Neurocognitive and somatic stabilization in pediatric patients with severe Mucopolysaccharidosis Type I after 52 weeks of intravenous brain-penetrating insulin receptor antibody-iduronidase fusion protein (valanafusp alpha): an open label phase 1-2 trial.

BACKGROUND: Mucopolysaccharidosis (MPS) Type I (MPSI) is caused by mutations in the gene encoding the lysosomal enzyme, α-L-iduronidase (IDUA), and a majority of patients present with severe neurodegeneration and cognitive impairment. Recombinant IDUA does not cross the blood-brain barrier (BBB). To enable BBB transport, IDUA was re-engineered as an IgG-IDUA fusion protein, valanafusp alpha, where the IgG domain targets the BBB human insulin receptor to enable transport of the enzyme into the brain. We report the results of a 52-week clinical trial on the safety and efficacy of valanafusp alpha in pediatric MPSI patients with cognitive impairment. In the phase I trial, 6 adults with attenuated MPSI were administered 0.3, 1, and 3 mg/kg doses of valanafusp alpha by intravenous (IV) infusion. In the phase II trial, 11 pediatric subjects, 2-15 years of age, were treated for 52 weeks with weekly IV infusions of valanafusp alpha at 1, 3, or 6 mg/kg. Assessments of adverse events, cognitive stabilization, and somatic stabilization were made. Outcomes at 52 weeks were compared to baseline. RESULTS: Drug related adverse events included infusion related reactions, with an incidence of 1.7%, and transient hypoglycemia, with an incidence of 6.4%. The pediatric subjects had CNS involvement with a mean enrollment Development Quotient (DQ) of 36.1±7.1. The DQ, and the cortical grey matter volume of brain, were stabilized by valanafusp alpha treatment. Somatic manifestations were stabilized, or improved, based on urinary glycosaminoglycan levels, hepatic and spleen volumes, and shoulder range of motion. CONCLUSION: Clinical evidence of the cognitive and somatic stabilization indicates that valanafusp alpha is transported into both the CNS and into peripheral organs due to its dual targeting mechanism via the insulin receptor and the mannose 6-phosphate receptor. This novel fusion protein offers a pharmacologic approach to the stabilization of cognitive function in MPSI. TRIAL REGISTRATION: Clinical Trials.Gov, NCT03053089 . Retrospectively registered 9 February, 2017; Clinical Trials.Gov, NCT03071341 . Registered 6 March, 2017.

Professional Caregivers' Oral Care Practices and Beliefs for Elderly Clients Aging In Place.

PURPOSE: As recently as the 1990s long-term care facilities (LTCFs) were the main housing option for semi- or fully-dependent elders. Today, 90% of those 65 and older want to "age in place." The growth of the elderly population that want to "age in place" will require increasing numbers of professional caregivers to assist in oral care practices. The purpose of this study was to address the gap in the knowledge about the oral care practices and beliefs of professional caregivers who work for non-medical in-home care companies charged in the care of "aging in place" elders. METHODS: The Nursing Dental Coping Belief Scale was used in a descriptive cross-sectional study. Professional caregivers (n=67) employed by 3 non-medical in-home care companies in South Texas completed the survey. The survey gathered demographic information, oral care practice questions and oral health belief questions. Statistics used for data analysis included chi-square contingency table analysis. The level of significance was set at p<0.05 for all analyses. RESULTS: Non-medical in-home care companies are not mandated by law to provide training, yet professional caregivers wanted more training in brushing and flossing (85%). A majority (60%) reported being trained. Most (85%) looked inside their client's mouth yet nearly 18% did not floss their client's teeth and only 31% knew if their clients wore dentures. CONCLUSION: While this was a small study, it provides preliminary information that professional caregivers, who serve clients aging in place, want more oral care training. Professional caregivers would be better served if there were more thorough and frequent training provided with managerial oversight.

Calculus detection calibration among dental hygiene faculty members utilizing dental endoscopy: a pilot study.

