48-week Follow-up Period Research Articles

A Prospective Cohort Study Evaluating Impact of Sarcopenia on Hospitalization in Patients on Continuous Ambulatory Peritoneal Dialysis

Data regarding the association of sarcopenia with hospitalization has led to inconclusive results in patients undergoing dialysis. The main goal of this research was to investigate the association between sarcopenia and hospitalization in Chinese individuals on continuous ambulatory peritoneal dialysis (CAPD). Eligible patients on CAPD were prospectively included, and followed up for 48 weeks in our PD center. Sarcopenia was identified utilizing the criteria set by the Asian Working Group on Sarcopenia in 2019 (AWGS 2019). Participants were categorized into sarcopenia (non-severe sarcopenia + severe sarcopenia) and non-sarcopenia groups. The primary outcome was all-cause hospitalization during the 48-week follow-up period. Association of sarcopenia with all-cause hospitalization was examined by employing multivariate logistic regression models. The risk of cumulative incidence of hospitalization in the 48-week follow-up was estimated using relative risk (RR and 95% CI). The cumulative hospitalization time and frequency at the end of 48-week follow-up were described as categorical variables, and compared by χ2 test or fisher's exact test as appropriate. Subgroup and sensitivity analyses were also conducted to examine whether the potential association between sarcopenia and hospitalization was modified. A total of 220 patients on CAPD (5 of whom were lost in follow-up) were included. Prevalences of total sarcopenia and severe sarcopenia were 54.1% (119/220) and 28.2% (62/220) according to AWGS 2019, respectively. A total of 113 (51.4%) participants were hospitalized during the 48-week follow-up period, of which, the sarcopenia group was 65.5% (78/119) and the non-sarcopenia group was 34.7% (35/101), with an estimated RR of 1.90 (95%CI 1.43–2.52). The cumulative hospitalization time and frequency between sarcopenia and non-sarcopenia groups were significantly different (both P < 0.001). Participants with sarcopenia (OR = 3.21, 95%CI 1.75–5.87, P < 0.001), non-severe sarcopenia (OR = 2.84, 95%CI 1.39–5.82, P = 0.004), and severe sarcopenia (OR = 3.66, 95%CI 1.68–8.00, P = 0.001) demonstrated a significant association with all-cause hospitalization compared to individuals in non-sarcopenia group in the 48-week follow-up. Moreover, participants in subgroups (male or female; < 60 or ≥ 60 years) diagnosed with sarcopenia, as per AWGS 2019, were at considerably high risk for hospitalization compared to those with non-sarcopenia. In sensitivity analyses, excluding participants lost in the follow-up, the relationships between sarcopenia and hospitalization (sarcopenia vs. non-sarcopenia; severe sarcopenia/non-severe sarcopenia vs. non-sarcopenia) were consistent. This research involving Chinese patients on CAPD demonstrated a significant association between sarcopenia and incident hospitalization, thereby emphasizing the importance of monitoring sarcopenia health in this population.

Real-world experience with letermovir for cytomegalovirus-prophylaxis after allogeneic hematopoietic cell transplantation: A multi-centre observational study

Efficacy and safety of letermovir as prophylaxis for clinically significant cytomegalovirus infections (csCVMi) was evaluated in randomised controlled trials while most of the real-world studies are single-centre experiences. We performed a retrospective, multi-centre case-control study at six German university hospitals to evaluate clinical experiences in patients receiving CMV prophylaxis with letermovir (n=200) compared to controls without CMV prophylaxis (n=200) during a 48-week follow-up period after allogeneic hematopoietic cell transplantation (aHCT). The incidence of csCMVi after aHCT was significantly reduced in the letermovir (34%, n=68) compared to the control group (56%, n=112; p<0.001). Letermovir as CMV prophylaxis (OR 0.362) was found to be the only independent variable associated with theprevention of csCMVi. Patients receiving letermovir showed significantly better survival compared to the control group (HR = 1.735, 95% CI: 1.111-2.712; p=0.014). Of all csCMVi, 46% (n=31) occurred after discontinuation of letermovir prophylaxis. Severe neutropenia (<500 neutrophils/µL) on the day of the stem cell infusion was the only independent variable for an increased risk of csCMVi after the end of letermovir prophylaxis. Our study highlights the preventive effects of letermovir on csCMVi after aHCT. A substantial proportion of patients developed a csCMVi after discontinuation of letermovir. In particular, patients with severe neutropenia require specific attention after drug discontinuation.

Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up.

