Risk of incident gout following exposure to recombinant zoster vaccine in US adults aged ≥50 years.

OBJECTIVE: To assess whether recombinant zoster vaccine (RZV) is associated with an increased risk of new-onset gout among US adults aged ≥50 years. METHODS: We conducted a real-world, retrospective safety study with a self-controlled risk interval (SCRI) design using administrative claims data. We included health plan members aged ≥50 years with RZV exposure, followed by incident gout within 60 days. Days 1-30 following RZV exposure were considered the risk window (RW), and days 31-60 were considered the control window (CW). We estimated the risk ratio (RR) of gout in the RW versus CW, using a conditional Poisson model. The primary analysis estimated the risk of incident gout following any RZV dose. Sensitivity analyses evaluated dose 1- and dose 2-specific risks, risk among patients compliant with recommended dose spacing of 60-183 days, adjustment for seasonality, and restriction to the pre-COVID-19 era (before December 1, 2019). RESULTS: A total of 461,323 individuals received ≥1 RZV dose; we included 302 individuals (mean age 72.5 years; 66 % male) with evidence of new-onset gout within 60 days in SCRI analyses. A total of 153 (50.7 %) individuals had gout events in the RW and 149 (49.3 %) in the CW (RR 1.03; 95 % confidence interval 0.81, 1.29). All sensitivity analyses had consistent results, with no association of RZV with incident gout. CONCLUSION: In a population of US adults aged ≥50 years, there was no statistically significant increase in the risk of gout during the 30 days immediately after RZV exposure, compared with a subsequent 30-day CW.

Risk of incident gout following exposure to recombinant zoster vaccine in US adults aged ≥65 years.

OBJECTIVE: Assess the risk of incident gout following exposure to recombinant zoster vaccine (RZV). METHODS: This case-only, self-controlled risk interval study included a cohort of US fee-for-service Medicare (Part A, B, and D) beneficiaries aged ≥65 years. The exposure was receipt of at least one dose of the two-dose RZV regimen in 2018 or 2019. The risk and control windows were days 1-30 and days 31-60, respectively, following vaccination. Incident gout was defined as the first episode of gout during the risk or control window, with no evidence of gout in the last 365 days. We estimated the relative risk (RR) and 95 % confidence interval (CI) of incident gout in the risk window relative to the control window, using conditional Poisson regression models. Sensitivity analyses included a dose-compliant subanalysis of individuals who received dose 2 60-183 days after dose 1; dose-specific analysis; seasonality adjustment; and COVID-19 adjustment for potential detection bias due to the pandemic. RESULTS: The 1290 RZV-exposed individuals with incident gout were primarily White (86.98 %), male (61.16 %), and aged 70-79 years (55.82 %). The RR of incident gout was 1.00 (95 % CI 0.90, 1.12). In the dose-compliant sensitivity analysis (n = 959 cases of incident gout), the RR of incident gout was 0.99 (95 % CI 0.87, 1.13). The findings were unchanged in the dose-specific, seasonality, and COVID-19 sensitivity analyses. CONCLUSION: The findings suggest that RZV is not significantly associated with an increased risk of incident gout in the Medicare population aged ≥65 years.

Real-world effectiveness of recombinant zoster vaccine in self-identified Chinese individuals aged ≥50 years in the United States.

We evaluated the vaccine effectiveness (VE) of two doses of recombinant zoster vaccine (RZV) against herpes zoster (HZ) and postherpetic neuralgia (PHN) in Chinese adults at Kaiser Permanente Southern California (KPSC). Chinese KPSC members were identified based on self-reported ethnicity or self-reported preferred spoken/written language. Those aged ≥50 years who received two doses of RZV 4 weeks to ≤ 6 months apart were matched 1:4 to RZV unvaccinated Chinese members and followed through June 2022; second doses were accrued 6/1/2018-12/31/2020. We estimated incidence and adjusted hazard ratios (aHRs) with 95% confidence intervals (CIs) comparing outcomes (HZ and PHN). Adjusted VE (%) was calculated as (1-aHR)×100. 3978 RZV vaccinated Chinese members were matched to 15,912 RZV unvaccinated Chinese members. The incidence per 1000 person-years (95% CI) of HZ in the vaccinated group was 1.5 (0.9-2.5) and 10.9 (9.8-12.1) in the unvaccinated group; aHR (95% CI) was 0.12 (0.07-0.21). Adjusted VE (95% CI) was 87.6% (78.9-92.7) against HZ. We identified 0 PHN cases in the vaccinated group and 19 in the unvaccinated group. Among Chinese adults aged ≥50 years, two doses of RZV provided substantial protection against HZ and PHN supporting the real-world effectiveness of the vaccine in this population.

