Family Members' Feedback on the "Quality of Death" of Adult Patients Who Died in Intensive Care Units and the Factors Affecting the Death Quality: A Systematic Review and Meta-Analysis.

Intensive care units (ICUs) are designed for critically ill patients who often experience high mortality rates owing to the severity of their conditions. Although the primary goal is patient recovery, it is crucial to understand the quality of death in the ICU setting. Nevertheless, there is a notable lack of systematic reviews on measured death quality and its associated factors. This study aims to conduct a quantitative synthesis of evidence regarding the quality of death in the ICU and offers a comprehensive overview of the factors influencing this quality, including its relationship with the post-intensive care syndrome-family (PICS-F). A thorough search without any language restrictions across MEDLINE, CINAHL, PsycINFO, and Igaku Chuo Zasshi databases identified relevant studies published until September 2023. We aggregated the results regarding the quality of death care for patients who died in the ICU across each measurement tool and calculated the point estimates and 95% confidence intervals. The quantitative synthesis encompassed 19 studies, wherein the Quality of Dying and Death-single item (QODD-1) was reported in 13 instances (Point estimate: 7.0, 95% CI: 6.93-7.06). Patient demographic data, including age and gender, as well as the presence or absence of invasive procedures, such as life support devices and cardiopulmonary resuscitation, along with the management of pain and physical symptoms, were found to be associated with a high quality of death. Only one study reported an association between quality of death and PICS-F scores; however, no significant association was identified. The QODD-1 scale emerged as a frequently referenced and valuable metric for evaluating the quality of death in the ICU, and factors associated with the quality of ICU death were identified. However, research gaps persist, particularly regarding the variations in the quality of ICU deaths based on cultural backgrounds and healthcare systems. This review contributes to a better understanding of the quality of death in the ICU and emphasises the need for comprehensive research in this critical healthcare domain.

Second victim syndrome in intensive care unit healthcare workers: A systematic review and meta-analysis on types, prevalence, risk factors, and recovery time.

INTRODUCTION: Patient safety incidents, including medical errors and adverse events, frequently occur in intensive care units, leading to a significant psychological burden on healthcare workers. This burden results in second victim syndrome, which impacts the psychological and psychosomatic well-being of these workers. However, a systematic review focusing specifically on this condition among intensive care unit healthcare workers is lacking. Therefore, we aimed to conduct a systematic review and meta-analysis to examine the occurrence of second victim syndrome among intensive care unit healthcare workers, including the types, prevalence, risk factors, and recovery time associated with this condition. METHODS: We conducted a comprehensive search of the MEDLINE, CINAHL, PsycINFO, and Igaku Chuo Zasshi databases. The eligibility criteria encompassed retrospective, prospective, and cross-sectional studies and controlled trials, with no language restrictions. Data on the type, prevalence, risk factors, and recovery time of second victim syndrome were extracted and pooled. Prevalence estimates from the included studies were combined using a random-effects meta-analytic model. RESULTS: Of the 2,245 records retrieved, 16 potentially relevant studies were identified. Following full-text evaluation, five studies met the inclusion criteria and were included in the review. The findings revealed that 58% of intensive care unit healthcare workers experienced second victim syndrome. Frequent symptoms included guilt (12-68%), anxiety (38-63%), anger at self (25-58%), and lower self-confidence (7-58%). However, specific risk factors exclusive to intensive care unit healthcare workers were not identified in the review. Furthermore, approximately 20% of individuals took more than a year to recover or did not recover at all from the second victim syndrome. CONCLUSIONS: Thus, this condition is prevalent among intensive care unit healthcare workers and may persist for extended periods, potentially exceeding a year. The risk factors for second victim syndrome in the intensive care unit setting are unclear and require further investigation.

Sustained exercise load by young adult females while wearing surgical mask raises core body temperature measured with zero-heat-flux thermometer.