Chronic prostatitis (CP) is one of the diseases that reduce the quality of life (QoL) of young men. To date, there is no consensus on the management of these patients. It is essential to continue research into the treatment of CP, despite the use of various therapies, including low-energy extracorporeal shockwave therapy (ESWT). The main objective of this study is to observe and record the clinical symptomatology of patients during a 48-week follow-up period after ESWT treatment. Between 2019 and 2021, 28 patients with type IIIB CP/chronic pelvic pain syndrome were enrolled. Patients underwent ESWT once weekly for 4 weeks (3,000 individual sessions, maximum total energy flux density 0.25 mJ/mm2, frequency 3 Hz). Participants were assessed at 0, 4, 12, 24, 36 and 48 weeks post-treatment using the visual analogue scale (VAS), National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI), and International Index of Erectile Function (IIEF)-5. The mean age of patients was 47.1 ± 13.7 years (range 28-4 years). The positive effect of LI-ESWT was reflected in improvements in VAS, NIH-CPSI, and IIEF-5 scores. Regression of patients' symptoms was observed as early as 4 weeks after treatment. The greatest progress was achieved at week 24. In addition, a slight worsening was observed at week 36 and 48, with stable progress. The treatment significantly improved the QoL of the patients, with the most significant improvement in the VAS score. In conclusion, this treatment approach is safe, most effective in the first 6 months. Thereafter, the efficacy of the treatment diminishes, but is sustained over a longer period.

Determinants of Antiretroviral Treatment Success and Adherence in People With Human Immunodeficiency Virus Treated for Tuberculosis.

In people with human immunodeficiency virus [HIV] presenting with advanced disease, rates of virologic success may be lower than expected. The Reflate TB2 trial did not show non-inferiority of raltegravir versus efavirenz in people with HIV (PWH) treated for tuberculosis. We aimed to identify factors associated with virologic success and higher adherence in the trial. In this analysis, we included participants enrolled in the Reflate TB2 trial with adherence data available. The primary outcome was virologic success (HIV-1 ribonucleic acid [RNA] <50 copies/mL) at week 48, and the secondary outcome was adherence as assessed by the pill count adherence ratio. We used logistic regression to study determinants of virologic success and optimal adherence in 2 separate analyses. Four hundred forty-four participants were included in the present analysis. Over the 48-week follow-up period, 290 of 444 (65%) participants had a pill count adherence ratio ≥95%. At week 48, 288 of 444 (65%) participants were in virologic success. In the multivariate analysis, female sex (adjusted odds ratio [aOR], 1.77; 95% confidence interval [CI], 1.16-2.72; P = .0084), lower baseline HIV-1 RNA levels (<100 000; aOR, 2.29; 95% CI, 1.33-3.96; P = .0087), and pill count adherence ratio ≥95% (aOR, 2.38; 95% CI, 1.56-3.62; P < .0001) were independently associated with virologic success. Antiretroviral pill burden was the only factor associated with pill count adherence ratio ≥95% (OR, 0.81; 95% CI, .71-.92; P = .0018). In PWH with tuberculosis receiving raltegravir or efavirenz-based regimens, female sex, optimal adherence, and baseline HIV-1 RNA <100 000 copies/mL were associated with virologic success, and the number of antiretroviral tablets taken daily was a strong predictor of adherence.

Association of Amyloid Reduction After Donanemab Treatment With Tau Pathology and Clinical Outcomes

β-amyloid plaques and neurofibrillary tau deposits biologically define Alzheimer disease. To perform post hoc analyses of amyloid reduction after donanemab treatment and assess its association with tau pathology and clinical measures. The Study of LY3002813 in Participants With Early Symptomatic Alzheimer's Disease (TRAILBLAZER-ALZ) was a phase 2, placebo-controlled, randomized clinical trial conducted from December 18, 2017, to December 4, 2020, with a double-blind period of up to 76 weeks and a 48-week follow-up period. The study was conducted at 56 centers in the US and Canada. Enrolled were participants from 60 to 85 years of age with gradual and progressive change in memory function for 6 months or more, early symptomatic Alzheimer disease, elevated amyloid, and intermediate tau levels. Donanemab (an antibody specific for the N-terminal pyroglutamate β-amyloid epitope) dosing was every 4 weeks: 700 mg for the first 3 doses, then 1400 mg for up to 72 weeks. Blinded dose-reduction evaluations occurred at 24 and 52 weeks based on amyloid clearance. Change in amyloid, tau, and clinical decline after donanemab treatment. The primary study randomized 272 participants (mean [SD] age, 75.2 [5.5] years; 145 female participants [53.3%]). The trial excluded 1683 of 1955 individuals screened. The rate of donanemab-induced amyloid reduction at 24 weeks was moderately correlated with the amount of baseline amyloid (Spearman correlation coefficient r, -0.54; 95% CI, -0.66 to -0.39; P &lt; .001). Modeling provides a hypothesis that amyloid would not reaccumulate to the 24.1-centiloid threshold for 3.9 years (95% prediction interval, 1.9-8.3 years) after discontinuing donanemab treatment. Donanemab slowed tau accumulation in a region-dependent manner as measured using neocortical and regional standardized uptake value ratios with cerebellar gray reference region. A disease-progression model found a significant association between percentage amyloid reduction and change on the integrated Alzheimer Disease Rating Scale only in apolipoprotein E (APOE) ε4 carriers (95% CI, 24%-59%; P &lt; .001). Results of post hoc analyses for donanemab-treated participants suggest that baseline amyloid levels were directly associated with the magnitude of amyloid reduction and inversely associated with the probability of achieving complete amyloid clearance. The donanemab-induced slowing of tau was more pronounced in those with complete amyloid clearance and in brain regions identified later in the pathologic sequence. Data from other trials will be important to confirm aforementioned observations, particularly treatment response by APOE ε4 status. ClinicalTrials.gov Identifier: NCT03367403.

