A mathematical model of COVID-19 transmission.

Disease transmission is studied through disciplines like epidemiology, applied mathematics, and statistics. Mathematical simulation models for transmission have implications in solving public and personal health challenges. The SIR model uses a compartmental approach including dynamic and nonlinear behavior of transmission through three factors: susceptible, infected, and removed (recovered and deceased) individuals. Using the Lambert W Function, we propose a framework to study solutions of the SIR model. This demonstrates the applications of COVID-19 transmission data to model the spread of a real-world disease. Different models of disease including the SIR, SIRmp and SEIRρqr model are compared with respect to their ability to predict disease spread. Physical distancing impacts and personal protection equipment use are discussed with relevance to the COVID-19 spread.

Absence of Meckel Cave: A Rare Cause of Trigeminal Neuralgia.

Trigeminal neuralgia is a debilitating condition with numerous etiologies. In this retrospective case series, we report a cohort of patients with a rarely described entity, absence of Meckel cave, and propose this as a rare cause of trigeminal neuralgia. A search of the electronic medical record was performed between 2000 and 2020 to identify MR imaging reports with terms including "Meckel's cave" and "hypoplasia," "atresia," "collapse," or "asymmetry." Images were reviewed by 2 blinded, board-certified neuroradiologists. Seven cases of the absence of Meckel cave were identified. Seven patients (100%) had ipsilateral trigeminal neuralgia and ipsilateral trigeminal nerve atrophy, suggesting an association between absence of Meckel cave and trigeminal neuralgia. Absence of Meckel cave is a rare entity of unknown etiology, with few existing reports that suggest the possibility of an association with trigeminal neuralgia. Its recognition may have important implications in patient management. Future studies and longitudinal data are needed to assess treatment outcomes and added risks from surgical intervention in these patients.

Differences in survival for patients with metastatic colorectal cancer by lines of treatment received and stage at original diagnosis.

OBJECTIVE: Few published studies have examined survival rates for patients with metastatic colorectal cancer (mCRC) by number of lines of treatment received or stage at diagnosis. This study aims to evaluate survival and numbers of lines of treatment in USA mCRC managed care patients. METHODS: To evaluate the impact of chemotherapy/biological on survival of patients with mCRC, adults with a diagnosis of CRC between 1 January 2005 and 31 May 2010 were identified from the Oncology Management registry. Registry data included stage and diagnosis date. Patients with stage IV CRC at original diagnosis or development of metastasis were included. Linked healthcare claims from a large USA database were used to identify lines of treatment after metastasis and patient characteristics. The patient population was enrolled in a commercial health insurance programme, with 10% of patients > 65 years of age. Patients were categorised by lines of treatment received (0, 1, 2, 3+) and stage at original diagnosis (0-3, 4, unknown). Survival following metastasis was evaluated using Cox proportional hazards models controlling for lines of treatment, disease stage, and other patient characteristics. RESULTS: Study population included commercially insured adult patients, ≥ 18 years of age (n = 598, mean age 54, 56% male), 16% of which did not receive chemotherapy/biological therapy after becoming metastatic, and 33% received only 1 line of treatment. Average follow-up was 653 days, and 19% of patients died during the study period. Mean unadjusted length of follow-up was 516, 511, 627 and 930 days for patients who received 0, 1, 2 and 3+ lines of treatment, respectively. In the Cox proportional hazards model, geographical region was the only variable significantly associated with survival (p < 0.05). CONCLUSION: Lines of treatment received and stage at original diagnosis were not statistically significantly associated with survival after metastasis development.

Safety and pharmacokinetics of nelfinavir during the second and third trimesters of pregnancy and postpartum.

