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  1. Zia A, Kamaruzzaman SB, Tan MP
    Postgrad Med, 2015 Mar;127(2):186-93.
    PMID: 25622817 DOI: 10.1080/00325481.2015.996505
    Hypertension is a highly prevalent condition among older people, but many physicians avoid aggressive treatment in this age group due to concerns about adverse effects such as orthostatic hypotension and falls. Orthostatic hypotension, which also increases in prevalence with increasing age, has been considered to be associated with antihypertensive therapy. Both orthostatic hypotension and antihypertensive medications are considered independent yet closely related predictors for falls among older people. The prescription of antihypertensive therapy among the elderly remains a long-standing controversy in geriatric medicine due to ongoing concerns about potential complications such as falls, despite conclusive evidence supporting the treatment of hypertension even among the very elderly. However, recent evidence suggests a dose-dependent relationship between blood pressure lowering therapy and falls among older individuals with preexisting risk factors for falls. In response to the spate of revisions in hypertension treatment targets for older patients in international guidelines and the recent evidence on antihypertensive therapy and falls, this review article examines the complex relationship between hypertension, antihypertensives, orthostatic hypotension, and falls among older patients.
  2. Zia A, Kamaruzzaman SB, Tan MP
    Postgrad Med, 2015 Apr;127(3):330-7.
    PMID: 25539567 DOI: 10.1080/00325481.2014.996112
    The term polypharmacy has negative connotations due to its association with adverse drug reactions and falls. This spectrum of adverse events widens when polypharmacy occurs among the already vulnerable geriatric population. To date, there is no consensus definition of polypharmacy, and diverse definitions have been used by various researchers, the most common being the consumption of multiple number of medications. Taking multiple medications is considered a risk factor for falls through the adverse effects of drug-drug or drug-disease interactions. Falls studies have determined that taking ≥ 4 drugs is associated with an increased incidence of falls, recurrent falls, and injurious falls. In light of existing evidence, careful and regular medication reviews are advised to reduce the effect of polypharmacy on falls. However, intervention studies on medication reviews and their effectiveness on falls reduction have been scarce. This article reviews and discusses the evidence behind polypharmacy and its association with falls among older individuals, and highlights important areas for future research.
  3. Zia A, Kamaruzzaman SB, Tan MP
    Geriatr Gerontol Int, 2017 Mar;17(3):463-470.
    PMID: 26822931 DOI: 10.1111/ggi.12741
    AIM: The presemt study aimed to determine the association between the risk of recurrent and injurious falls with polypharmacy, fall risk-increasing drugs (FRID) and FRID count among community-dwelling older adults.

    METHODS: Participants (n = 202) were aged ≥65 years with two or more falls or one injurious fall in the past year, whereas controls (n = 156) included volunteers aged ≥65 years with no falls in the past year. A detailed medication history was obtained alongside demographic data. Polypharmacy was defined as "regular use of five or more prescription drugs." FRID were identified as cardiovascular agents, central nervous system drugs, analgesics and endocrine drugs; multiple FRID were defined as two or more FRID. Multiple logistic regression analyses were used to adjust for confounders.

    RESULTS: The use of non-steroidal anti-inflammatory drugs was independently associated with an increased risk of falls. Univariate analyses showed both polypharmacy (OR 2.23, 95% CI 1.39-3.56; P = 0.001) and the use of two or more FRID (OR 2.9, 95% CI 1.9-4.5; P = 0.0001) were significantly more likely amongst fallers. After adjustment for age, sex and comorbidities, blood pressure, and physical performance scores, polypharmacy was no longer associated with falls (OR 1.6, 95% CI 0.9-2.9; P = 0.102), whereas the consumption of two or more FRID remained a significant predictor for falls (OR 2.8, 95% CI 1.4-5.3; P = 0.001).

    CONCLUSIONS: Among high risk fallers, the use of two or more FRID was an independent risk factor for falls instead of polypharmacy. Our findings will inform clinical practice in terms of medication reviews among older adults at higher risk of falls. Future intervention studies will seek to confirm whether avoidance or withdrawal of multiple FRID reduces the risk of future falls. Geriatr Gerontol Int 2017; 17: 463-470.

