A Pilot Study to Detect Agitation in People Living with Dementia Using Multi-Modal Sensors.

People living with dementia (PLwD) often exhibit behavioral and psychological symptoms, such as episodes of agitation and aggression. Agitated behavior in PLwD causes distress and increases the risk of injury to both patients and caregivers. In this paper, we present the use of a multi-modal wearable device that captures motion and physiological indicators to detect agitation in PLwD. We identify features extracted from sensor signals that are the most relevant for agitation detection. We hypothesize that combining multi-modal sensor data will be more effective to identify agitation in PLwD in comparison to a single sensor. The results of this unique pilot study are based on 17 participants' data collected during 600 days from PLwD admitted to a Specialized Dementia Unit. Our findings show the importance of using multi-modal sensor data and highlight the most significant features for agitation detection.

Stroboscopic Qubit Measurement with Squeezed Illumination.

Microwave squeezing represents the ultimate sensitivity frontier for superconducting qubit measurement. However, measurement enhancement has remained elusive, in part because integration with standard dispersive readout pollutes the signal channel with antisqueezed noise. Here we induce a stroboscopic light-matter coupling with superior squeezing compatibility, and observe an increase in the final signal-to-noise ratio of 24%. Squeezing the orthogonal phase slows measurement-induced dephasing by a factor of 1.8. This scheme provides a means to the practical application of squeezing for qubit measurement.

Incoherent Qubit Control Using the Quantum Zeno Effect.

The quantum Zeno effect is the suppression of Hamiltonian evolution by repeated observation, which pins the system to an eigenstate of the measurement observable. Using measurement alone, control of the state can be achieved if the observable is slowly varied, so that the state tracks the now time-dependent eigenstate. We demonstrate this using a circuit-QED readout technique that couples to a dynamically controllable observable of a qubit. Continuous monitoring of the measurement record allows us to detect an escape from the eigenstate, thus serving as a built-in form of error detection. We show this by postselecting on realizations with high fidelity with respect to the target state. Our dynamical measurement operator technique offers a new tool for numerous forms of quantum feedback protocols, including adaptive measurements and rapid state purification.

An open randomized active-controlled clinical trial with low-dose SKA cytokines versus DMARDs evaluating low disease activity maintenance in patients with rheumatoid arthritis.

BACKGROUND: Biologic agents are currently the strongest immunosuppressive drugs able to induce remission in rheumatoid arthritis (RA). One of the objectives of the medical scientific community now is how to maintain remission or low disease activity (LDA). The aim of this trial is to evaluate the contribution of low-dose sequential kinetic activation (SKA) IL-4, IL-10, and anti-IL-1 antibodies (10 fg/mL) in patients affected by RA in maintaining LDA or remission obtained after biological therapy. METHOD: This is a randomized, open, active-controlled, prospective, Phase IV trial. Disease activity score (DAS28), clinical disease activity index, simplified disease activity index, erythrocyte sedimentation rate and C-reactive protein levels, global health assessment, and pain visual analog scale were evaluated at baseline visit and then every 3 months together with an assessment of side effects till 12 months. Thirty-nine RA patients were enrolled and randomized to continue disease-modifying antirheumatic drugs (DMARDs) therapy or to receive a combination of SKA low-dose cytokines formulated in concentration of 10 fg/mL orally administered at a dose of 20 drops/d for 12 consecutive months. RESULTS: The rate of maintenance of LDA at 12 months was superior in the group treated with low-dose cytokines compared with patients treated with DMARDs, 66.7% and 42.1%, respectively; however, the difference between the groups was not statistically significant. No side effects were reported in both groups. CONCLUSION: This is the first study using a combination of three low-dose cytokines in RA, after data published on psoriasis. These data suggest that the use of a combination of low-dose SKA cytokines may be an opportunity to explore in the management of RA.

Approach in glucocorticoid-induced osteoporosis prevention: results from the Italian multicenter observational EGEO study.