PURPOSE: Evaluate the safety, tolerability, and pharmacokinetics (PK) of nelfinavir during pregnancy and postpartum in HIV-infected women. METHODS: Phase IV, non-randomized, open-label study of nelfinavir 625 mg tablets (1250 mg) in combination with lamivudine/zidovudine twice daily. Primary endpoint was treatment-related or possibly treatment-related gastrointestinal or hepatic adverse events (AEs). Selected maternal and infant outcomes were recorded. Frequent plasma samples were collected for PK studies during the 2nd and 3rd trimesters, and 6 weeks postpartum, to analyze total and free nelfinavir and M8 concentrations. RESULTS: Sixteen HIV+ pregnant women were enrolled. Six mild treatment-related AEs and 3 serious AEs occurred; 1 serious AE (elevated AST) met the primary endpoint. Compared with 6 weeks postpartum, levels of total nelfinavir were reduced by 44% and 46%, total M8 by 82% and 83%, free nelfinavir by 48% and 39%, and free M8 by 83% and 79% in the 2nd and 3rd trimesters, respectively. At 6 weeks postpartum, 75% and 50% of subjects maintained HIV-1 RNA levels <400 and <50 copies/mL, respectively. All pregnancies resulted in live births without transmission in 15 infants. CONCLUSIONS: Nelfinavir in combination with lamivudine/zidovudine was generally well tolerated. Total and free nelfinavir and M8 exposure were reduced in late pregnancy.

Ocular penetration of levofloxacin, ofloxacin and ciprofloxacin in eyes with functioning filtering blebs: investigator masked, randomised clinical trial.

BACKGROUND/AIMS: To compare the penetration of levofloxacin, ofloxacin and ciprofloxacin in the aqueous humour of eyes with functioning filtering blebs. METHODS: In this investigator-masked study, 48 patients with functioning filtering blebs requiring cataract surgery were randomised into six groups of eight patients. Groups 1, 2 and 3 received topical ofloxacin 0.3% (Ocuflox), ciprofloxacin 0.3% (Ciloxan) and levofloxacin (Quixin) respectively; Groups 4, 5 and 6 received the same treatment with the corresponding oral dose of ofloxacin 400 mg (Floxin), ciprofloxacin 400 mg (Cipro) and levofloxacin 250 mg (Levaquin). Aqueous antibiotic levels were determined by mass spectrometry of aqueous samples from each patient. RESULTS: The mean aqueous level for topical levofloxacin was significantly higher than those achieved by topical ofloxacin or ciprofloxacin (p value = 0.02 and 0.01, respectively). The combination of topical and oral levofloxacin was significantly higher than topical levofloxacin alone (p = 0.05) and the ciprofloxacin combination (p = 0.003) but not significantly higher than the ofloxacin combination therapy. CONCLUSIONS: Topical levofloxacin penetrates better than ofloxacin or ciprofloxacin into the aqueous of eyes with functioning filtering blebs. The combination of topical and oral levofloxacin may be preferable in the treatment of bleb-associated infections (NCT 00392275; Clinical trials.gov).

Integration of advanced process control and full-scale dynamic simulation

In the process control industry, multivariable model predictive controller and dynamic simulation for operator training are usually available in separate packages. It is very difficult for the operators and plant engineers to find good tools for them to get trained in multivariable advanced process control. This paper presents a system, which integrates the advanced process control and full-scale dynamic simulation. The advanced process control uses multivariable model predictive control techniques. The model used in the predictive control algorithms is generated from the dynamic simulated process. The advanced process controller can control the simulated plant directly, or through a DCS system to control the simulated plant. The combined system provides an excellent environment for training operators in process operation with multivariable advanced process control. The same environment is also very useful for engineers in designing and tuning the advanced process controllers, and in testing communication between the advanced process controller and the DCS systems, or the other type of process control systems.

Comparative corneal topography and refractive variables in monozygotic and dizygotic twins.

PURPOSE: To investigate the role of heredity in determining corneal shape, axial length, and overall refractive error. METHODS: Twenty monozygotic and 19 dizygotic twin pairs, age 12 to 73 years, were enrolled in the study. Zygosity was determined by physical similarity and by responses to questions adapted from surveys. Two twin pairs were excluded because of undetermined zygosity and one pair because of keratoconus (both siblings). Refractive error was determined by an automated refractor. Manifest refraction was also recorded, as well as cycloplegic refraction in subjects under age 18 years. Corneal topography data and manual keratometer readings were also obtained. Axial lengths were determined by A-scan ultrasound. Data were analyzed by Student t tests only in the right eye. Left-eye data were comparable for all variables. RESULTS: Mean intrapair difference in refractive error (spherical equivalent) was less for monozygotic than for dizygotic twins (RE: 0.41 vs 1.53; P = .001). Mean intrapair difference in axial length was less for monozygotic twins (RE: 0.39 vs 0.76 mm; P = .031). Corneal topography data (power and meridian) in all zones (3, 5, and 7 mm) also showed smaller mean differences among monozygotic pairs than dizygotic, but the difference was statistically significant only for the 5-mm zone. In addition, most Holladay Diagnostic Summary variables that were studied did not show any statistically significant differences. CONCLUSIONS: Axial length and overall refractive error have a significant genetic basis. Corneal topography data appear to have other overriding determining factors for several of the variables studied.