Impact of the Adalimumab Patient Support Program's Care Coach Calls on Persistence and Adherence in Canada: An Observational Retrospective Cohort Study.

PURPOSE: Adalimumab (ADA) is a tumor necrosis factor-α inhibitor indicated for use in various immune-mediated inflammatory diseases. Patients receiving ADA in Canada are eligible to enroll in the AbbVie Care's Patient Support Program (PSP), which provides personalized services, including tailored interventions in the form of nurse-provided care coach calls (CCCs), with the goal of improving patients' experiences and outcomes. The primary objective of this study was to evaluate the impact of PSP services, including CCCs and patient characteristics, on persistence with and adherence to ADA for those patients enrolled in the PSP. A secondary objective was to estimate the effect of initial CCCs on treatment-initiation abandonment (ie, failure to initiate therapy after enrollment in the PSP). METHODS: An observational retrospective cohort study was conducted. A patient linkage algorithm based on probabilistic matching was developed to link the AbbVie Care PSP database to the QuintilesIMS longitudinal pharmacy transaction database. Patients who started ADA therapy between July 2010 and August 2014 were selected, and their prescriptions were evaluated for 12 months after the date of ADA start to calculate days until drug discontinuation, that is, the end of persistence, defined as >90 days without therapy. Cox proportional hazards modeling was used for estimating hazard ratios for the association between persistence and patient characteristics and each PSP service. Adherence, measured by medication possession ratio, was calculated, and multivariate logistic regression provided adjusted odds ratios for the relationship between being adherent (medication possession ratio ≥80%) and patient characteristics and each PSP service. Treatment-initiation abandonment among patients who received an initial CCC compared with those who did not was analyzed using the χ2 test. FINDINGS: Analysis of 10,857 linked patients yielded statistically significant differences in the hazard ratio of discontinuation and the likelihood of being adherent across multiple variables between patients who received CCCs in comparison to patients who did not. Patients receiving CCCs were found to have a 72% decreased risk for therapy discontinuation (hazard ratio = 0.282; P < 0.0001), and a greater likelihood of being adherent (odds ratio = 1.483; P < 0.0001), when compared with those patients who did not receive CCCs. The rate of treatment-initiation abandonment was significantly higher in patients who did not receive initial CCCs (P < 0.0001). IMPLICATIONS: Ongoing CCCs, provided by AbbVie Care PSP, were associated with greater patient persistence and adherence over the first 12 months of treatment, while initial CCCs were associated with a lower rate of treatment-initiation abandonment. Results may inform the planning of interventions aimed at improving treatment adherence and patient outcomes.

Prevalence and predictors of anti-infective use during pregnancy.

PURPOSES: (1) Measure the prevalence and trends of anti-infective drug use before, during, and after pregnancy; (2) to list the doses, classes, types, and indications for anti-infective use during pregnancy; and (3) to identify predictors associated with anti-infective drug use during pregnancy. METHODS: Retrospective cohort study within the Quebec Pregnancy Registry, which was created by the linkage of three administrative databases: RAMQ, Méd-Echo, and ISQ. Women were eligible if they were (1) continuously insured by the RAMQ drug plan for at least 12 months before the first day of gestation, during pregnancy and 12 months after the end of the pregnancy and (2) if they gave birth to a live born between January 1998 and December 2003. Ninety-seven thousand six hundred and eighty pregnant women met the eligibility criteria. Data were collected for systemic agents. Logistic regression models were used to quantify predictors of use. RESULTS: Prevalence of anti-infective use during pregnancy was 24.5%. Penicillins use increased compared to other classes. The most frequently diagnosed infections were respiratory and urinary tract infections. Predictors associated with use at the beginning of gestation were having > or =2 different prescribers [OR = 3.83 (95% confidence interval 95%CI: 3.3-4.3)], diagnosis of urinary [OR = 1.50 (95%CI: 1.3-1.8)], and respiratory tract infection [OR = 1.40 (95%CI: 1.2-1.6)] in the year before pregnancy. Visits to an obstetrician/gynecologist were protective for use [OR = 0.81 (95%CI: 0.67-0.97)]. CONCLUSION: Anti-infective use during pregnancy is prevalent. The oldest and safest agents are preferred.

