Providing Hope: Developing a Viable Regulatory Framework for Providing Terminally Ill Patients With Adequate Access to Investigational Drugs

“If I die . . . I want my children to know I did everything I could.” This is a common feeling among terminally ill individuals facing death. This desire to exhaust every option often causes people to fight to receive potentially toxic and dangerous treatments that are still in the investigational phase if the treatment provides even a glimmer of hope for survival or improvement in condition. Investigational treatments, however, expose patients to myriad risks that can be difficult to predict. Jolee Mohr’s mysterious death provides a sad illustration of the dangers of investigational drugs. Mrs. Mohr’s physician recruited her for a clinical trial to test the safety of an investigational arthritis treatment. After she received the investigational treatment, Mrs. Mohr experienced intractable vomiting and increased body temperature. She subsequently slipped into unconsciousness, and her family made the decision to remove life support after doctors confirmed that she had no hope of recovery

Application of Alternative Nucleic Acid Extraction Protocols to ProGastro SSCS Assay for Detection of Bacterial Enteric Pathogens

As an alternative to automated extraction, fecal specimens were processed by investigational lysis/heating (i.e., manual) and by chromatography/centrifugation (i.e., column) methods. ProGastro SSC and Shiga toxin-producing Escherichia coli (i.e., STEC) indeterminate rates for 101 specimens were 1.0% to 3.0% for automated, 11.9% for manual, and 24.8% to 37.6% for column methods. Following freeze-thaw of 247 specimens, indeterminate rates were 1.6% to 2.4% for manual and 0.8 to 5.3% for column methods. Mean processing times for manual and column methods were 30.5 and 69.2 min, respectively. Concordance of investigational methods with automated extraction was ≥98.8%

Regulating Rare Disease: Safely Facilitating Access to Orphan Drugs

While approximately one in ten Americans suffers from a rare disease, only 5 percent of rare diseases have a U.S. Food and Drug Administration (FDA) approved treatment. Congressional and regulatory efforts to stimulate the development of rare-disease treatments, while laudable, have not resolved the fundamental issues surrounding rare-disease treatment development. Indeed, small patient populations, incomplete scientific understanding of rare diseases, and high development costs continually limit the availability of rare-disease treatments. To illustrate the struggle of developing and approving safe rare-disease treatments, this Note begins by discussing the approval of Eteplirsen, the first drug approved for treating a rare disease called Duchenne muscular dystrophy. After exploring the current drug regulation system and how this impacts the availability of rare-disease treatments, this Note examines the 21st Century Cures Act’s patient experience data provisions and the currently pending Trickett Wendler Right to Try Act. Ultimately, the unmet therapeutic needs of rare-disease patients can be met while protecting patient safety, this Note reasons that, if carefully implemented, the 21st Century Cures Act and the Trickett Wendler Right to Try Act could work in tandem to safely facilitate patient access to rare-disease treatments

Good clinical practice in clinical interventional studies

Good clinical practice (GCP) guidelines should always be implemented and obeyed in clinical interventional studies. In this mini-review, we will address several burning questions relating to GCP in a concise ‘frequently asked questions’ format.While compliance to current rules and regulations is our mission, we also wish to play devil’s advocate attempting to translate the rules into sizeable chunks using a high dose of common sense

Soft Tissue Grafting to Improve Implant Esthetics

Dental implants are becoming the treatment of choice to replace missing teeth, especially if the adjacent teeth are free of restorations. When minimal bone width is present, implant placement becomes a challenge and often resulting in recession and dehiscence around the implant that leads to subsequent gingival recession. To correct such defect, the author turned to soft tissue autografting and allografting to correct a buccal dehiscence around tooth #24 after a malpositioned implant placed by a different surgeon. A 25-year-old woman presented with the chief complaint of gingival recession and exposure of implant threads around tooth #24. The patient received three soft tissue grafting procedures to augment the gingival tissue. The first surgery included a connective tissue graft to increase the width of the keratinized gingival tissue. The second surgery included the use of autografting (connective tissue graft) to coronally position the soft tissue and achieve implant coverage. The third and final surgery included the use of allografting material Alloderm to increase and mask the implant from showing through the gingiva. Healing period was uneventful for the patient. After three surgical procedures, it appears that soft tissue grafting has increased the width and height of the gingiva surrounding the implant. The accomplished thickness of gingival tissue appeared to mask the showing of implant threads through the gingival tissue and allowed for achieving the desired esthetic that the patient desired. The aim of the study is to present a clinical case with soft tissue grafting procedures