Glucocorticoid-induced osteoporosis (GIO) is the most frequent cause of secondary osteoporosis. GIO is linked to glucocorticoids (GC) daily assumption with maximum effect within first months of treatment and decreasing to basal levels as the therapy is discontinued. In Italy, primary prevention of GIO is suggested when GC therapy (prednisone >5 mg/day or equivalent) is taken for longer than 3 months. Lazio GISMO (Italian Group for Study and Diagnosis of Bone Metabolism Diseases) group organized the GC and Osteoporosis Epidemiology study (EGEO) to evaluate physician's approach in preventing GIO. The study involved 19 osteoporosis centers. Patients taking long-term GC therapy were recruited and information collected: medical history and anthropometric data, GC therapy, primary disease, physician's specialty, osteopororosis screening, and pharmacological intervention. The study included 1334 patients. Mean age was 63 ± 13 yr; 243 (18%) patients had a history of falls from standing position in the previous 12 months, 78 (35%) vertebral fractures, 91 (41%) fractures other than vertebral, 27 (12%) femoral fractures, and 27 (12%) multiple sites fractures. The molecules of GC more often prescribed were prednisone and 6-metil prednisolone. One thousand and forty patients (78%) were taking GC for more than 6 months. GC therapy was prescribed more frequently by rheumatologists (62%). Antiosteoporotic drugs for GIO prevention were prescribed in 431 patients (32%). Among the patients, only 27% (360) received calcium and vitamin D supplements, and 39% (319) treated by rheumatologists received anti-resorptive drugs. In conclusion, our data show that in Italy, as already described elsewhere, only a small subpopulation of GC-treated patients was supported by an anti-osteoporotic therapy, indicating the need to further stimulate awareness of both patients and specialists, prescribing GC therapy, to an appropriate and prompt GIO prevention.

A new chance to maintain remission induced by anti-TNF agents in rheumatoid arthritis patients: CYnAR study II of a 12-month follow-up.

The advent of biological therapies represented the beginning of a new era in the therapy of Rheumatoid Arthritis (RA), as demonstrated in several studies, but still many questions about their safety, especially in long term use, and correct administration time remain unanswered. Once remission is achieved, the orientation of clinicians regarding the maintenance of biological therapy or the switch to another immunosuppressive therapy is still uncertain. In our previous study 21 patients affected by RA who reached remission by the use of a combined therapy of anti-TNF drugs and methotrexate (MTX) underwent CyA-MTX combination therapy for maintaining remission state and were evaluated during a 6-month follow-up. The present study aims to investigate these data by a longer follow-up (12 months) and on a larger population. Fifty-three RA patients, with a disease duration of less than 3 years and DAS28<3.2 that reached a level of low disease activity within 6-8 months from the beginning of anti-TNF and methotrexate therapy, were enrolled in the study. By the suspension of anti-TNF therapy, patients underwent A-Cyclosporine (2-3 mg/kg/day) and methotrexate (15mg/week) therapy. DAS28, Pain VAS, Erythrosedimentation rate (ESR), C Reactive Protein (CRP) were all tested at time 0 and every 2 months after the interruption of the anti-TNF therapy and the beginning of A-Cyclosporine and methotrexate therapy, as well as liver and kidney profiles. Side effects were also recorded. Of 53 patients, 50 completed the study with a 12-month follow-up. Twenty-one (42%) patients maintained clinical parameters within low disease activity values at 12 months, while 29 (58%) patients showed an increase in DAS28 and other parameters: 16 (32%) patients at the 6-month control, 13 (26%) patients at the 12-month control. Our data show that 42% of the patients undergoing A-Cyclosporin and Methotrexate therapy maintained low disease activity parameters of rheumatoid arthritis, obtained after 6-8 months of anti-TNF therapy. Further studies on larger populations are necessary in order to confirm such results and identify predictor factors for different responses.

Can Cyclosporine-A associated to methotrexate maintain remission induced by anti-TNF agents in rheumatoid arthritis patients? (Cynar pilot study).

Biological therapies, such as etanercept, adalimumab and infliximab, have demonstrated good efficacy in inducing rheumatoid arthritis to low disease activity levels. Nevertheless, their cost, as well as the related risk of side effects, especially in long-term therapies, are still high. Furthermore, there is a good deal of evidence proving loss of efficacy of such therapies in the long term, often necessitating the shift from one specific anti-TNF biological treatment to another. There are also other open debates on the amount of time a patient should undergo an anti-TNF therapy, on the possibility of inducing a complete remission in early arthritis and, once remission or low disease activity is obtained, on the possibility of interrupting the anti-TNF-based therapy. In this study we investigated whether A-Cyclosporin and Methotrexate association may be effective in maintaining low disease activity obtained by anti-TNF therapies. Twenty-three rheumatoid arthritis-affected patients, whose diagnosis was made according to ACR criteria, with a disease duration of less than 3 years, and DAS28<3.2 that reached a level of low disease activity within 6-8 months from beginning anti-TNF and Methotrexate therapy, were enrolled in the study. After the suspension of anti-TNF therapy, patients were started on A-Cyclosporine (2-3 mg/kg/day) and Methotrexate (15mg/week) therapy. DAS28, Pain VAS, Erythrosedimentation Rate (ESR), and C Reactive Protein (CRP) were all tested at time 0 and at 6 months, as well as liver and kidney profiles, after the interruption of the anti-TNF therapy and the beginning of A-Cyclosporine and Methotrexate therapy. Side effects were also recorded. Of 23 patients undergoing the A-Cyclosporin and Methotrexate therapy for maintaining low disease activity in rheumatoid arthritis obtained by 6-8 months of anti-TNF therapy, 21 completed the study with a 6 month follow-up. Thirteen patients maintained clinical parameters within low disease activity values, while 8 patients showed an increase in DAS28 and other parameters. Only two patients showed an increase in blood pressure that was diagnosed after two months from the beginning of the A-Cyclosporin and Methotrexate therapy. The reduction in the dosage of A-Cyclosporin from 3mg/kg/day to 2mg/kg/day caused a slow normalization of blood pressure values. Our data seem to suggest that more than half of the patients undergoing A-Cyclosporin and Methotrexate therapy seemed to maintain low disease activity parameters of rheumatoid arthritis, obtained after 6-8 months of anti-TNF therapy. Further studies on larger populations are necessary in order to confirm such results and identify predictor factors for different responses.

