The Italian Society of Rheumatology clinical practice guidelines for the management of large vessel vasculitis.

OBJECTIVE: Since of the last publication of last recommendations on primary large-vessel vasculitis (LVV) endorsed by the Italian Society of Rheumatology (SIR) in 2012, new evidence emerged regarding the diagnosis and the treatment with conventional and biologic immunosuppressive drugs. The associated potential change of clinical care supported the need to update the original recommendations. METHODS: Using the grading of recommendations assessment, development and evaluation (GRADE)-ADOLOPMENT framework, a systematic literature review was performed to update the evidence supporting the European Alliance of Associations for Rheumatology (EULAR) guidelines on LVV as reference. A multidisciplinary panel of 12 expert clinicians, a trained nurse, and a patients' representative discussed the recommendation in cooperation with an Evidence Review Team. Sixty-one stakeholders were consulted to externally review and rate the recommendations. RESULTS: Twelve recommendations were formulated. A suspected diagnosis of LVV should be confirmed by imaging or histology. In active GCA or TAK, the prompt commencement of high dose of oral glucocorticoids (40-60 mg prednisone-equivalent per day) is strongly recommended to induce clinical remission. In selected patients with GCA (e.g., refractory or relapsing disease or patients at risk of glucocorticoid related adverse effects) the use of an adjunctive therapy (tocilizumab or methotrexate) is recommended. In all patients diagnosed with TAK, adjunctive therapies, such as conventional synthetic or biological immunosuppressants, should be given in combination with glucocorticoids. CONCLUSIONS: The new set of SIR recommendations was formulated in order to provide a guidance on both diagnosis and treatment of patients suspected of or with a definite diagnosis of LVV.

Persistence of bDMARD therapy in Rheumatoid Arthritis after first-line TNF-inhibitor failure: the RECORD study of the Italian Society for Rheumatology.

OBJECTIVE: The optimal choice of a second biological disease-modifying anti-rheumatic drug (bDMARD) after failure with first line tumour necrosis factor inhibitor (TNFi) represents a critical therapeutic challenge. This study aims to evaluate the persistence with treatment using second line bDMARDs with different mechanisms of action in rheumatoid arthritis (RA) patients with inadequate response to first line TNFi. METHOD: A retrospective cohort study on administrative healthcare databases was conducted. We analysed the relationship between different bDMARDs and persistence with treatment in RA patients who started second line bDMARD therapy according to two different strategies: cycling (second TNFi) or switching [change in mechanism of action: abatacept (ABA), tocilizumab (TCZ), and rituximab (RTX)] with or without concomitant conventional synthetic (cs) DMARDs. RESULTS: The cohort comprised 1434 patients. The mean age was 53.8 years and 1142 (79.6%) were women. Among second line bDMARDs, 969 patients (67.6%) started TNFi, 204 (14.2%) ABA, 145 (10.1%) RTX, and 116 (8.1%) TCZ. A bDMARD was prescribed as monotherapy in 359 patients (25.0%). The switching strategy showed a lower overall discontinuation rate [hazard ratio (HR) 0.72], while switching compared to cycling showed significantly better survival for ABA (HR 0.61) and RTX (HR 0.76), but no significant difference for TCZ (HR 0.82). A lower impact of better drug survival in the switching strategy occurred in patients with concurrent methotrexate. CONCLUSIONS: Among RA patients failing a first TNFi, switching is associated with marginally better persistence, in particular for ABA and RTX, with only marginal differences in patients on concurrent csDMARDs.

The Italian Society for Rheumatology clinical practice guidelines for the diagnosis and management of fibromyalgia Best practices based on current scientific evidence.