Clinical trials on medicinal products in Malta following EU accession

Following EU Accession, Malta has to adopt EU Directives as part of its own legislation. Three such directives concern the conduct of clinical trials in European countries ­ 2001/20/EC, 2003/94/EC and 2005/28/EC. These directives, and the respective guidelines explaining their implementation, have considerably changed the way clinical trials are conducted. While the participation of Malta in clinical trials is to be encouraged for various reasons, these have to be regulated according to the legislation set out by the European Union. In themselves, what these Directives strive to achieve are mainly the safety of the study subject and the protection of the investigators from serious consequences. This short article aims to give a brief overview of these changes to prospective investigators and hospital administrators.peer-reviewe

Nontraumatic Dental Condition-related Visits to Emergency Departments on Weekdays, Weekends and Night Hours: Findings from the National Hospital Ambulatory Medical Care Survey

Objective: To determine whether the rates of nontraumatic dental condition (NTDC)-related emergency department (ED) visits are higher during the typical working hours of dental offices and lower during night hours, as well as the associated factors. Methods: We analyzed data from the National Hospital Ambulatory Medical Care Survey for 1997 through 2007 using multivariate binary and polytomous logistic regression adjusted for survey design to determine the effect of predictors on specified outcome variables. Results: Overall, 4,726 observations representing 16.4 million NTDC-related ED visits were identified. Significant differences in rates of NTDC-related ED visits were observed with 40%–50% higher rates during non-working hours and 20% higher rates on weekends than the overall average rate of 170 visits per hour. Compared with 19–33 year olds, subjects [relative rate ratio (RRR) = 1.6 to 1.8], whereas those aged 73 and older had lower relative rates during nonworking hours (RRR = 0.4; overall P = 0.0005). Compared with those having private insurance, Medicaid and self-pay patients had significantly lower relative rates of NTDC visits during nonworking and night hours (RRR = 0.6 to 0.7, overall P \u3c 0.0003). Patients with a dental reason for visit were overrepresented during the night hours (RRR = 1.3; overall P = 0.04). Conclusion: NTDC-related visits to ED occurred at a higher rate during non-working hours and on weekends and were significantly associated with age, patient-stated reason for visit and payer type

New Phosphated Poly(methyl Methacrylate) Polymers for the Prevention of Denture-induced Microbial Infection: an In Vitro Study

Purpose: Poly(methyl methacrylate) (PMMA) has been widely used as a denture-base acrylic resin due to its excellent physical and mechanical properties. However, the material is highly prone to microbial fouling that often leads to Candida-associated denture stomatitis. Incorporation of phosphate groups into PMMA could facilitate adsorption of salivary antimicrobials and inhibit microbial adherence on the polymer surface. An in vitro study evaluated PMMA polymers containing varying amounts of phosphate group for their efficacy to inhibit Candida albicans adhesion, adsorb salivary histatin 5, and exhibit candidacidal activity. Methods: Six PMMA polymers containing 0%, 5%, 15%, 10%, 20%, and 25% of phosphate group were synthesized by bead (suspension) polymerization technique using mixtures of methyl methacrylate and methallyl phosphate as monomers. The efficacy of the polymers to inhibit the adherence of C. albicans was examined by using human saliva-coated polymer beads and radio-labeled C. albicans cells, as compared with that of PMMA. The potency of the phosphated PMMA polymers to adsorb histatin 5 was determined by measuring the radioactivity of the adsorbed labeled-peptide on the polymer surface. The candidacidal activity of the histatin 5-adsorbed polymers was assessed by using the fluorescence technique. The percent release of the fluorescent probe calcein from the C. albicans membrane caused by the disruption of the cell membrane was determined. The data were analyzed statistically by one-way ANOVA followed by Scheffé’s test (α = 0.05 and n = 6). Results: The presence of ≥15% phosphate content in PMMA significantly reduced the saliva-mediated adhesion of C. albicans. Phosphated PMMA polymers showed significantly enhanced adsorption of histatin 5 in a phosphate density-dependent manner. The candidacidal activity of the histatin 5-bound polymers increased significantly with the increase in the phosphate content of the polymer. Conclusion: Phosphated PMMA polymers have the potential to serve as novel denture-base resins, which may reduce C. albicans colonization and prevent denture stomatitis