A new technical contribution for ultrasound-guided injections of sacro-iliac joints.

INTRODUCTION: Sacroiliac joint (SIJ) represents a difficult location for local therapies, as intra-articular injections may be hard to execute, especially in particular conditions such as chronic inflammatory diseases. However, in selected patients, local therapies may be considered. Some recent studies demonstrated the feasibility of ultrasound (US)-guided injection of SIJ, but still a complete explanation and definition of the technique is needed. MATERIALS AND METHODS: Seven patients, four males and 3 females, affected by mono or bilateral sacroiliitis entered the study. Each patient received 40 mg of acetonide triamcinolone for each SIJ, intra articular (IA) US-guided injection. The technical originality proposed in this study consists in the spinal needle insertion in the middle of the cranial long side of the linear transducer with an orientation of about 10 degrees, determining shorter needle insertion for reaching joint space and consequently probably granting lesser pain and traumatism for patients. RESULTS: A total of 22 injections was performed. The longer follow-up time obtained was 18 months in 3 patients. All patients reached at least a 6 month follow-up. All patients reported an amelioration in pain that lasted for at least 6 months. No systemic adverse events were reported or observed. Complete visualization of SIJ and of needle placement was performed by US imaging, while compound proper injection was also visualized by Color-Doppler US imaging. DISCUSSION: Actually, sacroiliac joint intraarticular injections are often performed under fluoroscopy or Computerized Tomography guidance. Such techniques present several limitations, especially for repeated injections, such as the use of ionizing radiations, the need of a contrast agent and the direct and indirect costs connected. US guidance in IA SIJ injections may represent an easily repeatable imaging technique for needle placement and a precious tool for detecting inflammatory activity of the joint.

The safety of anti-TNF agents in the elderly.

Rheumatoid arthritis, ankylosing spondylitis and psoriatic arthritis are commonly thought of as inflammatory diseases that affect younger individuals. Although the initial presentation of these diseases is common in a patients twenties or thirties, they usually persist for the duration of the patients life. In addition, up to one-third of patients with RA have disease onset after 60 years of age. Anti-TNF-a therapies now have well-recognized safety profiles that have been demonstrated in the usual clinical trial populations for these diseases, but such populations under-represent patients > or =65 years of age. This retrospective study aims to determine the safety profiles for etanercept, infliximab and adalimumab in patients of 65 years or more, undergoing anti-TNF treatment for an active inflammatory disease such as rheumatoid arthritis, ankylosing spondylitis or psoriatic arthritis, or skin disease like psoriasis. Our data show that admitting elderly patients into anti-TNF therapeutic regimens is a safe option and that it grants these patients access to the best current therapeutic option, possibly leading to better disease outcome. Quality of life in elderly patients affected by arthritis or psoriasis, often reduced by comorbidities, is as important as quality of life in younger patients. Applying the recommended screening before using biological treatment helps to reduce adverse events related to the therapy, and the application of the same screening in elderly patients seems to lead to comparable results.

Mixed panniculitis responding to cyclosporin-A with a 12-month follow-up: a case report.

