Exposure-response relationship between work-related hand-arm vibration exposure and musculoskeletal disorders of the upper extremities: the German hand-arm vibration study.

Objective. To quantify the exposure-response relationship between hand-arm vibration exposure and the risk of musculoskeletal disorders of the upper extremities (UMSDs), a case-control study was carried out among workers in the construction, mining, metal and woodworking industries. Methods. In total, 209 male cases and 614 controls were recruited. Cases were newly reported patients with UMSDs. Controls were a random sample of persons with compensable occupational injuries. Standardized personal interviews were performed among cases and controls by well-trained safety engineers. In addition to leisure activities and comorbidities, work histories of all participants were collected in detail. To quantify hand-arm vibration exposures, a database of vibration measurements of over 700 power tools was used. This database allows the detailed quantification of vibration exposures over time. A dose-response relationship between hand-arm vibration exposure and UMSDs was quantified by conditional logistic regression analyses. Results and conclusions. After adjusting for relevant confounders, statistically significant exposure-response relationships between cumulative hand-arm vibration exposure and UMSDs were established. A cumulative hand-arm vibration exposure of Dhv (vibration total value in three measuring directions) = 142,300 (95% confidence interval [CI] [90,600-333,200]) m2/s4·day or Dhw (vibration value in the direction along the forearm) = 38,700 (95% CI [25,400-80,900]) m2/s4·day is associated with a doubled risk of UMSDs.

Novel Surgical Techniques to Control Flow With PreserFlo MicroShunt for Late Hypotony After Baerveldt Drainage Device Implantation.

We report a new surgical technique for controlling flow with a PreserFlo MicroShunt, in patients with late postoperative hypotony, following a Baerveldt glaucoma drainage device implantation. We present 2 cases with late postoperative hypotony after Baerveldt-shunt implantations. In both cases, the outflow resistance of the Baerveldt tube was modulated by the insertion of a PreserFlo MicroShunt into the lumen of the Baerveldt tube. In the first case, the Microshunt was inserted through the distal opening of the tube in the anterior chamber. In the second case, an end plate, sided approach was chosen after opening the conjunctiva. In both cases, the hypotony was successfully treated. The intraocular pressure rose immediately after the procedure, and it remained well controlled within the targeted range during the first postoperative months without additional pressure-lowering medication. This novel surgical technique provided predictable flow reductions, according to the Hagen-Poiseuille equation. This approach offers a valuable alternative to permanent tube ligation.

[Personal factors influencing daytime sleepiness]. / Persönliche Einflussfaktoren auf die Tagesmüdigkeit: Eine Umfrage zum veränderten Schlafverhalten beim Arbeiten im Homeoffice während der ersten Coronawelle.

Background and objective: During the first corona wave public life largely came to a standstill. Many employees started to work from home to protect themselves from infection. The purpose of this study was to investigate changes in sleep behavior and daytime sleepiness when people changed from working in the office to mobile working from home. Method: Office workers were asked about their chronotype, their usual sleep routine and the occurrence of daytime sleepiness on office workdays and during mobile working. Data collection took place between 15 July 2020 and 7 August 2020. An anonymized online survey tool was used. The composite scale of morningness (CSM) in the German language version was used to determine the chronotype. The association of age, gender, chronotype, sleep quality and sleep duration with self-rated daytime sleepiness was examined using multivariable logistic regression analyses. Results: The data of n = 228 individuals could be analyzed. Sleep duration increased while working from home. The proportion of persons with less than 7.5 h time in bed decreased from 56.6% to 33.4% and the proportion of those with more than 8 h time in bed increased from 43.4% on office workdays to 66.6% when working from home. The percentage of people who always or often felt sleepy at work decreased from 47% on office workdays to 15% when working from home. The chronotype showed a significant association with daytime sleepiness on office workdays but not when working from home. Discussion: The reduction of daytime sleepiness could be explained by longer sleep duration and higher satisfaction with sleep quality. Late chronotypes seem to benefit particularly when working from home. A flexible start of work, the consideration of the chronotype and measures for health-promoting sleep could reduce daytime sleepiness and thus improve occupational safety and health.

