Variation and appropriateness of antipsychotic use in long-term care facilities across Newfoundland and Labrador

Objective: The use of antipsychotics to treat seniors in long-term care facilities (LTC Fs) has raised concern because of health consequences (i.e., increased risk of falls, stroke, death) in this vulnerable population. This study measured geographic patterns of antipsychotic utilization among seniors living in LTC Fs in Newfoundland and Labrador (NL) and assessed potential inappropriateness. Method: We analyzed prescription records among adults 66 years and older with provincial prescription drug coverage admitted to LTC Fs in NL between April 1, 2011, and March 31, 2014. Patterns of use were analyzed across the 4 regional health authorities (RHAs) in NL and LTC Fs. Logistic, Poisson and linear regression models were used to test variations in prevalence, rate and volume of antipsychotic utilization. To assess potential inappropriateness of antipsychotic use, we analyzed data from Resident Assessment Instrument–Minimum Data Set (RAI-MDS) 2.0 forms from NL LTC Fs between January 1, 2016, and December 31, 2018. Pearson chi-squared analysis was performed at the RHA and LTC F levels to determine changes in percentage of total prescriptions or antipsychotic prescriptions without psychosis. Results: Between 2011 and 2014, 2843 seniors were admitted to LTC Fs across NL; of these, 1323 residents were prescribed 1 or more antipsychotics. Within the 3-year period, the percentage of antipsychotic use across facilities ranged from 35% to 78%. Using data from 27,260 RAI-MDS 2.0 assessments between 2016 and 2018, 71% (6995/9851) of antipsychotic prescriptions were potentially inappropriate. Discussion: There is substantial variation across NL regions concerning the utilization of antipsychotics for senior in LTC Fs. Facility size and management styles may be reasons for this. Conclusion: With nearly three-quarters of antipsychotic prescriptions shown to be potentially inappropriate, systematic interventions to assess indications for antipsychotic use are warranted

Inter-regional comparisons in the pattern of use and needs for institutional care

As the percentage of elderly people increases so does the demand for long-term care services. To ensure that the elderly will be properly cared for in the future, the efficiency of resource utilization needs to be maximized. As a result, the current study looked at the appropriateness of client placement and the annual demands for long-term care in both Western and Labrador health care regions of Newfoundland and Labrador. Comparisons were then made to findings in the St. John's region. -- The appropriateness of client placement, the efficiency of the single entry system and an estimate of the annual demands for long-term care were determined for both Western and Labrador using study populations of 178 and 51 respectively. A tendency to recommend clients for a higher level of care than they required was consistent with previous findings in the St. John's region. The percentage of clients suffering from impaired cognition was also high and Labrador had long waiting times for placement and a high occupancy rate of acute care beds by clients awaiting placement. -- To overcome the issue of inappropriate placement, minimal criteria for placement into supervised care and nursing home care facilities may need to be established. Alternate housing facilities for those with low to modest disability and those suffering from impaired cognition may also reduce the number of inappropriate nursing home placements. To reduce waiting list sizes and time to placement, waiting lists must follow some management scheme, such as placement based on assessed need, and target times for placement must be developed

The impact of screening on the clinical course of lynch syndrome

Background & Aims: Lynch syndrome (LS) is an autosomal dominant disorder and is caused by mutations in one of the DNA mismatch repair (MMR) genes, in particular, MLH1, MSH2, MSH6 and PMS2. Lynch syndrome mutation carriers are at a high risk of developing colorectal cancer (CRC) and gynecological cancers, and as such, targeted screening programs have been developed. The primary objective of this thesis was to determine the phenotypic expression of three different MSH2 mutations causing LS in Newfoundland and to examine the impact of screening in this group of MSH2 mutation earners. -- Methods: Age to onset of first CRC, first extracolonic cancers and death were compared for those with an intron 5 splice site mutation, an exon 8 deletion and an exon 4-16 deletion. To determine the impact of colonoscopic screening in male and female MSH2 mutation carriers, CRC incidence and survival in the screened group was compared to that expected, derived from the non-screened group. To correct for survivor bias controls were matched for age at entry into screening and also for gender. Compliance with screening recommendations of colonoscopy every 1-2 years was also addressed. Gynecological cancer incidence and overall survival was compared in females who received gynecological screening and in matched controls. Controls were randomly selected from non-screened mutation carriers who were alive and disease-free at the age the case entered the screening program. One matched control was selected for each case. -- Results: For all three mutations males had a higher age-related risk of CRC and death compared to females. For the intron 5 splice site mutation carriers, the number of transitional cell cancers of the urinary tract was significantly lower and time to first ovarian cancer was significantly higher than in the carriers of the genomic deletions. Median age to CRC was 58 years in males who received colonoscopic screening whereas expected was 47 years (P<.0001), and median survival in screened males was 66 years compared to expected of 62 years (P=.034). In females, median age to CRC in the colonoscopic screened group was 79 years, whereas in the non-screened group it was 57 years (P=.000), and median survival was 80 years in the screened group compared to expected of 63 years (P=.001). Eight of 41 (20%) males and five of 68 (7%) females who had serial screening colonoscopies developed an interval CRC within 2 years of previous colonoscopy. Endometrial or ovarian cancer occurred in 14 of 54 (26%) women in the gynecological screened group. Median age to diagnosis of gynecological cancer was 54 years in the screened group compared to 56 years in matched controls (P=.50). Stage I or II cancer was diagnosed in 92% of screened patients compared to 71% in the control group (P=.17). Mean survival in the screened group was 79 years compared to 69 years in the matched control group (P=.11), likely associated with concomitant colonoscopic screen mg. -- Conclusions: The incidence of CRC in MSH2 mutation carriers, exposed to the same environment, is not modified by the specific mutation, although there is a suggestion that type of mutation may influence development of some extracolonic cancers. For both males and females, colonoscopic screening was associated with decreased CRC risk, later age of onset, and better survival than expected if non-screened; however, CRCs continued to occur. CRC development may be further reduced by decreasing the screening interval to one year in MSH2 mutation carriers and improving compliance and quality of colonoscopic examination. Gynecological screening did not result in earlier gynecologic cancer detection and despite screening two young women died from ovarian cancer suggesting that prophylactic hysterectomy with bilateral salpingo-oophorectomy be considered in female mutation carriers who have completed childbearing

