Cost of Tuberculosis Therapy Directly Observed on Video for Health Departments and Patients in New York City; San Francisco, California; and Rhode Island (2017-2018).

Objectives. To assess costs of video and traditional in-person directly observed therapy (DOT) for tuberculosis (TB) treatment to health departments and patients in New York City, Rhode Island, and San Francisco, California.Methods. We collected health department costs for video DOT (VDOT; live and recorded), and in-person DOT (field- and clinic-based). Time-motion surveys estimated provider time and cost. A separate survey collected patient costs. We used a regression model to estimate cost by DOT type.Results. Between August 2017 and June 2018, 343 DOT sessions were captured from 225 patients; 87 completed a survey. Patient costs were lowest for VDOT live ($1.01) and highest for clinic DOT ($34.53). The societal (health department + patient) costs of VDOT live and recorded ($6.65 and $12.64, respectively) were less than field and clinic DOT ($21.40 and $46.11, respectively). VDOT recorded health department cost was not statistically different from field DOT cost in Rhode Island.Conclusions. Among the 4 different modalities, both types of VDOT were associated with lower societal costs when compared with traditional forms of DOT.Public Health Implications. VDOT was associated with lower costs from the societal perspective and may reduce public health costs when TB incidence is high.

Contralateral weakness following botulinum toxin for poststroke spasticity.

INTRODUCTION: We describe 2 patients who received botulinum toxin A (BoNT) for poststroke spasticity and developed contralateral limb weakness. METHODS: Both patients received high doses of BoNT with large dilution volumes and injection in the proximal upper extremity muscles, and developed weakness of the contralateral upper limb. These patients then underwent electrodiagnostic testing of the affected limb. RESULTS: Repetitive nerve stimulation of the axillary and spinal accessory nerves revealed decrements of 23% and 16%, respectively. EMG revealed abnormal spontaneous activity and small polyphasic motor unit potentials with reduced recruitment. These findings indicated blockade of the neuromuscular junction. Both patients improved. CONCLUSIONS: Isolated weakness of the contralateral limb after BoNT injection for poststroke spasticity suggests diffusion of toxin through tissue planes from proximal upper extremity muscles, across the midline, to contralateral muscles. High doses of botulinum toxin, high dilution volumes, and injection of proximal upper extremity muscles appear to be risk factors for this adverse effect.

Laryngeal Electromyographic Findings in a Cohort of Recalcitrant Chronic Neurogenic Cough Patients.

OBJECTIVES: To evaluate the laryngeal electromyography findings of bilateral thyroarytenoid muscles in 10 patients with chronic, intractable coughing. METHODS: This is a retrospective cohort case series. Clinical records were reviewed for demographic information, symptoms, and findings on bilateral laryngeal EMG for 10 patients referred for chronic coughing. RESULTS: All thyroarytenoid muscles tested demonstrated electromyographic evidence of neuropathy, with signs of denervation and reinnervation. There was reduced recruitment in all 20 thyroarytenoid muscles studied. In addition, polyphasic motor units were seen in all thyroarytenoid muscles, with increased amplitude in 18 of 20 thyroarytenoid muscles and increased duration in 17 of 20 thyroarytenoid muscles. Additionally, there was electromyographic evidence of synkinesis in 19 of 20 thyroarytenoid muscles studied, a sign of aberrant reinnervation. CONCLUSION: Patients with intractable coughing, despite numerous modalities of treatment, potentially have bilateral neuropathy of the recurrent laryngeal nerves suggesting the potential peripheral as well as central neuropathic changes as the etiology.

Fragment-based discovery of nonpeptidic BACE-1 inhibitors using tethering.

BACE-1 (beta-site amyloid precursor protein cleaving enzyme), a prominent target in Alzheimer's disease drug discovery efforts, was surveyed using Tethering technology to discover small molecule fragment ligands that bind to the enzyme active site. Screens of a library of >15000 thiol-containing fragments versus a panel of BACE-1 active site cysteine mutants under redox-controlled conditions revealed several novel amine-containing fragments that could be selectively captured by subsets of the tethering sites. For one such hit class, defined by a central aminobenzylpiperidine (ABP) moiety, X-ray crystal structures of BACE mutant-disulfide conjugates revealed that the fragment bound by engaging both catalytic aspartates with hydrogen bonds. The affinities of ABP fragments were improved by structure-guided chemistry, first for conjugation as thiol-containing fragments and then for stand-alone, noncovalent inhibition of wild-type (WT) BACE-1 activity. Crystallography confirmed that the inhibitors bound in exactly the same mode as the disulfide-conjugated fragments that were originally selected from the screen. The ABP ligands represent a new type of nonpeptidic BACE-1 inhibitor motif that has not been described in the aspartyl protease literature and may serve as a starting point for the development of BACE-1-directed Alzheimer's disease therapeutics.