When a pandemic such as that caused by the novel coronavirus disease termed COVID-19 emerges, it is recommended to wear a mask when in public situations, with information regarding the impact on thermoregulation essential, especially during exercise or hard physical labor. The present study investigated changes in core body temperature (CBT) while wearing a surgical mask (SM) during exercise (TCBT) using a non-invasive zero-heat-flux (ZHF) thermometer. Nine young adult females performed ergometer exercise for 30 min at 60 W with (mask group) and without (control) a SM under a non-hot condition, shown by wet bulb globe temperature (WBGT) findings. TCBT, mean skin temperature (TMST), heart rate (HR), and humidity in the perioral region of the face (%RH) were determined. Each of those markers showed increased values during exercise, with the increases in TCBT, HR, and %RH, but not TMST, during exercise found to be significantly greater in the mask group. HR reserve (%HRR), derived as load intensity during exercise, was also significantly higher in the mask group. Each subject completed all of the experimental protocols without noting pain or discomfort. These results suggest that wearing a SM while performing mild exercise contributes to increased TCBT associated with increased exercise intensity, expressed as %HRR in a non-heated condition. Furthermore, the ZHF thermometer was shown to be safe and is considered useful for conducting such studies. Additional examinations will be necessary to examine gender and age group differences, as well as the use of different exercise methods and intensity and ambient conditions.

Smartphone-based mobile applications for adverse drug reactions reporting: global status and country experience.

BACKGROUND: Smartphone technology can support paperless reporting of adverse drug reactions (ADRs). The aims of this study were to systematically assess smartphone ADR-reporting applications, understand their qualitative and quantitative impact on ADR reporting, and garner key lessons from owners and developers. METHODS: This study had three components: (1) An assessment of ADR-reporting apps, (2) an online survey on the impact of app implementation on ADR reporting and the experiences of app developers and owners, and (3) a search of VigiBase, the World Health Organization global database of individual case safety reports (ICSRs), to observe trends in the number of ADR reports targeting countries where the apps were implemented. RESULTS: Twenty-two apps were included. Eight out of the 22 apps were for countries in the WHO African region. Features observed included E2B data elements (E stands for efficacy) and functions supporting reporting and user engagement. Seventeen app developers and owners answered to the survey and reported overall positive experiences with app features, and post-launch increases in the total number of ICSRs. User type and user environment were cited as factors influencing app use: Respondents said younger people and/or those with an inclination to use technology were more likely to use apps compared to older or more technology-averse people, while respondents in countries with limited internet connectivity reported persistent difficulties in app use. CONCLUSIONS: Smartphone apps for reporting ADRs offer added value compared to conventional reporting tools. Reporting tools should be selected based on interface features and factors that may influence app usage.

Adjuvant endocrine therapy effects on bone mineral density and microstructure in women with breast cancer.

INTRODUCTION: Although aromatase inhibitors (AIs) are typical drugs for cancer treatment-induced bone loss, their effects on the bone microstructure remain unclear. In this study, we evaluated changes in the bone mineral density (BMD) and bone microstructure associated with AI treatment using high-resolution peripheral quantitative computed tomography (HR-pQCT) in patients with early breast cancer. MATERIALS AND METHODS: This prospective, single-arm, observational study included non-osteoporotic, postmenopausal women with hormone receptor-positive breast cancer. Patients underwent dual-energy X-ray absorptiometry (DXA), HR-pQCT, and tartrate-resistant acid phosphatase-5b (TRACP-5b) or procollagen type-I N-terminal propeptide measurements at baseline and 6 and 12 months after AI therapy. The primary endpoint was changes in the total volumetric BMD (Tt.vBMD), trabecular vBMD (Tb.vBMD), and cortical vBMD (Ct.vBMD) longitudinally at the distal radius and tibia. RESULTS: Twenty women were included (median age 57.5 years; range 55-72 years). At 12 months, HR-pQCT indicated a significant decrease in the Tt.vBMD (median distal radius - 5.3%, p < 0.01; distal tibia - 3.2%, p < 0.01), Tb.vBMD (- 3.2%, p < 0.01; - 1.0%, p < 0.05, respectively), and Ct.vBMD (- 3.2%, p < 0.01; - 2.7%, p < 0.01, respectively). Estimated bone strength was also significantly decreased. The DXA BMD value in the total hip (p < 0.01) and femoral neck (p = 0.03), but not in the lumbar spine, was significantly decreased. The TRACP-5b levels was significantly negatively associated with changes in the Tt.vBMD in both the distal radius and tibia (r =  - 0.53, r =  - 0.47, respectively) CONCLUSION: Postmenopausal women who received AIs for early breast cancer experienced significant trabecular and cortical bone deterioration and a decrease in estimated bone strength within only 1 year.

