Treatment of open-angle glaucoma and ocular hypertension with preservative-free tafluprost/timolol fixed-dose combination therapy: 6 case reports and clinical outcomes.

BACKGROUND: Treatment of open angle glaucoma (OAG) and/or ocular hypertension (OHT) focuses on achievement of target intraocular pressure (IOP), with the objective of slowing disease progression. However, ocular surface health is an important consideration in the optimization of treatment. We report 6 patient cases in which enhanced IOP control was achieved following appropriate management of ocular surface inflammation and a therapeutic switch to the preservative-free (PF) tafluprost (0.0015%)/timolol (0.5%) fixed-dose combination (FC). CASE PRESENTATION: Six patient cases, aged 48-74 years, presented with OAG or OHT. Each patient had signs and symptoms of ocular surface disease (OSD). Cases 1-3 were each receiving maximal medical therapy for OAG; regimens comprising prostaglandin analogue (PGA), ß-blocker, carbonic anhydrase inhibitor (CAI) and α-2 agonist agents (including treatments containing preservative agent). Cases 1 and 2 reported IOP values ≥23 mmHg in each eye, and wide IOP fluctuations were identified when reviewing patient data concerning case 3 (11-20 mmHg). Maximal therapy was ceased and PF tafluprost/timolol FC was initiated, after which the signs and symptoms of OSD were improved and IOP was reduced (≤18 mmHg for cases 1-3) and stabilized. Cases 4 and 5 were diagnosed with OAG and case 6 had OHT. Each had symptoms and signs of OSD and were treated with a preserved PGA monotherapy (latanoprost 0.005% or bimatoprost 0.03%). At presentation, IOP was 24 mmHg in both eyes (case 4), ≥18 mmHg (case 5) and ≥ 22 mmHg (case 6). Following a switch to the PF tafluprost/timolol FC, OSD symptoms were improved and IOP was 14 mmHg (both eyes; case 4), ≤14 mmHg (case 5) and 16 mmHg (both eyes; case 6). CONCLUSIONS: In addition to IOP-lowering efficacy, approaches to the management of OAG and OHT should consider the impact of treatment tolerability and the susceptibility of these patients to OSD. The presence of ocular surface inflammation appears to be detrimental to adherence and therefore to the effectiveness of topical medications. Addressing OSD through the use of PF FC formations, such as the PF tafluprost/timolol FC, reduces exposure to potentially toxic agents and facilitates improvements in IOP control.

Impact of low skeletal muscle mass on postoperative complications in head and neck cancer patients undergoing free flap reconstructive surgery - A systematic review and meta-analysis.

Low skeletal muscle mass is emerging as an adverse predictive and prognostic factor in cancer patients. The use of this parameter as a risk factor for complications after surgery is not currently used in clinical practice. This meta-analysis aims to assess the association of low skeletal muscle mass defined by radiological criteria and complications after reconstructive microsurgery in head and neck cancer patients. A systematic review for articles was performed using the PubMed, EMBASE database and by manual search. Articles that assessed low skeletal muscle mass and its impact on postoperative complications in head and neck cancer patients undergoing free flap surgery were selected. Pooled estimates of postoperative outcome data were calculated by extracting the odds ratio (OR) and 95% confidence interval (CI). The search strategy returned with 6 studies meeting the inclusion criteria. A total of 1082 patients were analyzed. The prevalence of low skeletal muscle mass between studies ranged from 24.6% to 61.5%. The meta-analysis showed an OR for complications after surgery of 2.42 (95% CI 1.53-3.32, p = 0.00). The study therefore concludes that skeletal muscle mass is an independent risk factor for postoperative complications in head and neck cancer reconstructive surgery patients. This argues for implementing screening for low skeletal muscle in preoperative management to optimize surgical decision making.

Association of preoperative low skeletal muscle mass with postoperative complications after selective neck dissection.