Procurement, storage and utilization trends of eye banks in India.

Purpose: To study the trends in collection, storage and utilization of donor corneas in eye banks in India. Methods: The data was collected from 12 eye banks in India that collected more than 1000 corneas per year. The retrospective analysis of the parameters like characteristics of the donor and the host, storage media used, number of eyes collected, number of eyes utilized, causes of non-utilization of the tissue and the procedures performed was done. Results: A total of 20,564 eyes were collected by the 12 eye banks during the year 2013-2014. Voluntary eye donation (VED), and hospital cornea retrieval program (HCRP) contributed to 59.6% and 40.4% of tissue procurement respectively. Whole globe enucleation (52.3%) was more commonly performed as compared to in-situ excision of the donor corneas. The most commonly used storage media at all eye banks was McCarey-Kaufman (MK) media (83.3%). The utilization rate of the donor eyes was 50.5%. The most frequent indication for corneal transplantation was infection (active infection - 33.13%, healed infection - 10.78%) followed by Pseudophakic bullous keratopathy (PBK) (13.57%). Full thickness keratoplasty (optical penetrating keratoplasty - 47.23%, therapeutic penetrating keratoplasty - 31.74%) was performed most often followed by endothelial keratoplasty (12.41%) in the developing country. Conclusion: VED still contributes to majority of the donor tissue retrieval in India. The majority of the eye banks still utilize whole globe enucleation technique and store tissues in MK media. Trends from previous years showed a change towards HCRP, in-situ excision technique and preservation in the long-term storage media.

Aminoethylenes: a tetrahedral intermediate isostere yielding potent inhibitors of the aspartyl protease BACE-1.

A series of novel beta-site amyloid precursor protein cleaving enzyme (BACE-1) inhibitors containing an aminoethylene (AE) tetrahedral intermediate isostere were synthesized and evaluated in comparison to corresponding hydroxyethylene (HE) compounds. Enzymatic inhibitory values were similar for both isosteres, as were structure-activity relationships with respect to stereochemical preference and substituent variation (P2/P3, P1, and P2'); however, the AE compounds were markedly more potent in a cell-based assay for reduction of beta-secretase activity. The incorporation of preferred P2/P3, P1, and P2' substituents into the AE pharmacophore yielded compound 7, which possessed enzymatic and cell assay IC(50)s of 26 nM and 180 nM, respectively. A three-dimensional crystal structure of 7 in complex with BACE-1 revealed that the amino group of the inhibitor core engages the catalytic aspartates in a manner analogous to hydroxyl groups in HE inhibitors. The AE isostere class represents a promising advance in the development of BACE-1 inhibitors.

Adolescent sexuality and disability.

Regardless of what our beliefs about sex and disability may be, as health care providers we can promote the health and well being of our patients with disabilities in several ways. First and perhaps foremost, physical and programmatic barriers to accessing general health care including routine gynecologic care must be dramatically reduced. The promise of Title III of the Americans with Disabilities Act must be aggressively extended to our health care system to ensure equal access to routine health care for all. Second, knowledge of community resources that can support the healthy development and exercise of responsible and satisfying sexuality is critical. For example, health care providers should know about adaptive and assistive technologies as well as the use of personal care assistants to support the healthy although sometimes nontypical expression of one's sexuality. Centers for Independent Living are community resources that are often underutilized by the medical profession. These centers--run by and for people with disabilities--are likely resources and allies for providing education, role models, and peer mentoring around relationships, intimacy, sexuality, sexual expression, and parenting with a disability. Finally, sex education is a must and should include the following: Basic facts of life, reproduction, and sexual intercourse; Human growth and development Human reproduction and anatomy Self-pleasuring/masturbation and the use of sexual aids Intimacy and privacy Pregnancy and child birth Contraception and abortion Family life and parenthood Sexual response and consensual sex Sexual orientation Sexual abuse HIV/AIDS and other sexually transmitted diseases. The question should not be whether sex education is provided to persons with disabilities, but rather how it is most effectively provided. Health sex education must include the development of effective communication skills, decision-making skills, assertiveness, and the ability to say "no." It must also include ways to create satisfying relationships. For more information about sex education as it relates to people with disabilities, the following abbreviated resource list may be helpful: http://www.sexualhealth.com http://www.lookingglass.com Ludwig S, Hingsburger, D. Being sexual: an illustrated series on sexuality and relationships. SIECCAN, 850 Coxwell, Aven., East York, Ontario, M4C 5R1 Tel: 416-466-5304; Fax: 416-778-0785. Sexuality Information and Education Council of the United States (SIECUS), 130 West 42nd Street, Suite 350, New York, NY 10036. Tel: 212-819-9770. National Information Center for Children and Youth with Disabilities (NICHCY), P.O. Box 1492, Washington, DC 20013; Tel/TTY: 800-695-0285; Fax: 202-884-8641; Internet: www.nichcy.org Non-Latex Supplies (Ask your pharmacist if not available) Trojan-Supra: http://www.trojancondoms.com Durex-Avanti: http://www.durex.com Female Health Company-FC Female Condom http://www.femalehealth.com Pasante--EzOn http://www.postalcondoms.co.uk (available in Canada and U.K.).

