfanfall unter Protonenpumpeninhibitortherapie

We report about a female patient with severe hypomagnesemia under therapy with proton pump inhibitors (PPI) who presented with a cerebral seizure. Chronic use of PPIs can cause hypomagnesemia. Because of mostly unspecific symptoms which become symptomatic only with severe deficiency, the disease pattern is underdiagnosed. Hypomagnesemia is currently coming increasingly more to the forefront of medical literature.

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Introduction: There is a paucity of trials studying the role of intravenous (IV) proton pump inhibitors (PPIs) for stress ulcer prophylaxis (SUP) in the critically ill, and no trials comparing pantoprazole to famotidine, two commonly used agents for SUP. Methods: This is an ongoing prospective, open-label, randomized study of patients admitted to the ICU/CCU from January 2013 and onward. All patients are assessed for risk factors for stress-related mucosal bleeding (SRMB). Patients are randomized to famotidine 20 mg IV Q12H or pantoprazole 40 mg IV QAM. The primary endpoint is the incidence of overt and clinically significant upper gastrointestinal bleeding (CSUGB) until the patient is either transferred out of the ICU/CCU or expired. Secondary endpoints include length of stay (LOS), duration on mechanical ventilation, and drug-induced adverse drug events. Results: Patients were randomized to IV pantoprazole (n=68) and IV famotidine (n=61) with a median patient age of 72 years. Both groups had similar baseline characteristics including risk factors for SRMB (2.7 vs. 2.7, p=0.50), however the pantoprazole group had higher APACHE-II scores (23.9 vs. 20.1, p<0.01). The most common SRMB risk factors for pantoprazole and famotidine were mechanical ventilation (79.4% vs. 75.4%), acute renal failure (36.8% vs. 49.2%), coagulopathy (32.4% vs. 32.8%), and septic shock (33.8% vs. 27.9%). SRMB occurred in four patients in the pantoprazole group (3 overt bleeds, p=0.36 and 1 CSUGB, p=0.34) and one patient in the famotidine group (overt bleed). Patients given IV pantoprazole had similar mean ICU/CCU LOS (6.7 vs. 6.5 days, p=0.37) and duration on mechanical ventilation (6.5 vs. 6.3 days, p=0.39). Patients on pantoprazole (n=22) experienced more adverse effects than famotidine (n=10); hypomagnesemia (13 vs. 5) and nausea/vomiting (7 vs. 3); C. difficile diarrhea was the same in both groups (2 vs. 2). Conclusions: IV pantoprazole and IV famotidine are equally effective for SUP; however, more patients had UGB with pantoprazole indicating the plausible need for more frequent dosing. Pantoprazole was commonly associated with hypomagnesemia; questioning the prevailing belief that hypomagnesemia generally occurs only with chronic PPI use. The study is ongoing and will determine the efficacy and safety between both agents for SUP in the critical care setting.

Splenosis Mimicking Relapse of a Neuroendocrine Tumor at Gallium-68-DOTATOC PET/CT.

A 48-year-old female patient underwent splenopancreasectomy for a 4-cm pancreatic neuroendocrine tumor (pNET), grade G2, located in the pancreatic tail. One year after surgery, the patient presented an increased serum level of the tumor marker chromogranin A (value: 160 U/l). Therefore, she underwent somatostatin receptor PET/CT using gallium-68-DOTATOC for restaging. This imaging method showed a focal area of increased radiopharmaceutical uptake corresponding to a 2.5-cm nodule located in the left superior abdomen near a clip from the previous surgery, suggesting a possible relapse of pNET (Fig. 1). Based on this PET/CT finding, the patient underwent ultrasonography-guided core biopsy of this nodule. Histology did not reveal findings suggestive of pNET but identified spleen tissue most likely caused by splenosis accidentally seeded at the previous operation. It is likely that the increased serum level of the tumor marker chromogranin A was due to the chronic proton-pump inhibitors use. Fig. 1 A 48-year-old female patient previously treated with splenopancreasectomy for a 4-cm pNET, grade G2, located in the pancreatic tail underwent somatostatin receptor PET/CT for restaging because of an increase in the chromogranin A serum levels (value: ... Somatostatin receptor PET/CT is an accurate imaging method for staging and restaging pNET, presenting high sensitivity and specificity in this setting [1–7]. Nevertheless, possible sources of false-negative and -positive findings with this method should be taken into account [1]. Inflammatory lesions represent the most frequent causes of false-positive findings for pNET at somatostatin receptor imaging because inflammatory cells may overexpress somatostatin receptors on their cell surface [8, 9]. In our case, we showed that splenosis may represent a possible cause of false-positive findings for pNET relapse due to the physiological uptake of somatostatin analogs by the spleen tissue [10, 11].