Panniculitides represent a heterogeneous group of inflammatory diseases involving subcutaneous fat. Subcutaneous fat is normally organized into adipose cells, adipocytes, and septa of connective tissue. The inflammation involving such tissues can be more represented in septa (septal panniculitis) or in lobules (lobular panniculitis) or be equally distributed in both (mixed panniculitis). A bioptical study is necessary in order to discern between different forms. Vascular involvement is also different in such diseases, as it can interest arteries, or veins, or both. Different grades of fat necrosis can also be observed, such as adipocytes without nuclei, lipophagic necrosis, liquefactive fat necrosis, microcystic fat necrosis, ischaemic fat necrosis. Panniculitis can be idiopathic or secondary to other diseases such as systemic sclerosis, rheumatoid arthritis, systemic erithematous lupus and many others. Therapies usually vary on the single patient but the general orientation leads to the use of immunosuppressive drugs such as thalidomide, corticosteroids, cyclosporin-A, hydroxychloroquine and cyclophosphamide. We report a case of a 19-year-old female affected by primary mixed panniculitis, associated with fever and deep asthenia, that resolved in a few weeks and was maintained with oral cyclosporin-A.

[Correlation between radiologic and ultrasonographic patterns and clinical manifestations in symptomatic hip osteoarthritis]. / Correlazione tra quadro clinico e patterns radiologici ed ecografici in pazienti affetti da artrosi sintomatica dell'anca.

Increasing amounts of data have recently been published regarding ultrasonographic (US) findings of osteoarthritic joints, but very few data concern hip joints. In the current study we described US patterns concerning 490 patients affected by symptomatic hip osteoarthritis (OA) who underwent to intra-articular injections of hyaluronic products under US guidance. All patients were studied by US and X-ray of hip, clinical evaluation was assessed by the followings indexes: Lequesne, pain VAS, ICED, Global Physician Assessment and Global Patient Assessment. US findings were summarized in four main patterns, effusion and synovial proliferation were also detected. The aim of this study was to correlate US findings with clinical assessment and radiographic findings (according to Kellgren-Lawrence classification). Pearson's r correlation coefficient were computed and come out significant and positive between X ray and US patterns and between clinical indexes and US patterns. Also the correlation between K-L score and US patterns showed a significant positive correlation indicating that higher K-L scores are associated with increasing abnormal US findings. Our data suggest that ultrasonography of the hip may give useful information about the state of synovial membrane, synovial fluid, joint margins and bone profile in hip OA. Further studies are needed to evaluate their prevalence in hip OA symptomatic and not-symptomatic patients and their correlation to treatment outcome.

[Intra-articular treatment with Hylan G-F 20 under ultrasound guidance in hip osteoarthritis. Clinical results after 12 months follow-up]. / Terapia intra-articolare con acido ialuronico (Hylan G-F 20) sotto guida ecografica nell'artrosi dell'anca. Risultati clinici a 12 mesi.

Hip is a site very commonly affected by osteoarthritis (OA), yet few data exist in literature regarding intra-articular use of hyaluronic acid in this pathology. We evaluated the efficacy of Hylan G-F 20 hip viscosupplementation performed under ultrasound guidance. We enrolled 26 patients affected by symptomatic hip OA and treated them with a single intraarticular injection of Hylan G-F 20, which could be repeated every two months. The injection was performed under ultrasound guidance with an antero-superior approach. Treatment efficacy was assessed through Lequesne index, visual analogue scale (VAS) pain quantification, and NSAID intake at the timepoint zero (baseline), and after 2, 6 and 12 months. We observed a statistically significant reduction of all considered parameters at the timepoints 2 and 6 months, when compared to baseline. At 12 months the changes were still statistically significant for all parameters for about 50% of the patients. No side effect was observed, nor systemic complication. Viscosupplementation is a promising approach for hip OA, although further and wider studies are wanted to determine how long the beneficial effect lasts, and what is the optimal number of injections to administer.

[Safety profile of 185 ultrasound-guided intra-articular injections for treatment of rheumatic diseases of the hip]. / Profilo di sicurezza di 185 iniezioni intra-articolari sotto guida ecografica nelle coxopatie.

OBJECTIVE: We have developed a standardized technique for intra-articular injection of the hip joint with the purpose of extending routine intra-articular injection of hyaluronans and steroids to the hip, as commonly used in the knee. The purpose of this study was to examine the safety of this technique in an extended series of patients. METHODS: A 7 MHz linear or 3.5 MHz convex transducer was used with a sterilized biopsy guide attached. Intra-articular (IA) injection was performed by inserting into the biopsy guide a 20 gauge needle with the anterosuperior approach. Then, using biopsy real-time guidance software, the needle was advanced into the anterior capsular recess, at the level of the femoral head. RESULTS: The standardised technique was used to inject 97 patients (114 hips) with 185 injections of either steroid/local anaesthetic (10) or hyaluronan (175) over a three-year period. The treatment was well tolerated with few, and exclusively local, side effects. No systemic side effects or joint infections were observed in our study. The colour Doppler vision allowed us to avoid injecting blood vessels. In all cases direct visualization of needle introduction and progression into the articular space was shown by on-screen guidance. Ultrasound guidance is more economic and faster in comparison to the TC or fluoroscopic guidance. Contrary to TC or fluoroscopic techniques ultrasound does not require use of radiations or iodized contrast. CONCLUSION: Our data suggest that the administration of hyaluronans or steroids with ultrasound-guided intra-articular injection is a safe technique for treatment of rheumatic diseases of the hip.