[Clinical Investigation of Surgical Cases for Pulmonary Aspergillosis].

INTRODUCTIONS: The number of cases requiring surgical resection for pulmonary aspergillosis has increased in recent years. PATIENTS AND METHODS: From April 2008 to March 2019, 10 patients underwent pulmonary resection for chronic pulmonary aspergillosis(CPA) in our hospital. RESULTS: Five patients were diagnosed with simple pulmonary aspergilloma (SPA) and 5 were diagnosed with chronic progressive pulmonary aspergillosis( CPPA). The median age was 73 years, and 8 patients were men. A history of tuberculosis was present in 2 cases, diabetes was present in 3 cases, and prednisolone( PSL) administration was performed in 3 cases. The operative procedures included 1 pneumonectomy, 4 lobectomies, 1 segmentectomy, and 4 wedge resections. The median surgery time was 220.5 minutes, and the median blood loss was 301 ml, requiring perioperative transfusion in 2 cases. Postoperative pneumonia was observed in 2 cases. The median postoperative observation period was 11.5 months, and 6 out of 8 patients did not show postoperative recurrences. CONCLUSIONS: Although patients with pulmonary aspergillosis have a high rate of underlying disease and it is necessary to pay attention to postoperative complications, it has been shown that surgery can be performed safely on these patients by selecting appropriate cases and surgical procedures.

The angiogenic effects of exosomes secreted from retinal pigment epithelial cells on endothelial cells.

Exosomes are informative microvesicles associated with intercellular communication via the transfer of many molecular constituents such as proteins, lipids, and nucleic acids; environmental changes and the cellular status around cells greatly affect exosome components. Cells of the retinal pigment epithelium (RPE) are key players in retinal homeostasis. Transforming growth factor (TGF)-ß and tumour necrosis factor (TNF)-α are increased in the vitreous and retina in several retinal diseases and activate and undergo epithelial-mesenchymal transition (EMT) in RPE cells. EMT is closely associated with mechanisms of wound healing, including fibrosis and related angiogenesis; however, whether exosome components depend on the cell status, epithelium or mesenchyme and whether these exosomes have pro- or anti-angiogenic roles in the retina are unknown. We performed this study to investigate whether these EMT inducers affect the kinds of components in exosomes secreted from RPE cells and to assess their angiogenic effects. Exosomes were collected from culture media supernatants of a human RPE cell line (ARPE-19) stimulated with or without 10 ng/ml TNF-α and/or 5 ng/ml TGF-ß2. NanoSight tracking analysis and immunoblot analysis using exosome markers were used to qualify harvested vesicles. Angiogenic factor microarray analysis revealed that exosomes derived from ARPE-19 cells cultured with TNF-α alone (Exo-TNF) and co-stimulated with TNF-α and TGF-ß2 (Exo-CO) contained more angiogenic factors than exosomes derived from control cells (Exo-CTL) or ARPE-19 cells cultured with TGF-ß2 alone (Exo-TGF). To assess the effect on angiogenesis, we performed chemotaxis, tube formation, and proliferation assays of human umbilical vein endothelial cells (HUVECs) stimulated with or without exosomes. HUVECs migrated to RPE-derived exosomes, and exosomes derived from ARPE-19 cells accelerated HUVEC tube formation. In contrast, Exo-TNF and Exo-CO reduced HUVEC proliferation. Our findings provide insight into the mechanisms underlying the relation between angiogenesis and exosomes derived from RPE cells.

Fidaxomicin compared with vancomycin and metronidazole for the treatment of Clostridioides (Clostridium) difficile infection: A network meta-analysis.

