Early Detection of First Carpometacarpal Joint Osteoarthritis Using Magnetic Resonance Imaging Assessment in Women With High Hypermobility Scores.

OBJECTIVE: The aim of this study was to explore association between hypermobility and osteoarthritis (OA) at the first carpometacarpal (CMC) joint, using magnetic resonance imaging (MRI) to identify early change in women at high risk of developing OA but without yet established diagnoses. METHODS: For this observational study, 33 women (aged 30-50 years) with self-reported history of maternal hand OA but without personal diagnoses of OA were recruited. Participants completed a 5-point hypermobility questionnaire. The 20 participants with 2 or more positive responses were categorized with "high hypermobility scores." The remaining 13 were categorized with "low hypermobility scores." Data collection included functional index, hand pain measure, parity, smoking status, and body mass index. Each participant underwent dominant hand radiographic and MRI examination. Imaging studies were interpreted by assessors blinded to hypermobility score categorization. RESULTS: No significant differences in age, body mass index, parity, functional index, or pain scores were observed between higher and lower hypermobility score groups. Similarly, there were no significant differences between groups for radiographic changes. However, significantly higher proportions of women with higher hypermobility scores were observed on MRI to have abnormalities of trapezium cartilage (75% vs. 38%), metacarpal cartilage (80% vs. 38%), and trapezium bone (70% vs. 31%); p < 0.05 for all. CONCLUSIONS: First CMC joint structural abnormalities were more frequently observed in women with higher hypermobility scores. Identification of early preradiographic changes in this group supports the concept that early-life joint laxity may contribute to future OA predisposition. Magnetic resonance imaging may be a preferred imaging test for detection of early cartilage changes in people at high risk of CMC joint OA.

Higher mortality rates associated with rheumatoid arthritis in Saskatchewan, Canada, 2001-2019.

OBJECTIVES: To estimate provincial all-cause mortality rates of Saskatchewan people with rheumatoid arthritis (RA) for comparison with the general population over time and between different geographic regions. METHODS: Saskatchewan provincial administrative health databases (2001-2019) were utilized as data sources. Two RA case definitions were employed: (1) ≥ 3 physician billing diagnoses, at least 1 from a specialist (rheumatologist, general internist or orthopaedic surgeon) within 2 years; (2) ≥ 1 hospitalization diagnosis (ICD-9 code 714, and ICD-10-CA codes M05, M06). Data from these definitions were combined to create an administrative data RA cohort. All-cause mortality rates across geographic regions, between rural/urban residences and between sexes were examined. RESULTS: Over an 18-year span, between fiscal-year 2001-2002 and fiscal-year 2018-2019, age- and sex-adjusted mortality rates ranged from 17.10 to 21.04 (95% CI 14.77, 19.44; 18.03, 24.05)/1000 RA person-years, compared with mortality rates for the general Saskatchewan population without RA, which ranged from 9.37 to 10.88 (95% CI 9.23, 9.51; 10.72, 11.05)/1000 person-years. Fiscal-year mortality rate ratios ranged from 1.82 to 2.13 (95% CI 1.56, 2.13; 1.83, 2.46). Provincial mortality rates were higher in men than in women for both general and RA populations. Northern Saskatchewan mortality rates were significantly higher in the general population but did not achieve significance compared with other provincial regions for the RA population. Regression analysis identified age, male sex, RA and geographic region as factors contributing to increased mortality. A trend towards lower mortality rates over time was observed. CONCLUSION: Higher mortality rates were observed in the RA population overall. Men had higher mortality rates, as did residents of Northern Saskatchewan compared with residents of other regions for the general population.