Risk of Proton Pump Inhibitor–Induced Mild Hyponatremia in Older Adults

To the Editor: The incidence of hyponatremia, a side effect that can result from using proton pump inhibitors (PPIs), is unknown in elderly adults. A prospective clinical study of individuals with suspected drug-induced moderate hyponatremia was recently conducted; 47% of the population was being treated with PPIs, indicating that the risk of PPI-induced hyponatremia is significant in elderly adults (≥65).1 This was a retrospective study. The main objective was to determine the incidence of hyponatremia in the elderly population being treated with PPIs; other objectives were to determine the odds ratio of PPI inducing hyponatremia, the relationship between PPI dose and occurrence of hyponatremia, and risk of hyponatremia in association with other medications. The incidence of hyponatremia in individuals who had been taking PPIs for at least 1 year was compared with that in a control group of individuals who had not been exposed to PPIs. Hyponatremia risk factors, except drugs known to induce hyponatremia, were exclusion criteria. The study included individuals in a unit of a general hospital admitted during 2011. Of 302 individuals analyzed, 145 were included. Twenty-four (16.6%) had moderate hyponatremia, and 48 (33.1%) had been taking PPIs for longer than 1 year, 31.3% of whom (95% confidence interval (CI) = 18.7–46.3%) had moderate hyponatremia, versus 9.3% (95% CI = 14.3–16.9%) in the rest of the population (OR = 4.4, 95% CI = 1.8–11.1, P = .001). The relationship between dose and occurrence of hyponatremia was not significant (coefficient of determination = 0.05, P = .74). Individuals taking PPIs and tramadol had a significantly higher risk of having hyponatremia than those taking neither (OR = 7.7, 95% CI = 1.9–31.2). Table 1 describes the relationship between hyponatremia, medication use, and potentiation in association with PPIs. The results are expressed as incidence of hyponatremia and the number of affected subjects for each drug or each drug combined with PPIs. In the literature, cases of hyponatremia in conjunction with PPI use have been reported without reporting the incidence rate.2 Moreover, hyponatremia is described as a rare event in PPI product information (<0.1%).3 Between 18.7% and 46.3% of elderly PPI users had hyponatremia in the current study. This study demonstrates that the chronic use of PPIs increases the risk of hyponatremia in older adults. This could be a result of their antidiuretic activity or the potentiation of the reactive antidiuretic hormone secretion.2 The association between PPIs and tramadol also appears to potentiate the risk of hyponatremia. Risk of hyponatremia with tramadol has been described in the literature.4 This combination is frequently administered to elderly adults and requires further study. Drugs are an underestimated cause of hyponatremia in elderly adults.5 Moderate hyponatremia significantly increases morbidity, for example, by increasing the risk of falls and fractures, and increases the risk of osteoporosis. It is also a predictor of death, myocardial infarction, and longer duration of hospitalization in elderly adults.6, 7 The effectiveness of PPIs and their safety has led to their widespread use. The known potential consequences of chronic use of PPIs include hypergastrinemia, enterochromaffin-like cell hyperplasia, and parietal cell hypertrophy, which causes rebound acid hypersecretion. PPI use is also a risk factor for Clostridium difficile enteritis, pneumonia, nutritional deficiencies, and interactions with antiplatelet agents.8 Although PPI moderate hyponatremia is an unknown effect, more fractures are being reported. It may be that episodes of hyponatremia potentiate these events by causing attention deficits, with a higher incidence of falls causing fractures, which adds to the direct effect on bone remodeling.9, 10 Thus, the literature suggests a need for a benefit: risk balance assessment amended by the latest knowledge of pharmacovigilance, and the current study confirms the potential adverse effects of PPI use in the elderly population. PPIs are commonly administered to elderly adults: 33% in the current study. The extensive use of PPIs in elderly adults is often the result of a lack of therapeutic reevaluation or requests from the individual to avoid treatment interruption. PPIs must be discontinued when the risk-benefit balance becomes unfavorable. Reassessment of the prescription is useful, particularly because a recent study has shown that hyponatremia is reversible; the reduction of drugs that may induce hyponatremia was associated with significant clinical improvement.1 Future prospective studies that include follow-up laboratory results for comparisons of pre- and post-PPI therapy would be optimal and informative. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the authors and has determined that the authors have no financial or any other kind of personal conflicts with this paper. Author Contributions: Buon, Peyro Saint Paul: acquisition of subjects and data, analysis and interpretation of data, and preparation of manuscript. Gaillard, Fedrizzi, Mosquet, Coquerel: analysis and interpretation of data, preparation of manuscript. Martin: acquisition of subjects, analysis and interpretation of data, and preparation of manuscript. Sponsor's Role: No sponsor.