Skeletal muscle mass (SMM) is an emerging predictive and prognostic factor in head and neck cancer patients. The aim of this study was to investigate the predictive value of low SMM for postoperative complications in clinically T1-2 oral cavity cancer patients undergoing selective neck dissection. A retrospective study in clinically T1-2 oral cavity cancer patients who underwent selective neck dissection between 2011 and 2017 was performed. The predictive value of low SMM for the occurrence of postoperative complications and prolonged hospital stay was evaluated. SMM was measured using pre-treatment imaging (computed tomography or magnetic resonance imaging) at the level of the third cervical vertebra (C3). In total, 53 patients were included, of whom 42 (79.2%) had low SMM. Patients with low SMM were not significantly more likely to experience postoperative complications (odds ratio 1.28, P = 0.73) when compared to patients without low SMM. No statistically significant difference in mean duration of hospital stay was seen between these patient groups. In conclusion, low SMM was found not to predict postoperative complications in T1-2 oral cavity cancer patients who underwent neck dissection.

Intravenous frusemide does not interact pharmacodynamically with acetaminophen in critically ill preterm neonates with patent ductus arteriosus.

OBJECTIVE: Evidence is controversial regarding the effect of concomitant frusemide with acetaminophen therapy in neonates with patent ductus arteriosus (PDA). PATIENTS AND METHODS: Critically ill neonates diagnosed with hemodynamically significant PDA by echocardiography and receiving intravenous acetaminophen were recruited. Dosing regimens of frusemide, and acetaminophen, and the sizes of ductus arteriosus following treatment, were evaluated. RESULTS: Fifty-one neonates were recruited. Forty-six (90.2%) had moderate-sized, and five (9.8%) had large-sized ductus arteriosus. Forty (78.4%) neonates had a successful closure. Twenty-four received concomitant frusemide with a median (range) cumulative dose of 3 (0.8-13) mg; duration of 2 (1-13) days; and a fraction of overlapping days with acetaminophen therapy of 0.4 (0.2-1). Twenty-one (87.5%) neonates that received frusemide had a successful ductal closure compared to 70.4% of those without (p >0.05). CONCLUSIONS: We did not observe any significant influence in the outcomes of acetaminophen therapy with concomitant frusemide in preterm neonates with PDA.

Postoperative Imaging Appearance of Iliac Crest Free Flaps Used for Palatomaxillary Reconstructions.

The osteomyocutaneous iliac crest free flap is a reconstructive option for segmental mandibular or complex palatomaxillary defects. Familiarity with the radiographic appearance of free flaps such as the iliac crest is necessary for the postoperative evaluation of patients after mandibular, maxillary, or palatal reconstructions because it allows radiologists to properly monitor and interpret the appearance of the flap over time. This study presents a retrospective review of 5 patients who underwent palatomaxillary reconstruction with an iliac crest free flap at our institution. The imaging appearances of the 5 patients were analyzed to determine the key radiographic characteristics of a healthy and successful iliac crest free flap. Radiographic fluency with the imaging appearance of the iliac crest free flap, as well as the new anatomy of the region in the postoperative period, will allow for better interpretation of the flap appearance on imaging and will prevent false identification of tumor recurrence.

Biomarkers in neonates receiving potential nephrotoxic drugs.

OBJECTIVE: Novel biomarkers, such as kidney injury molecule-1 (KIM-1), cystatin, and neutrophil gelatinase-associated lipocalin (NGAL) were shown to predict acute kidney injury (AKI) earlier than serum creatinine in critically ill. We carried out the present study to evaluate these biomarkers in addition to conventional in our neonates. PATIENTS AND METHODS: We recruited 70 neonates of various gestational age groups receiving one or more potential nephrotoxic drug/s. Daily urine samples were collected for estimating KIM-1, cystatin, and NGAL. Modified neonatal kidney disease improving global outcomes (mKDIGO) classification was used in defining AKI. RESULTS: A significant trend in increased urine concentrations of KIM-1, cystatin, and NGAL were observed as we proceed from term to preterm categories. Strong positive correlation was observed between urine albumin and urine albumin creatinine ratio (ACR), and strong negative correlations between urine creatinine and urine cystatin, and between urine creatinine with urine NGAL. A moderate positive correlation was observed between urine KIM-1 and urine cystatin, between urine KIM-1 and urine NGAL, and between urine cystatin and urine NGAL; and a moderate negative correlation was observed between urine creatinine and urine KIM-1. Seven neonates met the mKDIGO criteria for AKI and ROC plot revealed that baseline KIM-1 and NGAL can significantly predict possible drug-induced AKI in neonates. CONCLUSIONS: Urine KIM-1, cystatin, and NGAL are significantly correlated with several other conventional biomarkers that reflect renal function in critically ill neonates. Baseline urine KIM-1 and NGAL concentrations can predict the AKI following potential nephrotoxic drug use in this population.