Dental and dental hygiene faculty members often do not provide consistent instruction in the clinical environment, especially in tasks requiring clinical judgment. From previous efforts to calibrate faculty members in calculus detection using typodonts, researchers have suggested using human subjects and emerging technology to improve consistency in clinical instruction. The purpose of this pilot study was to determine if a dental endoscopy-assisted training program would improve intra- and interrater reliability of dental hygiene faculty members in calculus detection. Training included an ODU 11/12 explorer, typodonts, and dental endoscopy. A convenience sample of six participants was recruited from the dental hygiene faculty at a California community college, and a two-group randomized experimental design was utilized. Intra- and interrater reliability was measured before and after calibration training. Pretest and posttest Kappa averages of all participants were compared using repeated measures (split-plot) ANOVA to determine the effectiveness of the calibration training on intra- and interrater reliability. The results showed that both kinds of reliability significantly improved for all participants and the training group improved significantly in interrater reliability from pretest to posttest. Calibration training was beneficial to these dental hygiene faculty members, especially those beginning with less than full agreement. This study suggests that calculus detection calibration training utilizing dental endoscopy can effectively improve interrater reliability of dental and dental hygiene clinical educators. Future studies should include human subjects, involve more participants at multiple locations, and determine whether improved rater reliability can be sustained over time.

A study of statistics anxiety levels of graduate dental hygiene students.

PURPOSE: In light of increased emphasis on evidence-based practice in the profession of dental hygiene, it is important that today's dental hygienist comprehend statistical measures to fully understand research articles, and thereby apply scientific evidence to practice. Therefore, the purpose of this study was to investigate statistics anxiety among graduate dental hygiene students in the U.S. METHODS: A web-based self-report, anonymous survey was emailed to directors of 17 MSDH programs in the U.S. with a request to distribute to graduate students. The survey collected data on statistics anxiety, sociodemographic characteristics and evidence-based practice. Statistic anxiety was assessed using the Statistical Anxiety Rating Scale. Study significance level was α=0.05. RESULTS: Only 8 of the 17 invited programs participated in the study. Statistical Anxiety Rating Scale data revealed graduate dental hygiene students experience low to moderate levels of statistics anxiety. Specifically, the level of anxiety on the Interpretation Anxiety factor indicated this population could struggle with making sense of scientific research. A decisive majority (92%) of students indicated statistics is essential for evidence-based practice and should be a required course for all dental hygienists. CONCLUSION: This study served to identify statistics anxiety in a previously unexplored population. The findings should be useful in both theory building and in practical applications. Furthermore, the results can be used to direct future research.

Iatro-compliance: an unintended consequence of excessive autonomy in long term care facilities.

PURPOSE: Periodontal disease and caries remain the most prevalent preventable chronic diseases for seniors. Seniors transitioning into long term care facilities (LTCFs) often present with oral health challenges linked to systemic diseases, plaque control, psychomotor skills and oral health literacy. Many retain a discernible level of physical and cognitive ability, establishing considerable autonomy. This study examines the effect of autonomy on residents' ability to perform oral hygiene. METHODS: Descriptive data were developed utilizing mixed methodology on a convenience sample of 12 residents and 7 care staff of a LTCF. One-on-one interviews consisted of questions about demographics, and exploration of the influence of ageism, respect and time constraints on resident autonomy in oral care practices. RESULTS: Data suggests shortcomings, such as failure of the staff to ensure oral hygiene oversight and failure of the resident to ask for assistance. Autonomy, while laudable, was used by residents to resist staff assistance, partially motivated by residents' lack of confidence in care staff oral hygiene literacy and skills. In turn, by honoring resident's independence, the staff enabled excessive autonomy to occur creating an environment of iatro-compliance. CONCLUSION: While it is beneficial to encourage autonomy, oversight and education must remain an integral component of oral hygiene care in this population. Improved oral hygiene skills can be fostered in LTCFs by utilizing the current oral health care workforce. Registered dental hygienists (RDHs), under indirect supervision of a dentist, can fulfill the role of an oral health care director (OHCD) in LTCFs. A director's presence in a facility can decrease staff caused iatro-compliance and increase oral hygiene skills and literacy of the residents, while enhancing their autonomy through education and support.

Preventing shoulder pain after cardiac rhythm management device implantation: a randomized, controlled study.