We conducted a systematic review of the literature and network meta-analysis (NMA) to compare the relative effectiveness of antibiotic treatments for Clostridioides (Clostridium) difficile infection (CDI) including vancomycin (VCM), metronidazole (MTZ) and fidaxomicin (FDX). Eligible studies were randomised controlled trials (RCTs) including adults with any severity of CDI that was treated with VCM, MTZ or FDX. The NMA was performed using a Bayesian framework, using a fixed-effects model. The searches identified seven publications for inclusion, which provided five RCTs for VCM versus MTZ, and three RCTs for FDX versus VCM. The NMA showed that for clinical cure rate, there was no difference for FDX versus VCM, and there was a significant difference in favour of FDX versus MTZ (odds ratio [OR]: 1.77; 95% credible interval [CrI] 1.11, 2.83]). For recurrence rate, there was a significant difference in favour of FDX versus both VCM (OR: 0.50; 95% CrI: 0.37, 0.68) and MTZ (OR: 0.44; 95% CrI: 0.27, 0.72). For sustained cure (clinical cure without recurrence), there was a significant difference in favour of FDX versus VCM (OR: 1.61; 95% CrI: 1.27, 2.05) and MTZ (OR: 2.39; 95% CrI: 1.65, 3.47). These findings suggest that FDX and VCM are effective first-line treatments for mild or moderate CDI, whereas MTZ is not, and FDX may be more effective at preventing CDI recurrence than VCM.

Early bleb parameters as long-term prognostic factors for surgical success: a retrospective observational study using three-dimensional anterior-segment optical coherence tomography.

BACKGROUND: The object of this study is to investigate the effect of early bleb parameters measured by three-dimensional anterior-segment optical coherence tomography on the surgical success of trabeculectomy. METHODS: This retrospective study included 45 patients with 19 of exfoliation glaucoma, 17 of primary open angle glaucoma, 4 of neovascular glaucoma, 4 of uveitic glaucoma and 1 of glaucoma caused from familial amyloid polyneuropathy who underwent trabeculectomy. Bleb parameters, such as total bleb height, the position and the width of filtration openings on the scleral flap, bleb wall thickness, fluid-filled cavity height, and bleb wall intensity were assessed by three-dimensional anterior-segment optical coherence tomography 0.5 months after trabeculectomy, and were subjected to a Cox proportional hazard model as potential prognostic factors. Surgical success was defined as: IOP < 21 mmHg (A), < 18 mmHg (B), < 15 mmHg (C) with (qualified success) or without medication (complete success). Complete failure was defined as hypotony and additional glaucoma surgeries required. RESULTS: The width of filtration openings was identified as a prognostic factor for all criteria. By multivariable analysis, the width of the filtration openings was a prognostic factor in all criteria tested, and the preoperative IOP were significant prognostic factors for surgical success in qualified success in criteria B and C. Separate from the median widths of filtration openings, wide filtration opening showed significant survival ratio for qualified success in criteria A and B and for complete success in all criteria, respectively. CONCLUSIONS: The width of filtration opening at an early stage is a prognostic factor for surgical success of trabeculectomy.

Health-care resource use and current treatment of adult atopic dermatitis patients in Japan: A retrospective claims database analysis.

The real-world evidence on the profiles of patients suffering from atopic dermatitis (AD) in Japan is sparse. A retrospective claim database analysis was conducted to estimate the health-care resource use (HCRU) and current AD treatment. Data from October 2013 to September 2016 were extracted from the JMDC (Tokyo, Japan) claims database. HCRU was assessed by a comparison of AD patients and matched non-AD controls. A multivariate analysis was performed to estimate HCRU attributable to AD. AD patients (n = 39 893) have more claims of certain diagnoses such as rhinitis, viral and fungal infections, sleep disorders and conjunctivitis as well as higher HCRU (outpatient visits, prescriptions of AD-related and non-AD-related medications, phototherapy, laboratory tests) than matched non-AD controls (n = 39 893). Treatment pattern analysis included treatment-naive patients (n = 8478) and previously treated AD patients (n = 30 109). Approximately 20% of previously treated patients were on the continuous systemic treatment during 18-month follow up. Systemic corticosteroids were the most frequently used systemic treatments. Oral cyclosporin was less frequently used in both groups, but for the longest duration. Almost half of previously treated patients with oral cyclosporin continued treatment for more than 3 months. In conclusion, HCRU was higher in AD patients than non-AD controls, indicating a high burden of the disease imposed on AD patients. Continuous administration of systemic treatment, such as oral cyclosporin, systemic corticosteroids and phototherapy, observed in AD patients sheds light on the difficulties of managing AD in Japanese clinical practise.

Impact of Hypertension on Hospitalizations for Cardiovascular Diseases in a Worksite Population: An Epidemiologic Study Using Claims Data for Workers.