Comparative Assessment of Retinal Blood Flow Velocity Changes Following Brimonidine and Brinzolamide Administration Using Retinal Function Imaging.

PURPOSE: Impaired ocular blood flow has been associated with the etiopathogenesis of glaucoma. Topical brimonidine lowers intraocular pressure, a major glaucoma risk factor. However, brimonidine's influence on retinal blood flow remains to be fully elucidated. Our aim was to compare the effect of topical brimonidine and brinzolamide administration on retinal blood flow velocity in second and third order vessels in healthy adults using the retinal function imager. METHODS: In 10 healthy probands between 23 and 32 years of age, one eye was randomly selected to receive 2 treatment rounds with 3 single doses of brimonidine 2 mg/mL and brinzolamide 10 mg/mL at 12-hour intervals each. The fellow eyes served as intra-individual controls. Immediately before the first drop and 2 hours after the last drop of each treatment round, all subjects were examined, including Goldmann tonometry, Pascal tonometry, assessment of retinal blood flow velocity using the retinal function imager, as well as blood pressure and pulse measurements. RESULTS: Intraocular pressure decreased significantly in treated eyes while remaining stable in control eyes, indicating reliable application of brimonidine and brinzolamide drops. In contrast, retinal blood flow velocities did not demonstrate any significant differences between groups after both treatment rounds. CONCLUSIONS: Neither brimonidine nor brinzolamide appear to alter retinal blood flow velocity in a clinically relevant manner. The slight velocity changes detected in our study are likely physiologic fluctuations. Our findings do not support the rationale of a detrimental effect of topical brimonidine on ocular blood flow and hence brimonidine may be further administered for lowering intraocular pressure with the appropriate caution. However, our study is strongly limited by the small sample size and, thus, further research with larger cohorts of healthy volunteers and patients with glaucoma is needed to confirm the results. TRANSLATIONAL RELEVANCE: The study provides information about the effect of the topically administered antiglaucoma medications brimonidine and brinzolamide on the ocular blood flow and its regulation. The findings indicate that beside the lowering of IOP there is no evidence for an additional effect on the development of glaucoma.

Surgical Outcomes of Gonioscopy-Assisted Transluminal Trabeculotomy (GATT) in Patients with Open-Angle Glaucoma - A Retrospective Case Series.

PURPOSE: To evaluate the outcome of gonioscopy-assisted transluminal trabeculotomy (GATT) in patients with open-angle glaucoma (OAG). PARTICIPANTS AND METHODS: A retrospective case series of patients with uncontrolled OAG treated by GATT at the cantonal Hospital Lucerne, a tertiary referral center, between October 2018 and July 2019 with a minimal 6-month follow-up period. Main outcome measures were intraocular pressure (IOP), number of antiglaucoma medications, and complications. RESULTS: Thirty-one eyes of 29 patients with a mean age of 70.9 years and a minimal follow-up period of 6 months were included in this study. Twenty eyes were treated for pseudoexfoliation (64.5%), seven for primary open-angle (22.6%), three for pigmentary (9.7%), and one for traumatic (3.2%) glaucoma. Twenty-six eyes had data at the 6-month follow-up and 12 eyes at the 12-month follow-up. Twenty-two eyes (70.9%) were pseudophakic prior to the operation. Mean preoperative IOP was 33 mmHg (standard deviation [SD] 8.0 mmHg). The postoperative IOP was 13.9 mmHg [SD 2.2] at the 6- and 13.9 mmHg [SD 3.1] at the 12-month follow-up. The postoperative IOP evolution translated into a 58% decrease between 6 and 12 months (p < 0.001). Thirteen patients (41.9%) were treated with oral Diamox prior to GATT. The number of antiglaucoma medications decreased from a preoperative average of 2.9 [SD 1.2] to postoperative 1 [SD 1] drug (p < 0.001). The most frequent adverse event was the occurrence of postoperative hyphema. Hyphema was observed in 21 (68.0%), 7 (22.6%), and 2 (6.4%) eyes at days 1, 7, and 30 after GATT, respectively. Intraocular hypertension over 25 mmHg was seen in eight eyes (25.8%), and in four of them, a steroid response was suspected. One patient developed an anterior uveitis and a macular edema. CONCLUSION: GATT is an effective and safe intervention for OAG, particularly in pseudoexfoliation glaucoma (PEX). The advantages of GATT compared to filtration surgery are the low rate of long-term complications and that the intervention is feasible even when difficult conjunctival conditions are encountered.