Fibromyalgia or fibromyalgia syndrome (FMS) is defined as a central sensitization syndrome characterized by the dysfunction of neurocircuits detecting, transmitting and processing nociceptive stimuli; the prevalent manifestation is musculoskeletal pain. In addition to pain, there are multiple accompanying symptoms, in common with other algo-dysfunctional syndromes, which are reflected in a broad spectrum of somatic, neurocognitive and neuro-vegetative manifestations. An evidence-based approach is essential in FMS management, in order to improve patient health and to reduce its social burden. Since in the last ten years new international guidelines for clinical practice (Clinical Practice Guidelines or CPGs) concerning FMS diagnosis and pharmacological/ non-pharmacological management have been published, the Italian Society of Rheumatology (SIR) has decided to adapt them to the Italian national setting. The framework of the Guidelines International Network Adaptation Working Group was adopted to identify, appraise (AGREE II), synthesize, and customize the most recent CPGs on FMS to the needs of the Italian healthcare context. A working group of rheumatologists from SIR epidemiology unit and FMS experts identified relevant clinical questions to guide the systematic review of the literature. The target audience of these CPGs included physicians and healthcare professionals who manage FMS. The adapted recommendations were finally assessed by an external multidisciplinary panel. From the systematic search in databases (Pubmed/Medline, Embase) and grey literature, 6 CPGs were selected and appraised by two independent raters. The combination of the scientific evidence underlying the original CPGs with expert opinion lead to the development of 17 recommendations. The quality of evidence for each recommendation was reported and their potential impact on clinical practice was assessed. These SIR recommendations are expected to be a valuable aid in the diagnosis and treatment of FMS, as they will contribute to disseminate the best practice on the basis of the current scientific evidence.

Role of comorbidities on therapeutic persistence of biological agents in rheumatoid arthritis: results from the RECord-linkage On Rheumatic Disease study on administrative healthcare databases.

Objectives: This study aimed to evaluate the impact of different comorbidities on thereflecting its safety profile persistence of biological disease-modifying anti-rheumatic drugs (bDMARDs) in rheumatoid arthritis (RA), taking advantage of a retrospective analysis of administrative healthcare databases (AHDs).Method: A retrospective observational study was conducted on AHDs of the Lombardy region, Italy (2004-2013). Among RA patients treated with bDMARDs, drug survival was estimated using Cox proportional hazard models [hazard ratio (HR), 95% confidence interval (CI)], crude and adjusted for prespecified confounders (gender, age, disease duration, concomitant use of non-steroidal anti-inflammatory drugs, glucocorticoids, conventional DMARDs, specific bDMARDs), in first-line and subsequent lines of treatment. The role of comorbidities in administration of specific bDMARDs was analysed through multinomial logistic models.Results: The study included 4657 RA patients. In the first-line treatment strategy, the Charlson Comorbidity Index (CCI) (RA excluded) was significantly associated with an increased rate of bDMARD failure (CCI = 1: HR 1.28, 95% CI 1.13-1.46; CCI ≥ 2: HR 1.26, 95% CI 1.03-1.53). Among selected comorbidities, chronic obstructive pulmonary disease (HR 1.38, 95% CI 1.01-1.91), diabetes (HR 1.18, 95% CI 1.01-1.37), and previous-year bacterial infections (HR 1.18, 95% CI 1.07-1.30) were slightly associated with risk of bDMARD failure, while acute myocardial infarction (HR 1.30, 95% CI 0.97-1.75), mild liver disease (HR 1.21, 95% CI 0.91-1.60), and solid tumours (HR 1.19, 95% CI 0.93-1.53) were not. In the following treatment lines, neoplasms were associated with reduced risk of failure (HR 0.64, 95% CI 0.41-0.99). Multiple comorbidities were associated with first-line abatacept and rituximab administration.Conclusions: Comorbidities affect treatment decisions in RA and influence bDMARD failure, and should be considered when analysing the persistence of biological therapy.

A seasonal pattern in the onset of polymyalgia rheumatica and giant cell arteritis? A systematic review and meta-analysis.

OBJECTIVES: Studies on the seasonality of onset of polymyalgia rheumatica (PMR) and giant cell arteritis (GCA) have shown conflicting results. The aim of this systematic literature review and meta-analysis is to determine from aggregated data whether there is a seasonal distribution for these diseases. METHODS: A literature search was performed using Pubmed Central and Embase scientific databases. The incidences per 6-month periods, season or month of onset, that were reported in the studies were summarised in tables considering the two diseases as separate conditions or together. The Incidence Rate Ratio (IRR) for the cold period versus the warm period was pooled across studies by random effects meta-analysis weighed by inverse variance. Funnel plots and Egger test were used to explore possible publication biases. A sensitivity analysis was performed to weigh articles with a disproportionate number of patients compared to the rest. RESULTS: In the scientific literature 22 suitable papers were found: 6 on PMR with 803 patients, 11 on GCA with 2,807 patients, and 5 studies considering both diseases with 19,613 patients. There was considerable heterogeneity amongst studies regarding their quality, the classification criteria used, and the definition of onset of symptoms. No seasonal aggregation was found for GCA and PMR. The pooled IRR estimate of the meta-analysis (1.13[0.89,1.36]) showed a non-significant, higher frequency of diseases onset in the warm season. CONCLUSIONS: Our meta-analysis did not confirm a seasonal onset for PMR and GCA.