Herbal products use during pregnancy: prevalence and predictors.

PURPOSES: (1) Measure the prevalence of herbal product (HP) use, alone, and concomitantly with prescribed medications during pregnancy, (2) identify the most frequently consumed HP during gestation and (3) determine predictors of HP use at the beginning of pregnancy, and during the third trimester. METHODS: A questionnaire was mailed to 8505 women selected from the Quebec Pregnancy Registry which was created by the linkage of three administrative databases: RAMQ, Méd-Echo and ISQ. Women were eligible if they were continuously insured by the RAMQ drug plan for at least 12 months before the first day of gestation and during pregnancy, and if they gave birth to a live born between January 1998 and December 2003 in one of the Quebec's hospitals. Women with diabetes and psychoses, and women who delivered a baby with birth defects were selected first. Descriptive statistics and multivariate logistic regression models were used to analyse data. RESULTS: Of the 3354 women (39%) who answered the questionnaire, and were included in the study, nine per cent used HP during pregnancy. 69% of users took at least one prescribed medication concomitantly. Chamomile, green tea, peppermint and flax were the most frequently HP used. Multivariate analyses showed that body mass index (BMI), multivitamin use and one to three prescribed medications used before pregnancy were predictors of HP use at the beginning of pregnancy; adherent women, smokers and users of HP prior to pregnancy were predictors of HP use during the third trimester. CONCLUSION: HP use alone and concomitantly with prescribed medications during pregnancy is common, and needs to be addressed by health professionals.

Health care providers' requests to Teratogen Information Services on medication use during pregnancy and lactation.

BACKGROUND: Medication use during pregnancy and lactation is prevalent. However, current knowledge of the risks and benefits of medication use during pregnancy and lactation is incomplete as the best available evidence has been obtained from cohort studies of inadvertent exposures and registries. This situation may partly explain health care providers' (HCP) risk perceptions and thus the increasing number of calls to Teratogen Information Services (TIS). OBJECTIVES: The objectives of this study were (1) to identify the medication classes for which HCP are seeking counseling from the IMAGe center, a Quebec TIS; (2) to identify the medical conditions for which medication classes were used during pregnancy and lactation; (3) to identify and quantify predictors of medication information requests during pregnancy and lactation. METHODS: A retrospective analysis of data was conducted within the population served by the IMAGe center, a TIS based at CHU Ste-Justine in Montreal, Quebec, Canada, that serves the French population of Canada. To be included, calls had to be received between January 1, 2004 and April 30, 2007, and the subject of the call had to be directly associated with the exposure, or not, of a pregnant or breastfeeding woman to medication. Multivariate generalized estimating equation (GEE) regression models were performed to identify the predictors of medication requests. RESULTS: A total of 11, 076 requests regarding medication exposure during pregnancy, 12 055 requests regarding pregnant women before the exposure took place, and 13, 364 requests regarding lactation were included for analyses. Pregnant women were most frequently exposed to antidepressants (17.3), antibiotics (6.3%), and benzodiazepines (5.3%). Prior to drug exposure, the most frequent inquiries by HCP were on antibiotics (11.0%), anti-inflammatory drugs (6.0%), and antiemetics (5.1%). Inquiries concerning lactating women most frequently requested information on the drug classes of antidepressants (10.8%), antibiotics (9.1%), and anti-inflammatory drugs (7.8%). Depressive disorders were an indication of antidepressant, benzodiazepine and antipsychotic exposures reported to IMAGe. Associations were found between medication use and maternal age, previous pregnancies, trimester of pregnancy at the time of the call and lifestyle habits. CONCLUSIONS: The IMAGe received frequent inquiries on antidepressant, antibiotic, and benzodiazepine exposures, with depressive disorders being the most frequently declared indication. Predictors of medication requests were identified among exposed women during pregnancy, and breastfeeding women. These results emphasize the need for effective studies on drug use during pregnancy and lactation and for better knowledge transfer programs.

Antidepressant therapy during pregnancy: an insight on its potential healthcare costs.