Role of hepatitis B surface antibody in seroreversion of hepatitis B surface antigen in patients achieving hepatitis B surface antigen loss with pegylated interferon-based therapy.

It is unclear whether hepatitis B surface antibody (HBsAb) confers clinical benefits after HBsAg seroclearance, especially in hepatitis B surface antigen (HBsAg) seroreversion and maintenance of HBsAb. We evaluated this in patients (n=222) with HBsAg loss following treatment with pegylated interferon (PEG-IFN)-based therapy who completed a 48-week follow-up period. Serum hepatitis B virus (HBV) markers and biochemical indicators were evaluated every 3months. The primary endpoint was HBsAg seroreversion. Factors associated with HBsAg seroreversion were also investigated. HBsAb ≥100 mIU/ml resulted in a lower HBsAg seroreversion rate than an HBsAb-negative status (5.5% vs. 29.5%, p &lt; .001); however, the seroreversion rate was not significantly different between patients with HBsAb 10-100 mIU/ml and those in the HBsAb-negative group. Patients with HBsAb ≥100 mIU/ml had a lower HBsAb loss rate than those with HBsAb 10-100 mIU/ml (7.3% vs. 21.7%, p=.005). The final HBsAg seroreversion and HBV DNA relapse rates were 13.5% and 1.8%, respectively. HBsAb ≥100 mIU/ml at the off-treatment time (odds ratio [OR] 0.110, 95% confidence interval [CI]: 0.034-0.353, p &lt; .001) and treatment time to attain HBsAg loss &gt;28 weeks (OR 2.508, 95% CI: 1.068-5.890, p=.035) were predictors of HBsAg seroreversion. Consolidation therapy for 12-24 weeks resulted in higher HBsAb titres than consolidation therapy for ≤12 weeks in HBsAb-negative patients at the off-treatment time (p &lt; .001). HBsAg seroconversion with HBsAb ≥100 mIU/ml decreases HBsAg seroreversion and provides an efficient maintenance rate of HBsAb. HBsAg seroconversion with high HBsAb titres may be clinically beneficial for chronic hepatitis B treated with PEG-IFN-based therapy.

Intermittent Tiotropium for Episodic Wheezing.

Approximately one third of children experience an episode of wheezing during the first 3 years of life, and nearly half of these children have recurrent wheezing episodes.1–3In spite of the substantial morbidity associated with this common condition, the optimal approach to management of acute wheezing episodes in young children is not known. Although short-acting β agonists and corticosteroids are frequently used, the effects of these medications in children younger than 3 years of age are less predictable than in school-aged children and adolescents.4 In addition, inhaled and systemic corticosteroids can be associated with harms, so effective corticosteroid-sparing therapies may be preferable.5,6Tiotropium, a selective long-acting anticholinergic agent, has been studied in older children and adults, mostly as adjunctive therapy in patients with moderate-to-severe asthma.7–12 Although not rigorously studied in young children, its anticholinergic mechanism of action offers potential benefits over—or in addition to—β agonists and corticosteroids by simultaneously promoting bronchodilation and preventing mucous secretion.In this issue of Pediatrics, Kotaniemi-Syrjänen et al report results from a randomized, open-label, controlled study of intermittent tiotropium for recurrent acute wheezing episodes in 80 children ages 6 to 35 months.13 Participants with 2 to 4 prior episodes of wheezing were randomized to receive either (1) tiotropium 5 µg once daily for 7 to 14 days, (2) fluticasone 125 µg twice daily for 7 to 14 days, or (3) albuterol 0.2 mg as needed 4 to 6 times daily, each at the onset of an acute respiratory tract infection. Participants in the tiotropium and fluticasone groups also used albuterol as needed. The primary outcome was the proportion of symptom-free days during the 48-week follow-up period, and secondary outcomes were the number of albuterol doses used and the number of adverse events requiring medical attention.Although recruitment was terminated early because of financial, logistical, and ethical reasons, the investigators found that treatment with tiotropium was associated with a greater proportion of symptom-free days (97%) compared with fluticasone (87%) or as-needed albuterol (88%). The differences in the primary outcome between the tiotropium group and the fluticasone and albuterol groups remained statistically significant after a 2-way factorial analysis of variance, accounting for baseline differences across groups. Because the distribution of the number of illness episodes was similar across study groups, the measured effect of tiotropium was attributed to less severe symptoms during illness episodes rather than to less frequent occurrence of illness. Patients in the tiotropium group used albuterol less frequently during illness episodes than those in fluticasone or albuterol groups, and all treatments were found to be safe.The investigators acknowledge important limitations of the study, including the small sample size, which—although not sufficiently small to obscure a difference in the main outcome measure across study groups—limited the study’s power to detect differences in rarer outcomes and may have contributed to imbalances in important baseline characteristics across groups. In addition, the lack of blinding may have led to biased measurement of treatment effects, particularly since the primary outcome was a parent-reported symptom score rather than an objective measure of lung function. Finally, some of the included patients who were less than 24 months of age may have had viral bronchiolitis, for which routine pharmacologic treatment has not been shown to be effective.14Despite these limitations, the investigators deserve praise for conducting an important exploratory study. Their results support prior findings that tiotropium is likely safe in young children15 and provide preliminary evidence that its intermittent use during respiratory tract infections could improve symptoms. If replicated in larger blinded studies, these results suggest that intermittent tiotropium use could prevent, on average, approximately 5 weeks of symptoms per year in young children with recurrent wheezing.This study also highlights the importance of ongoing work to define clinically useful phenotypes in young children with recurrent wheezing episodes. Existing classification systems define wheezing phenotypes according to epidemiologic characteristics, symptoms over time, genetics, and environmental factors.3,4,16–23 Although some of these tools have proven helpful to predict a future diagnosis of asthma, young children may express different phenotypes over time, and whether specific treatments are more effective among patients with different phenotypes is uncertain. In this way, studying the problem through the lens of precision medicine may help to better define which patients with wheezing are most likely to benefit from specific therapies.