Occurrence of motility disorders in patients undergoing tube surgery-consecutive, retrospective follow-up case series analysis.

BACKGROUND: The two glaucoma drainage devices (GDD) Ahmed and Baerveldt tubes are most commonly used for the treatment of refractory glaucoma. We noticed a significant number of patients with postoperative motility disorders resulting in diplopia. We investigated the occurrence and patterns of postoperative motility disorders overall and between the two GDD tubes using the Hess Screen Test. METHODS: Retrospective single-center matched case series of 20 patients undergoing Ahmed and 20 patients undergoing Baerveldt tube implantation with a follow-up of at least 1 year. In order to investigate the dynamic of GDD-induced motility disorder over time, from 25 patients, a follow-up examination from two different time periods (3 to 6 months and 12 to 24 months postoperatively) was available. From these 25 patients, 12 had received an Ahmed and 13 a Baerveldt GDD. To compare the different Hess Screen Tests, we developed nine categories of possible emerging motility disorder in the operated eye as a primary endpoint: Motility restriction in up-gaze, in down-gaze, in abduction, in adduction; combined motility disorders in up-gaze and adduction, up-gaze and abduction, down-gaze and adduction, down-gaze and abduction. If there was no motility disorder, this was also separately classified. RESULTS: Regardless of the used device, Ahmed or Baerveldt, most patients experienced motility disorders to some extent; mainly down-gaze and adduction were affected. However not every motility disorder resulted in diplopia. Although over time a decrease in ocular misalignment was seen, the incidence of diplopia was stable. Nevertheless, only few required therapy. We noted no difference between Ahmed and Baerveldt tube implant devices. CONCLUSION: Ocular misalignment and restriction of motility is a common finding after GDD. Although not every motility disorder results in diplopia, it is frequent. Therefore, it needs to be taken into consideration in informed consent.

Changes in higher order aberrations after central corneal regularization - a comparative two-year analysis of a semi-automated topography-guided photorefractive keratectomy combined with corneal cross-linking.

BACKGROUND: The optical quality in progressive keratoconus deteriorates due to ectasia and distortion of the corneal shape and optics. While corneal cross-linking (CXL) aims at stopping disease progression, "CXL-Plus" combines CXL with excimer laser ablation to improve visual function. Central Corneal Regularization (CCR) represents a therapeutic excimer laser modality specifically designed to smoothen the ectatic corneal shape and to reduce higher order aberrations (HOA). We set out to compare CXL-Plus, consisting of CXL combined with CCR, with CXL by itself for patients with progressive keratoconus. METHODS: Retrospective 2-year matched group analysis of patients who either underwent CXL-Plus (n = 28) or CXL as a sole procedure (n = 28) for progressive keratoconus. Main outcome parameters were HOA, visual function and tomographic results 12 and 24 months postoperatively. RESULTS: After 12 months, the total HOA root mean square wavefront error was reduced from 0.79 ± 0.30 to 0.40 ± 0.19 µm (CXL-Plus; p <  0.0001) and changed from 0.71 ± 0.28 to 0.73 ± 0.36 µm (CXL; p = 0.814). Uncorrected distance visual acuity improved from 0.70 ± 0.35 to 0.36 ± 0.29 logMAR (CXL-Plus; p = 0.0002) and from 0.65 ± 0.39 to 0.46 ± 0.37 logMAR (CXL; p = 0.067), translating to gains of three or more lines in 50% (CXL-Plus) and 36% (CXL) of patients. The steepest keratometry value (Kmax) regressed by 5.84 D (CXL-Plus; p <  0.0001) and 0.66 D (CXL; p = 0.752). For none of the investigated parameters a statistically significant change could be shown between 12 and 24 months. CONCLUSIONS: CXL-Plus in the form of a CCR reduces HOA and Kmax more effectively than CXL as a sole procedure.