BACKGROUND: Information on healthcare costs associated with poorly treated psychiatric disorders during and after pregnancy is limited. OBJECTIVE: To compare the direct healthcare costs, during and after pregnancy, between women who continue their antidepressant therapy during the whole gestational period and those who discontinue their treatment during the first trimester. METHODS: Data from a 'Medications and Pregnancy' registry were used. Eligible women were 1) aged 15 - 45, 2) insured by the Quebec drug plan for > or =12 months prior to, during, and > or =3 months after pregnancy, 3) had > or =1 diagnoses of psychiatric disorders before pregnancy, 4) used antidepressants for . or =30 days in the year before pregnancy, and 5) had delivered. Women who continued their antidepressant therapy throughout pregnancy (Group 1) were compared to those who discontinued during the first trimester (Group 2). Healthcare costs, expressed as mean total costs and cost ratios, were determined during and after pregnancy. RESULTS: In total, 2822 women met inclusion criteria. Of these, 501 (17.8%) were in Group 1, and 676 (23.4%) in Group 2. The median number of days of antidepressant use before pregnancy was higher in Group 1 (260 days vs. 144 days, p<.01); the proportion of women visiting a psychiatrist was also higher in Group 1 (33.7% vs. 26.8%, p<.01). The mean total cost during pregnancy in Groups 1 and 2 were $2981.5 vs. $1842.9 (p<.01), respectively, and after pregnancy were $1761.2 vs. $1024.9 (p<.01), respectively. When prescription costs were excluded, these differences in costs were no longer significant. CONCLUSIONS: Women who use antidepressants during pregnancy are likely to have disorders of greater severity compared to those who discontinue during the first trimester. They incur significantly greater healthcare costs. However, this increased cost is attributable to higher prescription costs.

Duration of antidepressant use during pregnancy and risk of major congenital malformations.

BACKGROUND: Antidepressant use during the gestational period is a controversial topic. AIMS: To determine whether duration of antidepressant use during the first trimester increases the risk of major congenital malformations in offspring of women diagnosed with psychiatric disorders. METHOD: A case-control study was performed among women who had been pregnant between January 1998 and December 2002. Data were obtained from a Medication and Pregnancy registry, built by linking three databases from the province of Quebec, and a self-administered questionnaire. Women eligible for this study had to be 15-45 years old at the beginning of pregnancy, have at least one diagnosis of psychiatric disorder before pregnancy, have used antidepressants for > or =30 days in the year prior to pregnancy and have a pregnancy ending with a delivery. Cases were defined as any major congenital malformation diagnosed in the offspring's first year of life. Odds ratios, adjusted for relevant confounders, were estimated using logistic regression. RESULTS: Among the 2329 women meeting the inclusion criteria, 189 (8.1%) infants were born with a major congenital malformation. Duration of antidepressant use during the first trimester of pregnancy was not associated with an increased risk of major congenital malformations: 1-30 days v. 0 day, adjusted OR=1.23 (95% CI 0.77-1.98); 31-60 days v. 0 day, adjusted OR=1.03 (95% CI 0.63-1.69); > or =61 days v. 0 day, adjusted OR=0.92 (95% CI 0.50-1.69). CONCLUSIONS: These data do not support an association between duration of antidepressant use during the first trimester of pregnancy and major congenital malformations in the offspring of women with psychiatric disorders. These findings should help clinicians decide whether to continue antidepressant therapy during pregnancy.

Isotretinoin, pregnancies, abortions and birth defects: a population-based perspective.