RéSUMé: OBJECTIFS: Estimer les taux de mortalité provinciaux, toutes causes confondues, des habitants de la Saskatchewan atteints de polyarthrite rhumatoïde (PR) pour les comparer aux taux dans la population générale au fil du temps et entre différentes régions géographiques. MéTHODE: Nos données sont extraites des bases de données administratives sur la santé de la Saskatchewan (2001­2019). Deux définitions de cas ont été employées pour la PR : 1) ≥ 3 factures de diagnostic médical, dont au moins une d'un(e) spécialiste (rhumatologue, interniste général[e] ou chirurgien[ne] orthopédiste) en l'espace de deux ans; 2) ≥ 1 diagnostic d'hospitalisation (code CIM-9 714 et codes CIM-10-CA M05 et M06). Les données de ces définitions ont été combinées pour créer une cohorte de personnes atteintes de PR dans les données administratives. Les taux de mortalité toutes causes confondues entre les régions géographiques, entre les lieux de résidence urbains et ruraux et entre les sexes ont été examinés. RéSULTATS: En l'espace de 18 ans, entre les exercices 2001-2002 et 2018-2019, les taux de mortalité rajustés selon l'âge et le sexe ont varié entre 17,10 et 21,04 (IC de 95 % : 14,77-19,44; 18,03-24,05)/1000 personnes-années pour les personnes atteintes de PR, tandis que les taux de mortalité de la population générale de la Saskatchewan non atteinte de PR se sont situés entre 9,37 et 10,88 (IC de 95 % : 9,23-9,51; 10,72-11,05)/1000 personnes-années. Les rapports de taux de mortalité par exercice ont varié entre 1,82 et 2,13 (IC de 95 % : 1,56-2,13; 1,83-2,46). Les taux de mortalité provinciaux des hommes étaient supérieurs à ceux des femmes, tant dans la population générale que chez les personnes atteintes de PR. Les taux de mortalité dans le Nord de la Saskatchewan étaient sensiblement plus élevés que dans les autres régions de la province pour la population générale, mais pas sensiblement plus élevés pour la population atteinte de PR. Selon les analyses de régression, l'âge, le sexe masculin, la PR et la région géographique étaient des facteurs contribuant à une mortalité accrue. Une tendance à la baisse des taux de mortalité au fil du temps a été observée. CONCLUSION: Dans la population atteinte de PR, des taux de mortalité plus élevés ont été observés globalement. Dans la population générale, les taux de mortalité des hommes et ceux des résidents du Nord de la Saskatchewan étaient plus élevés que ceux des résidents des autres régions.

Geographic variation in incidence and prevalence rates for rheumatoid arthritis in Saskatchewan, Canada 2001-2014.

OBJECTIVES: To estimate and compare incidence/prevalence of rheumatoid arthritis (RA) in different geographic health regions and between urban/rural locations of residence within the province of Saskatchewan. METHODS: Saskatchewan Provincial Administrative Health Databases (2001-2014) were utilized as data sources. Two RA case-definitions were employed: (1) three physician billing diagnoses, at least one of which was submitted by a specialist (rheumatologist, general internist, or orthopedic surgeon) within 2 years; (2) one hospitalization diagnosis (ICD-9-CM code-714 and ICD-10-CA codes-M05, M06). Data from these definitions were combined to estimate annual RA incidence and prevalence. Annual incidence and prevalence rates across geographic regions and between rural and urban residences were examined. RESULTS: An increasing RA prevalence gradient was observed in a south to north direction within the province. In the 2014-2015 Fiscal Year, the southern region of Sun Country had a 0.57% RA prevalence and the Northern Health Regions a prevalence of 1.15%. Incidence rates fluctuated over time in all regions but tended to be higher in Northern Health Regions. A higher RA prevalence trend was observed in rural residents over the study period. CONCLUSIONS: Higher prevalence rates were observed for RA in Northern Health Regions than elsewhere in the province. Rural prevalence rates were higher than for urban residents. Healthcare delivery strategic planning will need to ensure appropriate access for RA patients throughout the province.

Assessment of heavy metals in Averrhoa bilimbi and A. carambola fruit samples at two developmental stages.

