OBJECTIVE: Deprescribing opportunities may differ across health care systems, nursing home settings, and prescribing cultures. The objective of this study was to compare the prevalence of STOPPFrail medications according to frailty status among residents of nursing homes in Australia, China, Japan, and Spain.
METHODS: Secondary cross-sectional analyses of data from 4 cohort studies.
METHODS: A total of 1142 residents in 31 nursing homes.
METHODS: Medication data were extracted from resident records. Frailty was assessed using the FRAIL-NH scale (non-frail 0-2; frail 3-6; most-frail 7-14). Chi-square tests and prevalence ratios (PRs) were used to compare STOPPFrail medication use across cohorts.
RESULTS: In total, 84.7% of non-frail, 95.6% of frail, and 90.6% of most-frail residents received ≥1 STOPPFrail medication. Overall, the most prevalent STOPPFrail medications were antihypertensives (53.0% in China to 73.3% in Australia, P < .001), vitamin D (nil in China to 52.7% in Australia, P < .001), lipid-lowering therapies (11.1% in Japan to 38.9% in Australia, P < .001), aspirin (13.5% in Japan to 26.2% in China, P < .001), proton pump inhibitors (2.1% in Japan to 32.0% in Australia, P < .001), and antidiabetic medications (12.3% in Japan to 23.5% in China, P = .010). Overall use of antihypertensives (PR, 1.15; 95% CI, 1.06-1.25), lipid-lowering therapies (PR, 1.78; 95% CI, 1.45-2.18), aspirin (PR, 1.31; 95% CI, 1.04-1.64), and antidiabetic medications (PR, 1.31; 95% CI, 1.00-1.72) were more prevalent among non-frail and frail residents compared with most-frail residents. Antihypertensive use was more prevalent with increasing frailty in China and Japan, but less prevalent with increasing frailty in Australia. Antidiabetic medication use was less prevalent with increasing frailty in China and Spain but was consistent across frailty groups in Australia and Japan.
CONCLUSIONS: There were overall and frailty-specific variations in prevalence of different STOPPFrail medications across cohorts. This may reflect differences in prescribing cultures, application of clinical practice guidelines in the nursing home setting, and clinician or resident attitudes toward deprescribing.

Deprescribing reduces polypharmacy in older adults. A thorough study of the effect of deprescribing interventions on clinical outcomes in older adults is presently lacking. As a result, we evaluated the impact of deprescribing on clinical outcomes in older patients.
Meta-analysis and systematic review of randomized controlled trials (RCTs). PubMed, EMBASE, and Cochrane Library were searched from the time of creation to March 2023.
Randomized controlled trial with participants at least 60 years old.
Mortality, falls (number of fallers), hospitalization rates, emergency department visits, medication adherence, HRQoL (health-regulated quality of life), incidence of ADR (adverse drug reactions), PIM (potentially inappropriate medication), and PPO (potentially prescription omission) were evaluated in the meta-analysis.
A total of 32 RCTs (18,670 patients) were included. Deprescribing interventions significantly reduced proportions of older adults with PIM, PPO, and the incidence of ADRs. The interventions group also improved medication compliance.
Compared to routine care, deprescribing interventions significantly improve clinical outcome indicators for older adults.