AIMS: To estimate the population-based incidence rates of pregnancy, spontaneous and elective abortions, and birth defects associated with isotretinoin use, and to determine predictors of pregnancy while on isotretinoin. METHODS: Using the RAMQ (medical and pharmaceutical data), MED-ECHO (hospitalizations) and ISQ (births and deaths) databases for the period 1984-2002, a cohort of 8609 women between 13 and 45 years of age and with a first prescription for isotretinoin (date of entry in the cohort) was identified. Women were eligible if they were insured by RAMQ for their medications at least 12 months before entry in the cohort and until 1 month after the end of their isotretinoin treatment. Pregnancies, spontaneous and elective abortions, and birth defects were identified using procedure codes and medical diagnoses. RESULTS: Of the 8609 women included, 90 became pregnant, an annual incident pregnancy rate during isotretinoin treatment of 32.7 per 1000 person-years of treatment (95% confidence interval 26.6, 40.1). Of the 90 women who became pregnant while on the drug, 76 terminated the pregnancy (84%), three had a spontaneous abortion (3%), two had trauma during delivery resulting in neonatal deaths (2%) and nine had a live birth (10%). Among the live births, only one had a congenital anomaly of the face and neck (11%). Adjusting for potential confounders, predictors of becoming pregnant while on isotretinoin were lower socio-economic level, one or more visits to the doctor or to the emergency department, or one or more hospitalization while on isotretinoin; concomitant isotretinoin and oral contraceptive use had a preventive effect. CONCLUSIONS: This first non-interventional population-based study generated incidence rates of pregnancy while on isotretinoin four times greater than what has been reported in the literature thus far; elective abortion rates were also much higher in our study. This shows the importance of using population-based data for public health purposes.

First trimester exposure to paroxetine and risk of cardiac malformations in infants: the importance of dosage.

BACKGROUND: Conflicting findings with regard to the teratogenic risks of first trimester use of paroxetine have prompted the FDA, Health Canada, and the manufacturer of the drug to issue warnings against its use during pregnancy. Given that untreated depression during pregnancy can lead to deleterious effect on the mother and her unborn fetus, data on the relationship between the dose and the range of malformations is warranted. This study attempts to quantify the association between first trimester exposure to paroxetine and congenital cardiac malformations, adjusting for possible confounders, and to quantify the dose-response relationship between paroxetine use and cardiac defects. METHODS: The Medication and Pregnancy registry was used. This population-based registry was built by linking three administrative databases (RAMQ, Med-Echo, and ISQ), and includes all pregnancies in Quebec between 01/01/1997 and 06/30/2003. Date of entry in the registry is the date of the first day of the last menstrual period. To be eligible for this study, women had to: 1) be 15-45 years of age at entry; 2) be covered by the RAMQ drug plan >or=12 months before and during pregnancy; 3) be using only one type of antidepressant during the first trimester; and 4) have a live birth. Two nested case-control studies were carried out comparing the prevalence of paroxetine use in the first trimester of pregnancy to the prevalence of other antidepressant exposures during the same time period. Cases were defined as: 1) any major malformations; or 2) any cardiac malformations diagnosed in the first year of life; controls were defined as no major or minor malformations. Multivariate logistic regression techniques were used to analyze data. RESULTS: Among the 1,403 women meeting inclusion criteria, 101 infants with major congenital malformations were identified; 24 had cardiac malformations. Adjusting for possible confounders, the use of paroxetine (odds ratio [OR] = 1.38, 95% confidence interval [CI] = 0.49-3.92), and the use of other SSRIs (OR = 0.89, 95% CI = 0.28-2.84) during the first trimester of pregnancy did not increase the risk of congenital cardiac malformations compared with the use of non-SSRI antidepressants. When considering the dose, however, a dose-response relationship was observed, thus women exposed to >25 mg/day of paroxetine during the first trimester of pregnancy were at increased risk of having an infant with major congenital malformations (adjusted [adj] OR = 2.23, 95% CI = 1.19, 4.17), or major cardiac malformations (adj OR = 3.07, 95% CI = 1.00, 9.42). CONCLUSIONS: Gestational exposure to paroxetine is associated with major congenital malformations and major cardiac malformations for only first trimester exposure above 25 mg/day.

Risk of congenital anomalies in pregnant users of non-steroidal anti-inflammatory drugs: A nested case-control study.