Though the fruits of Averrhoa bilimbi and A. carambola are economically and medicinally important, they remain underutilized. The present study reports heavy metal quantitation in the fruit samples of A. bilimbi and A. carambola (Oxalidaceae), collected at two stages of maturity. Heavy metals are known to interfere with the functioning of vital cellular components. Although toxic, some elements are considered essential for human health, in trace quantities. Heavy metals such as Cr, Mn, Co, Cu, Zn, As, Se, Pb, and Cd were analyzed by atomic absorption spectroscopy (AAS). The samples under investigation included, A. bilimbi unripe (BU) and ripe (BR), A. carambola sour unripe (CSU) and ripe (CSR), and A. carambola sweet unripe (CTU) and ripe (CTR). Heavy metal analysis showed that relatively higher level of heavy metals was present in BR samples compared to the rest of the samples. The highest amount of As and Se were recorded in BU samples while Mn content was highest in CSU samples and Co in CSR. Least amounts of Cr, Zn, Se, Cd, and Pb were noted in CTU while, Mn, Cu, and As were least in CTR. Thus, the sweet types of A. carambola (CTU, CTR) had comparatively lower heavy metal content. There appears to be no reason for concern since different fruit samples of Averrhoa studied presently showed the presence of various heavy metals in trace quantities.

A questionnaire assessment of physical function in hyperlipidemic patients.

BACKGROUND: A spectrum of myopathic manifestations has been recognized as associated with lipid lowering drug therapy (LLT), but their effect on quality of life and physical functioning is uncertain. We conducted a prospective cohort study in which physical functioning was the dependent variable, in patients with and without exposure to LLT. METHODS: Consecutive patients attending a risk reduction clinic were invited to participate in a questionnaire study which included demographic data, muscular symptoms, the SF-36 Physical Function Score (PF), and the modified Health Assessment Questionnaire (mHAQ). Laboratory and co-morbidity data was recorded. RESULTS: Of 117 consecutive patients invited to participate, 112 consented. Of these, 81 were receiving statins and/or fibrates as LLT and 31 were participating in a non-pharmacologic therapeutic program (NPT) of diet and exercise therapy. The mean age for the total population was 56.7 years (20-78): the LLT group 58.6 and NPT group 51.9 years. Women comprised 53% of the LLT group and 58% of the NPT. No significant differences in baseline lipid profiles, CK level, BMI, waist measurement, gender, cigarette smoking, alcohol consumption, non-steroidal anti-inflammatory drugs or acetaminophen use, frequency of myalgias, SF-36 PF or mHAQ scores were observed between groups. On comparison of gender groups, we observed that men receiving LLT had significantly better SF- 36 PF (p = 0.037) than men on NPT. There were no differences in SF-36 PF or mHAQ scores between groups for females. CONCLUSION: We found no adverse effects of LLT on physical functioning or quality of life. Indeed, men treated with LLT had significantly better SF-36 PF scores than men treated non-pharmacologically.

The clinical assessment of patients with psoriatic arthritis: results of a reliability study of the spondyloarthritis research consortium of Canada.

OBJECTIVES: To evaluate whether rheumatologists experienced in psoriatic arthritis (PsA) assess peripheral and axial involvement in the same way and to consider core clinical measurements that should be included in clinical trials in PsA. METHODS: Ten patients with PsA, representing a broad range of joint inflammation, joint damage, and spinal involvement, were selected for the study. Each patient was examined by each of 10 rheumatologists, members of the Spondyloarthritis Research Consortium of Canada, according to a Latin Square design. Assessments included scoring actively inflamed joints and damaged joints, dactylitis, enthesitis, and spinal measurements. Variance components analyses were conducted for continuous measurements based on models with observer, patient, and order effects. Estimates of intraclass correlation coefficients and associated 95% confidence intervals were obtained. RESULTS: There was substantial reliability in the assessment of the number of actively inflamed joints and excellent agreement in the number of damaged joints. Only moderate agreement was found for the number of digits with dactylitis. There was excellent agreement among observers in the intermalleolar distance measurements, but there was not as good agreement in the other measurements of spinal mobility. There was good agreement among the observers in detecting plantar fasciitis, however, the other entheses did not fare as well. CONCLUSION: In this first multicenter study of the assessment of clinical evaluation of patients with PsA we found that the assessment of peripheral joint disease is reliable although training should be performed prior to initiation of drug trials or comparative studies in this disease. The assessment of back measurements in PsA and other spondyloarthritis requires further study.