INTRODUCTION: Shoulder pain and disability ipsilateral to the implant site is a common complication of cardiac rhythm device implantation, yet very little has been published about this morbidity. We designed a study to assess the potential benefit of a simple exercise protocol in preventing shoulder pain postoperatively. METHODS AND RESULTS: Patients undergoing subcutaneous device implantation were randomized to one of two groups. The control group received standard instructions, whereas the exercise group was instructed on specific exercises aimed at strengthening or stretching the shoulder girdle, to be completed 3 days per week. Groups were postoperatively monitored for the development of shoulder discomfort and shoulder impingement by using physical examination and disability questionnaires. At 1 month, seven of 21 control patients reported developing shoulder pain or discomfort compared to one of 23 in the exercise group (P = 0.02). At 6 months, four of 23 control patients still reported worsening shoulder symptoms, compared to none in the exercise group (P = 0.11). In the control group, five of 19 patients developed a positive impingement test at 1 month, versus none in the exercise group (P = 0.01). Scores for the questionnaires designed to assess shoulder pain and dysfunction were worse in the control group. There were no activity-related complications in either group. CONCLUSION: Shoulder pain and disability occurs often following cardiac rhythm management device implantation. A simple exercise program aimed at strengthening the shoulder girdle is effective at preventing this complication.

Safety of electromagnetic articulography in patients with pacemakers and implantable cardioverter-defibrillators.

PURPOSE: Electromagnetic articulography (EMA) uses a helmet to create alternating magnetic fields for tracking speech articulator movement. An important safety consideration is whether EMA magnetic fields interfere with the operation of speakers' pacemakers or implantable cardioverter-defibrillators (ICDs). In this investigation, individuals with pacemaker/ICD devices were exposed to EMA fields under controlled conditions while potential interference was examined. METHOD: Twelve adults with pacemaker/ICD devices from 3 major manufacturers were assessed for device function before, during, and after exposure to magnetic fields from a Carstens AG100 EMA system. Potential interference was probed, with EMA transmitters positioned at varying distances from the implantable devices and with the EMA system set at different operating strengths. RESULTS: No adverse affects in device operation were observed under any conditions. The only potential complication was temporary telemetry-link interference during device testing in some cases. CONCLUSION: The results suggest that EMA technology may be safely used with patients who have pacemakers and ICDs. However, the present findings do not rule out potential interference with other pacemaker/ICD manufacturers or with different articulography systems. Precautions are suggested for testing individuals with pacemaker/ICDs under EMA conditions.

Frequency and outcome of arrhythmias complicating admission during pregnancy: experience from a high-volume and ethnically-diverse obstetric service.

BACKGROUND: Arrhythmias are reported during pregnancy, although hospitalization for these infrequent events is not fully characterized. The frequency and outcome of arrhythmias during pregnancy are unknown. METHODS: Between 1992 and 2000, there were 136,422 pregnancy-related admissions to Parkland Memorial Hospital (Dallas, TX, USA). Using the discharge diagnosis data bank and the International Classification of Disease, 9th revision, Clinical Modification (ICD-9-CM) coding system, we identified 226 admissions (218 patients) where cardiac arrhythmias and intrauterine pregnancy were both reported. RESULTS: The most common rhythm disturbances during pregnancy were sinus tachycardia (ST), sinus bradycardia (SB), or sinus arrhythmia (SA) (104 episodes/100,000 pregnancies). This was followed by paroxysmal supraventricular tachycardia (PSVT) and premature beats, with a frequency of 24/100,000 and 33/100,000, respectively. Paroxysmal supraventricular tachycardia occurred most frequently in the third trimester or peripartum. All episodes terminated spontaneously or were safely terminated with medical therapy. Advanced heart block or lethal arrhythmias were exceedingly rare during pregnancy. CONCLUSION: Most frequently reported cardiac arrhythmias in pregnancy are benign and do not require intervention. Supraventricular tachycardia (SVT), being one of the most common complicated cardiac arrhythmias during pregnancy, can be treated effectively and safely with standard medical therapy. Ventricular arrhythmias or high-degree atrioventricular block (AVB) during pregnancy are extremely rare. Cardiac arrest is also rare, and is often caused by a different etiology from the conventional ones for sudden cardiac death.