Providing updated guidelines for the management of rheumatic diseases in Italy with the ADAPTE methodology: a project by the Italian Society for Rheumatology.

Not available.

The Italian Society for Rheumatology clinical practice guidelines for rheumatoid arthritis.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disorder characterised by chronic joint inflammation, leading to functional disability and increased risk of premature death. Clinical practice guidelines (CPGs) are expected to play a key role in improving management of RA, across the different phases of the disease course. Since new evidence has become available, the Italian Society for Rheumatology (SIR) has been prompted to update the 2011 recommendations on management of RA. The framework of the Guidelines International Network Adaptation Working Group was adopted to identify, appraise (AGREE II), synthesize, and customize the existing RA CPGs to the Italian healthcare context. The task force consisting of rheumatologists from the SIR Epidemiology Research Unit and a committee with experience in RA identified key health questions to guide a systematic literature review. The target audience includes physicians and health professionals who manage RA in practice, and the target population includes adult patients diagnosed as having RA. An external multi-disciplinary committee rated the final version of the CPGs. From the systematic search in databases (Medline, Embase) and grey literature, 6 CPGs were selected and appraised by two independent raters. Combining evidence and statements from these CPGs and clinical expertise, 8 (Management) +6 (Safety) recommendations were developed and graded according to the level of evidence. The statements and potential impact on clinical practice were discussed and assessed. These revised recommendations are intended to provide guidance for the management of RA and to disseminate the best evidence-based clinical practices for this disease.

Early Lupus Project: one-year follow-up of an Italian cohort of patients with systemic lupus erythematosus of recent onset.

Objective To describe the clinical and serological features of a prospectively followed cohort of early diagnosed systemic lupus erythematosus (SLE) patients during a one-year follow-up period. Methods SLE patients with disease duration less than 12 months were consecutively enrolled in a multicentre, prospective study. At study entry and then every 6 months, a large panel of data was recorded. Results Of 260 patients enrolled, 185 had at least 12 months of follow-up; of these, 84.3% were female, 92.4% were Caucasians. Mean diagnostic delay was about 20 months; higher values of European Consensus Lupus Activity Measurement (ECLAM) and of organs/systems involved were both associated with shorter diagnostic delay. Clinical and serological parameters improved after study entry. However, patients' quality of life deteriorated and cardiovascular risk factors significantly increased. About one-third of patients with active disease at study entry went into remission (ECLAM = 0). Negative predictors for remission were: oral ulcers, arthritis, low C4, anti-SSB (Ro) antibodies and therapy with mycophenolate. There was a widespread use of glucocorticoids both at baseline and during follow-up. Conclusion Clinical symptoms and serological parameters improve during the first period after diagnosis. However, patients' quality of life deteriorates. The widespread use of glucocorticoids is probably the reason for the early significant increase of some cardiovascular risk factors.

Effect of sarcopenia and visceral obesity on mortality and pancreatic fistula following pancreatic cancer surgery.

BACKGROUND: Analytical morphometric assessment has recently been proposed to improve preoperative risk stratification. However, the relationship between body composition and outcomes following pancreaticoduodenectomy is still unclear. The aim of this study was to assess the impact of body composition on outcomes in patients undergoing pancreaticoduodenectomy for cancer. METHODS: Body composition parameters including total abdominal muscle area (TAMA) and visceral fat area (VFA) were assessed by preoperative staging CT in patients undergoing pancreaticoduodenectomy for cancer. Perioperative variables and postoperative outcomes (mortality or postoperative pancreatic fistula) were collected prospectively in the institutional pancreatic surgery database. Optimal stratification was used to determine the best cut-off values for anthropometric measures. Multivariable analysis was performed to identify independent predictors of 60-day mortality and pancreatic fistula. RESULTS: Of 202 included patients, 132 (65·3 per cent) were classified as sarcopenic. There were 12 postoperative deaths (5·9 per cent), major complications developed in 40 patients (19·8 per cent) and pancreatic fistula in 48 (23·8 per cent). In multivariable analysis, a VFA/TAMA ratio exceeding 3·2 and American Society of Anesthesiologists grade III were the strongest predictors of mortality (odds ratio (OR) 6·76 and 6·10 respectively; both P < 0·001). Among patients who developed major complications, survivors had a significantly lower VFA/TAMA ratio than non-survivors (P = 0·017). VFA was an independent predictor of pancreatic fistula (optimal cut-off 167 cm(2) : OR 4·05; P < 0·001). CONCLUSION: Sarcopenia is common among patients undergoing pancreaticoduodenectomy. The combination of visceral obesity and sarcopenia was the best predictor of postoperative death, whereas VFA was an independent predictor of pancreatic fistula.