Final report on the safety assessment of stearoxy dimethicone, dimethicone, methicone, amino bispropyl dimethicone, aminopropyl dimethicone, amodimethicone, amodimethicone hydroxystearate, behenoxy dimethicone, C24-28 alkyl methicone, C30-45 alkyl methicone, C30-45 alkyl dimethicone, cetearyl methicone, cetyl dimethicone, dimethoxysilyl ethylenediaminopropyl dimethicone, hexyl methicone, hydroxypropyldimethicone, stearamidopropyl dimethicone, stearyl dimethicone, stearyl methicone, and vinyldimethicone.

Dimethicone is a fluid mixture of fully methylated linear siloxane polymers end-blocked with trimethylsiloxy units. Methicone is a linear monomethyl polysiloxane. The other dimethicones and methicones covered in this review are siloxane polymers of Dimethicone and Methicone. Most of these ingredients function as conditioning agents in cosmetic formulations at current concentrations of use of < or =15%. Clinical and animal absorption studies reported that Dimethicone was not absorbed following oral or dermal exposure. Dimethicone, Methicone, and Vinyldimethicone were not acutely toxic following oral exposure. No adverse reactions were found in rabbits following short-term dermal dosing with 6% to 79% Dimethicone, yet adverse effects were noted with a hand cream formulation containing 1% Dimethicone, suggesting something else in the preparation was toxic. Mice and rats were dosed for 90 days with up to 10% Dimethicone without adverse effect. Dimethicone did not produce adverse effects in acute and short-term inhalation-route studies, Methicone and Vinyldimethicone were negative in acute exposure studies using rats, but Hexyl Methicone was toxic to rats at 5 mg/L delivered in small particle (mean diameter of 0.29 micro) aerosols. Most dermal irritation studies using rabbits classified Dimethicone as a minimal irritant. Dimethicone (tested undiluted and at 79%) was not a sensitizer in four assays using mice and guinea pigs. It was not a sensitizer at 5.0% in a clinical repeated insult patch test using 83 panelists. Most ocular irritation studies using rabbits classified Dimethicone as a mild to minimal irritant. Dimethicone was tested in numerous oral-dose (using rats) and dermal-dose (using rats, rabbits, and monkeys) reproductive and developmental toxicity studies. In a few studies, treated males had significantly decreased body weight and/or decreased testes or seminal vesicles weights. No treatment-related adverse findings were noted in dosed pregnant females or fetuses. Dimethicone was negative in all genotoxicity assays. It was negative in both an oral (tested at 91%) and dermal (tested at an unknown concentration) dose carcinogenicity assay using mice. The Cosmetic Ingredient Review (CIR) Expert Panel considered it unlikely that any of these polymers would be significantly absorbed into the skin due to their large molecular weight. Although adverse effects were noted in one inhalation study with small aerosol particles, the expected particle sizes for cosmetic products would primarily be in the range of 60 to 80 micro, and less than 1% would be under 10 micro, which is an upper limit for respirable particles. Overall, the safety test data support the safety of these ingredients at the concentrations they are known to be used in cosmetic formulations. Accordingly, the CIR Expert Panel was of the opinion that Stearoxy Dimethicone, Dimethicone, Methicone, Amino Bispropyl Dimethicone, Aminopropyl Dimethicone, Amodimethicone, Amodimethicone Hydroxystearate, Behenoxy Dimethicone, C24-28 Alkyl Methicone, C30-45 Alkyl Methicone, C30-45 Alkyl Dimethicone, Cetearyl Methicone, Cetyl Dimethicone, Dimethoxysilyl Ethylenediaminopropyl Dimethicone, Hexyl Methicone, Hydroxypropyldimethicone, Stearamidopropyl Dimethicone, Stearyl Dimethicone, Stearyl Methicone, and Vinyldimethicone are safe as used in cosmetic formulations.