Low skeletal muscle mass is a strong predictive factor for surgical complications and a prognostic factor in oral cancer patients undergoing mandibular reconstruction with a free fibula flap.

BACKGROUND: Fibula free flaps (FFF) are effective in accomplishing successful reconstruction for segmental defects of the mandible. Potential risk factors for FFF complications have been described in previous research, e.g. age, comorbidity and smoking. Low skeletal muscle mass (SMM) has shown to be an emerging predictive factor for complications and prognostic factor for survival in head and neck cancer. This study aims to identify the predictive and prognostic value of low SMM for surgical FFF related complications, postoperative complications and survival in patients who underwent mandibular reconstruction with FFF after oral cavity cancer resection. MATERIALS AND METHODS: A retrospective study was performed between 2002 and 2018. Pre-treatment SMM was measured at the level of the third cervical vertebra and converted to SMM at the level of the third lumbar vertebra (L3). SMM at the level of L3 was corrected for squared height. Low SMM was defined as a lumbar skeletal muscle index (LSMI) below 43.2 cm2/m2. RESULTS: 78 patients were included, of which 48 (61.5%) had low SMM. Low SMM was associated with an increased risk of FFF related complications (HR 4.3; p = 0.02) and severe postoperative complications (Clavien-Dindo grade III-IV) (HR 4.0; p = 0.02). In addition low SMM was a prognosticator for overall survival (HR 2.4; p = 0.02) independent of age at time of operation, ACE-27 score and TNM stage. CONCLUSION: Low SMM is a strong predictive factor for FFF reconstruction complications and other postoperative complications in patients undergoing FFF reconstruction of the mandible. Low SMM is also prognostic for decreased overall survival.

Evolution of large area TiS2-TiO2 heterostructures and S-doped TiO2 nano-sheets on titanium foils.

We report a novel and facile method to synthesize sulfur-doped titanium oxide sheets and realize TiS2-TiO2 heterostructures by means of a sequential sulfurization and oxidation step in a dual-zone chemical vapor deposition furnace. The inclusion of chlorine and argon gases during the growth of such titanium-based compounds plays a critical role in the formation of desired geometries and crystalline structures. These heterostructures possess nano-whisker and nanosheet configurations, controlled by adjusting the growth parameters such as temperature, carrier gas and the sequencing between different steps of the growth. The evolution of these complex heterostructures has been investigated using Raman spectroscopy and EDS characterization. The presence of chlorine gas during the growth results in local TiS2 formation as well as faceted growth of TiO2 nanosheets through anatase to rutile phase change prohibition. The electron microscopy (TEM) images and diffraction pattern (SAED) characterization reveal the crystallinity and layered nature of grown structures, further demonstrating the 2D characteristics of S-doped nanosheets. The evolution of TiO2 on TiS2 heterostructures has also has been verified using XPS analysis. These highly featured nanostructures are suitable candidates to enhance the photocatalytic behavior of TiO2 nanostructures.

Application of Bayes' to the prediction of referral decisions made by specialist optometrists in relation to chronic open angle glaucoma.

PURPOSE: To determine the accuracy of a Bayesian learning scheme (Bayes') applied to the prediction of clinical decisions made by specialist optometrists in relation to the referral refinement of chronic open angle glaucoma. METHODS: This cross-sectional observational study involved collection of data from the worst affected or right eyes of a consecutive sample of cases (n = 1,006) referred into the West Kent Clinical Commissioning Group Community Ophthalmology Team (COT) by high street optometrists. Multilevel classification of each case was based on race, sex, age, family history of chronic open angle glaucoma, reason for referral, Goldmann Applanation Tonometry (intraocular pressure and interocular asymmetry), optic nerve head assessment (vertical size, cup disc ratio and interocular asymmetry), central corneal thickness and visual field analysis (Hodapp-Parrish-Anderson classification). Randomised stratified tenfold cross-validation was applied to determine the accuracy of Bayes' by comparing its output to the clinical decisions of three COT specialist optometrists; namely, the decision to discharge, follow-up or refer each case. RESULTS: Outcomes of cross-validation, expressed as means and standard deviations, showed that the accuracy of Bayes' was high (95%, 2.0%) but that it falsely discharged (3.4%, 1.6%) or referred (3.1%, 1.5%) some cases. CONCLUSIONS: The results indicate that Bayes' has the potential to augment the decisions of specialist optometrists.