Short-term Outcomes of the Use of Intraventricular Ribavirin in Filipino Patients with Subacute Sclerosing Panencephalitis

Background. Subacute sclerosing panencephalitis (SSPE) is a fatal neurodegenerative disease caused by prolonged persistent infection of the central nervous system with a measles virus mutant. Though various treatment modalities have been tried, there is no effective treatment to completely cure SSPE and new therapeutic strategies are needed.&#x0D; Objective. This is a prospective uncontrolled observational open label trial to describe the short-term outcomes and safety of intraventricular ribavirin in combination with oral isoprinosine in Filipino SSPE patients.&#x0D; Methods. Sixteen (16) unrelated SSPE patients between ages 3-26 years and in various clinical stages were included in this study. Demographic data were described. Intraventricular instillation of ribavirin (1-3 mg/kg/dose) through an Ommaya reservoir was given for a duration of 3-6 months in 13 patients. The duration of follow-up was 48 weeks. The clinical outcome was assessed before, during, and after treatment using the Neurological Disability Index (NDI), Brief Assessment Examination (BAE), and clinical staging using the Jabbour Classification. Adverse side effects from intraventricular ribavirin were enumerated.&#x0D; Results. Six of 13 (46.15%) patients mostly in Stage III illness had clinical improvement showing decreasing NDI and BAE scores during treatment and the clinical improvement was maintained or improved further during the 48-week follow-up period. Clinical improvement manifested as improved mental alertness, decrease in spasticity and reduction of seizures. The clinical staging of those who improved remained stable during and after treatment was discontinued. Five (38.46%) patients in Stage II disease worsened and progressed to Stage III despite ribavirin therapy including 1 (7.6%) patient who died after the treatment phase due to pneumonia and brainstem failure. The clinical course of two (15.38%) patients remained unchanged. Minor adverse side effects of ribavirin included transient fever, rash, oral sores, seizure episodes, drowsiness, bladder retention and mild increase in transaminases. Ommaya reservoir infection was a serious adverse event in 5 (31.25%) patients.&#x0D; Conclusion. There is still no definitive cure for SSPE. Although ribavirin may help alleviate some of the symptoms of SSPE and prolong life, it may not reverse or halt the progression of the disease. Long term follow-up of these patients and continuous use of intraventricular ribavirin will better clarify its role in modifying the fatal course of SSPE. The role of ribavirin in Stage I patients and a controlled clinical trial in Stage II SSPE needs further studies.

Factors Contributing to Residual Low Back Pain after Osteoporotic Vertebral Fractures.

Although osteoporotic vertebral fractures (OVFs) are the most common type of osteoporotic fracture, few reports have investigated the factors contributing to residual low back pain in the chronic phase after OVFs by using radiographic evaluation. We examined the contribution of nonunion, vertebral deformity, and thoracolumbar alignment to the severity of residual low back pain post-OVF. This post hoc analysis of a prospective randomized study included 195 patients with a 48-week follow-up period. We investigated the associations between radiographic variables with the visual analog scale (VAS) scores for low back pain at 48 weeks post-OVF using a multiple linear regression model. Univariate analysis revealed that analgesic use, the local angle on magnetic resonance imaging, anterior vertebral body compression percentage on X-ray, and nonunion showed a significant association with VAS scores for low back pain. Multiple regression analysis produced the following equation: VAS for low back pain at 48 weeks = 15.49 + 0.29 × VAS for low back pain at 0 weeks + (with analgesics: +8.84, without analgesics: −8.84) + (union: −5.72, nonunion: −5.72). Among local alignment, thoracolumbar alignment, and nonunion, nonunion independently contributed to residual low back pain at 48 weeks post-OVF. A treatment strategy that reduces the occurrence of nonunion is desirable.

Outcomes of iliac crest bone marrow aspirate injection for the treatment of recalcitrant Achilles tendinopathy.

