Medical care of adults with Down Syndrome a clinical guideline

Down syndrome is the most common chromosomal condition, and average life expectancy has increased substantially, from 25 years in 1983 to 60 years in 2020. Despite the unique clinical comorbidities among adults with Down syndrome, there are no clinical guidelines for the care of these patients. To develop an evidence-based clinical practice guideline for adults with Down syndrome. The Global Down Syndrome Foundation Medical Care Guidelines for Adults with Down Syndrome Workgroup (n = 13) developed 10 Population/Intervention/ Comparison/Outcome (PICO) questions for adults with Down syndrome addressing multiple clinical areas including mental health (2 questions), dementia, screening or treatment of diabetes, cardiovascular disease, obesity, osteoporosis, atlantoaxial instability, thyroid disease, and celiac disease. These questions guided the literature search in MEDLINE, EMBASE, PubMed, PsychINFO, Cochrane Library, and the TRIP Database, searched from January 1, 2000, to February 26, 2018, with an updated search through August 6, 2020. Using the GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology and the Evidence-to-Decision framework, in January 2019, the 13-member Workgroup and 16 additional clinical and scientific experts, nurses, patient representatives, and a methodologist developed clinical recommendations. A statement of good practice was made when there was a high level of certainty that the recommendation would do more good than harm, but there was little direct evidence. From 11 295 literature citations associated with 10 PICO questions, 20 relevant studies were identified. An updated search identified 2 additional studies, for a total of 22 included studies (3 systematic reviews, 19 primary studies), which were reviewed and synthesized. Based on this analysis, 14 recommendations and 4 statements of good practice were developed. Overall, the evidence base was limited. Only 1 strong recommendation was formulated: screening for Alzheimer-type dementia starting at age 40 years. Four recommendations (managing risk factors for cardiovascular disease and stroke prevention, screening for obesity, and evaluation for secondary causes of osteoporosis) agreed with existing guidance for individuals without Down syndrome. Two recommendations for diabetes screening recommend earlier initiation of screening and at shorter intervals given the high prevalence and earlier onset in adults with Down syndrome. These evidence-based clinical guidelines provide recommendations to support primary care of adults with Down syndrome. The lack of high-quality evidence limits the strength of the recommendations and highlights the need for additional research.

Workmen's compensation for occupational hand injuries.

BACKGROUND: The Compensation for Occupational Injuries and Diseases Act No. 130 of 1993, as amended in 1997 (COIDA), provides payment to healthcare providers for treatment of occupational injuries in South Africa (SA). Patients and employers are often unaware of procedures for claiming, and patients then carry the burden of costs themselves. Additionally, under-billing results in a loss of income for treating hospitals. Hand injuries are common occupational injuries and form the focus of this study. OBJECTIVES: To investigate whether occupational hand injuries treated at the Martin Singer Hand Unit at Groote Schuur Hospital, Cape Town, were accurately captured and allocated correct professional fee coding and billing. Accurate capturing and billing would allow for access to the Compensation Fund and allocation of finances to improve service delivery, as well as avoid unnecessary costs to otherwise uninsured patients. METHODS: All new hand injuries presenting to the hand unit at the hospital in August 2017 were sampled in a retrospective folder review. Injuries on duty (IODs) were identified and analysed further. Coding and billing were compared with independent private quotes. RESULTS: Sixty new hand injuries presented during the month. Fifteen were IODs, but only 6 were recognised by administration. The other 9 were billed at minimum income rates and 5 of these patients also had operations, which were not billed for. A total of ZAR88 871.99 was under-billed in terms of professional fees only. The 9 incorrectly classified patients had to bear costs themselves at a median of ZAR130.00 each. CONCLUSIONS: There were large discrepancies in billing for occupational hand injuries. This resulted in costs to the patients and loss of income for the facility. Access to the Compensation Fund is vital in financing resources in the overburdened public sector. Suggestions for improvement include accessing COIDA funds in order to improve administration at the unit, so improving identification, coding and billing of occupational hand injuries.

Exposure to wind turbine noise: Perceptual responses and reported health effects.