Monitoring of Vitamin D in Chronic PPI Users Is Influenced by Patient Age and Duration of Therapy

Purpose: Proton pump inhibitors (PPIs) are commonly prescribed medications. Chronic use of PPIs has been associated with bone fractures. The risk is enhanced with increased patient age and longer duration of therapy. Monitoring and supplementing vitamin D levels may reduce fracture risk. This study evaluated the rate of vitamin D measurement based upon patient age and the duration of PPI therapy. Methods: A retrospective medical record review was performed utilizing a multispecialty electronic health record. Consecutive patients on chronic PPIs during a 6-month period seen in an urban, academic gastroenterology clinic were included. There were no exclusion criteria. Patient age, gender, PPI dose and duration, and vitamin D level were obtained. A database, maintaining patient confidentiality, was created. Statistical analysis was performed using Fisher's exact test with two-tailed p-values and 95% confidence intervals (CIs) computed for continuous variables. Statistical significance set at p<0.05. This study was approved by the university's IRB. Results: Two hundred thirty-four records (88 men, 146 women; mean age 54.9 years) were reviewed. One hundred sixteen (49.6%) had vitamin D levels checked. There was no significant difference (p=0.345) in vitamin D measurement based upon gender. The mean age of patients with vitamin D measured was 60.6 years (95% CI 58.2-63.1) and 49.2 years (95% CI 48.6-51.7) in those with vitamin D not measured (p=1.16x10-9). There was a significant difference (p<0.0001) in the rate at which vitamin D was checked in patients 60 years and older (65 of 90; 68.4%) compared to patients younger than 60 years (51 of 139; 36.7%). There was a significant difference (p<0.0001) in the rate of vitamin D measurement in patients treated 24 months and longer (56 of 80; 70%) compared to those treated less than 24 months (60 of 154; 39%). Conclusion: Chronic use of PPIs has been associated with increased fracture risk. The risk is increased with longer duration of therapy and increased patient age. Supplementation of low vitamin D levels may mitigate the risk of fractures. This study revealed that there was inconsistent measurement of vitamin D, with only half of chronic PPI users having a vitamin D level documented in their medical record. Patients on PPIs 24 months or longer and patients who were 60 years and older had vitamin D measured more frequently. These results suggest that physicians recognize the factors that increase fracture risk in patients maintained on PPIs. However, increased efforts are needed to encourage monitoring of vitamin D levels in all patients on chronic PPI therapy.

Physician Measurement of Vitamin B12 Is Not Influenced by Proton Pump Inhibitor Dose

Purpose: Proton pump inhibitors (PPIs) are among the most commonly prescribed medications in the U.S. These medications target parietal cell hydrogen potassium ATPase to potently reduce gastric acid. Chronic use of PPIs is speculated to decrease vitamin B12 absorption. This study evaluated the impact of PPI dose upon the rate of physician vitamin B12 measurement. Methods: A retrospective medical record review was performed utilizing a multispecialty electronic health record. Consecutive patients on chronic PPIs during a 6-month period seen in an urban, academic gastroenterology clinic were included. There were no exclusion criteria. Patient age, gender, PPI dose and duration, and vitamin B12 were obtained. Low-dose PPI was considered to be an over-the-counter regimen. High-dose PPI was a prescribed regimen. A database, maintaining patient confidentiality, was created. Statistical analysis was performed using Fisher's exact test with statistical significance set at p<0.05. The study was approved by the university's IRB. Results: Two hundred thirty-four records (88 men, 146 women; mean age 54.9 years) were reviewed. Eighty-nine (38%) patients (28 men, 61 women) had vitamin B12 checked. There was no significant difference (p=0.1644) in the rate at which vitamin B12 was checked based on gender. The average age at which patients with vitamin B12 checked was 59.67 years. Forty-one patients were on a low-dose PPI regimen and 193 patients were on a high-dose PPI regimen. Twenty-two of 41 (53.7%) low-dose PPI users had vitamin B12 measured. Sixty-seven of 193 (34.7%) patients on prescribed PPIs had vitamin B12 measured. There was a statistically significant difference (p=0.0327) in the rate at which low-dose and high-dose chronic PPI users had vitamin B12 measured. There was no significant difference in vitamin B12 level based on PPI dose. The mean vitamin B12 level in those on high-dose PPI was 750 pg/mL (618-883) and low dose PPI was 736 pg/mL (636-836). Conclusion: Vitamin B12 is necessary for neurologic function, blood cell formation, DNA synthesis, and cellular metabolism. Deficiency can result in a variety of disorders, including irreversible damage to the brain and nervous system. It has been speculated that chronic PPI use can result in low vitamin B12 levels and may influence clinicians to evaluate for B12 deficiency. However, this study revealed that vitamin B12 was inconsistently measured in patients on chronic PPIs. Additionally, patients on low-dose PPIs more frequently had vitamin B12 measured than those on high-dose PPIs. Continued attention to the potential relationship of PPIs and vitamin B12 is important to determine if vitamin B12 monitoring is important in chronic PPI users.