Exposure-Response Relationship and Doubling Risk Doses-A Systematic Review of Occupational Workload and Osteoarthritis of the Hip.

In this review, we critically evaluated the evidence of exposure-response relationships between occupational workload and the risk of hip osteoarthritis. The existing evidence was evaluated in order for us to extrapolate possible doubling risk doses for hip osteoarthritis. Comprehensive searches for epidemiological studies of hip osteoarthritis and occupational workload were performed in literature databases (PubMed, EMBASE, Cochrane Work and Google Scholar) and recent reviews up to February 2019. In total, 85 papers met the preliminary inclusion criteria, and 10 studies indicating an exposure-response relationship between occupational workload and hip osteoarthritis were identified. All studies were assessed on the basis of their study design, defined quality scores and relevant confounders considered. An exposure-response relationship between heavy lifting and the risk of hip osteoarthritis is consistently observed among the male populations but not among the female populations. We quantified the doubling risk doses in two studies in which both an exposure-response relationship and cumulative exposure doses were stated. These two studies provided the highest quality level of all studies published to date. The estimated doubling risk doses in these two studies lie between 14,761 and 18,550 tons (daily lifting 2.2-2.8 tons, 220 days/year for 30 years). These results can be used for workplace interventions to prevent hip osteoarthritis.

Hip Osteoarthritis and Physical Workload: Influence of Study Quality on Risk Estimations-A Meta-Analysis of Epidemiological Findings.

In this paper, we critically evaluate the quality of epidemiological evidence on hip osteoarthritis and workload published so far. The influence of study quality on risk estimations was analyzed in sensitivity meta-analyses and meta-regression analyses. Comprehensive searches for epidemiological studies of hip osteoarthritis and occupational workload were performed in literature databases and current reviews. All studies were assessed on the basis of study design, defined quality scores, and relevant confounders considered. In total, 34 suitable studies were identified for critical evaluation. Of these, 20 are prevalence studies and 14 incidence studies. Strong heterogeneity is observed in study design, quality level, and estimated exposure parameters. A consistent positive association between heavy physical workload and hip osteoarthritis was observed only among the male populations, not among the female populations. In general, cohort studies provided lower effect estimates than cross-sectional and population-based case-control studies. Studies with high quality scores also produced lower effect estimates than studies with low quality scores. Consideration of BMI as a confounder in published studies also yielded lower effect estimates than studies without consideration of BMI as a confounder. Our analyses indicate that high-quality studies of the association between occupational workload and hip osteoarthritis provide lower effect estimates than studies of lower quality.

Development and Validation of a Practical Instrument for Injury Prevention: The Occupational Safety and Health Monitoring and Assessment Tool (OSH-MAT).

BACKGROUND: The Occupational Safety and Health Monitoring and Assessment Tool (OSH-MAT) is a practical instrument that is currently used in the German woodworking and metalworking industries to monitor safety conditions at workplaces. The 12-item scoring system has three subscales rating technical, organizational, and personnel-related conditions in a company. Each item has a rating value ranging from 1 to 9, with higher values indicating higher standard of safety conditions. METHODS: The reliability of this instrument was evaluated in a cross-sectional survey among 128 companies and its validity among 30,514 companies. The inter-rater reliability of the instrument was examined independently and simultaneously by two well-trained safety engineers. Agreement between the double ratings was quantified by the intraclass correlation coefficient and absolute agreement of the rating values. The content validity of the OSH-MAT was evaluated by quantifying the association between OSH-MAT values and 5-year average injury rates by Poisson regression analysis adjusted for the size of the companies and industrial sectors. The construct validity of OSH-MAT was examined by principle component factor analysis. RESULTS: Our analysis indicated good to very good inter-rater reliability (intraclass correlation coefficient = 0.64-0.74) of OSH-MAT values with an absolute agreement of between 72% and 81%. Factor analysis identified three component subscales that met exactly the structure theory of this instrument. The Poisson regression analysis demonstrated a statistically significant exposure-response relationship between OSH-MAT values and the 5-year average injury rates. CONCLUSION: These analyses indicate that OSH-MAT is a valid and reliable instrument that can be used effectively to monitor safety conditions at workplaces.