Discrimination of glaucomatous optic neuropathy by digital stereoscopic analysis.

PURPOSE: To evaluate the diagnostic power of a novel digital stereoscopic imaging system in the diagnosis of glaucomatous optic neuropathy. DESIGN: Prospective cross-sectional analysis of the diagnostic accuracy of digital stereoscopic optic disc analysis in the diagnosis of glaucomatous optic neuropathy exhibiting mild to moderate field loss. PARTICIPANTS: Fifty-two patients with open-angle glaucoma and 54 normal individuals were recruited. The presence of a reproducible visual field loss characteristic of glaucoma was used as the reference standard for the presence of glaucoma independent of the optic nerve head appearance. Patients were excluded if the optic disc, fundus, or visual field indicated other disease. One eye from each patient and individual was included in the study, the eye with the least field loss and a randomly designated normal eye, respectively. METHODS: Simultaneous stereoscopic optic disc photography was performed on each specified eye. Three experienced observers viewed the resultant stereoscopic image of each nerve head using a Z screen, recorded a subjective clinical diagnosis, and undertook digital stereoscopic planimetry. Separate linear regression analysis was performed, post hoc, from the planimetric results for each observer of the logarithm of neuroretinal rim (NRR) against optic disc area derived from each normal eye. Eyes with NRR areas below the 95th prediction interval of the normal cohort were then classified as glaucomatous. MAIN OUTCOME MEASURES: Sensitivity and specificity for the detection of glaucomatous optic neuropathy. RESULTS: With subjective stereoscopic analysis, sensitivity for glaucoma detection among the 3 observers was 80.8%, 76.9%, and 90.4%, with respective specificities of 94.4%, 79.6%, and 79.6%. Regression analysis of the NRR in 30 degrees segments gave sensitivities between 69.2% and 80.8% and specificities between 83.3% and 90.7%. A combination of the subjective and quantitative analysis did not significantly improve discrimination. CONCLUSIONS: The subjective analysis of digital stereoscopic images provides a useful method for the discrimination of normal and glaucomatous optic nerves. Planimetric analysis does not significantly improve the diagnostic precision of this technique.

Digital imaging of the optic nerve head: monoscopic and stereoscopic analysis.

AIMS: To compare monoscopic and stereoscopic assessment of the optic disc using novel software for the digital stereoscopic analysis of optic disc stereopairs. METHODS: Software was developed for the stereoscopic display of digital optic disc images using an interlaced display method. Neuroretinal rim width was determined at 10 degree intervals around the optic disc using a custom (stereoscopic) cursor whose depth was adjusted to that of Elschnig's rim. Measurements were taken, first viewing the disc monoscopically and at a separate sitting, stereoscopically. RESULTS: Measurements were made in 35 eyes from 35 patients (1260 estimates for each observer) using three observers. The mean cup to disc ratio (CDR) ranged from 0.57 to 0.66 (SD 0.13-0.14) for monoscopic viewing compared with 0.64 to 0.69 (SD 0.12-0.14) for stereoscopic viewing. Stereoscopic assessments gave higher CDRs in temporal, superior, nasal, and inferior aspects of the optic disc (p<0.001, Mann-Whitney U test). Agreement between observers in estimating CDR was high for monoscopic assessment (intraclass correlation coefficient 0.74 (CI 0.72 to 0.76) increasing to 0.80 (0.78 to 0.82) for stereoscopic assessment. CONCLUSION: Digital stereoscopic optic disc assessment provides lower estimates of neuroretinal rim width and higher levels of interobserver agreement compared with monoscopic assessments.

Prospective study of alcoholism treatment in Kuwait: a 5-year follow-up report.

The outcome of a 5-year prospective follow-up study of 100 patients treated in the Kuwait Hospital for alcohol-related problems is reported using two parameters computed from weighted follow-up variables, i.e., Offset Score measuring patients' initial follow-up status and Direction of Slope summarizing consequent follow-up scores. Nineteen patients had died representing 14 times the age-corrected national rate. Univariate and multivariate analyses of outcome measures against prefollow-up patients' characteristics revealed that variables indicating heavy alcohol use independent of each other predicted negative outcome and mortality. The tendency of the group score distribution towards normalization uninfluenced by treatment is demonstrated. The pertinence of these findings to the medical profession in Kuwait is stressed.

