Deprescribing Clonazepam in Primary Care Older Patients: A Feasibility Study

Background: Inappropriate use of clonazepam by the elderly patients is associated with cognitive impairment, delirium and falls. Strategies to optimize its use are important to increase patient safety. Objective: To evaluate the feasibility of a clonazepam deprescription protocol in the elderly. Methods: This is a quasi-experimental study. Elderly people with chronic use of clonazepam and attended in primary care units in two Brazilian municipalities were selected. A deprescription protocol was used, which included five fortnightly meetings between the older adults and the research team, to reduce the dose by 25 %. Patients received instructions on sleep hygiene behaviors and the advantages of clonazepam deprescription; family physicians followed a flowchart for gradual dose reduction. In the 1st and 5th meetings, there were medical appointments for anamnesis and discharge. The monitoring of patients and the application of tests were carried out by the research team. Results: Of the 35 elderly people included in the study, 27 reached the end; 81.5 % achieved deprescription: 22.2 % stopped completely and 59.3 % decreased the dose. At the last meeting, 20 % of elderly patients reported an increase in blood pressure. Conclusions: The high rate of deprescription and the little relevance of clonazepam withdrawal reactions, showed that the use of the protocol was effective. However, the increase in blood pressure and the worsening of sleep quality in the last meeting show the need for adjustment in the last stage of the deprescription process.Trial Registration: The Brazilian Registry of Clinical Trials (ReBEC) RBR-524ys9; registered June 10, 2019.

Efficacy and Safety of TLANDO, A Novel Oral Easy to Prescribe and Use TRT Option

Most widely used testosterone replacement therapy (TRT) products can be inconvenient and cumbersome topical and invasive injectable requiring dose adjustments to attain efficacy. In a pivotal study, a recently approved oral TRT only 26% of patients did not require any dose adjustment. Typically, patients start on a sub-therapeutic dose with gradual dose increases to attain efficacy resulting in additional visit(s) to clinic and pharmacy. Physician research data (N=402) suggested it typically takes 3-6 months of titrations to reach an efficacious dose for majority of patients, a significant barrier in effecting a switch without a period of “efficacy gap”. The requirement of additional visit(s) presents significant challenges for new and current patients desiring to start and to switch to a convenient TRT option, especially in the current COVID-19 pandemic. Recent reports suggest increase of disease severity/mortality in men with low testosterone is possibly due to underlying co-morbidities commonly associated with male hypogonadism. There remains a need for an effective, safe, and easy to use and prescribe product that does not require dose titration. TLANDO is a “triglyceride-free” oral single strength TRT with single dose designed to lymphatically deliver effective and safe levels of testosterone regardless of meal fat content. Moreover, dose titration is prone to some inherent titration decision errors and requires understanding of often complex titration rules. The objective is to assess whether TLANDO, an oral TRT without requiring dose titration, safely restores effective testosterone (T) levels in hypogonadal men. An open-label, single-arm, multicenter study (NCT03242590) was performed with TLANDO in hypogonadal males (N=95). Subjects received orally 225 mg twice a day testosterone undecanoate (TU) for 24 days without dose adjustment. Efficacy was evaluated by % of subjects who achieved daily T Cavg within the eugonadal range. Using 450mg daily dose without dose adjustment, 80% of subjects (95% CI of 72% to 88%) achieved a T Cavg in the normal range and safely restored with mean T Cavg of 476±184 ng/dL post steady state. T restoration was comparable to other non-oral TRT products. TLANDO was well tolerated with no deaths, no drug-related severe AEs, and no hepatic AEs. In conclusion, effective T restoration using TLANDO, an easy to use and prescribe oral TRT option, was confirmed. Minimal AEs were reported with no hepatic AEs. Upon approval, TLANDO will be the first convenient TRT option without requiring dose adjustments; therefore, enabling selection of an efficacious dose from the start of therapy. TLANDO is well suited for new or existing TRT patients desiring a convenient oral option.

Implementing Psychosocial and Environmental Practices for Persons With Dementia in Assisted Living

Assisted living (AL) provides care for a large proportion of residents with dementia. Coincident with the increased focus on reducing off-label use of antipsychotics for people with dementia, providers are encouraged to turn to non-pharmacological practices to address behavioral expressions. This analysis used data from 250 AL communities in seven states, and examined familiarity, use, and practicality of twelve evidence-based practices, including music, pets, and social contact. Although a high percentage of staff reported familiarity and use of some of the practices, interviews with staff indicated that administration was not always consistent with evidence on implementation. Familiarity, use and practicality were associated with AL communities that had more residents with dementia, training on antipsychotics and non-pharmacological practices, policies on gradual dose reduction of psychotropics, and leadership that supported use of practices (p<.05 to <.001). Opportunities and barriers to implementation of these practices will be discussed.