Objective: This study aimed to observe whether the treatment-free remission (TFR) of second-generation tyrosine kinase inhibitors (TKI) in chronic myeloid leukemia (CML) is better than imatinib (IM) . Methods: The clinical data of 274 CML patients who discontinued treatment and with complete clinical data were retrospectively studied from June 2013 to March 2021. Using both univariate and multivariate Cox proportional hazards regression models, risk factors influencing TFR outcomes after drug withdrawal in CML patients were assessed. Results: A total of 274 patients were enrolled, 140 patients were women (51.1%) , with a median age of 48 (9-84) years at the time of TKI discontinuation. Prior to TKI discontinuation, 172 (62.8%) patients were treated with IM, and 102 (37.2%) had received second-generation TKI treatment, including 73 patients who had shifted from IM to a second-generation TKI and 29 patients who used second-generation TKI as the first-line treatment. The rationale for converting to a second-generation TKI are as follows: 37 patients aimed deep molecular response (DMR) to achieve TFR, seven patients changed due to IM intolerance, and 29 patients changed because of failure to achieve the optimal treatment response. The use of the last type of TKI included 96 patients (94.1%) with nilotinib, three patients (2.9%) with dasatinib, and two patients (2%) with flumatinib, including one patient who changed to IM due to second-generation TKI intolerance. No statistical differences were found in the median age at diagnosis and TKI discontinuation, sex, Sokal score, IFN treatment before TKI, median time of TKI treatment to achieve DMR, and the reasons for TKI discontinuation between the second TKI and IM (P>0.05) .The median cumulative treatment time of TKI (71.5 months vs 88 months, P<0.001) , the last TKI median treatment time (60 months vs 88 months, P<0.001) , and the median duration of DMR (58 months vs 66 months, P=0.002) were significantly shorter in the second-generation TKI compared with IM. In the median follow-up of 22 (6-118) months after TKI discontinuation, 88 patients (32.1%) had lost their MMR at a median of 6 (1-91) months; of the 53 patients (60.2%) who lost MMR within 6 months, the overall TFR rate was 67.9%, and the cumulative TFR rates at 12 and 24 months were 70.5% and 67.5%, respectively. Withdrawal syndrome occurred in 26 patients (9.5%) . For patients who restarted TKI treatment, 72 patients (83.7%) achieved DMR again at a median treatment of 4 (1 to 18) months. The univariate analysis showed that the TFR rate of patients treated with second-generation TKI was significantly higher than those who were treated with IM (77.5% vs 62.2%, P=0.041) . A further subgroup analysis found that the TFR rate of the second-generation TKI patients was significantly higher than those treated with IM (80.8% vs 62.2%, P=0.026) . No significant difference was found in the second-generation TKI used as the first line treatment compared with those who were treated with IM (69.0% vs 62.2%, P=0.599) . The multivariate analysis results showed that second-generation TKI treatment was an independent prognostic factor affecting TFR in patients who discontinued TKI (RR=1.827, 95%CI 1.015-3.288, P=0.044) . Conclusion: In the clinical setting, more CML patients rapidly achieved TFR using second-generation TKI than IM treatment.
目的： 观察真实世界中酪氨酸激酶抑制剂（TKI）治疗慢性髓性白血病（CML）停药患者的无治疗缓解（treatment free remission, TFR）情况，及二代TKI在TFR方面是否优于伊马替尼（IM）。 方法： 对来自国内8家血液病治疗中心的自2013年6月至2021年3月期间停用TKI且有明确停药结局和相对完整临床资料的274例CML患者进行回顾性分析，使用单因素分析和多因素Cox比例风险回归模型评估影响CML患者停药后TFR结局的危险因素。 结果： 274例患者，女性140例（51.1%），停药时中位年龄48（9~84）岁。停药前，172例（62.8%）患者应用IM治疗，102例（37.2%）接受过二代TKI治疗，包括73例IM转换二代TKI者和29例一线二代TKI治疗者。转换二代TKI的原因包括：37例因追求TFR在IM治疗获得深层分子学反应（DMR）期间转换二代TKI、7例因IM不良反应不耐受、29例因TKI治疗未达最佳治疗反应。接受过二代TKI者末次应用TKI类型包括：尼洛替尼96例（94.1%），达沙替尼3例（2.9%），氟马替尼2例（2.0%），1例为二代TKI不耐受再次更换为IM治疗。IM治疗组和二代TKI治疗组在确诊时中位年龄、停药时中位年龄、性别、Sokal评分、TKI治疗前是否应用干扰素、TKI治疗至获得DMR中位时间、停药原因等基线特征差异均无统计学意义（P值均>0.05）。停药前TKI中位累积治疗时间（71.5个月对88个月，P<0.001）、末次TKI中位治疗时间（60个月对88个月，P<0.001）、DMR中位持续时间（58个月对66个月，P=0.002），二代TKI治疗组均较IM治疗组显著缩短。停药后中位随访22（6~118）个月，88例（32.1%）患者在中位6（1~91）个月失去主要分子学反应（MMR），其中53例（60.2%）患者在≤6个月内失去MMR，总体的TFR率67.9%，12个月和24个月的累积TFR率分别为70.5%和67.5%。26例（9.5%）患者发生停药综合征。72例（83.7%）重启TKI治疗患者在中位治疗4（1~18）个月再次获得DMR。单因素分析结果显示，停药前应用二代TKI治疗组患者的TFR率显著高于IM治疗组（77.5%对62.2%，P=0.041）。进一步亚组分析发现，IM转换二代TKI治疗组患者的TFR率显著高于IM治疗组（80.8%对62.2%，P=0.026），二代TKI一线治疗组和IM治疗组TFR率差异无统计学意义（69.0%对62.2%，P=0.599）。多因素分析结果显示，应用二代TKI治疗是影响停药患者TFR的独立预后因素（RR=1.827，95%CI 1.015~3.288，P=0.044）。 结论： 真实世界中，二代TKI治疗较IM治疗使更多的CML患者更早获得更好的TFR。.