Health Canada, in collaboration with Statistics Canada, and other external experts, conducted the Community Noise and Health Study to better understand the impacts of wind turbine noise (WTN) on health and well-being. A cross-sectional epidemiological study was carried out between May and September 2013 in southwestern Ontario and Prince Edward Island on 1238 randomly selected participants (606 males, 632 females) aged 18-79 years, living between 0.25 and 11.22 km from operational wind turbines. Calculated outdoor WTN levels at the dwelling reached 46 dBA. Response rate was 78.9% and did not significantly differ across sample strata. Self-reported health effects (e.g., migraines, tinnitus, dizziness, etc.), sleep disturbance, sleep disorders, quality of life, and perceived stress were not related to WTN levels. Visual and auditory perception of wind turbines as reported by respondents increased significantly with increasing WTN levels as did high annoyance toward several wind turbine features, including the following: noise, blinking lights, shadow flicker, visual impacts, and vibrations. Concern for physical safety and closing bedroom windows to reduce WTN during sleep also increased with increasing WTN levels. Other sample characteristics are discussed in relation to WTN levels. Beyond annoyance, results do not support an association between exposure to WTN up to 46 dBA and the evaluated health-related endpoints.

Cardiovascular Risk in Diabetes Mellitus: Complication of the Disease or of Antihyperglycemic Medications.

Cardiovascular disease is the principal complication and the leading cause of death for patients with diabetes (DM). The efficacy of antihyperglycemic treatments on cardiovascular disease risk remains uncertain. Cardiovascular risk factors are affected by antihyperglycemic medications, as are many intermediate markers of cardiovascular disease. Here we summarize the evidence assessing the cardiovascular effects of antihyperglycemic medications with regard to risk factors, intermediate markers of disease, and clinical outcomes.

Hybrid reactor based on combined cavitation and ozonation: from concept to practical reality.

The present work gives an in depth discussion related to the development of a hybrid advanced oxidation reactor, which can be effectively used for the treatment of various types of water. The reactor is based on the principle of intensifying degradation/disinfection using a combination of hydrodynamic cavitation, acoustic cavitation, ozone injection and electrochemical oxidation/precipitation. Theoretical studies have been presented to highlight the uniform distribution of the cavitational activity and enhanced generation of hydroxyl radicals in the cavitation zone, as well as higher turbulence in the main reactor zone. The combination of these different oxidation technologies have been shown to result in enhanced water treatment ability, which can be attributed to the enhanced generation of hydroxyl radicals, enhanced contact of ozone and contaminants, and the elimination of mass transfer resistances during electrochemical oxidation/precipitation. Compared to the use of individual approaches, the hybrid reactor is expected to intensify the treatment process by 5-20 times, depending on the application in question, which can be confirmed based on the literature illustrations. Also, the use of Ozonix® has been successfully proven while processing recycled fluids at commercial sites on over 750 oil and natural gas wells during hydraulic operations around the United States. The superiority of the hybrid process over conventional chemical treatments in terms of bacteria and scale reduction as well as increased water flowability and better chemical compatibility, which is a key requirement for oil and gas applications, has been established.

A quantitative measure of diabetes risk in community practice impacts clinical decisions: the PREVAIL initiative.

BACKGROUND AND AIMS: While predictive tools are being developed to identify those at highest risk for developing diabetes, little is known whether these assays affect clinical care. METHODS AND RESULTS: Thirty sites who used the PreDx(®) (Tethys BioScience, Emeryville, CA) abstracted clinical information from baseline clinic visits prior to a PreDx test and from the most recent visit at time of abstraction. All visits occurred between May 2008-April 2011 (median follow-up 198 days, IQR 124-334). The primary analysis was the influence of the PreDx test (5-year diabetes prediction) on subsequent care; descriptive statistics were used to summarize baseline and follow-up variables. Overall 913 patients with 2 abstracted visits were included. Relative to baseline, median SBP decreased 1.5 mmHg (p = 0.039), DBP decreased 2 mmHg (p < 0.001), LDL-C decreased 4 mg/dL (p = 0.009), and HDL-C increased 2 mg/dL (p < 0.001) at follow-up. Behavioral or lifestyle counseling was not significantly different from baseline to follow-up (71.2% vs. 68.1% (p = 0.077), but BMI was lower by 0.2 kg/m(2) at follow up (p = 0.013). At follow-up, more patients were prescribed metformin (13.7% vs. 9.7%, p < 0.001). A higher PreDx score was significantly associated with metformin prescription (p = 0.0003), lifestyle counseling (p = 0.0099), and a lower BMI at follow-up (p = 0.007). CONCLUSION: The use of a prognostic test in patients perceived to be high risk for diabetes was associated with a modest but significant increase in the prescription of metformin and lifestyle interventions and a reduction in BMI.

Progress in stem cell therapy for major human neurological disorders.