Lifestyle and dietary habits of patients with gout followed in rheumatology settings.

Diet and lifestyles modification are core aspects of the non-pharmacological management of gout, but a poor consistency with suggested guidelines is reported. This study aimed to investigate dietary and lifestyle habits of patients with gout followed in rheumatology settings. Data were retrieved from the baseline dataset of the KING study, a multicentre cohort study of patients with gout followed in rheumatology settings. Dietary habits were assessed with the Italian National Institute of Statistics (ISTAT) food-frequency questionnaire and compared with reported data about general population. The relative increase of exposure was estimated by standardized prevalence ratios adjusted for gender, age and geographical distribution. The study population included 446 patients, with a mean age of 63.9 years and a M/F ratio of 9:1. Compared to the Italian population, gouty patients showed a higher prevalence of obesity [1.82 (1.52-2.18)] and a higher consumption of wine [1.85 (1.48-2.32)] and beer [2.21 (1.68-2.90)], but a lower prevalence of smoking and a lower intake of liquor. They showed a lower intake of red meat [0.80 (0.71-0.91)], but a similar intake of other tested dietary factors. Gouty patients' lifestyle is still partially different from the recommended.

A distinct MR imaging phenotype in amyotrophic lateral sclerosis: correlation between T1 magnetization transfer contrast hyperintensity along the corticospinal tract and diffusion tensor imaging analysis.

BACKGROUND AND PURPOSE: In the search for a diagnostic marker in ALS, we focused our attention on the hyperintense signal intensity in T1 MTC MR images along the CST, detected in some patients and not found in other patients with ALS and in control subjects. The aim of this study was to investigate the relationship between the hyperintense signal intensity in T1 MTC images and white matter damage. To this purpose, we studied potential heterogeneities in DTI values within our patients by using TBSS without a priori anatomic information. MATERIALS AND METHODS: In 43 patients with ALS and 43 healthy control subjects, the presence or absence of T1 MTC hyperintense signal intensity was evaluated. With a DTI analysis with a TBSS approach, differences in FA distribution between the 2 groups (patients with T1 MTC hyperintense signal intensity and patients without it) compared with each other and with control subjects were investigated. RESULTS: We found regional differences in white matter FA between patients with T1 MTC hyperintense signal intensity (37.2%) and patients without it. Patients with T1 MTC abnormal signal intensity showed lower FA strictly limited to the motor network and the posterior aspect of the body of the CC without extramotor FA reductions, whereas patients without this sign showed FA reductions in several confluent regions within and outside the CST and in the whole CC. CONCLUSIONS: T1 MTC hyperintense signal intensity in the CST and posterior CC, when present, is specific for ALS and represents, among patients with ALS, a possible distinct phenotype of presentation of the disease with prominent UMN involvement.

The presence of ochratoxin A in cord serum and in human milk and its correspondence with maternal dietary habits.

BACKGROUND: Ochratoxin A (OTA) is a mycotoxin present in food that can be found in human blood and milk. PURPOSE: The link between the nutritional habits of pregnant women both of Italian and foreign nationality resident in Italy and the presence of ochratoxin A in cord blood and in maternal milk was investigated. METHODS: The study involved 130 pregnant women. Food consumption during pregnancy was evaluated by means of the EPIC questionnaire; OTA content was determined in cord serum and maternal milk by HPLC. RESULTS: The mean daily dietary intake of OTA was 1.02 ± 1.20 and 0.87 ± 0.78 ng/kg of bodyweight for Italian and non-Italian women, respectively, but this difference was not statistically significant. The incidence of positive milk samples was 73.0 and 85.0% among the Italian and non-Italian mothers, respectively. Pork meat, soft drinks, sweets and red wine showed a significant relationship with OTA level in serum. As far as milk is concerned, a positive relationship resulted for pork meat, sweets, soft drinks and seed oils. A positive relationship between serum OTA level and the ratio serum/milk OTA was found. The intake of OTA had no effect on the cord blood creatinine level. CONCLUSIONS: This study confirms that OTA is widely present in human milk and therefore could pose a risk for the newborn.