BACKGROUND: Few of studies investigated the effect of antihypertensives among working population. We aimed to describe the impact of hypertension with and without antihypertensives on hospitalizations because of cardiovascular diseases (CVDs) in the Japanese working population. METHODS: This retrospective study included adults aged 40-64 years whose systolic and diastolic blood pressure (BP) readings taken between 2008 and 2015 were available in the Japanese claims database. Individuals were categorized as treated (T) or untreated (UT) depending on their hypertension treatment history. Time to first CVD-related hospitalization was compared among individuals with different BP levels using Cox models that included baseline characteristics with either baseline BP level or a time-dependent variable reflecting BP changes over time. RESULTS: Of 740,784 UT individuals (male: 61.9%, mean age: 47.9 years), 2,121 individuals were hospitalized due to a CVD over a 957.3-day average follow-up. Among 72,828 T individuals (male: 74.3%, mean age: 53.7 years), the corresponding figure was 470 individuals over an 813.4-day average follow-up. The risk of hospitalization increased with baseline hypertension severity among UT (hazard ratios [HRs] = 1.93, 2.82, and 6.32 for grade 1, grade 2, and grade 3, respectively; P < 0.0001, reference: optimal) but not among T individuals. UT individuals with hypertension at any given time had a significantly higher probability of hospitalization compared to nonhypertensive individuals (HR = 1.74, P < 0.0001). CONCLUSIONS: This study adds quantitative evidence on the impact of hypertension on the risk of CVD-related hospitalization in the Japanese working population. It suggests that antihypertensive treatment had beneficial effects in this relatively young, working population aged 40-64 years.

The impact of anti-vascular endothelial growth factor agents on visual impairment/blindness prevention in patients with diabetic macular edema and on associated patient and caregiver burden in Japan.

AIMS: To estimate the impact of anti-vascular endothelial growth factor (VEGF) agents on visual impairment and blindness avoided in patients with diabetic macular edema (DME) and on associated patient and caregiver productivity loss in Japan. METHODS: This study compared the impact of current care (estimated at 53.8% utilization of anti-VEGF agents using current data) with that of hypothetical care (characterized by a higher utilization of anti-VEGF agents [80.0%], as estimated by an expert panel) of DME patients. A population-based Markov model (two-eye approach) simulated visual acuity (Early Treatment Diabetic Retinopathy Study [ETDRS] letters) transitions over 5 years with DME treatments (intravitreal aflibercept, ranibizumab, and triamcinolone acetonide, and grid/focal laser) in patients with DME. Patient and caregiver productivity loss was determined using the human capital method. RESULTS: In total, 570,000 DME patients were included in the model over 5 years. Increased utilization of anti-VEGF agents resulted in 6,659 fewer cases of severe visual impairment (SVI; 26-35 ETDRS letters) or blindness (0-25 ETDRS letters) compared with the current care approach (26,023 vs 32,682 cases; 20.38% reduction) over this period. Increased utilization of anti-VEGF agents also contributed to productivity loss savings of ¥12.58 billion (US $115.64 million) (i.e., 17.01%) at the end of year 5. The total overall saving over 5 years was ¥45.83 billion (US $421.27 million) (13.45%). LIMITATIONS: Few Japanese data were available, and assumptions were made for some inputs. Vision changes dependent on the function of both eyes were not studied. Only intravitreal (not sub-Tenon's) injections of triamcinolone were considered in this model. Direct costs were not considered. CONCLUSIONS: Increased utilization of anti-VEGF agents can reduce SVI and legal blindness in patients with DME in Japan. This would also be associated with substantial savings in patient and caregiver productivity loss.

Burden of Anemia in Chronic Kidney Disease Patients in Japan: A Literature Review.

