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Arthritis, general [keywords]
- Distinct trajectories of multimorbidity in primary care were identified using latent class growth analysis. [JOURNAL ARTICLE]
- J Clin Epidemiol 2014 Jul 22.
To investigate the use of latent class growth analysis (LCGA) in understanding onset and changes in multimorbidity over time in older adults.This study used primary care consultations for 42 consensus-defined chronic morbidities over 3 years (2003-2005) by 24,615 people aged >50 years at 10 UK general practices, which contribute to the Consultations in Primary Care Archive database. Distinct groups of people who had similar progression of multimorbidity over time were identified using LCGA. These derived trajectories were tested in another primary care consultation data set with linked self-reported health status.Five clusters of people representing different trajectories were identified: those who had no recorded chronic problems (40%), those who developed a first chronic morbidity over 3 years (10%), a developing multimorbidity group (37%), a group with increasing number of chronic morbidities (12%), and a multi-chronic group with many chronic morbidities (1%). These trajectories were also identified using another consultation database and associated with self-reported physical and mental health.There are distinct trajectories in the development of multimorbidity in primary care populations, which are associated with poor health. Future research needs to incorporate such trajectories when assessing progression of disease and deterioration of health.
- Measuring Family HRQoL Spillover Effects Using Direct Health Utility Assessment. [JOURNAL ARTICLE]
- Med Decis Making 2014 Jul 23.
Applications of cost-effectiveness analysis do not typically incorporate effects on caregiver quality of life despite increasing evidence that these effects are measurable.Using a national sample of US adults, we conducted 2 cross-sectional surveys during December 2011 and January 2012. One version asked respondents to value their own experience as the family member of a person with a chronic illness (experienced sample), and the other version asked respondents to value hypothetical scenarios describing the experience of having a family member with a chronic illness (community sample). Conditions included Alzheimer's disease/dementia, arthritis, cancer, and depression. Using standard gamble questions, respondents were asked to value the spillover effects of a family member's illness. We used regression analysis to evaluate the disutility (loss in health-related quality of life) of having a family member with a chronic illness by condition and relationship type, controlling for the respondent's own conditions and sociodemographic characteristics.For the experienced sample (n = 1389), regression analyses suggested that greater spillover was associated with certain conditions (arthritis, depression) compared with other conditions (Alzheimer's disease, cancer). For the community sample (n = 1205), regression analyses indicated that lower spillover was associated with condition (cancer) but not the type of relationship with the ill family member (parent, child, spouse).The effects of illness extend beyond the individual patient to include effects on caregivers of patients, parents of ill children, spouses, and other close family and household members. Cost-effectiveness analyses should consider the inclusion of health-related quality of life spillover effects in addition to caregiving time costs incurred by family members of ill individuals.
- [Implantation of a Salto 2 total ankle prosthesis.] [JOURNAL ARTICLE]
- Oper Orthop Traumatol 2014 Jul 25.
Operative treatment of advanced primary and secondary arthritis of the ankle was carried out with the aim of achieving pain-free movement and retention of mobility.Surgery is indicated when conservative therapy is no longer sufficient for treatment of arthritis of the ankle with painful limited movement, sufficient bony joint conditions and correctable instability or axis malpositioning.Surgery is not recommended with general surgical or anesthesiological contraindications, rampant infections, severe disturbances of peripheral perfusion, bony defects in areas relevant for anchoring, unstable soft tissue conditions, talus necrosis >30 %, manifest osteoporosis and severe non-correctable instability or malpositioning.Tibial and talar bone resection was carried out via ventral access to the ankle through an incision and if present, soft tissue correction of instability after insertion of test components. Cement-free implantation of the original implants followed by subtle reconstruction of the extensor retinaculum and layer for layer closure of the wound.Additional measures were necessary on the periarticular soft tissues, the hindfoot and lower leg due to movement restrictions, instability and axis malpositioning which could be carried out in a one or two stage procedure depending on the extent and morphology.Between February 2009 and February 2010 a total of 115 patients (52 % with posttraumatic arthritis) received a cement-free implantation with a Salto 2 prosthesis. Additional corrective interventions were carried out in the presence of varus and valgus deformities. The degree of movement for dorsal extension and plantar flexion could be increased by an average of 8.3°. The interventions resulted in a significant reduction in pain from an average preoperative visual analogue pain scale (VAS) score of 7.8 (range 5-10) to an average postoperative score of 1.9 (range 0-6.1).
