Medications That Cause Dry Mouth As an Adverse Effect in Older People: A Systematic Review and Metaanalysis.

OBJECTIVES: To assess and quantify the risk of drug-induced dry mouth as a side effect in older people. DESIGN: Systematic review and metaanalysis. SETTING: A search of the literature was undertaken using Medline, Embase, Cochrane, Web of Science, and PubMed from 1990 to 2016. PARTICIPANTS: Older people (aged ≥60) who participated in intervention or observational studies investigating drug use as an exposure and xerostomia or salivary gland hypofunction as adverse drug outcomes. MEASUREMENTS: Two pairs of authors screened titles and abstracts of studies for relevance. Two authors independently extracted data, including study characteristics, definitions of exposure and outcome, and methodological quality. For the metaanalyses, random-effects models were used for pooling the data and I2 statistics for exploring heterogeneity. RESULTS: Of 1,544 potentially relevant studies, 52 were deemed eligible for inclusion in the final review and 26 in metaanalyses. The majority of studies were of moderate methodological quality. In the intervention studies, urological medications (odds ratio (OR) = 5.91, 95% confidence interval (CI) = 4.04-8.63; I2  = 62%), antidepressants (OR = 4.74, 95% CI = 2.69-8.32, I2  = 21%), and psycholeptics (OR = 2.59, 95% CI = 1.79-3.95, I2  = 0%) were significantly associated with dry mouth. In the observational studies, numbers of medications and several medication classes were significantly associated with xerostomia and salivary gland hypofunction. CONCLUSION: Medication use was significantly associated with xerostomia and salivary gland hypofunction in older adults. The risk of dry mouth was greatest for drugs used for urinary incontinence. Future research should develop a risk score for medication-induced dry mouth to assist with prescribing and medication management.

Use of antiepileptic drugs and risk of falls in old age: A systematic review.

OBJECTIVE: The aim of this study is to systematically review the scientific literature to investigate if use of antiepileptic drugs (AEDs) is associated with falls and/or recurrent falls in old age. METHOD: We searched the literature for relevant articles in PubMed and Embase published up until 3rd December 2015. Studies on people aged 60 years and over with an observational design assessing the risk of fall in people exposed to AEDs compared to people not exposed to AED were included. RESULTS: We found 744 studies by searching Medline and Embase and an additional 9 studies by reviewing relevant reference lists. Of these studies, 13 fulfilled our predefined criteria. The articles were of various study design, sizes and follow-up times, and presented the results in different ways. Also, confounder adjustment varied considerably between the studies. Ten studies presented results for the association between use of any AED and any fall/injurious fall. Of these studies, 6 presented adjusted estimates, of which all but one showed statistically significant associations between use of any AED and any fall/injurious fall. Six studies investigated the association between use of any AED and recurrent falls. Of these, only 3 studies presented adjusted effect estimates of which 2 reached statistical significance for the association between use of AEDs and recurrent falls in elderly people. CONCLUSION: Our results indicate an association between use of AEDs and risk of falls and recurrent falls in older people. This finding may be clinically important given that a substantial amount of older people use these drugs. However, further research is needed to increase the knowledge about the actual risk of falls when using these drugs in old age.

Use of Fall-Risk Inducing Drugs in Patients Using Anti-Parkinson Drugs (APD): A Swedish Register-Based Study.

OBJECTIVES: Many drugs increase the risk of falls in old age. Although persons with Parkinson's disease (PD) are at increased risk of experiencing falls and fractures, the use of fall-risk inducing drugs (FRIDs) in this population has not previously been investigated. The objective of this study was to investigate the burden of use of FRIDs in older persons treated with anti-Parkinson drugs (APD; used as a proxy for PD), compared to persons without APD. METHODS: We analyzed individual data on age, sex, type of housing and drug use in 1 346 709 persons aged ≥ 65 years in the Swedish Prescribed Drug Register on the date of 30 September 2008. Main outcome measure was the use of FRIDs. RESULTS: FRIDs were used by 79% of persons with APD and 75% of persons without APD. Persons with APD were more likely to use ≥ 1 FRIDs compared to persons without APD (adjusted OR: 1.09; 95% CI: 1.06-1-12). The association was stronger for concomitant use of ≥ 5 FRIDS (adjusted OR: 1.49; 95% CI: 1.44-1.55). CONCLUSIONS: The high use of FRIDs among persons with APD indicates that these patients may be at increased risk of drug-induced falls. Further studies are needed to investigate how these drugs affect the risk of falling in persons with PD.