Anemia is a common complication for patients with chronic kidney disease (CKD) and is associated with cardiovascular comorbidities and reduced quality of life. The incidence of anemia increases as kidney function declines and affects approximately 32% of Japanese patients with stage 3-5 CKD. This review examined the current literature on anemia in CKD patients in Japan to provide an overview of the burden of anemia in CKD. Medline, Embase, and Igaku Chuo Zasshi databases were searched to identify relevant manuscripts and abstracts published from 2004 onward. The population included CKD patients with anemia, and the outcomes of interest were epidemiology, economic, humanistic, and treatment patterns. Observational studies, database analysis, and economic evaluation studies were included in the analysis. A total of 1151 references were identified, and 50 were eligible for final review. Economic burden was reported in most studies (n = 37) followed by treatment patterns (n = 26), and epidemiological (n = 25) and humanistic (n = 1) burdens. Prevalence of anemia varied largely (0-95%) based on the different definitions of anemia, and increased with CKD severity. Higher mortality was associated with erythropoiesis-stimulating agent (ESA) resistance and lower hemoglobin levels among patients treated with ESA. Drug dosage was the most reported economic burden (n = 33), followed by medical, and non-medical outcomes. Costs associated with anemia were considerable and depended on dialysis status and ESA treatment. Only one study reported data on quality of life, suggesting that further investigation on the humanistic burden of anemia in CKD is needed.

Prospective 3D Investigation of Bleb Wall after Trabeculectomy Using Anterior-Segment OCT.

PURPOSE: We used three-dimensional anterior-segment optical coherence tomography (3D AS-OCT) to evaluate time-dependent posttrabeculectomy changes in bleb wall volume and intensity. METHODS: This prospective observational study included patients with open-angle glaucoma who underwent fornix-based trabeculectomy between January 2012 and October 2012. Twenty-nine eyes met inclusion criteria, and the bleb walls of 22 were amenable to three-dimensional analysis by 3D AS-OCT for 1 year after surgery. The high-intensity volume ratio was calculated as the proportion of the high-intensity region in the total bleb wall. Changes in the high-intensity volume ratio were of high intensity, and parameters influencing the ratio were analyzed using 3D AS-OCT. RESULTS: The mean high-intensity volume ratios (±SDs) were 43.5 ± 21.4, 44.1 ± 14.8, 41.5 ± 22.6, and 43.2 ± 19.7% at 0.5, 3, 6, and 12 months after trabeculectomy, respectively. When the volume ratios obtained 0.5 and 12 months posttrabeculectomy were compared, four and five eyes exhibited decreases and increases of over 20%, respectively. The volume ratios at 12 months correlated with the intraocular pressure (IOP) at that time (t = 2.44, P = 0.024) and the bleb wall vascularity score at 12 months (t = 5.44, P < 0.001). CONCLUSIONS: The high-intensity bleb wall at 12 months posttrabeculectomy reflected the IOP and the bleb wall vascularity at that time.

Prospective observation of filtration blebs in high-risk eyes with limbal-based conjunctival flap.

OBJECTIVE: To evaluate time-dependent changes in filtering bleb parameters using 3-dimensional anterior segment optical coherence tomography (3-D AS-OCT) in high-risk eyes after a limbal-based trabeculectomy procedure. DESIGN: Prospective, observational study. PARTICIPANTS: Twenty-three patients who underwent uncombined limbal-based trabeculectomy surgery and who also had a history of prior intraocular surgery. METHODS: Of 23 eyes, 15 eyes were followed for 1 year without additional glaucoma surgeries, and their bleb parameters were measured 0.5, 3, 6, and 12 months after the trabeculectomy using 3-dimensional anterior segment optical coherence tomography. The correlations of these parameters to other clinical data were investigated. RESULTS: Statistical analysis showed significant changes in the bleb wall thickness (0.7 ± 0.4 mm vs 0.4 ± 0.2 mm; p = 0.007) and fluid cavity height (0.3 ± 0.2 mm vs 0.7 ± 0.4 mm; p = 0.005) between 0.5 and 3 months only. The width of the filtration openings at 0.5 months after trabeculectomy (2.1 ± 1.0 mm) was significantly associated with the intraocular pressure at 12 months (15.1 ± 5.7 mm Hg; R2 = 0.37, t = -2.65, and p = 0.021). CONCLUSIONS: The width of the filtration opening in the early stage may be a prognostic factor for long-term intraocular pressure control.

Comparison of Inhaled Antibiotics for the Treatment of Chronic Pseudomonas aeruginosa Lung Infection in Patients With Cystic Fibrosis: Systematic Literature Review and Network Meta-analysis.