Human neurological disorders such as Alzheimer's disease (AD), Parkinson's disease, stroke or spinal cord injury are caused by the loss of neurons and glial cells in the brain or spinal cord in the Central Nervous System (CNS). Stem cell technology has become an attractive option to investigate and treat these diseases. Several types of neurons and glial cells have successfully been generated from stem cells, which in some cases, have ameliorated some dysfunctions both in animal models of neurological disorders and in patients at clinical level. Stem cell-based therapies can be beneficial by acting through several mechanisms such as cell replacement, modulation of inflammation and trophic actions. Here we review recent and current remarkable clinical studies involving stem cell-based therapy for AD and stroke and provide an overview of the different types of stem cells available nowadays, their main properties and how they are developing as a possible therapy for neurological disorders.

Distal radius attachments of the radiocarpal ligaments: an anatomical study.

Background Understanding the anatomy of the ligaments of the distal radius aids in the surgical repair of ligamentous injuries and the prediction of intraarticular fracture patterns. Purposes (1) to measure the horizontal and vertical distances of the origins of the radiocarpal ligaments from the most ulnar corner of the sigmoid notch and the joint line, respectively; and (2) to express them as a percentile of the total width of the bony distal radius. Methods We dissected 8 cadaveric specimens and identified the dorsal radiocarpal, radioscaphocapitate, and the long and short radiolunate ligaments. Results The dorsal radiocarpal ligament attached from the 16th to the 52nd percentile of the radial width. The radioscaphocapitate ligament attached around the radial styloid from the 86th percentile volarly to the 87th percentile dorsally. The long radiolunate ligament attached from the 59th to the 85th percentile, and the short radiolunate ligament attached from the 14th to the 41st percentile. Discussion There was a positive correlation between the radial width and the horizontal distance of the ligaments from the sigmoid notch. These findings may aid individualized surgical repair or reconstruction adjusted to patient size and enable further standardized research on distal radial fractures and their relationship with radiocarpal ligaments.

Pyrocarbon proximal interphalangeal joint arthroplasty: outcomes of a cohort study.

Pyrocarbon arthroplasty of the proximal interphalangeal joint is a relatively new concept. Early studies have been encouraging, reporting improved pain and function, but a largely unchanged arc of motion. Subsidence of the implant is common, but how it relates to outcome has not been analyzed. This study was performed to review the results of 57 pyrocarbon proximal interphalangeal implanted joints. Results showed a statistically significant increase in the arc of motion, excellent pain relief, and improved function. Subsidence was observed on radiographs in 40% of joints, but no correlation was found compared with arc of motion or function. The incidence of complications is fairly high and usually related to the peri-articular soft tissues, but they are usually minor and do not require further treatment. From this review, we can recommend the use of this implant for treatment of arthritis of the proximal interphalangeal joint.

Continuous CSF drainage in AD: results of a double-blind, randomized, placebo-controlled study.

BACKGROUND: Alzheimer disease (AD) has been associated with abnormal cerebral clearance of macromolecules, such as amyloid and microtubule-associated-protein tau (MAP-tau). We hypothesized that improving clearance of macromolecules from the CNS might slow the progression of dementia. OBJECTIVE: This prospective, randomized, double-blinded, placebo-controlled trial evaluated the safety and effectiveness of a surgically implanted shunt in subjects with probable AD. METHODS: A total of 215 subjects with probable AD by National Institute of Neurological Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria received either a low-flow ventriculoperitoneal shunt or a sham (occluded) shunt for 9 months. Longitudinal CSF sampling was performed in both active and control subjects. Primary outcome measures were the Mattis Dementia Rating Scale and the Global Deterioration Scale. CSF Abeta((1-42)) and MAP-tau also were assayed. RESULTS: After a planned interim analysis, the study was halted for futility. Using the intent-to-treat population, no between-group differences were observed in the primary outcome measures. The surgical procedure and device were associated with 12 CNS infections, some temporally associated with CSF sampling. All were treated successfully. CONCLUSIONS: We found no benefit to low-flow CSF shunting in subjects with mild to severe Alzheimer disease. CSF infections, while treatable, occurred more frequently than expected, in some cases likely related to CSF sampling.

Non-traditional risk factors predict coronary calcification in chronic kidney disease in a population-based cohort.

The increased burden of cardiovascular disease in chronic kidney disease cannot be explained by traditional risk factors alone. Here, we evaluated the impact of non-traditional factors on the association of chronic kidney disease with coronary artery calcification using logistic regression among 2672 Dallas Heart Study patients of whom 220 had chronic kidney disease. The prevalence of coronary calcification significantly increased across all chronic kidney disease stages and this remained independently associated with coronary calcification after adjusting for traditional factors. The calcium x phosphorus product, homocysteine, and osteoprotegerin each diminished the magnitude of association between kidney disease and coronary calcification. After adjustment for these, the association between kidney disease and coronary calcification was no longer significant with the effects most prominent in the stages 3-5 subgroup. Our study has identified three non-traditional independent predictors of coronary calcification that diminished the association between chronic kidney disease and coronary calcification. These factors may represent novel mechanistic links warranting further investigation.