Chronic and Intermittent Angle Closure Caused by In-The-Bag Capsular Tension Ring and Intraocular Lens Dislocation in Patients With Pseudoexfoliation Syndrome.

PURPOSE: A subluxation or dislocation of the intraocular lens (IOL) is a well-known complication after cataract surgery in patients with pseudoexfoliation syndrome (PEX). Capsular tension rings (CTR) are frequently used to prevent postoperative complications caused by zonular weakness. Here we present a series of 7 cases, 2 with intermittent and 5 with acute angle closure caused by a combination of PEX-associated zonular weakness and a resulting unstable capsular bag-CTR-IOL complex. MATERIALS AND METHODS: We describe the typical clinical course with elevated intraocular pressure, myopic shift, and shallowing of the anterior chamber in 7 patients with a new type of secondary angle closure. The diagnostic challenges and treatment options are discussed in detail. RESULTS: In all cases, the mechanism of angle closure identified by ultrasound biomicroscopy was an anterior dislocation of the peripheral iris by the capsular bag-CTR-IOL complex. The IOL was removed together with the capsular bag and the CTR and replaced by an iris-fixated IOL in all cases. CONCLUSIONS: We present a new type of secondary angle closure caused by an anterior dislocated capsular bag-CTR-IOL complex. The cause of both, this atypical presentation and the ineffectiveness of the laser peripheral iridotomy is the large diameter CTR. Therefore CTR implantation might also be the source of late postoperative complications. If a secondary angle closure associated with PEX and unstable capsular bag-CTR-IOL complex is encountered, IOL explantation and replacement by an iris-fixated IOL is a simple and effective treatment option.

Visual Recovery and Endothelial Cell Survival After Descemet Stripping Automated Endothelial Keratoplasty for Failed Penetrating Keratoplasty Grafts­A Cohort Study.

PURPOSE: To assess visual recovery and donor cell survival after Descemet stripping automated endothelial keratoplasty (DSAEK) for the repair of failed penetrating keratoplasty (PK) grafts. METHODS: Best spectacle-corrected Snellen visual acuity results after DSAEK were compared with best-ever documented visual acuity (BDVA) results obtained with the previous PK graft in a prospective cohort study. Donor cell survival after DSAEK for PK repair was compared with cell survival after DSAEK for Fuchs endothelial dystrophy and pseudophakic bullous keratopathy. Differences in the logMAR best spectacle-corrected Snellen visual acuity and endothelial cell loss rates were calculated. RESULTS: Twenty-eight eyes with DSAEK for PK repair were identified, 21 of which lacked vision-limiting comorbidities. The mean follow-up was 18.4 ± 10.6 months. At 3 months postoperatively, 10/21 eyes (48%) regained their BDVA. By 24 months, only 14% remained with 0.2 logMAR below their BDVA. Endothelial cell counts decreased significantly faster in patients with DSAEK for failed PK (P = 0.024) or pseudophakic bullous keratopathy (P = 0.018) than in patients with DSAEK for Fuchs endothelial dystrophy. CONCLUSIONS: DSAEK for the restoration of failed PK grafts promotes rapid visual recovery within the visual limits of the previous PK graft. Increased endothelial cell loss is noted relative to other DSAEK indications, which may result in earlier endothelial graft failure in renovated PK.