- Combined oral contraceptives: health benefits beyond contraception. [Journal Article]
- Panminerva Med 2014 Sep; 56(3):233-44.
It has been recognized for over 50 years that combined oral contraceptives (COCs) are also capable of offering health benefits beyond contraception through the treatment and prevention of several gynaecological and medical disorders. During the last years a constant attention was given to the adverse effects of COCs, whereas their non-contraceptive benefits were underestimated. To date, most women are still unaware of the therapeutic uses of hormonal contraceptives, while on the contrary there is an extensive and constantly increasing of these non-contraceptive health benefits. This review summarizes the conditions of special interest for physicians, including dysmenorrhoea, menorrhagia, hyperandrogenism (acne, hirsutism, polycystic ovary syndrome), functional ovarian cysts, endometriosis, premenstrual syndrome, myomas, pelvic inflammatory disease, bone mineral density, benign breast disease and endometrial/ovarian and colorectal cancer. The benefits of COCs in rheumatoid arthritis, multiple sclerosis, menstrual migraine and in perimenopause have also been treated for more comprehensive information. Using COCs specifically for non-contraceptive indications is still outside the product licence in the majority of cases. We strongly believe that these aspects are not of minor relevance and they deserve a special consideration by health providers and by the mass media, which have the main responsibility in the diffusion of scientific information. Thus, counseling and education are necessary to help women make well-informed health-care decisions and it is also crucial to increase awareness among general practitioners and gynaecologists.
- Pre-operative anesthetic assessment of patients with rheumatoid arthritis. [JOURNAL ARTICLE]
- Rev Bras Reumatol 2014 Jun; 54(3):213-219.
The management and surgical interventions of problems directly or indirectly arising from rheumatoid arthritis vary drastically. Anesthesiologists and rheumatologists should be aware of the peculiarities of the anesthetic preoperative assessment of these patients, including the assessment of possible disorders of the airways, in addition to the intra-operative management and analysis of relevant pharmacological parameters. It is critical that the anesthetist is familiar with the peculiarities of the disease and the specific characteristics of drugs used in its treatment: thus, he/she will be able to plan the best possible anesthetic technique for the surgery in question, offering safety and comfort to his/her patient. It is up to the rheumatologist to know the procedure to which the patient will be submitted to and be aware of the most appropriate anesthetic technique in each case. This will allow a better interaction between the rheumatologist and the anesthesiologist in the pre-anesthetic evaluation, through the sharing of relevant information on the articular and systemic involvement by the disease that might interfere with preoperative and intraoperative management. Furthermore, the information on the pre-anesthetic assessment and the choice of anesthetic technique will enable the rheumatologist to clarify any doubts that his/her patient and family may have, as well as to guide them as to whether or not the medications in use should be maintained, and eventually about the need for a supplemental dose of corticosteroid. The objective of this review is to acquaint the rheumatologist with key concepts related to the anesthetic preoperative assessment of patients diagnosed with RA, mainly including general notions that dictate the choice of the anesthetic technique.
- Denervation protects limbs from inflammatory arthritis via an impact on the microvasculature. [JOURNAL ARTICLE]
- Proc Natl Acad Sci U S A 2014 Jul 21.
Two-way communication between the mammalian nervous and immune systems is increasingly recognized and appreciated. An intriguing example of such crosstalk comes from clinical observations dating from the 1930s: Patients who suffer a stroke and then develop rheumatoid arthritis atypically present with arthritis on only one side, the one not afflicted with paralysis. Here we successfully modeled hemiplegia-induced protection from arthritis using the K/BxN serum-transfer system, focused on the effector phase of inflammatory arthritis. Experiments entailing pharmacological inhibitors, genetically deficient mouse strains, and global transcriptome analyses failed to associate the protective effect with a single nerve quality (i.e., with the sympathetic, parasympathetic, or sensory nerves). Instead, there was clear evidence that denervation had a long-term effect on the limb microvasculature: The rapid and joint-localized vascular leak that typically accompanies and promotes serum-transferred arthritis was compromised in denervated limbs. This defect was reflected in the transcriptome of endothelial cells, the expression of several genes impacting vascular leakage or transendothelial cell transmigration being altered in denervated limbs. These findings highlight a previously unappreciated pathway to dissect and eventually target in inflammatory arthritis.