Gradual painless visual loss: anterior segment causes.

There are estimated to be 40 million blind individuals throughout the world. The majority of blind people in developing and developed countries are older adults. As the number of people over 60 years of age increases, the number of blind people also will increase. The primary care physician can play a major role in diagnosing and preventing many blinding diseases. This article discusses some of the major anterior segment causes of visual impairment in older adults in the industrialized nations.

Ocular toxicity associated with systemic drug therapy.

Systemic drug-induced ocular side effects are increasing because of the vast numbers of new drugs being introduced. Reports of drug-induced ocular toxicity must be well documented, and other causes of these side effects must be ruled out to help establish causality. We reviewed the most recent reports of the most commonly used and newest systemic drugs that have been implicated in ocular toxicity. Using toxicologic criteria needed to establish causality, data from reports of ocular toxicity associated with systemic cidofovir (Vistide), sildenafil (Viagra), vigabatrin (Sabril), tamoxifen (Nolvadex), hydroxychloroquine (Plaquenil)/chloroquine (Aralen), amiodarone (Cordarone), and lovastatin (Mevacor)/simvastatin (Zocor) were evaluated and summarized. The probability for causality was determined to be high for all these drugs except for vigabatrin and lovastatin/simvastatin. Methods for detecting, preventing, and treating ocular toxic reactions were then reviewed for each drug.

Drug-induced uveitis.

Uveitis has been reported in association with a variety of topical, intraocular, periocular, and systemic medications. To establish causality of adverse events by drugs, in 1981, Naranjo and associates proposed seven criteria, which are related to the frequency and documentation of the event; circumstances of occurrence, recovery, and recurrence; and coexistence of other factors or medications. Rarely does a drug meet all seven criteria. The authors review reports of drug-associated uveitis, applying the seven criteria and examining possible mechanisms. Only systemically administered biphosphonates and, perhaps, topical metipranolol meet all seven criteria. Systemic sulfonamides, rifabutin, and topical glucocorticoids fulfill at least five criteria.

Efficacy and safety of the ProTek (Vifilcon A) therapeutic soft contact lens after photorefractive keratectomy.

PURPOSE: To test the ProTek (Vifilcon A) therapeutic soft contact lens in the alleviation of post-photorefractive keratectomy pain, its effect on epithelial healing, and its safety. METHODS: Forty-seven consecutive eligible patients undergoing unilateral excimer laser photorefractive keratectomy for myopia were randomly assigned to receive standard postoperative care with or without the use of a ProTek soft contact lens. Patients prospectively graded a self-administered 5-point scale for pain and a 4-point scale for abnormal sensations at 4, 8, 12, 16, and 20 hours after surgery. They also recorded the type and dose of all medications taken during that time period. All patients were examined on the first and third days after surgery. The lenses were worn continuously for 3 days. RESULTS: The soft contact lens group (n = 24) disclosed a statistically significant (P < .05) reduction in pain intensity and abnormal sensations that was greatest at 8, 12, 16, and 20 hours postoperatively. Compared with control patients (n = 23), the soft contact lens group showed significant decreased dependence on most pain medications after the 12th hour (P < .05) and faster epithelial healing (P = .03). However, one case of bacterial keratitis, two cases of subepithelial infiltrates, and seven cases of contact lens intolerance were present in the soft contact lens group. CONCLUSIONS: The ProTek therapeutic soft contact lenses were effective in decreasing pain and other related abnormal sensations after excimer photorefractive keratectomy. They decreased dependence on pain medications and hastened epithelial healing but were not well tolerated in some patients.