[Abnormalities in the central nervous system and alterations in the upper limbs in patients with myelomeningocele]. / Anormalidades del sistema nervioso central y alteraciones de los miembros superiores en pacientes con mielomeningocele.

INTRODUCTION: Myelomeningocele is a neural tube defect resulting in motor and sensory deficit below the level of the lesion, bowel and neurogenic bladder, sexual dysfunction, cognitive dysfunction, neurodevelopment delay and motor skills disability. During the past decades, hand function impairment has been described in myelomeningocele patients, probably due to central nervous system abnormalities. AIM. To determine the occurrence of upper limb impairment and additional central nervous system abnormalities in patients with myelomeningocele. SUBJECTS AND METHODS: A transversal study including 33 patients with myelomeningocele, 6 years and older, referred to pediatric rehabilitation program at Sarah Network of Rehabilitation Hospital (Fortaleza, Brazil), and 33 control subjects. All patients underwent brain and spinal cord magnetic resonance imaging. RESULTS: Hydrocephalus, Chiari type II malformation with or without kinking of the medullocervical junction, hydrosyringomyelia, spinal cord and brain atrophy were the most common central nervous system abnormalities. Dysmetria, evaluated by the Index-Index Test, was exhibited by 87.9% of the patients and 21.2% of them exhibited dysdiadochokinesia. The mean hand grip strength of the myelomeningocele group was significantly lower compared with the control group (p < 0,001). CONCLUSIONS: High occurrence of upper limb dysfunction and additional central nervous system abnormalities was detected in patients with myelomeningocele, supporting previous studies. Further investigation is still necessary to elucidate the upper limb impairment impact on the daily live activities of the patient with myelomeningocele.

Anormalidades del sistema nervioso central y alteraciones de los miembros superiores en pacientes con mielomeningocele / Abnormalities in the central nervous and alterations in the upper limbs in patients with myelomeningocele

El mielomeningocele es un defecto del cierre del tubo neural cuyo cuadro clínico incluye déficit defuerza muscular y sensibilidad por debajo del nivel de la lesión, vejiga e intestino neurogénicos, disfunción sexual, déficit cognitivo, retraso en el desarrollo neuropsicomotor y lentitud en la realización de actos motores. En las últimas décadas se ha documentadoel perjuicio de la función manual, que puede deberse principalmente a anormalidades asociadas al sistema nervioso central. Objetivo. Describir las alteraciones de los miembros superiores y anormalidades del sistema nervioso central en pacientes con mielomeningocele. Sujetos y métodos. Estudio transversal donde participaron 33 pacientes con mielomeningocele,de edad superior a 6 años, en seguimiento en el Centro de Rehabilitación Sarah Fortaleza, Brasil, junto con 33 sujetos control. Todos los pacientes se sometieron a resonancia magnética de encéfalo y médula. Resultados. Hidrocefalia, malformación de Chiari tipo II con o sin kinking cervicomedular, hidrosiringomielia y atrofia medular y cerebral fueron las anormalidadesmás encontradas. Se halló dismetría, evaluada a través del test índice-índice, en el 87,9% de los pacientes, y disdiadococinesia en el 21,2%. La media de la fuerza de prensión de los pacientes con mielomeningocele fue significativamente inferior a la del grupo de control (p < 0,001). Conclusiones. Se detectó una alta ocurrencia de anormalidades del sistema nerviosocentral y alteraciones de los miembros superiores en los pacientes con mielomeningocele, corroborando estudios previos. Se precisan investigaciones futuras para evaluar el impacto de las alteraciones de los miembros superiores en las actividades de la vida diaria