PURPOSE: In Europe, 4 inhaled antibiotics (tobramycin, colistimethate sodium, aztreonam, and levofloxacin) are currently approved for the treatment of chronic Pseudomonas aeruginosa lung infection in patients with cystic fibrosis (CF). Levofloxacin inhalation solution (LIS) is the most recently approved inhaled antibiotic for adult patients with CF. A systematic literature review and Bayesian network meta-analysis (NMA) was conducted to compare the relative short-term (4 weeks) and long-term (24 weeks) outcomes of these inhaled antibiotics versus LIS. METHODS: A systematic literature search was conducted on February 16, 2016, using EMBASE and Medline via OvidSP. All randomized controlled trials comparing any of the aforementioned inhaled antibiotics with 4 or 24 weeks of follow-up were evaluated. NMA was performed for the following outcomes: relative and absolute percent changes from baseline in forced expiratory volume in 1 second (FEV1%) predicted, change in P aeruginosa sputum density, respiratory symptoms score from the CF questionnaire-revised, hospitalization, additional antibiotics use, and study withdrawal rates. RESULTS: Of the 685 articles identified, 7 unique studies were included in the 4 weeks' NMA and 9 unique studies were included in the 24 weeks' NMA. Aztreonam was predicted to result in the greatest numerically increase in FEV1% predicted at 4 weeks, whereas LIS were predicted to be numerically greater than colistimethate sodium, tobramycin inhaled solution (TIS), and tobramycin inhaled powder (TIP). However, all of the 95% credibility intervals (CrIs) of these comparisons included zero. At 24 weeks, none of the treatments was significantly more effective than LIS. The estimates for the mean change from baseline to 24 weeks in relative FEV1% versus LIS was -0.55 (95% CrI, -3.91 to 2.80) for TIS, -2.36 (95% CrI, -7.32 to 2.63) for aztreonam, -2.95 (95% CrI, -10.44 to 4.51) for TIP, and -9.66 (95% CrI, -15.01 to -4.33) for placebo. Compared with LIS, the odds ratio for hospitalization at 24 weeks was 1.92 (95% CrI, 1.01-3.30) for TIS, 2.25 (95% CrI, 1.01-4.34) for TIP, and 3.16 (95% CrI, 1.53-5.78) for placebo, all statistically worse than LIS. P aeruginosa sputum density scores, additional use of antipseudomonal antibiotics, and study withdrawal rates were comparable among all inhaled antibiotics at all times. IMPLICATIONS: Based on this NMA, the analyses for many of the outcomes did not provide significant evidence to indicate that the other approved inhaled antibiotics were more effective than LIS for the treatment of chronic P aeruginosa lung infection in patients with CF. Study withdrawal rates seemed to be comparable among these inhaled antibiotics.

Effects of mechanical stress and vitreous samples in retinal pigment epithelial cells.

In rhegmatogenous retinal detachment (RRD), scattered RPE cells from the basement membrane into the vitreous cavity undergo an epithelial mesenchymal transition (EMT) and form the intraocular fibrous membrane in response to vitreous fluid. We investigated whether exposure to vitreous samples was associated with EMT-associated signals and mesenchymal characters. Human vitreous samples were collected from patients with RRD, epiretinal membrane (ERM), or macular hole (MH). We evaluated the effects of vitreous on ARPE-19 cells in suspension cultures using poly 2-hydroxyethyl methacrylate-coated dishes and three-dimensional (3D) Matrigel cultures. We found that exposure to vitreous samples did not induce morphological changes or accelerate wound closure in monolayers. Several samples showed increased phosphorylation of Smad2 and nuclear translocation of nuclear factor-κB. Mechanical stress triggered an elevation of phosphorylation levels in Smad2. In addition, exposure to vitreous fluid increased the phosphorylation of p38 mitogen-activated protein kinase in cell suspension cultures after mechanical stress. Moreover, ARPE-19 cells showed a stellate invasive phenotype in 3D Matrigel cultures with vitreous samples. In this study, we demonstrated that mechanical stress and vitreous were associated with EMT-associated signals and invasive phenotypes in 3D cultures but not in monolayers. These results have important implications for the role of vitreous humor in the induction of EMT and intraocular fibrosis.

Filtering blebs using 3-dimensional anterior-segment optical coherence tomography: a prospective investigation.