- Differential regulatory role of Pituitary Adenylate-Cyclase Activating Polypeptide in the serum-transfer-induced arthritis model. [JOURNAL ARTICLE]
- Arthritis Rheumatol 2014 Jul 21.
Objective: Pituitary adenylate-cyclase activating polypeptide (PACAP) expressed in capsaicin-sensitive sensory neurons and immune cells has divergent functions in inflammatory and pain processes. This study analyses PACAP's involvement in a mouse model of rheumatoid arthritis. Methods: K/BxN arthritis was induced in PACAP gene-deficient (PACAP(-/-) ) and wildtype (PACAP(+/+) ) mice. General features of the disease were investigated by semiquantitative scoring, plethysmometry and histopathological analysis. Mechano and thermonociceptive thresholds and the motor functions were also evaluated. Metabolic activity was analysed with positrone emission tomography. Bone morphology was measured with in vivo micro-CT, myeloperoxidase activity and superoxide production with luminescent imaging of luminol and lucigenin, respectively, vascular permeability with fluorescent indocyanine green dye. Results: PACAP(+/+) mice developed remarkable joint swelling, decreased grasping ability, and mechanical (but not thermal) hyperalgesia. In PACAP(-/-) mice clinical score and edema were significantly reduced, mechanical hyperalgesia and motor impairment were absent throughout the two-week-experiment. Metabolic activity and superoxide production increased in the tibiotarsal joints of wildtype mice, but were significantly less in PACAP(-/-) animals. Myeloperoxidase activity in the ankle joints of PACAP(-/-) mice was significantly lower in the early, but greater in the late phase. Synovial hyperplasia was also significantly greater and progressive bone spur formation was only observed in PACAP-deficient mice. Conclusion: In case of PACAP deficiency joint swelling, vascular leakage, hyperalgesia and early inflammatory cell accumulation decreases, but immune cell functions and bone neoformation in the late phase increase. Unraveling the underlying pathways of PACAP opens promising new perspectives in the therapy inflammatory arthritis. © 2014 American College of Rheumatology.
- Genetic evidence for a normal-weight "metabolically obese" phenotype linking insulin resistance, hypertension, coronary artery disease and type 2 diabetes. [JOURNAL ARTICLE]
- Diabetes 2014 Jul 21.
The mechanisms that predispose to hypertension, coronary artery disease (CAD) and type 2 diabetes (T2D) in individuals of normal weight are poorly understood. In contrast, in monogenic primary lipodystrophy - a reduction in subcutaneous adipose tissue - it is clear that it is adipose dysfunction that causes severe insulin resistance (IR), hypertension, coronary artery disease and type 2 diabetes. We aimed to test the hypothesis that common alleles associated with insulin resistance also influence the wider clinical and biochemical profile of monogenic insulin resistance. We selected 19 common genetic variants associated with fasting insulin based measures of insulin resistance. We used hierarchical clustering and results from genome wide association studies of 8 non-disease outcomes of monogenic insulin resistance, to group these variants. We analysed genetic risk scores against disease outcomes including 12,171 T2D cases, 40,365 CAD cases and 69,828 individuals with blood pressure measurements. Hierarchical clustering identified 11 variants associated with a metabolic profile consistent with a common, subtle, form of lipodystrophy. A genetic risk score consisting of these 11 IR risk alleles was associated with higher triglycerides (ß=0.018; p=4x10(-29)), lower HDL cholesterol (ß=-0.020; p=7x10(-37)), greater hepatic steatosis (ß=0.021; p=3x10(-4)) higher alanine transaminase (ß=0.002; p=3x10(-5)), lower SHBG (ß=-0.010; p=9x10(-13)) and lower adiponectin (ß=-0.015; p=2x10(-26)). The same risk alleles were associated with lower BMI (per-allele ß=-0.008; p=7x10(-8)), and increased visceral-to-subcutaneous adipose tissue ratio (ß=-0.015; p=6x10(-7)). Individuals carrying >= 17 fasting insulin raising alleles (5.5% population) were slimmer (0.30 kgm(-2)) but at increased risk of T2D (odds ratio [OR] 1.46, per-allele p=5x10(-13)), CAD (OR 1.12, per-allele p=1x10(-5)), and increased blood pressure (systolic and diastolic blood pressure of 1.21 mmHg (per-allele p=2x10(-5)), and 0.67 mmHg (per-allele p=2x10(-4)), respectively, compared to individuals carrying <=9 risk alleles (5.5% population). Our results provide genetic evidence for a link between the three diseases of the "metabolic syndrome" and point to reduced subcutaneous adiposity as a central mechanism.
