Symptoms and age of prodromal Alzheimer's disease in Down syndrome: a systematic review and meta-analysis.

The diagnostic criteria for adult-onset Alzheimer's disease (AD) in patients with Down syndrome (DS) have not been standardised. This study investigated the specific symptoms of AD in the prodromal stage of DS, the mean age at diagnosis at each stage of dementia, and the relationship between intellectual disability (ID) and dementia. PubMed, Web of Science, and Embase were searched for studies on DS, AD, early-stage disease, initial symptoms, and prodromal dementia registered between January 2012 and January 2022. We also performed a meta-analysis of the differences between the mean age at prodromal symptoms and AD diagnosis and the proportion of mild cognitive impairment in patients with mild and moderately abnormal ID. We selected 14 articles reporting the behavioural and psychological symptoms of dementia (BPSD) and memory- and language-related impairments as early symptoms of AD in patients with DS. The specific symptoms of BPSD were classified into five categories: irritability (agitation), apathy, abnormal behaviour, adaptive functioning, and sleep disturbance. The mean age at the diagnosis of prodromal symptoms and AD dementia was 52.7 and 56.2 years, respectively (mean difference, + 3.11 years; 95% CI 1.82-4.40) in the meta-analysis. The diagnosis of mild dementia tended to correlate with ID severity (odds ratio [OR], 1.38; 95% CI 0.87-2.18). The features of behaviour-variant frontotemporal dementia may be clinically confirmed in diagnosing early symptoms of DS-associated AD (DSAD). Moreover, age-appropriate cognitive assessment is important. Further studies are required to evaluate DSAD using a combination of biomarkers and ID-related data.

Comorbidities and co-medications among 28 089 people living with HIV: A nationwide cohort study from 2009 to 2019 in Japan.

OBJECTIVES: Comorbidities are associated with a high burden of disease in people living with HIV (PLWH). The objective was to investigate the prevalence of chronic comorbidities and use of co-medications in PLWH in Japan. METHODS: This study retrospectively analysed clinical information from PLWH receiving antiretroviral therapy (ART) between April 2009 and March 2019. Demographic characteristics, numbers and types of chronic comorbidities, and numbers and types of non-ART co-medications, were described by age groups. The source of data was the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB). RESULTS: Overall, 28 089 PLWH (male 91.9%) who used ART were identified. Out of 28 089 PLWH, 81.5% had at least one chronic comorbidity. The numbers of AIDS-defining cancers and non-AIDS-defining cancers in this Japanese cohort were 2432 (8.7%) and 2485 (8.8%), respectively. The cumulative burden of comorbidities including non-AIDS-defining cancer increased with age. Changes in trend between 2009 and 2019 were observed, including a higher proportion of PLWH diagnosed at ≥ 70 years old [2019 (4.7%) vs. 2009 (2.4%)] and a decreasing percentage of patients with AIDS-defining cancers (down from 6.3% to 4.8% between 2009 and 2019). The most common co-medications during the most recent 3-month period were lipid-regulating/anti-atheroma preparations (11.3%), antacids, antiflatulents and anti-ulcerants (9.6%), and agents acting on the renin-angiotensin system (8.1%). The three most common therapeutic categories of co-medications during the study period were antacids, antiflatulents and anti-ulcerants (35.0%), systemic antihistamines (33.7%) and psycholeptics (27.1%). More than 30% of PLWH aged > 40 years used at least one co-medication in a 3-month period, while more than half of PLWH aged > 30 years had at least one co-medication prescribed concomitantly for a total of ≥ 90 days during the study period, and the numbers of co-medications used were greater in the older age groups. CONCLUSIONS: The burden of chronic comorbidities and co-medication were found to be greater in older, as compared to younger patients, among 28 089 PLWH in a nationwide study in Japan. This finding suggests the need to identify elderly PLWH and to appropriately manage their HIV and comorbidities.

Delayed diagnosis of human immunodeficiency virus infection in people diagnosed with syphilis: A nationwide cohort study from 2011 to 2018 in Japan.

Early treatment of HIV infection depends on timely diagnosis, but many persons living with HIV/AIDS (PLWHA) are unaware of their infection. Though many patients seeking medical attention for sexually transmitted diseases have HIV, many patients' HIV co-infection is undiagnosed in Japan. This is the first report to analyze the timing of syphilis infection in PLWHA of all ages through the use of the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), containing clinical data of the largest group of HIV-positive patients available in Japan. Overall, 1521 PLWHA (male 93.2%) newly diagnosed and started on antiretroviral therapy were identified in 2016, and 646 (42.5%) patients had a diagnosis of syphilis between 2011 and 2018. Although 100 patients were diagnosed with syphilis before their HIV diagnosis, only 17 (17.0%) had been tested for HIV. Over 50 patients per year became infected with syphilis even after their HIV diagnosis (2017, n = 65 (4.3%); 2018, n = 58 (3.8%)). Although early diagnosis of HIV infection is important, most syphilis patients in Japan had not been properly tested for HIV infection. Since a certain number of HIV patients developed syphilis after HIV diagnosis, education for newly diagnosed HIV patients is important.

Syphilis in people living with HIV does not account for the syphilis resurgence in Japan.