Inappropriate prescribing of medications and polypharmacy among older adults are associated with a wide range of adverse outcomes. It is critical to understand the attitudes towards deprescribing-reducing the use of potentially inappropriate medications (PIMs)-among this vulnerable group. Such information is particularly lacking in low - and middle-income countries.
In this study, we examined Chinese community-dwelling older adults\' attitudes to deprescribing as well as individual-level correlates. Through the community-based health examination platform, we performed a cross-sectional study by personally interviews using the revised Patients\' Attitudes Towards Deprescribing (rPATD) questionnaire (version for older adults) in two communities located in Suzhou, China. We recruited participants who were at least 65 years and had at least one chronic condition and one prescribed medication.
We included 1,897 participants in the present study; the mean age was 73.8 years (SD = 6.2 years) and 1,023 (53.9%) were women. Most of older adults had one chronic disease (n = 1,364 [71.9%]) and took 1-2 regular drugs (n = 1,483 [78.2%]). Half of the participants (n = 947, 50%) indicated that they would be willing to stop taking one or more of their medicines if their doctor said it was possible, and 924 (48.7%) older adults wanted to cut down on the number of medications they were taking. We did not find individual level characteristics to be correlated to attitudes to deprescribing.
The proportions of participants\' willingness to deprescribing were much lower than what prior investigations among western populations reported. It is important to identify the factors that influence deprescribing and develop a patient-centered and practical deprescribing guideline that is suitable for Chinese older adults.

BACKGROUND: Prolactinoma is the major cause of hyperprolactinemia, and dopamine agonists (DAs) are generally the first-line treatment for them. Several studies have reviewed the recurrent rate of hyperprolactinemia after DAs withdrawal. However, few of them have concerned the recurrence risk of prolactinoma following the withdrawal of DAs.
METHODS: Three medical databases, PubMed, EMBASE and Cochrane library, were retrieved up to February, 14, 2021 to identify studies related to recurrence of prolactinoma and withdrawal of DAs. Statistical analyses including meta-analysis, sensitivity analysis, meta-regression, funnel plot and Egger test were performed through software R.
RESULTS: A total of 3225 studies were retrieved from the three data bases, and 13 studies consisted of 616 patients and 19 arms were finally included in this systematic analysis. There was no significant heterogeneity among the included studies, and fixed effect model was thus used. The pooled recurrence proportion of prolactinoma after withdrawal of DA was 2% with a 95% confidence interval (CI) of 1-3%.
CONCLUSIONS: Our study showed a very low recurrent rate of prolactinomas after DAs withdrawal. Much more prospective studies with larger cases and longer follow-up period are encouraged to confirm our finding.
BACKGROUND: Registration number CRD42021245888 (PROSPERO).