Achilles tendinopathy is a common cause of posterior ankle and heel pain in both active and sedentary patients. Though the majority of patients respond to first-line non-operative management including activity modification, immobilization, orthotics, and physical therapy with stretching and eccentric strengthening, there is no consensus for patients who fail these treatments. We evaluate the role of iliac crest bone marrow aspirate (BMA) injections as a treatment option for recalcitrant cases. A retrospective chart review was conducted of patients with refractory Achilles tendinopathy treated with iliac crest BMA concentrate injection. Symptoms were assessed using the numeric rating system (NRS) pain score at the pre-operative visit and at six, 12, 24, and 48weeks postoperatively. Post-operative complications were recorded. A total of 15 patients (15 feet) with recalcitrant Achilles tendinopathy (5 insertional, 8 non-insertional, 2 combined) treated with iliac crest BMA concentrate injections were included in the study. Average age was 53.2years (range, 25 to 64), average BMI was 27.1kg/m2 (range, 18.4 to 34.4), and average duration of symptoms prior to BMA injection was 2.3years (range, 1 to 7). Pre-operatively, average NRS was 6.26 (95% CI, 5.04 to 7.49), with significant improvement at sixweeks (mean, 4.26; 95% CI, 2.94 to 5.59; p = 0.04), tenweeks (mean, 4.13; 95% CI, 2.91 to 5.35; p = 0.012), 24weeks (mean, 3.40; 95% CI, 2.05 to 4.75; p = 0.03), and 48weeks (mean, 2.60; 95% CI, 1.14 to 4.06; p = 0.007) post-operatively. Overall, there was trending improvement over the 48-week follow-up period, with a mean improvement in NRS of - 3.22 (95% CI, - 1.06 to - 5.38; p = 0.007) at final follow-up. There was no discernable difference between insertional and non-insertional tendinopathy, and there were no incidences of post-operative complications. Iliac crest BMA appears to be a safe, effective, and potentially lasting treatment option for patients with intractable, insertional and non-insertional Achilles tendinopathy. Patients demonstrated and maintained statistically significant decrease in NRS pain score post-operatively with no complications at the donor or injection site.

Efficacy of group-based multi-component psycho-education for caregivers of people with dementia: A randomized controlled study.

The aim of this study was to examine the ability of a group-based multi-component psycho-educational intervention (GMC-PEI) to reduce depression, and improve caregiving appraisals, coping skills of informal caregivers and the condition of people with dementia. In this randomized controlled and blinded trial, we enrolled 54 informal caregivers of people with dementia visiting the Japan National Center of Geriatrics and Gerontology, and divided them into GMC-PEI and control groups. The intervention group received a 12-week GMC-PEI program that included six 2-h structured sessions to enhance their knowledge of dementia, caregiving skills and coping skills. The control group received leaflets containing information about dementia. We evaluated caregivers' depression, caregiving time, subjective burden, caregiving appraisal and care coping skills. We also evaluated people with dementia at baseline and 12 weeks, and reassessed 20 participants from the intervention group at 24 and 48 weeks. The GMC-PEI significantly improved depression, positive appraisals of fulfillment in caregiving, affection for care recipients, self-growth and coping skills, such as seeking formal support. Depression, fulfillment and affection for people with dementia showed a peak improvement at 24 weeks; formal support-seeking showed a linear improvement throughout the 48-week follow-up period. The group-based multi-component psycho-educational intervention reduced depression, improved self-appraisal and enhanced coping skills in caregivers. However, emotional enhancements dissipated sooner than support-seeking skills, suggesting that caregivers should be reviewed every 12-24 weeks. Geriatr Gerontol Int 2021; 21: 561-567.

Timing of antiretroviral therapy for HIV-infected patients with cytomegalovirus retinitis: study protocol of a multi-center prospective randomized controlled trial

BackgroundCytomegalovirus retinitis (CMVR) is an important opportunistic infection (OI) occurring mainly in patients with acquired immunodeficiency syndrome (AIDS) and has the potential to cause severe visual impairment and blindness among AIDS patients. Subsequent to the adoption and implementation of widespread antiretroviral therapy (ART), the prognosis of AIDS-associated CMVR has been substantially improved. Nevertheless, the equivocal clinical evidence as regards the optimal timing for ART initiation in patients with an established CMVR diagnosis is required. We therefore designed the present study in order to investigate the optimal timing for ART initiation in AIDS/CMVR patients.MethodsThis will be a prospective, randomized controlled trial to be performed at 17 hospitals in mainland China. A total of 300 participants with CMVR will be randomly assigned to an early ART initiation group (ART initiation within 2 weeks after anti-CMV therapy), or a deferred ART initiation group (initiation of ART more than 2 weeks after anti-CMV therapy) at a 1:1 ratio. All participants will receive 48 weeks of follow-up after anti-CMV therapy initiation. Our primary outcome will be the incidence of visual loss (to a visual acuity worse than 20/40 or 20/200) in the two groups during the 48-week follow-up period. Secondary outcomes will include changes in HIV virological suppression and serum CD4+ T-cell counts, the incidence of mortality, retinitis progression (movement of the peripheral border of a CMV lesion ≥ ½ disc diameter, or occurrence of a new CMV lesion), retinal detachment, immune recovery uveitis (IRU), and other OIs and adverse events between the two study groups during the 48 weeks of follow-up.DiscussionThe study aims to investigate the optimal timing for ART initiation in AIDS/CMVR patients. We hope to be able to extract robust clinical evidence for use in optimal AIDS/CMVR management should our trial be successful.Trial registrationThis research was registered as one of the twelve clinical trials under the name of a general project “A study for precision diagnosing and treatment strategies in difficult-to-treat AIDS cases and HIV-infected patients with highly fatal or highly disabling opportunistic infections”, ChiCTR1900021195. Registered on 1 February 2019, http://www.chictr.org.cn/showproj.aspx?proj=35362.