OBJECTIVES: This study aimed to determine whether the current syphilis resurgence in Japan is attributable to incident syphilis in people living with HIV (PLWH). METHODS: This observational, retrospective, population-based study used data from the Japanese National Database. Data were extracted for PLWH who received antiretroviral treatment between January 2009 and December 2018. Using these data, along with the annual number of PLWH and syphilis diagnoses in the total population of Japan acquired from the National Institute of Infectious Diseases, the fraction of PLWH with syphilis compared to the total number of syphilis patients reported each year was calculated. RESULTS: There was a dramatic increase in syphilis cases during the study period. However, the incidence of syphilis in PLWH was stable during 2010-2018; the fraction of PLWH with newly diagnosed syphilis remaining at approximately 2% of the total PLWH cases in Japan each year. The proportion of newly diagnosed syphilis cases in PLWH decreased during the study period and accounted for <10% of the total syphilis cases in Japan since 2016 (14.9% in 2015 to 9.5% in 2016 and 5.9% in 2018). An increasing trend in the number of newly diagnosed syphilis cases in PLWH aged >50 years was observed (7.4% in 2010 to 10.4% in 2014 and 14.9% in 2018). CONCLUSIONS: The recent dramatic increase in syphilis cases in Japan was not seen in PLWH. Thus, the resurgence of syphilis in Japan cannot be attributed to its transmission in the PLWH population.

Cost-effectiveness of follow-up invasive coronary angiography after percutaneous coronary stenting: a real-world observational cohort study in Japan.

OBJECTIVES: Follow-up invasive coronary angiography (FUICA) after percutaneous coronary intervention (PCI) has been shown to increase the rate of early coronary revascularisation without reducing the incidence of subsequent myocardial infarction or death. However, no studies have evaluated the cost-effectiveness of FUICA in patients after coronary stenting. Therefore, this study aimed to evaluate the cost-effectiveness of FUICA after PCI. DESIGN: Retrospective observational cohort study. SETTING: 497 hospitals. PARTICIPANTS AND INTERVENTIONS: Overall, 558 patients who underwent coronary artery stenting between April 2014 and March 2015 were matched and included in the invasive angiographic follow-up (AF) group (n=279), in which patients underwent FUICA 6-12 months after PCI, or in the clinical follow-up alone group (CF; n=279) using propensity scores. PRIMARY AND SECONDARY OUTCOME MEASURES: The primary endpoint was the composite outcome of death, myocardial infarction, urgent coronary revascularisation, stroke or hospitalisation for the heart failure. The secondary endpoints included all-cause death, non-fatal myocardial infarction, urgent revascularisation, coronary artery bypass grafting, stroke, hospitalisation for the heart failure and any coronary revascularisation after a minimum of 6 months of follow-up. RESULTS: Costs were calculated as direct medical expenses based on medical fee billing information. The cumulative 3-year incidence of the primary endpoint was 5.3% in the AF group and 4.7% in the CF group (HR 1.02; 95% CI 0.47 to 2.20; p=0.98). The total incremental cost at the 3-year endpoint in the AF group was US$1874 higher than that in the CF group (US$8947±US$5684 vs US$7073±US$6360; p≤0.001). CONCLUSIONS: FUICA increased the costs but did not improve clinical benefits. Thus, FUICA is not economically more attractive than CF alone. TRIAL REGISTRATION NUMBER: UMIN000039768.

Analysis of antiretroviral therapy switch rate and switching pattern for people living with HIV from a national database in Japan.

To report the status of switch rates and time-to-switch of antiretroviral therapy (ART) regimens by evaluating anchor drug classes and common switching patterns in Japanese people living with human immunodeficiency virus (HIV, PLWH). This cross-sectional cohort study extracted data of 28,089 PLWH from the National Database of Health Insurance Claims and Specific Health Checkups of Japan (NDB), which contains data representing the entire population of Japan. PLWH with first prescription records of ART administered between January 2011 and March 2019 were identified (n = 16,069). The median time-to-switch and switch rates of anchor drug classes were estimated by Kaplan-Meier analysis. Brookmeyer-Crowley and Greenwood methods were used to estimate 95% confidence intervals for switch rates and median days, respectively. Switch rates were compared between anchor drug classes by year using log-rank tests. A total of 3108 (19.3%) PLWH switched anchor drug classes from first to second regimens. Switch rates increased continuously over 8 years for non-nucleoside reverse transcriptase inhibitors (NNRTIs) (14.9-65.5%) and protease inhibitors (PIs) (13.2-67.7%), with median time-to-switch of 1826 and 1583 days, respectively. Integrase strand transfer inhibitors (INSTIs) maintained a low switch rate (3.0-7.6%), precluding median-days calculation. Overall, the majority of patients treated initially with NNRTIs and PIs switched to INSTIs regardless of switching times (< 1 year: 67.3% and 85.9%, respectively; ≥ 1 year: 95.5% and 93.6%, respectively). The foremost switching strategies for first-to-second ART regimens are from NNRTIs or PIs to INSTIs regimens that maintain low switch rates long term. There was no observable difference in trend between sex, age and status of AIDS disease at first ART regimen. INSTIs HIV agents may be the most durable anchor drug class for PLWH receiving ART.