Chronic Proton Pump Inhibitor Use Is Not Associated with Vitamin B12 Deficiency

Chronic Proton Pump Inhibitor Use Is Not Associated with Vitamin B12 Deficiency

Use of proton pump inhibitors is associated with lower trabecular bone density in older individuals

Proton pump inhibitors (PPIs) are highly effective in the treatment of upper gastrointestinal acid-related conditions and are fast becoming one of the most frequently prescribed treatments in adult or older persons. Recent data show that long-term use of PPIs in older subjects is associated with important undesirable effects, including a higher risk of osteoporotic fractures. The mechanisms of this association are unclear and the relationship between the use of PPIs and parameters of bone mass and geometry has never been fully explored.This study investigates the relationship between the chronic use of PPIs and the parameters of bone mass (cortical and trabecular bone mineral density — vBMDc and vBMDt) and bone geometry (cortical and trabecular cross sectional area — tCSA and cCSA) in older individuals.The study population consisted of 1038 subjects (452 men and 586 women) 65years or older, selected from the InCHIANTI study, with complete information on computerized tomography performed at tibial level (pQCT) and on medications. Participants were classified as PPI users and nonusers based on self-report of PPI use over the last 15days, with PPI users (36 subjects, 14 men and 22 women) making up 3.4% of the study population (mean age 75.7±7.4years). The relationship between use of PPIs and pQCT bone parameters was tested by multivariate linear regression analysis adjusted for age, sex and several clinical factors and/or statistically confounding variables identified by partial correlation coefficient and Spearman partial rank order correlation coefficients, as appropriate (age, sex, BMI, caloric intake, IGF-1, IL-6, calcium, estradiol, bioavailable testosterone, vitamin D, parathyroid hormone, cross-sectional muscle area, and level of physical activity). PPI users showed age- and sex-adjusted lower vBMDt than nonusers (180.5±54.8 vs. 207.9±59.4, p=0.001). The inverse association between PPI use and vBMDt remained almost unchanged after adjustment for multiple confounders. There was no statistically significant difference in vBMDc, tCSA and cCSA between PPI users and nonusers.In community dwelling older persons, the use of PPIs is inversely associated with vBMDt, an early marker of the osteoporotic process. These findings suggest that PPI use might increase the risk of fractures in older subjects through its detrimental effects on trabecular bone.

Inadequate prescription of chronic consumption of proton pump inhibitors in a hospital in Mexico: Cross-sectional study

PPIs have been an enormous therapeutic advance in acid-related diseases. However, it has been detected an abuse in its consumption. The aim of this study was to determine the frequency of inadequate prescription of chronic use of PPIs in outpatients in a speciality hospital. we performed a cross-sectional descriptive study review. The study population were patients, chronic users of proton pump inhibitors (PPIs), attending outpatient consult in a hospital of government workers. We defined as chronic user of PPIs that patient that takes medication daily for over a year and inappropriate prescription, that one that has not been approved by the clinical guidelines. A simple random sampling was utilized. The following parameters were investigated: diagnosis and prescription of PPIs, time of use, at which level of care PPIs were prescribed (primary care or specialist), self-medication, with or without endoscopy. Forthe statistical analysis, we used Student´s t-test and Chi-square, 95 % confidence intervals and significance 0.05 %. we reviewed 153 patients, 40 (26.1 %) men and 113 (73.9 %) women, mean age 58 ± 11.4 years. The prescription of chronic treatment with PPIs was adequate in 64.7 % of patients and inadequate in 35.3 %. The most common appropriate prescription (31.3 %) of chronic use of PPIs was due to gastroesophageal reflux disease. The most common inadequate prescription was absence of diagnosis (22.2 %), polypharmacy without nonsteroidal anti-inflammatory drugs (16.6 %) and chronic gastritis (16.6 %). History of endoscopy were not statistically significant. the frequency of inappropriate prescriptions of chronic use of PPIs was high, around 35.3 %, similar to those reported in hospitals in developed countries.