Risk factors for subsequent vertebral fracture after acute osteoporotic vertebral fractures.

To investigate the incidence and characteristics of subsequent vertebral fracture after osteoporotic vertebral fractures (OVFs) and identify risk factors for subsequent vertebral fractures. This post-hoc analysis from a prospective randomized multicenter trial included 225 patients with a 48-week follow-up period. Differences between the subsequent and non-subsequent fracture groups were analyzed. Of the 225 patients, 15 (6.7%) had a subsequent fracture during the 48-week follow-up. The annual incidence of subsequent vertebral fracture after fresh OVFs in women aged 65-85years was 68.8 per 1000 person-years. Most patients (73.3%) experienced subsequent vertebral fractures within 6months. At 48weeks, European Quality of Life-5 Dimensions, the Japanese Orthopedic Association Back Pain Evaluation Questionnaire pain-related disorder, walking ability, social life function, and lumbar function scores were significantly lower, while the visual analog scale (VAS) for low back pain was higher in patients with subsequent fracture. Cox proportional hazards analysis showed that a VAS score ≥ 70 at 0weeks was an independent predictor of subsequent vertebral fracture. After adjustment for history of previous fracture, there was a ~ 67% reduction in the risk of subsequent vertebral fracture at the rigid-brace treatment. Women with a fresh OVF were at higher risk for subsequent vertebral fracture within the next year. Severe low back pain and use of soft braces were associated with higher risk of subsequent vertebral fractures. Therefore, when treating patients after OVFs with these risk factors, more attention may be needed for the occurrence of subsequent vertebral fractures. III.

Sexual Behavior and Sexually Transmitted Infection Outcomes Among Men Who Have Sex With Men and Transgender Women Participating in a Study of the Timing of Antiretroviral Therapy in Lima, Peru.

We assessed sexual behavior and incidence of sexually transmitted infections (STIs) among men who have sex with men and transgender women participating in Sabes, a study of an expanded treatment as prevention strategy focused on early diagnosis and treatment of HIV infection in Lima, Peru (2013-2017). Sabes participants were tested monthly for HIV to identify acute or early infections, and HIV-positive participants were randomized to receive antiretroviral therapy immediately (immediate arm) or after 24 weeks (deferred arm) during a 48-week follow-up period. Sexual behavior was assessed at randomization (baseline) and every 12 weeks thereafter. Participants were tested for urethral and rectal chlamydia and gonorrhea and for syphilis at baseline, 12, 24, and 48 weeks. We describe patterns of sexual behavior during the 48-week follow-up period and compare sexual behavior and STI incidence between study arms. After randomization, 207 HIV-positive participants completed questionnaires and STI testing at 2 or more visits. After HIV diagnosis, participants in both arms reported increases in condom use with main and casual partners and decreased drug and alcohol use before or during anal sex. We observed no between-arm differences in sexual behavior. Deferred arm participants had higher incidence of chlamydia (incidence rate ratio, 2.33; 95% confidence interval, 1.14-4.77) but not gonorrhea or syphilis. Despite reported increases in condom use, the overall high incidence of STIs reflects some ongoing condomless sex among HIV-positive men who have sex with men and transgender women, highlighting the importance of regular STI screening and counseling to support consistent condom use among HIV-positive individuals at risk for STIs.

Longitudinal Effects of Active Learning Education on Lifestyle Behavior and Physical Function in Older Adults

ObjectivesSustaining benefits of an exercise program is difficult as adherence is often poor after supervised intervention is over. This study aimed to determine whether the effects of active learning education on physical activity, dietary habits, and physical function were maintained 24 weeks after intervention termination in older adults. DesignNon-randomized controlled trial. Setting and ParticipantsCommunity-dwelling older adults aged ≥65 years who were independent in activities of daily living. MethodsThe intervention group (n = 36) underwent 24 weeks of active learning education. The control group (n = 59) attended a health education class didactically. In both groups, the education program focused on exercise, diet and nutrition, and cognitive activity for health promotion. Active learning included exploratory learning, group work, and self-planning for behavior change that promoted healthy lifestyles. Outcome measures were obtained at baseline (pre), 24 weeks (post), and 48 weeks (follow-up). Physical activity was objectively measured as physical activity level (PAL) using a triaxial accelerometer. Food intake was assessed by obtaining a dietary variety score. Physical function, including gait speed and Timed Up & Go score, was tested as secondary outcome. We used a linear mixed model to estimate the effects of intervention in intention-to-treat analyses. ResultsAll outcomes in the intervention group significantly improved compared with the control group at 24 weeks, and the improvements were sustained over a 48-week follow-up period. For PAL, between-group difference in change from baseline was 0.043 (95% confidence interval = 0.007, 0.080) at 24 weeks and 0.061 (0.023, 0.099) at 48 weeks. Conclusions and ImplicationsActive learning education is effective in enhancing healthy lifestyles and physical function sustainability beyond intervention cessation. A randomized controlled trial with a larger sample size is needed to conclusively clarify the beneficial effects of active health education learning on sustainable behavior change and functional improvement.