Final report on the safety assessment of sodium sulfite, potassium sulfite, ammonium sulfite, sodium bisulfite, ammonium bisulfite, sodium metabisulfite and potassium metabisulfite.

Sodium Sulfite, Ammonium Sulfite, Sodium Bisulfite, Potassium Bisulfite, Ammonium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite are inorganic salts that function as reducing agents in cosmetic formulations. All except Sodium Metabisulfite also function as hair-waving/straightening agents. In addition, Sodium Sulfite, Potassium Sulfite, Sodium Bisulfite, and Sodium Metabisulfite function as antioxidants. Although Ammonium Sulfite is not in current use, the others are widely used in hair care products. Sulfites that enter mammals via ingestion, inhalation, or injection are metabolized by sulfite oxidase to sulfate. In oral-dose animal toxicity studies, hyperplastic changes in the gastric mucosa were the most common findings at high doses. Ammonium Sulfite aerosol had an acute LC(50) of >400 mg/m(3) in guinea pigs. A single exposure to low concentrations of a Sodium Sulfite fine aerosol produced dose-related changes in the lung capacity parameters of guinea pigs. A 3-day exposure of rats to a Sodium Sulfite fine aerosol produced mild pulmonary edema and irritation of the tracheal epithelium. Severe epithelial changes were observed in dogs exposed for 290 days to 1 mg/m(3) of a Sodium Metabisulfite fine aerosol. These fine aerosols contained fine respirable particle sizes that are not found in cosmetic aerosols or pump sprays. None of the cosmetic product types, however, in which these ingredients are used are aerosolized. Sodium Bisulfite (tested at 38%) and Sodium Metabisulfite (undiluted) were not irritants to rabbits following occlusive exposures. Sodium Metabisulfite (tested at 50%) was irritating to guinea pigs following repeated exposure. In rats, Sodium Sulfite heptahydrate at large doses (up to 3.3 g/kg) produced fetal toxicity but not teratogenicity. Sodium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite were not teratogenic for mice, rats, hamsters, or rabbits at doses up to 160 mg/kg. Generally, Sodium Sulfite, Sodium Metabisulfite, and Potassium Metabisulfite were negative in mutagenicity studies. Sodium Bisulfite produced both positive and negative results. Clinical oral and ocular-exposure studies reported no adverse effects. Sodium Sulfite was not irritating or sensitizing in clinical tests. These ingredients, however, may produce positive reactions in dermatologic patients under patch test. In evaluating the positive genotoxicity data found with Sodium Bisulfite, the equilibrium chemistry of sulfurous acid, sulfur dioxide, bisulfite, sulfite, and metabisulfite was considered. This information, however, suggests that some bisulfite may have been present in genotoxicity tests involving the other ingredients and vice versa. On that basis, the genotoxicity data did not give a clear, consistent picture. In cosmetics, however, the bisulfite form is used at very low concentrations (0.03% to 0.7%) in most products except wave sets. In wave sets, the pH ranges from 8 to 9 where the sulfite form would predominate. Skin penetration would be low due to the highly charged nature of these particles and any sulfite that did penetrate would be converted to sulfate by the enzyme sulfate oxidase. As used in cosmetics, therefore, these ingredients would not present a genotoxicity risk. The Cosmetic Ingredient Review Expert Panel concluded that Sodium Sulfite, Potassium Sulfite, Ammonium Sulfite, Sodium Bisulfite, Ammonium Bisulfite, Sodium Metabisulfite, and Potassium Metabisulfite are safe as used in cosmetic formulations.

Final report on the safety assessment of aluminum starch octenylsuccinate.