Use of antidepressants in Parkinson's disease: A Swedish register-based study of over 1.5 million older people.

INTRODUCTION: It has been suggested that depression in Parkinson's Disease (PD) is often unrecognized and undertreated. However, few previous studies have studied the use of antidepressants in a large sample of both home-dwelling and institutionalized elderly persons with PD. We aimed to study the use of antidepressants in older persons using anti-parkinson drugs (APD, used as a proxy for PD), stratified by residential setting. METHODS: We analyzed individual data on age, sex, residential setting and drug use in over 1.5 million older persons in the Swedish Prescribed Drug Register on 31th of December 2013. RESULTS: Twenty-two percent of the home-dwellers and 50% of the institutionalized elderly persons with APD used antidepressants. Persons with APD had a higher probability of use of any antidepressant compared to persons without APD. A selective serotonin reuptake inhibitor (SSRI) was the most commonly used antidepressants in both settings followed by mirtazapin. CONCLUSIONS: The high use of antidepressants among older persons with APD warrants further studies on the quality of treatment of depression in PD.

Different patterns in use of antibiotics for lower urinary tract infection in institutionalized and home-dwelling elderly: a register-based study.

PURPOSE: We compared the quality and pattern of use of antibiotics to treat urinary tract infection (UTI) between institutionalized and home-dwelling elderly. METHODS: We analyzed the quality of use of UTI antibiotics in Swedish people aged ≥ 65 years at 30 September 2008 (1,260,843 home-dwelling and 86,721 institutionalized elderly). Data regarding drug use, age and sex were retrieved from the Swedish Prescribed Drug Register and information about type of housing from the Social Services Register. In women, we assessed: (1) the proportion who use quinolones (should be as low as possible); (2) the proportion treated with the recommended drugs (pivmecillinam, nitrofurantoin, or trimethoprim) (proportions should be about 40 %, 40 % and 15-20 %, respectively); In men, we assessed: (1) the proportion who used quinolones or trimethoprim (should be as high as possible). RESULTS: The 1-day point prevalence for antibiotic use for UTI was 1.6 % among institutionalized and 0.9 % among home-dwelling elderly. Of these, about 15 % of institutionalized and 19 % of home-dwelling women used quinolones. The proportion of women treated with the recommended drugs pivmecillinam, nitrofurantoin or trimethoprim was 29 %, 27 % and 45 % in institutions and 40 %, 28 % and 34 % for home-dwellers. In men treated with antibiotics for UTI, quinolones or trimethoprim were used by about 76 % in institutions and 85 % in home-dwellers. CONCLUSIONS: Our results indicate that recommendations for UTI treatment with antibiotics are not adequately followed. The high use of trimethoprim amongst institutionalized women and the low use of quinolones or trimethoprim among institutionalized men need further investigation.

Institutionalization as a risk factor for inappropriate drug use in the elderly: a Swedish nationwide register-based study.