Changes in intraocular pressure after descemet stripping automated endothelial keratoplasty: a retrospective analysis.

PURPOSE: To analyze the occurrence of postoperative intraocular pressure (IOP) elevation and types of pressure-lowering treatment in patients after Descemet stripping automated endothelial keratoplasty (DSAEK) with and without previous diagnoses of glaucoma and/or pseudoexfoliation (PXF) syndrome. METHODS: This retrospective assessment considered 211 consecutive DSAEK cases (176 patients) performed by 1 surgeon between January 2007 and November 2010 with at least 1-year follow-up. Salient patient characteristics, IOP, and type of antiglaucoma treatment registered in postoperative visits up to 36 months were extracted from medical records. IOP elevation and its association with glaucoma, PXF, and combination of the 2 were assessed using multivariate ordinal logit models. RESULTS: Of 211 eyes, 97 eyes (45%) showed at least 1 increase in IOP >25 mm Hg after DSAEK. Of these 97 eyes, 17 eyes (17.5%) had a history of glaucoma alone, another 17 eyes (17.5%) had a history of glaucoma combined with PXF, 10 eyes (9.7%) had PXF alone, and 53 eyes (54.6%) were steroid responders only. To control IOP elevation, steroid reduction alone was performed in 6 eyes (6.2%) and IOP-lowering medication as the only measure was performed in 26 eyes (26.8%). In 46 eyes (47.4%), steroids were reduced in combination with IOP-lowering medication and 16 eyes (16.5%) required surgery. In 3 eyes (3.1%), no action was required. Presence of PXF (odds ratio, 1.71; 95% confidence interval, 0.62-2.81; P = 0.002) and PXF glaucoma (1.14; 95% confidence interval, 0.06-2.21; P = 0.038) required a more intensive IOP-lowering management than patients without PXF with IOP problems. CONCLUSIONS: Increased IOP is common after DSAEK, and a significant number of patients need IOP-lowering treatment. PXF syndrome and PXF glaucoma are risk factors for significant IOP elevation after DSAEK. In most cases, IOP remains controlled with conservative management, but some patients require glaucoma surgery.

Diesel exhaust exposure and the risk of lung cancer--a review of the epidemiological evidence.

To critically evaluate the association between diesel exhaust (DE) exposure and the risk of lung cancer, we conducted a systematic review of published epidemiological evidences. To comprehensively identify original studies on the association between DE exposure and the risk of lung cancer, literature searches were performed in literature databases for the period between 1970 and 2013, including bibliographies and cross-referencing. In total, 42 cohort studies and 32 case-control studies were identified in which the association between DE exposures and lung cancer was examined. In general, previous studies suffer from a series of methodological limitations, including design, exposure assessment methods and statistical analysis used. A lack of objective exposure information appears to be the main problem in interpreting epidemiological evidence. To facilitate the interpretation and comparison of previous studies, a job-exposure matrix (JEM) of DE exposures was created based on around 4,000 historical industrial measurements. The values from the JEM were considered during interpretation and comparison of previous studies. Overall, neither cohort nor case-control studies indicate a clear exposure-response relationship between DE exposure and lung cancer. Epidemiological studies published to date do not allow a valid quantification of the association between DE and lung cancer.

Corneal patch graft for the repair of late-onset hypotony or filtering bleb leak after trabeculectomy: a new surgical technique.