Glaucoma: squaring the psychophysics and neurobiology.

Advances in our understanding of the pathophysiology of retinal ganglion cell death in glaucoma are providing important insights into the functional changes occurring in retinal ganglion cells in the early stages of the disease. These exciting new findings may help us develop psychophysical tests to monitor early retinal ganglion cell damage, possibly before neurons are committed to the process of cell death.

Psychophysical characterisation of early functional loss in glaucoma and ocular hypertension.

AIM: The psychophysical evaluation of selective cell loss in early glaucoma and ocular hypertension. METHODS: Contrast sensitivity was measured for the detection of luminance modulated gratings at a range of spatial (0.5, 2, 8 c/deg) and temporal (0, 16 Hz) frequency combinations in three groups of age matched patients (primary open angle glaucoma, ocular hypertension, normal controls; n=16). Stimuli of 5 degrees were presented foveally and at 15 degrees along the nasal horizontal meridian under photopic conditions. RESULTS: Fovea: Compared to the normal group, the thresholds for the glaucoma patients were significantly elevated at all spatial and temporal frequencies (p<0.0001), but this reduction was not significantly different at any particular spatial or temporal frequency (p>0.1). There was no difference in contrast sensitivity between the normals and OHTs (p>0.10). Periphery: The thresholds of the glaucoma patients were elevated compared to the normal controls (p<0.01). The loss of sensitivity was slightly greater at the higher spatial frequencies for both stationary and flickering patterns but this did not reach significance (p=0.09). The contrast sensitivity in normal and OHT groups was not significantly different (p>0.10). CONCLUSIONS: In early glaucoma, the reduction in contrast sensitivity to stimuli which isolate the magnocellular pathway (0.5 c/deg, 16 Hz) was not significantly different compared with the reduction in contrast sensitivity to stimuli that isolate the parvocellular pathway. These findings are not consistent with the hypothesis that the magnocellular pathway is selectively damaged in early glaucoma.

Ocular signs and symptoms and vitamin A status in patients with cystic fibrosis treated with daily vitamin A supplements.

BACKGROUND/AIMS: Patients with cystic fibrosis (CF) may have low plasma vitamin A levels from malabsorption, zinc deficiency, liver disease, or poor compliance with prescribed supplements. In view of the increasing number of adults with CF, many of whom drive cars, it is important to assess vitamin A status. In our centre an attempt has been made to achieve normal levels of fat soluble vitamins by annual estimation of plasma levels and appropriate oral supplementation. This study aimed to determine if this approach prevents vitamin A deficiency and the consequent problems with dark adaptation. METHODS: The study was conducted at the regional adult and paediatric cystic fibrosis unit and the patients were recruited from there. Dark adaptation studies were conducted at the department of ophthalmology, St James's University Hospital. All patients are regularly seen in the outpatient department by a CF specialist dietitian and have a comprehensive annual dietary assessment. 28 patients had the following investigations: serum retinol, plasma zinc, serum retinol binding protein, liver function tests, dark adaptation, contrast sensitivity, and anterior ocular surface status. 25 age and sex matched controls without CF or ocular pathology were also recruited for the dark adaptation study. RESULTS: None of the patients had vitamin A deficiency, the median value of serum retinol being 48 microg/dl, range 31-80 microg/dl (normal range 30-80 microg/dl). Dark adaptation was normal in all cases compared with the control group where the mean value was 3.4 log units of threshold luminance (95% confidence interval 2.4-4.0). None of the test group had a value of threshold luminance 2 SD above the mean value for the control group. Eight patients had reduced contrast sensitivity. The median value for serum zinc was 14.2 micromol/ l, range 13-81 micromol/l (normal range 8-23 micromol/l) and the median value for retinol binding protein was 36 mg/l, range 13-81 mg/l (normal range 35-58 mg/l). There was no correlation between dark adaptation and serum retinol, zinc, or retinol binding protein. Two patients had clinical evidence of dry eye. CONCLUSION: Regular estimates of plasma vitamin A together with appropriate supplementation and expert dietetic review can maintain normal dark adaptation in patients with cystic fibrosis. The occurrence of reduced contrast sensitivity function is well documented but remains an unexplained phenomenon and deserves further study.