Myelomeningocele is a neural tube defect resulting in motor and sensory deficit below the level of thelesion, bowel and neurogenic bladder, sexual dysfunction, cognitive dysfunction, neurodevelopment delay and motor skills disability. During the past decades, hand function impairment has been described in myelomeningocele patients, probably dueto central nervous system abnormalities. Aim. To determine the occurrence of upper limb impairment and additional central nervous system abnormalities in patients with myelomeningocele. Subjects and methods. A transversal study including 33 patients with myelomeningocele, 6 years and older, referred to pediatric rehabilitation program at Sarah Network ofRehabilitation Hospital (Fortaleza, Brazil), and 33 control subjects. All patients underwent brain and spinal cord magnetic resonance imaging. Results. Hydrocephalus, Chiari type II malformation with or without kinking of the medullocervical junction,hydrosyringomyelia, spinal cord and brain atrophy were the most common central nervous system abnormalities. Dysmetria, evaluated by the Index-Index Test, was exhibited by 87.9% of the patients and 21.2% of them exhibited dysdiadochokinesia. The mean hand grip strength of the myelomeningocele group was significantly lower compared with the control group (p < 0,001).Conclusions. High occurrence of upper limb dysfunction and additional central nervous system abnormalities was detected in patients with myelomeningocele, supporting previous studies. Further investigation is still necessary to elucidate the upper limb impairment impact on the daily live activities of the patient with myelomeningocele

[Effect of iron depletion on long-term response to interferon in patients with chronic hepatitis C with increased plasma iron without accumulation of liver iron]. / Effetto della ferrodeplezione sulla risposta a lungo termine all'interferone in pazienti affetti da epatite cronica C con aumentato ferro plasmatico senza accumulo di ferro epatico.

We studied the effect of iron depletion on the response to subsequent interferon therapy in a population of 83 patients affected by chronic hepatitis C who had not previously undergone any specific therapy and who had laboratory confirmation of iron overload (serum ferritin > 400 ng/mL in the males and > 300 ng/mL in the females). The population was divided into two homogeneous groups. Group A consisted of 43 patients who underwent phlebotomy (300 mL every 10-15 days for an average total of 8 sessions) until serum ferritin levels of < 100 ng/mL were obtained. The 40 patients in Group B were treated with interferon without prior iron depletion. Iron depletion alone, induced in Group A, brought about a highly significant (p < 0.01) reduction of alanine aminotransferase serum values: from 165 U/L (range 60-370 U/L) to 67 U/L (range 27-158 U/L). Seventy-six patients completed therapy and follow-up: a complete and sustained response was obtained in 12/39 cases in Group A and in 6/37 cases in Group B (p < 0.05). Iron depletion carried out in patients with chronic hepatitis C, who have elevated base values of serum ferritin, induces a significant reduction in necro-inflammatory activity (notable decrease in average alanine aminotransferase values) and improves the response to subsequent treatment with interferon, although it does not modify the viral load.

Management of patients with HCV infection poorly tolerant to recombinant interferon alpha.

BACKGROUND/AIMS: To evaluate leukocyte interferon-alpha tolerability and efficacy in the retreatment of patients poorly tolerant to recombinant interferon-alpha. METHODOLOGY: Patients with chronic hepatitis C, poorly tolerant to a previous interferon-alpha treatment (118 patients; 73 "relapsers": Group I; 45 "non-responders": Group II) were retreated with 6 MU tiw of leukocyte interferon-alpha for 6 months and then followed-up for 12-34 months. Only patients with complete regression of any previous interferon-related adverse event were included. RESULTS: Three patients dropped out due to recurrence of a severe depressive syndrome. In 86/115 patients (75%) no significant lifestyle changes versus baseline were observed during retreatment, while 29 subjects experienced a moderately negative interference on their living habits. The different influence on the patients' quality of life of leukocyte interferon in comparison with the previous treatment was significant (P < 0.001). In 98 patients the interferon-related adverse events significantly decreased. After 12 months of follow-up, a sustained biochemical response was observed in 40 patients (Group I:31; Group II:9), and a persistent virological response in 28 (Group I:23; Group II:5). CONCLUSIONS: The good compliance with leukocyte interferon administration shown by poorly tolerant patients, non-responders/relapsers to recombinant interferon, permitted a retreatment with full doses, so increasing the chance to obtain a larger number of sustained responses.

Psychological constructs associated with emotional blood pressure response and white coat phenomenon.