Aluminum Starch Octenylsuccinate is the aluminum salt of the reaction product of octenylsuccinic anhydride with starch. It is used in cosmetics at concentrations as high as 30% as an anticaking agent and a nonaqueous viscosity increasing agent. No information was available on the presence of impurities in the cosmetic-grade ingredient. When used in foods, Aluminum Starch Octenylsuccinate is identified as a modified food starch, and is subject to limitations on heavy metal residues. Oral studies using Aluminum Starch Octenylsuccinate or its related sodium salt produced no adverse systemic, reproductive, or developmental effects. Dermal injections produced no abnormal skin or systemic reactions in guinea pigs. Ocular toxicity was assessed in rabbits and using an in vitro test (chorioallantoic membrane vascular assay). In both cases no toxicity was seen. An acute inhalation toxicity study in rats was negative. Clinical tests indicated little irritation potential and no sensitization. Absent data on impurities in cosmetic-grade material, it was determined that such material should meet the same impurities requirements established for modified food starches. Based on these available data the Cosmetic Ingredient Review Expert Panel concluded that Aluminum Starch Octenylsuccinate is safe as used in cosmetic formulations provided that established limitations imposed on heavy metal concentrations are not exceeded.

Final report on the safety assessment of human placental protein, hydrolyzed human placental protein, human placental enzymes, human placental lipids, human umbilical extract, placental protein, hydrolyzed placental protein, placental enzymes, placental lipids, and umbilical extract.

Various proteins, lipids, or other extracts from human or other animal placentas are described as cosmetic ingredients. Human Placental Protein comprises protein derived from human placentas. Placental Protein is derived from animal placentas. Similarly, Human Placental Lipids and Placental Lipids are the lipid fractions from the same source materials. Hydrolyzed Human Placental Protein and Hydrolyzed Placental Protein are produced from the respective protein extracts by acid, enzyme, or other hydrolysis methods. Human Placental Enzymes and Placental Enzymes are enzymes obtained by aqueous extraction of human or other animal placental material. Human Umbilical Extract and Umbilical Extract are unspecified extracts of material from human or other animal umbilical cords. Different materials called Human Placental Extracts and Placental Extracts, assumed to contain estrogenic hormones or other biologically active substances, are not recognized as cosmetic ingredients, even though the use of these ingredients in cosmetics have been reported to the Food and Drug Administration (FDA). Human-derived ingredients are prohibited from use under the provisions of the European Union cosmetics directive based on concerns about transmission of human spongiform encephalopathies and viral diseases, for example, human immunodeficiency virus (HIV). Umbilical Extract has precedent for unrestricted use in Japan, except for certain products. Most of these ingredients are described as hair-conditioning agents and miscellaneous skin-conditioning agents, although the umbilical extracts function as biological additives in cosmetics. Of the human-derived ingredients, only Human Placental Protein is currently reported to be used. Animal-derived placental proteins, hydrolyzed proteins, lipids, and enzymes were all currently reported to be used. No current uses of the umbilical extracts were reported. Most of the available data relates to placental derivatives that appear to have estrogenic or other biological activity. The one clinical study that appears to utilize proteinaceous material only reported no irritant reaction. Clearly, the available data are insufficient to support safety of these ingredients in cosmetics. The additional data needed include (1) skin sensitization at concentration of use; (2) gross pathology and histopathology in skin and other major organ systems associated with repeated exposures, and dermal reproductive and developmental toxicity data; (3) photosensitization; (4) one genotoxicity assay in a mammalian system; if positive, then a 2-year dermal carcinogenicity study using National Toxicology Program (NTP) methods may be needed; (5) ocular toxicity, if available. Any studies should be done on all ingredients unless chemical analysis data show similarity among ingredients. Because there is confusion and concern about the use of substances with estrogenic or other biological activity in cosmetic formulations, it was concluded that none of these ingredients used in cosmetics should deliver any metabolic/endocrine activity. In addition, any current use of these ingredients should be free of detectable pathogenic viruses or infectious agents.