BACKGROUND: Few studies have investigated institutionalization as a potential risk factor for potentially inappropriate drug use (PIDU). Sweden now has unique possibilities for comparisons of drug use in large populations of institutionalized and home-dwelling elderly through linkage of the Swedish Prescribed Drug Register (SPDR) with the Swedish Social Services Register. OBJECTIVE: To compare PIDU in institutionalized versus home-dwelling elderly persons in Sweden. METHODS: We conducted a cross-sectional retrospective study of 1,260,843 home-dwelling and 86,721 institutionalized elderly individuals. We analyzed data on age, sex, and dispensed drugs for individuals aged 65 years or older registered in the SPDR from July to September 2008. Data on type of housing were retrieved from the Social Services Register. The main outcome measures of PIDU were use of anticholinergic drugs, long-acting benzodiazepines, concurrent use of 3 or more psychotropics, and potentially serious drug-drug interactions (DDIs). RESULTS: Thirty percent of the institutionalized and 12% of the home-dwelling elderly were exposed to PIDU. Living in an institution was strongly associated with overall PIDU (OR 2.36; 95% CI 2.29 to 2.44), use of anticholinergic drugs (OR 2.58; 95% CI 2.48 to 2.68), long-acting benzodiazepines (OR 1.50; 95% CI 1.41 to 1.60), and concurrent use of 3 or more psychotropics (OR 7.26; 95% CI 6.96 to 7.59), after controlling for age, sex, and number of drugs (used as proxy for comorbidity). However, institutionalization was associated with a lower probability of potentially serious DDIs (OR 0.60; 95% CI 0.55 to 0.65). CONCLUSIONS: Our results indicate that institutionalization is a potential risk factor for PIDU. This implies that more cautious prescribing is warranted in institutions, where the frailest and most vulnerable elderly individuals reside. Research is needed to identify underlying risk factors for PIDU within these settings.

Pain treatment in elderly persons with and without dementia: a population-based study of institutionalized and home-dwelling elderly.

BACKGROUND: Several previous studies have reported an undertreatment of pain in elderly persons with dementia. It has also been suggested that persons with dementia may be at risk for inappropriate treatment of pain with psychotropics. OBJECTIVES: The objective of this study was to investigate if persons with dementia are as likely as persons without dementia to receive pharmacological pain treatment, after taking into account residential setting and pain-related disorders. We also aimed to investigate whether use of psychotropics is related to pain in persons with and without dementia. METHODS: We used baseline data from the SNAC-K (Swedish National Study of Aging and Care - Kungsholmen). We analysed use of analgesics and psychotropics, prevalence of pain-related diagnoses, self-reported pain, dementia status and residential setting in 2610 participants aged > 65 years. RESULTS: Of the persons with dementia, 46% used at least one analgesic drug compared with 25% of those without dementia. Although persons with dementia reported pain less frequently than persons without dementia, the prevalence of pain-related diagnoses was similar. After adjustment for individual factors and residential setting (own home/institution), persons with dementia had a higher probability of use of paracetamol (acetaminophen) and psychotropics, whereas there were no significant differences in use of any analgesic, opioids and NSAIDs. Furthermore, having a pain-related diagnosis was associated with use of psychotropics in persons with dementia. CONCLUSIONS: Persons with dementia had a higher probability of use of paracetamol and were about as likely as persons without dementia to use any analgesic, opioids and NSAIDs, after adjustment for confounders. This may reflect a recent increased awareness of pain and pain management in persons with dementia, compared with previous studies that have reported an underuse of analgesics in persons with dementia. However, further research is needed to analyse if persons with dementia are appropriately treated for pain with regard to type of analgesic drug, pain intensity, indication, dosage and regimen.

A proteolytic cascade of kallikreins in the stratum corneum.

Serine proteases belonging to the kallikrein group may play a central role in desquamation. We have identified human kallikreins 5, 7, and 14 (hK5, hK7, hK14) in catalytically active form in stratum corneum. All three enzymes are produced as inactive precursors. In this work, we prepared recombinant enzymes and enzyme precursors and characterized the catalytic properties of hK5 and hK14. With peptide substrates hK5 and hK14 both showed trypsin-like specificity and alkaline pH-optima. For the substrates tested, hK14 was superior to hK5 as regards maximum catalytic rate as well as catalytic efficiency. hK5, but not hK14, could activate pro-hK7 in a reaction which was optimal at pH 5-7. hK5 could activate its own precursor as well as pro-hK14. This was in contrast to hK14, which could activate pro-hK5 but not its own precursor. The activation of pro-hK5 either by auto-activation or by hK14 occurred at maximum rate at neutral or weakly alkaline pH, whereas activation of pro-hK14 by hK5 was optimal at pH 6-7. We conclude that the enzymes studied may be part of a protease cascade in the stratum corneum, and that the observed pH effects may have physiological relevance.