A new mathematical model based on clinical and laboratory variables for the diagnosis of Sjögren's syndrome.

Sjögren's syndrome (SS) is a systemic autoimmune disease that mainly affects exocrine glands. A diagnosis of SS in its early stages has a potential clinical relevance, but it is difficult and cannot be made solely on clinical grounds. Several sets of diagnostic criteria have been proposed, but none has met with a general consensus. Minor salivary gland has been judged to be the "gold standard" for the diagnosis of SS. However, it is a painful procedure and has a small but significant proportion of both false positive and false negative results. The aim of our study was to develop a simple mathematical score that uses clinical and laboratory variables for diagnosing SS, thereby reducing the need of minor salivary gland. The following variables were included in the model: ANA, SS-A/SS-B, Schirmer's Test/BUT, C3/C4, serum gammaglobulin levels. One hundred consecutive individuals reporting clinical syndromes consistent with a sicca syndrome were included in the study. The application of our multifactorial mathematical model has shown a high predictive value for SS vs controls or vs patients with other autoimmune disorders (Sensitivity 93%, Specificity 100%), with an estimated minor salivary gland reduction of 77%. We conclude that our mathematical model can be considered a useful non-invasive approach for diagnosing Sjogren's Syndrome and recommend its validation on a larger scale.

Extreme elevation of maternal serum alpha-fetoprotein associated with mosaic trisomy 8 in a liveborn.

Constitutional mosaic trisomy 8 has been associated with syndromic dysmorphology, corneal opacities, leukemias, and trophoblastic disease. However, abnormal maternal serum alpha-fetoprotein (MSAFP) has not been reported in association with mosaic trisomy 8. Our case first presented for evaluation of an extremely elevated MSAFP with mild elevation of MShCG in an otherwise normal pregnancy: MSAFP 13.89 MoM, MShCG 3.57 MoM, and MSuE3 1.04 MoM. Fetal dysmorphism was limited to bilateral pyelectasis and a prominent third ventricle. Spontaneous labor at 38 weeks resulted in the birth of a 3,570-gram AGA male with APGARs 7(1)/8(5). The neonate had facial asymmetry, 5th finger clinodactyly, 2-3 toe syndactyly, undescended testicle, abnormal prepuce, and mild pyelectasis. CT scan revealed hypoplasia of the corpus callosum, while echocardiography demonstrated bicuspid aortic valve, and the neonatal karyotype (blood) returned 46,XY/47,XY+8. Evaluation at 3 months revealed more prominent facial asymmetry, plagiocephaly, plantar creases, descent of the testis, and mild developmental delay. Review of the literature does not include any previously reported maternal serum alpha-fetoprotein aberrations in mosaic trisomy 8.

[Autonomic neuropathy in a diabetic population. Validity of cardiovascular tests and correlations with the complications]. / Neuropatia autonomica in una popolazione diabetica. Validità dei test cardiovascolari e correlazione con le complicanze.

The disfunction of the autonomic system nervous is a frequent finding in diabetes mellitus. Among objective tests proposed for its diagnosis, those assessing cardiovascular reflexes (cardiovascular tests: CVTs) explore the autonomic functionality by means of a group of standardized manoeuvres of relatively easy execution that study the baroreceptorial reflex arc. In our study, CVTs were performed in a population of 207 diabetic patients with no symptoms of autonomic neuropathy. A computerized automatic system (Cardionomic) was utilized. CTVs included: Deep Breathing, Lying to Standing, Valsalva Manoeuvre, Orthostatic Hypotension, Standing to Lying and Cough Test. Diabetic patients were broken down in groups according to: a) age, b) HbA1c levels, c) disease duration. We have then compared the presence of diabetic complications between the group of diabetics positive for cardiovascular disautonomia (CVD+) with another group of diabetics who were negative for cardiovascular disautonomia (DCV-). Our results show a remarkable correlation between autonomic neuropathy and patients age, HbA1c levels and disease duration. Also they show a strong positive correlation between CDV+ and the severity of arteriopathy. We conclude that autonomic neuropathy may play an important role in the pathogenesis of diabetic arteriopathy.