Corneal perforation and decompensation after automated lamellar keratoplasty for hyperopia.

We describe a case of corneal perforation and decompensation after automated lamellar keratoplasty (ALK) in a middle-aged hyperopic man who had had unsuccessful holmium laser thermokeratoplasty. The corneal decompensation responded to gluing and application of a bandage contact lens but despite treatment, the corneal flap remained precariously poised with a localized area of thinning that is predisposed to future perforation and decompensation. This case highlights the potential for serious complications and subsequent visual morbidity after ALK.

Psychiatric disorders in two general hospitals: a survey of prevalence and treatment by nonpsychiatrist physicians.

This study reports an opinion survey of 211 nonpsychiatrist physicians in two general hospitals who estimated that 16.1% of their patients have psychiatric disorders and that they spent 13.8% of their time in treating the psychiatric components of their patients' illnesses. Physicians indicated that anxiety and psychosomatic and depressive illness were the most frequent psychiatric disorders and that one-third of them would personally treat such disorders without referral to psychiatric consultation. The findings also suggest that adequate undergraduate psychiatric education was associated with increased recognition of psychiatric disorders and more preference for their personal treatment. In addition, it provides a possible explanation for the discrepancy between the high prevalence of psychiatric disorders in general hospital patients and the low referral rate to psychiatric consultation.

Patterns of psychiatric consultations in Kuwait general hospitals.

Two hundred and nineteen consecutive referrals to psychiatric consultation services from all general hospitals in Kuwait over a 3-month period were studied and compared with a control group of 100 patients who were not referred for psychiatric consultation. The two groups differed significantly in age, sex, marital status, employment, and past psychiatric treatment. Inpatients were more often referred than outpatients with an overall low referral rate of 0.3%. The department of general medicine referred 74.4% of patients in contrast to 11.4% referred by the department of general surgery. The most common reason for referral was for assessment of a suicide attempt in the inpatient group, and the absence of organic cause for patients' physical symptoms in the outpatient group. Acute situational disturbance that resulted in a suicide attempt was the most common psychiatric diagnosis (26%), followed by depressive illness (19.5%) and organic psychotic disorders (8.2%). Our findings are similar to those reported in the literature, and the present study suggests a national underutilization of psychiatric consultation services in general hospitals.

Ocular injury with xylene--a report of two cases.

Xylene is a hydrocarbon solvent found in various industrial preparations such as paint and is widely used in pathology laboratories. When inadvertently instilled into the eye significant ocular injury can occur with the potential for blindness. Such injuries to the ocular surface resemble those due to alkali. Ocular surface injury due to xylene has not been reported previously in the literature. We strongly recommend that these injuries be treated as emergencies in a similar way to alkali burns in the Eye department since the chemical mixture of which xylene forms a part may be alkaline. Such an approach is vital in order to save sight.

AIDS-related knowledge and misconceptions among high secondary school teachers and students in Kassala, Sudan.

An AIDS-related knowledge study was carried out on a sample of 462 high secondary school teachers and students, in Kassala, eastern Sudan. The results showed high scores of knowledge about AIDS-transmission and general knowledge about the disease. However, there was a high frequency of AIDS-related misconceptions, especially among females and among teachers and students in the science education track. The study calls for more focus on these misconceptions in health education campaigns regarding AIDS.

PIP: 416 secondary school students in Kassala, Sudan, and 46 of their teachers responded to self-administered questionnaires about the nature and extent of their AIDS-related knowledge. The students were of mean age 18.4 years and 68.8% were male. The teachers were of mean age 35.9 years and 81.1% were male. The respondents were well informed about HIV transmission and general knowledge related to AIDS. The overall mean score for AIDS transmission knowledge was 2.9 out of a possible total of three. The overall mean score for general knowledge about AIDS was 5.0 out of a possible total of seven. There was, however, a high frequency of AIDS-related misconceptions, especially among females and among students and teachers in the science education track. Significantly more females than males were enrolled in the science track. The overall mean score for misconceptions was 5.4 out of a possible total of seven. Health education campaigns on HIV/AIDS need to focus upon correcting these misconceptions.