Influences of Clinician Technique on Performance and Interpretation of the Lachman Test.

OBJECTIVE: To examine the influences of clinician technique on performance and interpretation of the Lachman test. DESIGN AND SETTING: Blinded, controlled, and randomized-block design clinical study conducted in an athletic training laboratory classroom. SUBJECTS: Twenty-two certified athletic trainer clinicians and 12 model patients. MEASUREMENTS: We used video analyses of 3-dimensional kinematics to identify variations in clinician technique. Each clinician's technique was classified according to the demonstrated grip configuration and test style. RESULTS: Clinician grip configuration was found to relate to performance and interpretation of the Lachman test. Clinicians demonstrating proximal "tibia-hand" placement were more likely to correctly perform and interpret the Lachman test than clinicians demonstrating distal tibia-hand placement. CONCLUSIONS: Clinicians should use the correct techniques when attempting to evaluate and interpret athletic injuries.

Topotecan in the treatment of acquired immunodeficiency syndrome-related progressive multifocal leukoencephalopathy.

Progressive multifocal leukoencephalopathy (PML) affects about 1 in 20 individuals with the acquired immunodeficiency syndrome (AIDS) and has been associated with poor survival. This report describes the results of a phase II clinical trial using the drug topotecan, a semisynthetic analogue of camptothecan, administered to a cohort of subjects with AIDS-related PML. Data were evaluated on 11 of 12 subjects enrolled in the study. Three responded to therapy. Additionally, one patient was treated off-protocol and showed a response to treatment. Progression occurred after the first course; however, a partial response was noted after five courses. One study patient died from accidental overdose of topotecan. Overall, responders had higher pretreatment Karnofsky and lower Kurtzke expanded disability status scale scores than nonresponders. The most frequent toxicities were hematologic (anemia, neutropenia, and thrombocytopenia). Five patients had dose delays; all delays were due to hematologic adverse events. This study demonstrates that topotecan treatment may be associated with decreased lesion size and prolonged survival from the infection. Because of the small number of subjects in the study, further studies are required to evaluate the efficacy of topotecan in treating this disease.

Assessment of low-flow CSF drainage as a treatment for AD: results of a randomized pilot study.

OBJECTIVE: This prospective, randomized, controlled study was designed to investigate the safety, feasibility, and preliminary efficacy of long-term CSF drainage via a low-flow ventriculoperitoneal shunt in subjects suffering from AD. METHODS: Twenty-nine subjects selected for probable AD (National Institute of Neurological and Communicative Diseases and Stroke-Alzheimer's Disease and Related Dementias Association criteria) were screened to exclude normal pressure hydrocephalus or other etiologies of dementia and randomized to treatment (shunt) or no treatment groups. The study endpoint was the comparison of group performance on psychometric testing at quarterly intervals for 1 year. Shunted subjects had CSF withdrawn for MAP-tau and Abeta((1-42)) assays at the same time intervals. RESULTS: There was no mortality from the surgical procedure, and no patient sustained a subdural hematoma. Five notable postoperative adverse events, which resolved without permanent neurologic deficit, were reported in the shunt group. Group mean Mattis Dementia Rating Scale total scores showed little change over the year in the shunt-treatment group, in contrast to a decline in the control group (p = 0.06). Mini-Mental State Examination mean scores supported a trend in favor of shunt treatment (p = 0.1). There was a concomitant decrease in ventricular CSF concentrations of AD biomarkers MAP-tau and Abeta((1-42)). CONCLUSIONS: The surgical procedure and the device are reasonably safe. Adverse events were consistent with shunt procedures for hydrocephalus in this older population. The endpoint data show a trend in favor of the treated group. A larger, randomized, double-blinded, controlled, clinical trial is underway.

A postmortem examination of poly-L lactic acid interference screws 4 months after implantation during anterior cruciate ligament reconstruction.

This is a report of a postmortem examination of an implanted bioabsorbable interference screw used for patellar tendon graft fixation during anterior cruciate ligament reconstruction. Examination was conducted 4 months after implantation. Examination included radiographic, arthroscopic, and magnetic resonance evaluations as well as histologic and mechanical pullout testing. Examination showed no evidence of tunnel widening, lytic bone changes, or inflammatory or foreign body reaction. Pullout and histologic testing indicated that appropriate bone plug incorporation was occurring. We believe the results of this case suggest that the use of bioabsorbable poly-L lactic acid interference screws is a safe and efficacious alternative to metallic screws during anterior cruciate ligament reconstruction.