Comprehensive medication review is a patient-centered approach to optimize medication use and improve patient outcomes. This study outlines a pilot model of care in which a remote corporate-based clinical pharmacist implemented comprehensive medication reviews for a cohort of medically complex home-based primary care (HBPC) patients.
Ninety-six medically complex patients were assessed for medication-related problems. Data collected on these patients were: number of chronic conditions, number of medications, appropriate indication for each medication, dose appropriateness, drug interactions, recommendations for medication optimization and deprescribing. The number of accepted recommendations by the HBPC practice was analyzed.
On average, the patients were 82 years old and had 13 chronic conditions. They were taking a median of 17 medications. Over a four-month pilot period, 175 medication recommendations were made, and 53 (30.3%) of them were accepted, with most common being medication discontinuation, deprescribing, and dose adjustments. Sixty-four (66.7%) patients were on a medication listed as potentially inappropriate for use in older adults. The most common potentially inappropriate medication was a proton-pump inhibitor (38.5%), followed by aspirin (24%), tramadol (15.6%), a benzodiazepine (13.5%) or an opioid (8.3%). Eighty-one medications were recommended for deprescribing and 27 medications were discontinued (33.3%). There were 24 recommended dose adjustments and 11 medications were dose adjusted (45.8%). Thirty-four medications were suggested as an addition to the current patient regimen, 2 medications were added (5.9%).
Pharmacist comprehensive medication review is a necessary component of the HBPC healthcare continuum. Additional research is needed to examine whether aligning pharmacists to deliver support to HBPC improves clinical outcomes, reduces healthcare expenditures and improves the patient\'s experience.

This study aimed to examine factors, healthcare utilization, and medical costs associated with potentially inappropriate use of benzodiazepines in persons living with HIV (PLWH). We used big data from Medicare claims in 2017. Potentially inappropriate use of benzodiazepines was defined as having any benzodiazepine claims in individuals 65+ years or having benzodiazepine claims for more than four weeks in individuals 18-64 years. Logistic regressions, zero-inflated negative binomial regressions, and generalized linear models were used. This study included 1,211 PLWH and 235 (19.41%) had potentially inappropriate use of benzodiazepines. PLWH who were 65+ years (OR: 0.56; 95% CI: 0.33, 0.96), non-Hispanic blacks (OR: 0.29; 95% CI: 0.20, 0.41), or Hispanics (OR: 0.55; 95% CI: 0.35, 0.88) were less likely to use benzodiazepines inappropriately. PLWH who had potentially inappropriate use of benzodiazepines had more inpatient (IRR: 1.46; 95% CI: 1.10, 1.94), outpatient (IRR: 1.14; 95% CI 1.02, 1.28), and emergency room (IRR: 1.32; 95% CI: 1.03, 1.68) visits. Potentially inappropriate use of benzodiazepines was associated with higher total (β: 0.16; 95% CI: 0.07, 0.25), Medicare (β: 0.18; 95% CI: 0.07, 0.28), and out-of-pocket (β: 0.21; 95% CI: 0.05, 0.36) costs. This study provides real-world evidence to support deprescribing benzodiazepines in PLWH.