Financial incentives for achieving and maintaining viral suppression among HIV-positive adults in Uganda: a randomised controlled trial

Viral suppression among HIV-positive individuals is essential for protecting health and preventing HIV transmission. Financial incentives have shown promise in modifying various health behaviours in low-income countries but few studies have assessed whether they can improve HIV treatment outcomes. We aimed to determine the impact of time-limited financial incentives on viral suppression among HIV-positive adults in rural Uganda. We did a randomised controlled trial in four rural Ugandan parishes. We recruited HIV-positive individuals (aged ≥18 years) from community health campaigns that included HIV testing services or at a local government health facility where HIV treatment is offered. Participants included those who were initiating antiretroviral therapy (ART) or already receiving ART. Eligibility to participate in the study did not depend on current ART or viral suppression status. Participants were randomly allocated (1:1) to the financial incentive intervention or the control group in computer-generated blocks (block size 10 participants) and pre-printed scratch cards were used to reveal study group assignment. We measured participants' viral load at baseline and at weeks 6, 12, 24, and 48. At each timepoint, we provided results and viral load counselling. Participants in the intervention group received financial incentives for viral suppression at weeks 6, 12, and 24, with incentive amounts increasing from US$4 to $12·5. The primary outcome was viral suppression (viral load <400 copies per mL) at 24 weeks in the intention-to-treat population. This trial is registered with ClinicalTrials.gov, number NCT02890459. Between June 27, 2016, and May 25, 2018, we enrolled 400 adults in the study, of whom 203 were randomly assigned to the intervention group and 197 to the control group. Of these, 324 were enrolled from community health campaigns and 76 from the government clinic. Eight (2%) withdrew from the study and were not included in analyses. Over the 48-week follow-up period, 35 (9%) died or were lost-to-follow-up. Participants' median daily income was $0·79. At baseline, 300 participants (77%) were virally suppressed. In intention-to-treat analyses, 168 participants (84%) in the intervention group and 156 (82%) in the control group were virally suppressed at 24 weeks (odds ratio 1·14, 95% CI 0·68-1·93, p=0·62). Six participants (3%) in the control group and four (2%) in the intervention group had adverse events. Six of the adverse events were serious, including two deaths in the intervention group, three deaths in the control group, and one serious injury (tibia fracture) after an auto accident. No adverse events or deaths were related to study participation. Financial incentives had no effect on viral suppression among HIV-positive adults. High baseline viral suppression and provision of viral load results might have contributed to high viral suppression among participants. These findings highlight the need for interventions that promote achievement of viral suppression among unsuppressed individuals. National Institute of Mental Health at the US National Institutes of Health.

Intermittent oral levetiracetam reduced recurrence of febrile seizure accompanied with epileptiform discharge: a pilot study

BackgroundIn previous study, we have found intermittent oral levetiracetam (LEV) can effectively prevent recurrence of febrile seizure (FS). This study aimed to analyze the effects of the preventive on the patients with frequent FS accompanied with epileptiform discharge.MethodsPatients with frequent FS were assigned to undergo Electroencephalogram (EEG). At the onset of fever, the patients who presented epileptiform discharge were orally administered with LEV with a dose of 15–30 mg/kg per day twice daily for 1 week, thereafter, the dosage was gradually reduced until totally discontinued in the second week. The seizure frequency associated with febrile events and FS recurrence rate during a 48-week follow-up were analyzed.Resultsamong the 19 patients presented epileptiform discharge on EEG, 31.58% (6 of 19) had complex FS, 68.42% (13 of 19) had simple FS. Up to 57.89% (11 of 19) had a family history of seizure disorder and 36.84% (7 of 19) had a family history of FS in first-degree relatives. 42.11% (8 of 19) happened the first FS episode at the age < 18 months. 36.84% (7/19) presented generalized spikes, 63.16% (12/19) showed focal spikes. During the 48-week follow-up period, the patients experienced 26 febrile episodes, none of them presented seizure recurrence.ConclusionIntermittent oral LEV can prevent the seizure recurrence of FS accompanied with epileptiform discharge in 48-week. However, further randomized controlled trials should be conducted.Trial registrationChiCTR-IPR-15007241; Registered 1 January 2014 - Retrospectively registered.

Aqueous cytokine levels associated with severity of type 1 retinopathy of prematurity and treatment response to ranibizumab.