BACKGROUND: Many women take non-steroidal anti-inflammatory drugs (NSAIDs) during pregnancy but the risks for the infant remain controversial. We carried out a study to quantify the association between those women prescribed NSAIDs in early pregnancy and congenital anomalies. METHODS: A population-based pregnancy registry was built by linking data from three administrative databases in Quebec between 1997-2003. The inclusion criteria were mothers of live singleton infants, between 15-45 years of age, covered by the RAMQ drug plan > or =12 months before and during pregnancy, and prescribed an NSAID or other medications during pregnancy. We selected as cases infants with any congenital anomaly (ICD-9; 740-759) diagnosed in the first year of life. Up to 10 controls, defined as infants with no congenital anomalies detected were selected for each case. Adjusted odds ratios (OR) and 95% confidence intervals (CI) were estimated. RESULTS: Within the registry, 36,387 pregnant women met the inclusion criteria. We identified 93 births with congenital anomalies in 1056 women (8.8%) who filled prescriptions for NSAIDs in the first trimester of pregnancy, compared to 2478 in 35,331 (7%) women who did not. The adjusted OR for any congenital anomalies for women who filled a prescription for NSAIDs in the first trimester was 2.21 (95% CI = 1.72-2.85). The adjusted OR for the anomalies related to cardiac septal closure was 3.34 (95% CI = 1.87-5.98). There were no significant associations with anomalies of other major organ systems. CONCLUSIONS: Our study suggests that women prescribed NSAIDs during early pregnancy may be at a greater risk of having children with congenital anomalies, specifically cardiac septal defects.

Patterns and utilization of isotretinoin for acne from 1984 to 2003: is there need for concern?

OBJECTIVES: To (1) describe the patterns and trends of isotretinoin utilization between 1984 and 2003, (2) describe the characteristics of isotretinoin users within that same time period, (3) identify and quantify predictors of isotretinoin use, and (4) describe the impact of guidelines on isotretinoin utilization between 1984 and 2003. METHODS: Using the Régie de l'Assurance Maladie du Québec (healthcare utilization, medications) and Med-Echo (hospitalizations) administrative databases, we conducted a descriptive study on a population-based sample of first-time isotretinoin users from 1984 to 2003. We determined the characteristics of these users, predictors of an isotretinoin treatment >or=20 weeks, and impact of guidelines on the number of new isotretinoin users. Guidelines included the implementation of the Pregnancy Prevention Program (PPP - 1988) and the Dear Healthcare Professional Letter regarding possible psychiatric risks issued to Canadian physicians (DHPL - 2001). RESULTS: Mean (SD) age was 23.9 (7.6) years; 50% males, 52% welfare recipients, 77% urban dwellers, and 55% of prescriptions were written by dermatologists. Sixty-four percent of patients did not receive any anti-acne medications in the 12 months prior to receiving isotretinoin. Thirty-five percent of patients had an isotretinoin treatment >or=20 weeks suggested by product guidelines. The odds ratio of having a treatment >or=20 weeks significantly increased after the implementation of the PPP and other guidelines. There was no statistically significant decrease in the number of new isotretinoin users following the implementation of the PPP and DHPL. CONCLUSION: These data suggest inappropriate isotretinoin utilization, even more so after guidelines were promulgated.

Inappropriate medication prescribing in community-dwelling elderly people living in Iran.

OBJECTIVES: To determine the prevalence of inappropriate medication prescribing in Middle Eastern community-dwelling elderly persons, and to determine factors associated with inappropriate prescribing. METHODS: Prescriptions from 3,000 elderly-patient visits (> or =65 years) to physicians in Isfahan, Iran were collected between September and December 2002; only the first patient visit was considered in the study. Inappropriate prescriptions were defined according to Beers' explicit criteria (1997). The presence of at least one drug-drug interaction (DDI) and at least one drug-class duplication within each patient visit was also determined. Multivariate analyses were performed to determine factors associated with receiving at least one inappropriate medication. These factors included age, gender, number of prescribed medications per visit, DDIs, duplications, and physician's number of years of experience. Similar analyses were performed to determine whether these factors were associated with a composite index (defined as having at least one of the following: receiving at least one inappropriate prescription, DDI, or duplication). RESULTS: The mean age of our cohort was 72.6 (+/-5.7) years, and 1,735 (57.8%) were females. A total of 829 (27.6%) patients received at least one inappropriate prescription, 285 (9.5%) had at least one DDI during the visit, and 746 (24.9%) had at least one duplication during the visit. The three most inappropriately prescribed medication classes were antihistamines (29%), non-steroidal anti-inflammatory agents (23%) and benzodiazepines (16%). In multivariate analyses, the number of prescribed medications per visit was the only factor significantly associated with receiving at least one inappropriate prescription (OR 1.24; 95%CI: 1.16-1.32); analyses using the composite index as outcome gave similar results (OR: 1.70; 95%CI: 1.60-1.80). CONCLUSION: Our findings indicate a high prevalence of inappropriate prescribing in elderly patients. Given the potential severity of this problem, further steps need to be implemented to prevent this occurrence.