IMPORTANCE: Posttrabeculectomy changes in bleb parameters measured using 3-dimensional (3-D) anterior-segment optical coherence tomography (OCT) remain uncharacterized and might be related to postsurgical intraocular-pressure (IOP) control. OBJECTIVE: To evaluate time-dependent posttrabeculectomy changes in filtering bleb parameters using 3-D anterior-segment OCT. DESIGN, SETTING, AND PARTICIPANTS: This prospective observational study was conducted at Kumamoto University Hospital, Kumamoto, Japan. Patients with open-angle glaucoma who underwent uncombined fornix-based trabeculectomy at Kumamoto University Hospital between January 1, 2012, and October 31, 2012, were included. Twenty-nine eyes were enrolled, 23 of which were followed up for 1 year without additional glaucoma surgical procedures; 3 required additional glaucoma surgery. INTERVENTIONS: Imaging filtering blebs using 3-D anterior-segment OCT. MAIN OUTCOMES AND MEASURES: The primary end points were changes in bleb parameters including the position and width of the filtration openings on the scleral flap, the total bleb height, fluid-filled cavity height, bleb wall thickness, and bleb wall intensity, which were measured using 3-D anterior-segment OCT. The secondary end points were postsurgical IOP measured 0.5, 3, 6, and 12 months after trabeculectomy, and the effects of aqueous cytokine levels on the bleb parameters. RESULTS: We observed increased total bleb height (0.82 to 1.25 mm; difference: 95% CI, 0.10 to 0.75; P = .01), bleb wall thickness (0.46 to 0.61 mm; difference: 95% CI, 0.02 to 0.28; P = .03), and distance from the top of the scleral flap to the filtration opening (1.69 to 2.16 mm; difference: 95% CI, 0.28 to 0.70; P < .001), as well as decreased width of the filtration opening (2.08 to 1.12 mm; difference: 95% CI, -1.75 to -0.49; P = .002) between 0.5 and 12 months posttrabeculectomy. The filtration openings tended to close from the fornix side of the scleral flap during the wound healing process. Moreover, the width of the filtration opening at 0.5 months posttrabeculectomy correlated with the IOP at 12 months (P = .02). The aqueous humor level of monocyte chemoattractant protein-1 was correlated with the width of the filtration opening at 3 and 6 months posttrabeculectomy. CONCLUSIONS AND RELEVANCE: The width of the filtration opening at 0.5 months posttrabeculectomy correlated with the IOP at 12 months. The width of the filtration opening at the early stage may be a prognostic factor for long-term IOP control. Large-scale studies with longer follow-up periods are required.

Evaluation of filtering blebs exhibiting transconjunctival oozing using anterior segment optical coherence tomography.

PURPOSE: To explore the features of filtering blebs exhibiting transconjunctival oozing via three-dimensional anterior segment optical coherence tomography (3D AS-OCT). METHODS: In this cross-sectional study, 131 eyes of 131 patients exhibiting filtering blebs were examined. Of those, 20 eyes were excluded as flat-shaped, non-functioning bleb. Transconjunctival oozing was defined as transconjunctival aqueous egress evident on the bleb surface, in the absence of any point leak observable using a slit-lamp, as confirmed by application of digital pressure. Total bleb height, the height of the fluid-filled cavity, and bleb wall thickness and density were measured using 3D AS-OCT. Patient age, the etiology of glaucoma, postoperative follow-up period, number of glaucoma medication classes prescribed, intraocular pressure (IOP), grade of bleb vascularity, and bleb parameters were compared in eyes with and without bleb oozing. RESULTS: Sixty (54.0 %) of 111 eyes excluding non-functioning flat blebs exhibited oozing; mean IOP value (11.7 ± 4.5 vs. 14.8 ± 4.0 mmHg) and bleb vascularity grade (1.5 ± 0.7 vs. 2.4 ± 1.0) were lower than those of eyes without oozing. Total bleb height (1.1 ± 0.4 vs. 0.9 ± 0.4 mm), bleb wall thickness (0.7 ± 0.4 vs. 0.5 ± 0.3 mm), and bleb wall density (131.3 ± 45.7 vs. 180.9 ± 39.8 optical density units) differed significantly between the two groups (oozing vs. non-oozing). CONCLUSION: Transconjunctival oozing after trabeculectomy with MMC was associated with a low IOP, low-level bleb vascularity, an elevated total bleb height, a thicker bleb wall, and low bleb wall density.