In vitro and in vivo effects of polyhexamethylene biguanide against herpes simplex virus infection.

PURPOSE: The differential diagnosis of Acanthamoeba keratitis frequently includes herpes simplex viral keratitis. Previous in vitro studies with chlorhexidine, a drug with antiacanthamoebic action, have suggested concomitant antiviral activity against herpes simplex virus. We tested another related antiacanthamoebic compound, polyhexamethylene biguanide (PHMB), to determine its activity against herpes simplex virus (HSV) in vitro and herpes simplex viral keratitis in vivo. METHODS: Equal aliquots of HSV-1 (McKrae) strain were incubated in a medium with no PHMB or with PHMB at 0.01, 0.02, or 0.05 for 5 min at 35 degrees C and the inoculum was then titered on a monolayer of E-2 cells (human corneal fibroblasts). Monolayers were examined on consecutive days and the percentage of plaque reduction was calculated. Eighteen rabbits (36 eyes) were inoculated with HSV-1 McKrae strain (10(5) pfu [plaque-forming units]/per eye). Rabbits were divided into three groups and treatment was initiated on day 3 postinfection. Group I received trifluorothymidine, group II received PHMB, and group III received artificial tears, each given five times daily in both eyes until day 10. Daily corneal swabbing to detect viral shedding and slit-lamp examination every 3 days were performed during this period. RESULTS: In vitro studies showed 62.5, 100, and 100% plaque reduction with 0.01, 0.02, and 0.05% PHMB, respectively. Slit-lamp examination of the rabbit corneas revealed faster resolution of dendrites in animals in group I treated with trifluorothymidine. Virus was not recoverable from corneal swabs in nine of 10 rabbits in group I by day 5, but all animals in groups II and III were still shedding HSV through day 8. CONCLUSION: Although PHMB has potent in vitro activity against HSV, it was not an effective treatment in the in vivo rabbit model of primary HSV keratitis at the concentration commonly used for treatment of Acanthamoeba infection. This suggests that 0.02% PHMB will not provide adequate antiherpetic coverage with treatment of keratitis of undetermined etiology in which the clinical differential diagnosis includes both herpes simplex and Acanthamoeba.

Surgical removal of subfoveal choroidal neovascularization in presumed ocular histoplasmosis: stability of early visual results.

PURPOSE: The authors assess the stability of visual acuity outcomes after the surgical removal of subfoveal choroidal neovascularization in a large series of patients with presumed ocular histoplasmosis syndrome (POHS). METHODS: A retrospective study of 117 consecutive patients undergoing vitrectomy between February 1990 and December 1994 was performed. All patients underwent the surgical removal of subfoveal choroidal neovascularization due to POHS and had at least 3 months of follow-up. Postoperative Snellen visual acuity was the primary study endpoint. RESULTS: With a median follow-up of 13 months (range, 3-46 months), 35% of patients had postoperative visual acuity of 20/40 or better, and 40% had improvement of three or more Snellen lines after surgery. In a subset of 54 eyes followed for at least 1 year, 91% showed stable or improved vision between the 3- and 12-month time points, and 85% showed stable or improved vision between 3 months and final visit. CONCLUSION: Follow-up of a large number of patients appears to confirm initially encouraging results and to suggest stability of beneficial effect after the surgical removal of subfoveal choroidal neovascularization in POHS.

Diagnostic indocyanine green angiography in preeclampsia.

PURPOSE: To determine the role of the choroidal vasculature in the pathogenesis of exudative retinal detachments in preeclampsia using indocyanine green angiography. METHODS: We reviewed both fluorescein and indocyanine green angiographic findings for four patients with preeclampsia. RESULTS: Indocyanine green angiographic findings in patients with preeclampsia include nonperfusion in the early phases of the angiogram and staining of the choroidal vasculature with subretinal leakage in the late phases of the angiogram and multiple punctate areas of blocked fluorescence. CONCLUSION: Indocyanine green angiography indicates that damage to the choroidal vasculature leads to many of the retinal changes seen in preeclampsia.