Tinnitus associated with benzodiazepine withdrawal syndrome: A case report and literature review

In light of the ongoing opioid crisis, many have encouraged the medical community as well as local and national US government agencies to reconsider the prevalent use of benzodiazepines. As prescribers continue to weigh the risks and benefits of ongoing benzodiazepine use, care must be taken when the decision is made to taper and discontinue these medications in patients who have been maintained on them chronically. We present a case of an adult patient maintained on a benzodiazepine for several years who developed tinnitus during a gradual dose taper. This patient developed tinnitus within 7 weeks of gradual reduction of the patient's clonazepam dose to 50% of the original dose in an outpatient clinic. The persistence of these symptoms prevented further dose reductions. Upon review of the available literature, several other cases were identified describing development of tinnitus upon discontinuation or tapering of a benzodiazepine. In weighing the risks and benefits of chronic benzodiazepine therapy, tinnitus must be considered as a rare but debilitating and long-term risk of benzodiazepine withdrawal. Providers must be prepared to individualize benzodiazepine tapers and be vigilant about emergence of withdrawal symptoms to prevent undue stress in patients.

Canadian Guidelines on Benzodiazepine Receptor Agonist Use Disorder Among Older Adults

Background Benzodiazepine receptor agonist (BZRA) use disorder among older adults is a relatively common and challenging clinical condition. Method The Canadian Coalition for Seniors’ Mental Health, with financial support from Health Canada, has produced evidencebased guidelines on the prevention, identification, assessment, and management of this form of substance use disorder. Results Inappropriate use of BZRAs should be avoided by considering non-pharmacological approaches to the management of late life insomnia, anxiety, and other common indications for the use of BZRA. Older persons should only be prescribed BZRAs after they are fully informed of alternatives, benefits, and risks associated with their use. Clinicians should have a high index of suspicion for the presence of BZRA use disorders. The full version of these guidelines can be accessed at www.ccsmh.ca Conclusions A person-centred, stepped care approach utilizing gradual dose reductions should be used in the management of BZRA use disorder.

Determination of the Effect of High-Dose Intralipid in Compared to Its Gradual Dose in Very Low Birth Weight Newborns: A Case-control Study

Objective: The aim of this study was to determine the effect of high dose intralipid in compared to its gradual dose in very low birth weight newborns in Iran. Methods: This study was a case-control study that conducted on 104 very low birth weight infants (<1500 g) referred to Akbarabadi hospital of Tehran (Iran) in 2016. The infants were randomly assigned to two groups (case group: 52 vs. control group: 52). The control group received intralipid 20% with a dose of 1 g/kg/24 h in the first and second day of the study, then from 3rd day to 3 g/kg /24h was raised. But, the case group received 3 g/kg/24 h of intralipid 20% from the first day and continued until the end of the study. In both groups, the study lasted for up to 30 days. Data were collected and analyzed using SPSS22 software. Also P-Value <0.05 was considered as a significant level. Results: The results showed mean daily weight gain in case group is higher than control group and this difference was significant statistically (P-Value < 0.05). Also, although the mean of blood sugar, triglyceride, HCO3, the number of positive blood culture and the number of positive CPR in case group were higher than control group, but these differences were not statistically significant (P-Value >0.05). Conclusion: Given that the better and faster growth of newborns in the intralipid group with high-dose in compared to intralipid group with gradual dose, the use of higher initial doses is recommended in newborns with very low birth weight.

Dose Escalation of Vitamin D3 Yields Similar Cryosurgical Outcome to Single Dose Exposure in a Prostate Cancer Model

Vitamin D3 (VD3) is an effective adjunctive agent, enhancing the destructive effects of freezing in prostate cancer cryoablation studies. We investigated whether dose escalation of VD3 over several weeks, to model the increase in physiological VD3 levels if an oral supplement were prescribed, would be as or more effective than a single treatment 1 to 2 days prior to freezing. PC-3 cells in log phase growth to model aggressive, highly metabolically active prostate cancer were exposed to a gradually increasing dose of VD3 to a final dose of 80 nM over a 4-week period, maintained for 2 weeks at 80 nM, and then exposed to mild sublethal freezing temperatures. Results demonstrate that both acute 24-hour exposure to 80 nM VD3 and dose escalation resulted in enhanced cell death following freezing at −15°C or colder, with no significant differences between the 2 exposure regimes. Apoptotic analysis within the initial 24-hour period postfreeze revealed that VD3 treatment induced both caspase 8- and 9-mediated cell death, most notably in caspase 8 at 8-hour postfreeze. These results indicate that both the intrinsic and extrinsic apoptotic pathways are involved in VD3 sensitization prior to freezing. Additionally, both acute and gradual dose escalation regimes of VD3 exposure increase prostate cancer cell sensitivity to mild freezing. Importantly, this study expands upon previous reports and suggests that the combination of VD3 and freezing may offer an effective treatment for both slow growth and highly aggressive prostate cancers.