PURPOSE: Repair of leaking filtering blebs after trabeculectomy is a surgical challenge, especially when the patient presents with hypotony. Repair of the filtering bleb using only conjunctiva reconstruction often fails when deeper tissue structures do not provide sufficient outflow resistance. Here, we present a technique that uses anterior stromal lamellae left over from donor corneas used for descemet stripping automated endothelial keratoplasty procedures as patch grafts to repair the scleral tissue wound as a way to treat ocular hypotony. MATERIALS AND METHODS: We describe a new surgical technique to reconstruct the outflow resistance of melted trabeculectomy scleral flaps and present the course of 5 cases of severe hypotony treated using this technique. RESULTS: All 5 patients suffered from severe hypotony several years after trabeculectomy with antiproliferative agents. Multiple surgical and nonsurgical attempts to treat hypotony had failed. Lamellar corneal tissue was used as a patch graft to replace the weakened sclera near the site of the earlier trabeculectomy. This procedure successfully reversed hypotony in all cases. During the follow-up periods of at least 9 months, no recurrences of bleb leak or hypotony were observed. Intraocular pressure (IOP) remained controlled with topical IOP-lowering treatment in 4 cases. In 1 case, a glaucoma drainage implant was used to control IOP. CONCLUSIONS: The use of lamellar corneal donor tissue to restore scleral outflow resistance is a safe and effective treatment for severe hypotony after mitomycin C-assisted trabeculectomy with or without filtering bleb leaks.

Penetration of a topically administered anti-tumor necrosis factor alpha antibody fragment into the anterior chamber of the human eye.

OBJECTIVE: To determine whether topically applied ESBA105, a single-chain antibody fragment against tumor necrosis factor (TNF)-α, could efficiently penetrate into the anterior chamber of the human eye. DESIGN: Multicenter, interventional cohort study. PARTICIPANTS: Otherwise healthy patients undergoing cataract surgery (cohorts I-III) or combined cataract surgery and vitrectomy (cohort IV). METHODS: ESBA105 (n = 57) or placebo (n = 22) was preoperatively applied as eye drops to 1 eye in patients scheduled for cataract surgery (n = 73) or combined cataract surgery and vitrectomy (n = 6). ESBA105 was administered on the day of surgery at 1-hour intervals (last dose 1 hour preoperatively) as 1.6 mg in 4 drops for cohort I (n = 15) and as 3.2 mg in 8 drops for cohorts II (n = 15) and IV (n = 6). Cohort III (n = 43) was randomized 1:1 in double-masked fashion to receive either ESBA105 6.4 mg or placebo over 4 days using 4 drops per day at 4-hour intervals (last dose 12 hours preoperatively). Aqueous humor (all cohorts), vitreous humor (cohort IV only), and blood samples (all cohorts) were collected for measurement of ESBA105. MAIN OUTCOME MEASURES: ESBA105 intraocular concentration. RESULTS: Both 4 times daily over 4 days dosing (cohort III) and 8 times daily dosing (cohorts II and IV) resulted in reliably high ESBA105 concentrations in aqueous humor. Mean molar excess of intraocular ESBA105 over its target (intraocular TNF-α) was calculated as 96-fold (cohort III) to 359-fold (cohorts II and IV). Results from the cohorts receiving 4 and 8 hourly drops per 1 day (cohorts I, II, and IV) indicated that dose-dependent intraocular concentrations of ESBA105 were achieved within hours of dosing. After 8 times daily dosing, 5 of 6 vitreous samples (cohort IV) had undetectable ESBA105 levels. ESBA105 was detected in 17 of 55 preoperative serum samples but no longer detectable in serum 1 day after surgery (0 of 19 samples). In cohort III, treatment-emergent adverse events were identical between ESBA105 and placebo groups (2 cases each of eye irritation). CONCLUSIONS: These results demonstrate that the topically applied single-chain antibody fragment ESBA105 penetrated into the anterior chamber of the human eye at therapeutic levels.

Interventions for late trabeculectomy bleb leak.