- Oral bisphosphonate use and total knee/hip implant survival: validation of results in an external population-based cohort. [JOURNAL ARTICLE]
- Arthritis Rheumatol 2014 Jul 21.
OBJECTIVE Aseptic loosening is the most common cause of revision arthroplasty. Bisphosphonates could minimise this through their anti-resorptive effects. We aimed to study the association between bisphosphonate use and implant survival. METHODS A retrospective cohort study was conducted within the Danish registries (5.5 million residents). We identified patients aged >=40 years undergoing total joint replacement in 1998-2007 using ICD10 codes. DMARD users, patients with rheumatoid arthritis, bone Paget, or hip fracture were excluded. Participants were classified as bisphosphonate users if they had been on treatment for ≥6 months. A time-varying exposure was used to avoid immortal-time bias. Up to six bisphosphonate non-users undergoing arthroplasty were matched to each user using propensity scores. Stratified Cox regression was used to model implant survival according to bisphosphonate use. Further, we studied the association between duration of use, adherence (medication possession ratio), timing of therapy initiation (pre/post-op) and implant survival. RESULTS 80,342/95,392 (84.2%) subjects were eligible. We identified 1,590 (2.0%) bisphosphonate users, and 1,558 (98.0%) of them were matched to 8,966 non-users. 27/1,558 (1.73%) bisphosphonate users and 399/8,966 (4.45%) matched non-users underwent revision surgery during study follow-up (median 2.61 years, inter-quartile range 1.04-5.41). Cox regression showed reduced revision risk in bisphosphonate users (HR 0.41 [95% Confidence Interval 0.27-0.61]). This association was strongest in patients with longest treatment duration and/or best adherence. CONCLUSION Oral bisphosphonate users are at 59% reduced risk of revision. This association is only present when bisphosphonates are started after arthroplasty surgery. Confirmation in randomized controlled trials is urgently needed. © 2014 American College of Rheumatology.
- Validity of psoriatic arthritis and capture of disease modifying antirheumatic drugs in the health improvement network. [JOURNAL ARTICLE]
- Pharmacoepidemiol Drug Saf 2014 Jul 5.
The aims of this study are to examine the validity of diagnostic codes for psoriatic arthritis in The Health Improvement Network (THIN) and to examine the agreement between General Practitioner (GP) report and prescription records for disease modifying antirheumatic drugs (DMARDs).Questionnaires were sent to the GPs of 100 randomly selected patients with at least one medical record code for psoriatic arthritis. The positive predictive value (PPV) for a GP confirmed diagnosis was calculated, and alternative algorithms were examined to determine which method resulted in the highest PPV.The PPV for a single code for psoriatic arthritis was 85% (95%CI: 75.8-91.7%). Adding a prescription for a DMARD increased the PPV to 91% but with a substantial loss in sensitivity. Agreement between GPs and prescription data for use of an oral DMARD was 69%.The diagnosis codes for psoriatic arthritis used in THIN are valid. All prescriptions for DMARDs may not be accounted for in THIN. Copyright © 2014 John Wiley & Sons, Ltd.