Serotonin Transporter Gene (<em>SLC6A4</em>) Variations Are Associated with Poor Survival in Colorectal Cancer Patients

<div><p>Prognosis in colorectal cancer patients is quite variable, even after adjustment for clinical parameters such as disease stage and microsatellite instability status. It is possible that the psychological distress experienced by patients, including anxiety and depression, may be correlated with poor prognosis. In the present study, we hypothesize that genetic variations within three genes biologically linked to the stress response, namely serotonin transporter (<em>SLC6A4</em>), brain-derived neurotrophic factor (<em>BDNF</em>), and arginine vasopressin receptor (<em>AVPR1B</em>) genes are associated with prognosis in colorectal cancer patients. We used a population-based cohort of 280 patients who were followed for up to 12.5 years after diagnosis. Our multivariate analysis showed that a tagSNP in the <em>SLC6A4</em> gene (rs12150214) was a predictor of shorter overall survival (HR: 1.572, 95%CI: 1.142–2.164, p = 0.005) independent of stage, age, grade and MSI status. Additionally, a multivariate analysis using the combined genotypes of three polymorphisms in this gene demonstrated that the presence of any of the minor alleles at these polymorphic loci was an independent predictor of both shorter overall survival (HR: 1.631, 95%CI: 1.190–2.236, p = 0.002) and shorter disease specific survival (HR: 1.691, 95%CI: 1.138–2.512, p = 0.009). The 5-HTT protein coded by the <em>SLC6A4</em> gene has also been implicated in inflammation. While our results remain to be replicated in other patient cohorts, we suggest that the genetic variations in the <em>SLC6A4</em> gene contribute to poor survival in colorectal cancer patients.</p> </div

Kaplan-Meier survival curves for patients grouped based on the <i>SLC6A4</i>-rs12150214 genotype data.

<p><b>a)</b> OS (p = 0.030, log-rank test), <b>b)</b> DFS (p = 0.225, log-rank test), and <b>c)</b> DSS (p = 0.159, log-rank test). Time is shown in years.</p

Multivariate analysis results for the combined genotypes of three SNPs within the <i>SLC6A4</i> gene (OS).

<p>Multivariate analysis results for overall survival. <b>(+):</b> patients with at least one minor (variant) allele in any of the three <i>SLC6A4</i> SNPs, <b>(−):</b> patients who did not have the variant allele in any of the three <i>SLC6A4</i> SNPs, <b>OS:</b> overall survival.</p

Multivariate analysis results for the combined genotypes of three SNPs within the <i>SLC6A4</i> gene (DSS).

<p>Multivariate analysis results for disease-specific survival. <b>(+):</b> patients with at least one minor (variant) allele in any of the three <i>SLC6A4</i> SNPs, <b>(−):</b> patients who did not have the variant allele in any of the three <i>SLC6A4</i> SNPs, <b>DSS:</b> disease-specific survival.</p

Genes and SNPs investigated in this study.

<p>Summary of the genetic variations included in this study. <b>MAF:</b> minor allele frequency, <b>SNP ID:</b> dbSNP database <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0038953#pone.0038953-Sherry1" target="_blank">[41]</a> SNP identifiers.</p

Kaplan-Meier survival curves for the combined genotypes of three <i>SLC6A4</i> polymorphisms.

<p> <b>a)</b> OS (p = 0.005, log-rank test), <b>b)</b> DFS (p = 0.104, log-rank test), and <b>c)</b> DSS (p = 0.008, log-rank test). Time is shown in years.</p

The 5-HTT activity may be altered as a response to changing cellular environment (such as inflammation) or by the genetic variations in the <i>SLC6A4</i> gene.

<p>The direct links between the altered 5-HTT activity as well as the depression and prognosis in colorectal cancer patients (arrows with broken lines) remain to be established by further studies.</p