Reduction of costs for anemia-management drugs associated with the use of ferric citrate.

BACKGROUND: Ferric citrate is a novel phosphate binder which has the potential to reduce usage of erythropoietin-stimulating agents (ESAs) and intravenous (IV) iron used for anemia management during hemodialysis (HD) among patients with end-stage renal disease (ESRD). Currently, the potential health care cost savings on a national scale due to the use of ferric citrate in ESRD are undetermined. METHODS: Per-patient-per-year costs of ESAs (Epogen(®) and Aranesp(®) [Amgen Inc., CA, USA]) and IV iron (Venofer(®) [American Regent, Inc., NY, USA] and Ferrlecit(®) [Sanofi US, Bridgewater, NJ, USA]) were based on RED BOOK™ (Truven Health Analytics New York, NY, USA) costs combined with the Centers for Medicare and Medicaid Services (CMS) base rate and actual usage in 2011 for the four drugs. The annual number of outpatients undergoing HD in the US was based on frequencies reported by the USRDS (United States Renal Data System). Monte Carlo uncertainty analysis was performed to determine total annual costs and cost reduction based on ferric citrate usage. RESULTS: Total annual cost of ESAs and IV iron for anemia management in ESRD determined by Monte Carlo analysis assuming CMS base rate value was 5.127 (3.664-6.260) billion USD. For actual utilization in 2011, total annual cost of ESAs and IV iron was 3.981 (2.780-4.930) billion USD. If ferric citrate usage reduced ESA utilization by 20% and IV iron by 40%, then total cost would be reduced by 21.2% to 4.038 (2.868-4.914) billion USD for the CMS base rate, and by 21.8% to 3.111 (2.148-3.845) billion USD, based on 2011 actual utilization. CONCLUSION: It is likely that US health care costs for anemia-management drugs associated with ESRD among HD patients can be reduced by using ferric citrate as a phosphate binder.

Pleiotrophin gene therapy for peripheral ischemia: evaluation of full-length and truncated gene variants.

Pleiotrophin (PTN) is a growth factor with both pro-angiogenic and limited pro-tumorigenic activity. We evaluated the potential for PTN to be used for safe angiogenic gene therapy using the full length gene and a truncated gene variant lacking the domain implicated in tumorigenesis. Mouse myoblasts were transduced to express full length or truncated PTN (PTN or T-PTN), along with a LacZ reporter gene, and injected into mouse limb muscle and myocardium. In cultured myoblasts, PTN was expressed and secreted via the Golgi apparatus, but T-PTN was not properly secreted. Nonetheless, no evidence of uncontrolled growth was observed in cells expressing either form of PTN. PTN gene delivery to myocardium, and non-ischemic skeletal muscle, did not result in a detectable change in vascularity or function. In ischemic hindlimb at 14 days post-implantation, intramuscular injection with PTN-expressing myoblasts led to a significant increase in skin perfusion and muscle arteriole density. We conclude that (1) delivery of the full length PTN gene to muscle can be accomplished without tumorigenesis, (2) the truncated PTN gene may be difficult to use in a gene therapy context due to inefficient secretion, (3) PTN gene delivery leads to functional benefit in the mouse acute ischemic hindlimb model.