BACKGROUND: Late trabeculectomy bleb leaks are a common complication after filtering glaucoma surgery. Although asymptomatic, late bleb leaks may lead to hypotony and are associated with bleb related infections. OBJECTIVES: To assess the effects of interventions for late trabeculectomy bleb leak. SEARCH METHODS: We searched CENTRAL (which contains the Cochrane Eyes and Vision Group Trials Register) (The Cochrane Library 2012, Issue 7), MEDLINE (January 1946 to July 2012), EMBASE (January 1980 to July 2012), the metaRegister of Controlled Trials (mRCT) (www.controlled-trials.com), ClinicalTrials.gov (www.clinicaltrials.gov) and the WHO International Clinical Trials Registry Platform (ICTRP) (www.who.int/ictrp/search/en). We did not use any date or language restrictions in the electronic searches for trials. We last searched the electronic databases on 18 July 2012. SELECTION CRITERIA: We included randomised and quasi-randomised trials in which any treatments for eyes with late bleb leak (interventional and non-interventional) were compared with each other. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. We contacted study authors when additional information was needed. MAIN RESULTS: The review included one multicentre trial based in the USA with 30 eyes of 30 participants. The trial compared two surgical procedures (conjunctival advancement and amniotic membrane transplant) to cover a filtering bleb leak. Conjunctival advancement has been shown to be more effective in sealing filtering bleb leaks. AUTHORS' CONCLUSIONS: Although a variety of treatments have been proposed for bleb leaks, there is no evidence of their comparative effectiveness.The evidence in this review was provided by a single trial that compared two surgical procedures (conjunctival advancement and amniotic membrane transplant). The trial did show a superiority of conjunctival advancement, which was regarded as standard treatment, to amniotic membrane transplantation. There is a need for more randomised trials to validate the findings of this single trial and provide more information on the different types of interventions, especially non-surgical treatments compared to surgical procedures. We recommend that any intervention should be compared to a standard procedure, which is to date conjunctival advancement.

Long-term exposure to silica dust and risk of total and cause-specific mortality in Chinese workers: a cohort study.

BACKGROUND: Human exposure to silica dust is very common in both working and living environments. However, the potential long-term health effects have not been well established across different exposure situations. METHODS AND FINDINGS: We studied 74,040 workers who worked at 29 metal mines and pottery factories in China for 1 y or more between January 1, 1960, and December 31, 1974, with follow-up until December 31, 2003 (median follow-up of 33 y). We estimated the cumulative silica dust exposure (CDE) for each worker by linking work history to a job-exposure matrix. We calculated standardized mortality ratios for underlying causes of death based on Chinese national mortality rates. Hazard ratios (HRs) for selected causes of death associated with CDE were estimated using the Cox proportional hazards model. The population attributable risks were estimated based on the prevalence of workers with silica dust exposure and HRs. The number of deaths attributable to silica dust exposure among Chinese workers was then calculated using the population attributable risk and the national mortality rate. We observed 19,516 deaths during 2,306,428 person-years of follow-up. Mortality from all causes was higher among workers exposed to silica dust than among non-exposed workers (993 versus 551 per 100,000 person-years). We observed significant positive exposure-response relationships between CDE (measured in milligrams/cubic meter-years, i.e., the sum of silica dust concentrations multiplied by the years of silica exposure) and mortality from all causes (HR 1.026, 95% confidence interval 1.023-1.029), respiratory diseases (1.069, 1.064-1.074), respiratory tuberculosis (1.065, 1.059-1.071), and cardiovascular disease (1.031, 1.025-1.036). Significantly elevated standardized mortality ratios were observed for all causes (1.06, 95% confidence interval 1.01-1.11), ischemic heart disease (1.65, 1.35-1.99), and pneumoconiosis (11.01, 7.67-14.95) among workers exposed to respirable silica concentrations equal to or lower than 0.1 mg/m(3). After adjustment for potential confounders, including smoking, silica dust exposure accounted for 15.2% of all deaths in this study. We estimated that 4.2% of deaths (231,104 cases) among Chinese workers were attributable to silica dust exposure. The limitations of this study included a lack of data on dietary patterns and leisure time physical activity, possible underestimation of silica dust exposure for individuals who worked at the mines/factories before 1950, and a small number of deaths (4.3%) where the cause of death was based on oral reports from relatives. CONCLUSIONS: Long-term silica dust exposure was associated with substantially increased mortality among Chinese workers. The increased risk was observed not only for deaths due to respiratory diseases and lung cancer, but also for deaths due to cardiovascular disease. Please see later in the article for the Editors' Summary.