To determine the aqueous humor levels of cytokines in eyes with type 1 retinopathy of prematurity (ROP) before primary intravitreal injection of ranibizumab (IVR). Forty-nine infants with type 1 ROP (56 eyes of 28 infants in the threshold ROP group and 42 eyes of 21 infants in the type 1 pre-threshold ROP group) received primary IVR and 49 aqueous humor samples were obtained preoperatively. Aqueous humor samples from 15 infants (15 eyes) undergoing congenital cataract surgery were used as controls. The concentrations of 27 cytokines were measured by a multiplex bead assay. Infants with persistent, recurrent, or progressive ROP after IVR were retreated. The preoperative aqueous levels of 16 cytokines were significantly different among type 1 pre-threshold, threshold ROP, and control groups (P < 0.05). The concentrations of vascular endothelial growth factor (VEGF) (P < 0.001), interferon-γ (P < 0.001), interleukin (IL)-10 (P < 0.001), and IL-12 (P < 0.001) were the highest in the threshold ROP group, less in the type 1 pre-threshold ROP group, and the lowest in the control group. Retreatment was given to 55% of infants with ROP within a 48-week follow-up period after primary IVR. Higher VEGF (hazard ratio [HR] = 1.001, P = 0.001) and macrophage inflammatory protein-1β (HR = 1.085, P = 0.022) levels were independently correlated with ROP retreatment. Higher aqueous levels of VEGF and inflammatory cytokines were associated with more severe type 1 ROP and ROP retreatment after primary IVR.

Circadian Rhythm Sleep-Wake Disorders Predict Shorter Time to Relapse of Mood Episodes in Euthymic Patients With Bipolar Disorder: A Prospective 48-Week Study.

Circadian rhythm dysfunction has been considered to be common in bipolar disorder (BD) and plays an important role in mood dysregulation in this disorder. However, no study has investigated whether circadian rhythm dysfunction would affect the clinical course of BD. The aim of this study was to test the hypothesis that circadian rhythm dysfunction could be a predictor of relapse in euthymic BD patients. One hundred four euthymic outpatients with BD diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), participated in this prospective follow-up study from August 2014 to April 2015. At baseline, data on demographic variables and clinical descriptive variables of bipolar disorder were ascertained via clinical interviews. The diagnoses of circadian rhythm sleep-wake disorders (CRSWDs) were made based on participants' sleep logs for 4 weeks and according to the International Classification of Sleep Disorders, Third Edition (ICSD-3). The BD symptoms of the subjects were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) scores every 4 weeks throughout the 48-week study period. Relapse of BD was defined as scores higher than the cutoff points (MADRS score ≥ 13 and YMRS score ≥ 7). The primary outcome was time to relapse of mood episodes. Thirty-four subjects met criteria for CRSWD at baseline, most frequently delayed sleep-wake phase disorder (n = 27). Of the total 104 subjects, 51 (49.0%) experienced relapse during the 48-week follow-up period. Multivariate Cox hazard regression analyses revealed that 2 or more previous mood episodes within the past year and comorbidity of CRSWD were significantly associated with the time to relapse of mood episodes (P < .001). Comorbid CRSWD, mainly delayed sleep-wake phase disorder, could be a significant predictor of relapse in BD patients.

Circadian rhythm sleep-wake disorders predict shorter time to relapse of mood episodes in euthymic patients with bipolar disorder: a prospective 48-week study

OBJECTIVE Circadian rhythm dysfunction has been considered to be common in bipolar disorder (BD) and plays an important role in mood dysregulation in this disorder. However, no study has investigated whether circadian rhythm dysfunction would affect the clinical course of BD. The aim of this study was to test the hypothesis that circadian rhythm dysfunction could be a predictor of relapse in euthymic BD patients. METHODS One hundred four euthymic outpatients with BD diagnosed according to the criteria of the Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5), participated in this prospective follow-up study from August 2014 to April 2015. At baseline, data on demographic variables and clinical descriptive variables of bipolar disorder were ascertained via clinical interviews. The diagnoses of circadian rhythm sleep-wake disorders (CRSWDs) were made based on participants' sleep logs for 4 weeks and according to the International Classification of Sleep Disorders, Third Edition (ICSD-3). The BD symptoms of the subjects were evaluated using the Montgomery-Asberg Depression Rating Scale (MADRS) and Young Mania Rating Scale (YMRS) scores every 4 weeks throughout the 48-week study period. Relapse of BD was defined as scores higher than the cutoff points (MADRS score ≥ 13 and YMRS score ≥ 7). The primary outcome was time to relapse of mood episodes. RESULTS Thirty-four subjects met criteria for CRSWD at baseline, most frequently delayed sleep-wake phase disorder (n = 27). Of the total 104 subjects, 51 (49.0%) experienced relapse during the 48-week follow-up period. Multivariate Cox hazard regression analyses revealed that 2 or more previous mood episodes within the past year and comorbidity of CRSWD were significantly associated with the time to relapse of mood episodes (P < .001). CONCLUSIONS Comorbid CRSWD, mainly delayed sleep-wake phase disorder, could be a significant predictor of relapse in BD patients.