  4. Zia A, Kamaruzzaman S, Myint PK, Tan MP
    Maturitas, 2016 Feb;84:32-7.
    PMID: 26531071 DOI: 10.1016/j.maturitas.2015.10.009
    OBJECTIVE: While the anticholinergic activity of medications has been linked to cognitive decline, few studies have linked anticholinergic burden with falls in older people. We evaluated the relationship between anticholinergic burden and recurrent and injurious falls among community-dwelling older adults.
    STUDY DESIGN: This case-control study was performed on 428 participants aged ≥65 years, 263 cases with two or more falls or one injurious fall in the preceding 12 months, and 165 controls with no falls in the preceding 12 months. Anticholinergic burden was determined using the anticholinergic cognitive burden (ACB) scale. Upper and lower limb functional abilities were assessed with timed up and go (TUG), functional reach (FR) and grip strength (GS). Logistic regression analysis was employed to calculate the mediation effect of TUG, FR and GS on ACB associated falls.
    RESULTS: Univariate analysis revealed a significant association between an ACB score of ≥1 with falls (OR, 1.8; 95% CI; 1.1-3.0; p=0.01) and significantly poorer TUG and FR. The association between ACB≥1 and falls was no longer significant after adjustment for either TUG (OR for ACB associated falls, 1.4; 95% CI, 0.88-2.4; p=0.14) or FR (OR for ACB associated falls, 1.4; 95% CI, 0.89-2.4, p=0.12) but remained significant with GS.
    CONCLUSION: The association between recurrent and injurious falls and the use of any medications listed in the ACB scale was mediated through gait and balance impairment but not by muscular weakness, providing a novel insight into the potential mechanistic link between ACB and falls. Future studies should determine whether TUG and FR measurements could help inform risk to benefit decisions where ACB medications are being considered.
    KEYWORDS: Aged; Anticholinergic Cognitive Burden; Falls; Functional Reach; Scale; Timed up and go
  5. Zia A, Kamaruzzaman SB, Myint PK, Tan MP
    Eur J Clin Invest, 2015 Oct;45(10):1069-76.
    PMID: 26214159 DOI: 10.1111/eci.12508
    A drop in postural blood pressure (BP) may contribute to falls, while antihypertensives have been considered to induce postural drop or orthostatic hypotension (OH) and falls among older people. However, this relationship between antihypertensives, postural BP and the risk of falls has never been evaluated in a single study.
  6. Taher AT, Origa R, Perrotta S, Kouraklis A, Ruffo GB, Kattamis A, et al.
    Health Qual Life Outcomes, 2018 Nov 19;16(1):216.
    PMID: 30453981 DOI: 10.1186/s12955-018-1041-5
    BACKGROUND: Adherence to long-term chelation therapy in transfusion-dependent patients is critical to prevent iron overload-related complications. Once-daily deferasirox dispersible tablets (DT) have proven long-term efficacy and safety in patients ≥2 years old with chronic transfusional iron overload. However, barriers to optimal adherence remain, including palatability, preparation time, and requirements for fasting state. A new film-coated tablet (FCT) formulation was developed, swallowed once daily (whole/crushed) with/without a light meal.

    METHODS: The open-label, Phase II ECLIPSE study evaluated patient-reported outcomes (PROs) in transfusion-dependent thalassemia or lower-risk myelodysplastic syndromes patients randomized 1:1 to receive deferasirox DT or FCT over 24 weeks as a secondary outcome of the study. Three PRO questionnaires were developed to evaluate both deferasirox formulations: 1) Modified Satisfaction with Iron Chelation Therapy Questionnaire; 2) Palatability Questionnaire; 3) Gastrointestinal (GI) Symptom Diary.

    RESULTS: One hundred seventy three patients were enrolled; 87 received the FCT and 86 the DT formulation. FCT recipients consistently reported better adherence (easier to take medication, less bothered by time to prepare medication and waiting time before eating), greater satisfaction/preference (general satisfaction and with administration of medicine), and fewer concerns (less worry about not swallowing enough medication, fewer limitations in daily activities, less concern about side effects). FCT recipients reported no taste or aftertaste and could swallow all their medicine with an acceptable amount of liquid. GI summary scores were low for both formulations.

    CONCLUSIONS: These findings suggest a preference in favor of the deferasirox FCT formulation regardless of underlying disease or age group. Better patient satisfaction and adherence to chelation therapy may reduce iron overload-related complications.

    TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT02125877; registered April 26, 2014.

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