BACKGROUND: In most situations, many patients undergoing coronary artery bypass graft (CABG) are on dual antiplatelet therapy (DAPT), which is also required after CABG. The adjustment of antiplatelet strategy remains controversial. In this study, we systematically review current guidelines, seeking consensus and controversies to facilitate clinical practice.
RESULTS: Guidelines are searched in PubMed, Embase, ECRI Guidelines Trust and websites of guidelines organizations and professional society. Guidelines with recommendations of DAPT for patients undergo CABG are included. Two reviewers appraised guidelines with the Appraisal of Guidelines for Research and Evaluation II (AGREE II). Relevant recommendations are extracted and summarized. A total of 14 guidelines meeting inclusion criteria are selected, with average AGREE II scores from 44% to 86%. Most guidelines score high in domains other than \'applicability\'. Many guidelines are not detailed enough in reporting considerations behind recommendations. Current guidelines are consistent on the management of antiplatelet strategy before elective CABG and using DAPT after surgery for preventing graft vessel occlusion. Evidence is still lacking in urgent CABG and resumption of the previous DAPT after surgery.
CONCLUSIONS: Current guidelines on DAPT in CABG are generally satisfying. Suspending P2Y12 inhibitors while aspirin continued before elective CABG is recommended, as well as 12 months of DAPT following CABG. More evidence is needed to guide antiplatelet therapy in urgent CABG and to prove the benefits of resuming previous DAPT.

To evaluate the efficacy and safety of 2 canakinumab monotherapy tapering regimens in order to maintain complete clinical remission in children with systemic juvenile idiopathic arthritis (JIA).
The study was designed as a 2-part phase IIIb/IV open-label, randomized trial. In the first part, patients received 4 mg/kg of canakinumab subcutaneously every 4 weeks and discontinued glucocorticoids and/or methotrexate as appropriate. Patients in whom clinical remission was achieved (inactive disease for at least 24 weeks) with canakinumab monotherapy were entered into the second part of the trial, in which they were randomized 1:1 into 1 of 2 treatment arms. In arm 1, the dose of canakinumab was reduced from 4 mg/kg to 2 mg/kg and then to 1 mg/kg, followed by discontinuation. In arm 2, the 4 mg/kg dose interval was prolonged from every 4 weeks, to every 8 weeks, and then to every 12 weeks, followed by discontinuation. In both arms, canakinumab exposure could be reduced provided systemic JIA remained in clinical remission for 24 weeks with each step. The primary objective was to assess whether >40% of randomized patients in either arm maintained clinical remission of systemic JIA for 24 weeks in the first part of the study.
In part 1 of the study, 182 patients were enrolled, with 75 of those patients randomized before entering part 2 of the trial. Among the 75 randomized patients, clinical remission was maintained for 24 weeks in 27 (71%) of 38 patients in arm 1 (2 mg/kg every 4 weeks) and 31 (84%) of 37 patients in arm 2 (4 mg/kg every 8 weeks) (P ≤ 0.0001 for arm 1 versus arm 2 among those meeting the 40% threshold). Overall, 25 (33%) of 75 patients discontinued canakinumab, and clinical remission was maintained for at least 24 weeks in all 25 of these patients. No new safety signals were identified.
Reduction of canakinumab exposure may be feasible in patients who have achieved clinical remission of systemic JIA, but consistent interleukin-1 inhibition appears necessary to maintain this response.

Recurrences of COVID-19 were observed in a patient with long-term usage of hydroxychloroquine, leflunomide, and glucocorticoids due to her 30-year history of rheumatoid arthritis (RA). Tocilizumab was applied and intended to target both COVID-19 and RA. However, disease of this patient aggravated after usage of tocilizumab. After the discussion of a multiple disciplinary team (MDT) including rheumatologists, antimicrobial treatments were applied to target the potential opportunistic infections (Pneumocystis jirovecii and Aspergillus fumigatus), which were authenticated several days later via high throughput sequencing. As an important cytokine in immune responses, IL-6 can be a double-edged sword: interference in the IL-6-IL-6 receptor signaling may save patients from cytokine release storm (CRS), but can also weaken the anti-infectious immunity, particularly in rheumatic patients, who may have received a long-term treatment with immunosuppressive/modulatory agents. Thus, we suggest careful considerations before and close monitoring in the administration of tocilizumab in rheumatic patients with COVID-19. Besides tocilizumab, several disease-modifying antirheumatic drugs (DMARDs) can also be applied in the treatment of COVID-19. Therefore, we also reviewed and discussed the application of these DMARDs in COVID-19 condition.