Some hypertensive and non-hypertensive subjects have a striking blood pressure response to a medical environment (white coat phenomenon), although it is unlikely that its presence, degree, and duration can be routinely predicted. Despite the common observation that "anxious" patients may present with this reaction when a physician measures their blood pressure, no psychological variables have thus far been linked to white coat phenomenon in formal analyses. Ambulatory blood pressure monitoring is a useful tool to disclose the phenomenon since it allows precise evaluation of repeated blood pressure measurements outside the medical environment. To investigate the possible relationship between psychological profile and white coat phenomenon, we have planned to administer a series of psychometric tests to 120 subjects undergoing ambulatory blood pressure monitoring. The present data are derived from an analysis of the first set of 70 patients. Thirty-four subjects who presented with white coat phenomenon (defined as office blood pressure elevated by at least 15% over the mean 24-hour ambulatory blood pressure value) and 36 comparable subjects who did not have this reaction underwent a series of psychometric tests evaluating cognitive behavior, hostility, cynicism, anger, anxiety state, coping ability and strategies, and quality of life. Of the various psychometric tests, the scores of three relevant scales (healthcare-related fears, mental efficiency and behavioral disengagement) were significantly higher in the group of patients with white coat phenomenon, while in both groups, emotional instability was higher than the clinical cut-off point. There were no significant differences between the two groups regarding signs and repression of anger (anger-out and anger-in), cynicism, hostility, or anxiety state. Our data seem to indicate that the subjects most likely to show an overt blood pressure increase in the medical environment are those who evidence healthcare-related fears and emotional instability but are not necessarily anxious. They exhibit high coping skills in cognitive resolution of stressing situations (such as blood pressure measurement) but do not combine these strategies with an adequate behavioral response and do not feel that behavioral involvement is necessary for the management of their clinical condition.

Severe postpartum hypertension and reversible cerebral angiopathy associated with ergot derivative (methergoline) administration.

A 36-year-old woman (gravida 2, para 2) delivered a healthy child by cesarean section at the 37th week of an unremarkable gestation. Blood pressure remained within normal range throughout the pregnancy, surgery, and for the 9 following days. On day 10, about 36 hours after the initiation of oral methergoline to suppress lactation, the patient complained of severe posterior headache, flashing scotomata, hypertension, tonico-clonic seizures and then homonymous left hemianopsia and hemiparesis. Blood pressure monitoring confirmed intermittent and severe hypertension. Angiography demonstrated diffuse narrowing of the small and medium cerebral arteries. Transcranial Doppler ultrasound examination disclosed a bilateral increase in mean flow velocity. Progressive normalization of blood pressure, obtained with labetalol and oral clonidine, was accompanied by amelioration of the neurological deficits until a complete recovery and normalization of transcranial Doppler flow velocity occurred. This case provides further evidences that hypertension might play a major pathogenetic role in reversible cerebral angiopathy. Some ergot derivatives (including methergoline) might trigger the initial rise in blood pressure.

[The retreatment with natural leukocyte interferon alfa-n3 of chronic hepatitis C patients: the intolerant and nonresponsive results to prior treatment with recombinant alfa interferon]. / Ritrattamento con interferone naturale leucocitario alfa-n3 di pazienti con epatite cronica C: risultati intolleranti e non responsivi a precedente trattamento con interferone alfa ricombinante.

To evaluate leukocyte interferon alpha-n3 tolerability and efficacy in the retreatment of patients with chronic hepatitis C poorly tolerant to previous treatment with recombinant interferon alpha, 142 patients (73 "relapsers" and 69 "nonresponders") were retreated with leukocyte interferon alpha-n3 (6 MU thrice weekly for 6 months) and followed up for 12-42 months. Only patients with complete regression of any previous interferon-related adverse events were included. Three patients dropped out due to recurrence of a severe depressive syndrome. In 104/139 patients (75%) no significant life-style changes vs baseline were observed during retreatment, while 35 subjects experienced moderately negative interference with their living habits. The different influence on the patients' quality of life during leukocyte interferon alpha-n3 treatment in comparison with the previous treatment was significant. In 118 patients (85%) the interferon-related adverse events significantly decreased. After 12 months of follow-up, a sustained biochemical response was observed in 48 patients (35%), and a persistent biochemical and virological response was seen in 33 (23%). The good compliance with leukocyte interferon alpha-n3 administration shown by poorly tolerant patients, "relapsers/nonresponders" to recombinant interferon, permitted retreatment with full doses and thus increased the chance of obtaining a larger number of sustained responses.