Managing recurrent neovascularization after subfoveal surgery in presumed ocular histoplasmosis syndrome.

PURPOSE: To report the authors' experience with recurrent neovascularization after subfoveal surgery in the presumed ocular histoplasmosis syndrome (POHS). METHODS: One-hundred seventeen patients with POHS and subfoveal choroidal neovascularization were followed a median of 13 months after submacular surgery. RESULTS: Recurrent neovascularization developed in 51 eyes (44%). The median time to recurrence was 3 months (range, 0.5-28 months). Recurrence location was extrafoveal in 16%, juxtafoveal in 18%, and subfoveal in 66%. Sixteen eyes were treated with laser photocoagulation, 17 eyes underwent repeat submacular surgery, and 18 eyes were observed. The visual outcome for patients with recurrences amenable to laser was better than that for patients who were observed or who underwent surgery. CONCLUSION: Recurrent neovascularization after surgery is common; prompt recognition may allow laser photocoagulation.

Air bag-related corneal rupture after radial keratotomy.

PURPOSE: We studied a case of air bag-associated corneal rupture in a patient who had previously undergone radial keratotomy surgery. METHODS: The patient was struck in the right eye when his driver's side air bag inflated during a low-speed collision. RESULTS: Inflation of the air bag resulted in rupture of the patient's right cornea. The rupture involved all but one of his old radial keratotomy wounds. CONCLUSIONS: Patients who have undergone radial keratotomy may be at increased risk for corneal rupture caused by air bag trauma. These patients may benefit by wearing protective eyewear while driving cars equipped with air bags.

Ocular pathologic findings of chronic granulomatous disease of childhood.

PURPOSE/METHODS: To demonstrate ocular histopathologic findings of chronic granulomatous disease of childhood. The histopathologic results of two enucleated eyes from two patients with chronic granulomatous disease were studied using light microscopy. RESULTS/CONCLUSION: Histopathologic changes in the eye specimens in patients with chronic granulomatous disease included multiple foci of granulomatous inflammation of choroid and sclera.

Combination treatment of intraocular lymphoma.

BACKGROUND: Primary intraocular lymphoma is an uncommon clinical entity with poor visual and systemic prognosis. Optimal management of intraocular lymphoma remains uncertain. METHODS: Three patients with intraocular lymphoma, two of whom had documented CNS involvement, were treated based on a modification of the Sloan-Kettering Cancer Center protocol for primary CNS lymphoma. All patients underwent diagnostic pars plana vitrectomy and histopathologic confirmation of primary intraocular large B-cell lymphoma. Treatment involved systemic chemotherapy with methotrexate and high-dose ARA-C, radiation therapy of the brain and orbits, and intrathecal methotrexate delivered via an Ommaya reservoir. RESULTS: Resolution of the ocular lymphoma was seen in all three patients, and resolution of the intracranial disease also was seen in the two patients with CNS involvement. All patients have remained disease free, with lymphoma in remission for at least 24 months after completion of treatment. CONCLUSION: The Sloan-Kettering protocol for the treatment of primary CNS lymphoma also appears to be effective in some cases of primary intraocular large cell lymphoma. Furthermore, the Ommaya reservoir works well for intrathecal delivery of methotrexate in patients with CNS or leptomeningeal spread.

Choroidal melanomas in Hispanic patients.

The initial clinical manifestation and subsequent pathologic characteristics of choroidal melanomas were reviewed in 20 enucleated eyes of Hispanic patients identified between 1974 and 1992. We compared them to 125 choroidal melanomas of randomly selected white patients identified over the same time period. At the time of diagnosis and at subsequent enucleation, the Hispanic patients were younger (P = .002) than the white patients. Eye pain (P = .016), red eye (P = .0002), and tearing (P = .012) were reported more commonly by the Hispanic patients, and on clinical examination the intraocular pressure was higher (P = .001) and more rubeosis iridis was noted (P < .0001) in the Hispanic patients than in the white patients. The tumors of the Hispanic patients were larger in their greatest base dimension (P = .003), and were heavily pigmented compared with those of the white patients (P = .0001). A trend toward less inflammation within the tumor and toward more epithelioid cell type was noted in the Hispanic patients.