Effects of cannabis smoking on the respiratory system: A state-of-the-art review.

The diminished perception of the health risks associated with the consumption of cannabis (marijuana) lead to a progressive increase in its inhalational use in many countries. Cannabis can be smoked through the use of joints, spliffs and blunts, and it can be vaporised with the use of hookah or e-cigarettes. Delta-9 tetrahydrocannabinol (THC) is the main psychoactive component of cannabis smoke but contains numerous other substances. While the recreational use of cannabis smoking has been legalised in several countries, its health consequences have been underestimated and undervalued. The purpose of this review is to critically review the impact of cannabis smoke on the respiratory system. Cannabis smoke irritates the bronchial tree and is strongly associated with symptoms of chronic bronchitis, with histological signs of airway inflammation and remodelling. Altered fungicidal and antibacterial activity of alveolar macrophages, with greater susceptibility to respiratory infections, is also reported. The association with invasive pulmonary aspergillosis in immunocompromised subjects is particularly concerning. Although cannabis has been shown to produce a rapid bronchodilator effect, its chronic use is associated with poor control of asthma by numerous studies. Cannabis smoking also represents a risk factor for the development of bullous lung disease, spontaneous pneumothorax and hypersensitivity pneumonitis. On the other hand, no association with the development of chronic obstructive pulmonary disease was found. Finally, a growing number of studies report an independent association of cannabis smoking with the development of lung cancer. In conclusion, unequivocal evidence established that cannabis smoking is harmful to the respiratory system. Cannabis smoking has a wide range of negative effects on respiratory symptoms in both healthy subjects and patients with chronic lung disease. Given that the most common and cheapest way of assumption of cannabis is by smoking, healthcare providers should be prepared to provide counselling on cannabis smoking cessation and inform the public and decision-makers.

Expert consensus on the treatment of patients with adult-onset still's disease with the goal of achieving an early and long-term remission.

We performed a comprehensive systematic targeted literature review and used the Delphi method to formulate expert consensus statements to guide the treatment of adult-onset Still's disease (AOSD) to achieve an early and long-term remission. Seven candidate statements were generated and reached consensus in the first round of voting by the panel of experts. We postulate: (i) In patients with AOSD with predominant arthritis at onset who achieved no disease control with glucocorticoids (GCs), the use of methotrexate can be considered, whereas the use of cyclosporin A and low-dose GCs should not (Statements 1-3); (ii) In patients with AOSD with poor prognostic factors at diagnosis, an IL-1 inhibitor (IL-1i) in addition to GCs should be taken into consideration as early as possible (Statement 4); (iii) A switch to an IL-6 inhibitor (IL-6i) may be considered in patients with AOSD with prevalent joint involvement, who are unresponsive or intolerant to IL-1i (Statement 5); (iv) Drug tapering or discontinuation may be considered in patients who achieved a sustained clinical and laboratory remission with IL-1i (Statement 6); (v) In patients with AOSD who failed to attain a good clinical response with an IL-1i, switching to an IL-6i may be considered in alternative to a different IL-1i. TNF-inhibitors may be considered as a further choice in patients with a prominent joint involvement (Statement 7). These statements will help clinicians in treatment decision making in patients with AOSD.

Kaniadakis's Information Geometry of Compositional Data.

We propose to use a particular case of Kaniadakis' logarithm for the exploratory analysis of compositional data following the Aitchison approach. The affine information geometry derived from Kaniadakis' logarithm provides a consistent setup for the geometric analysis of compositional data. Moreover, the affine setup suggests a rationale for choosing a specific divergence, which we name the Kaniadakis divergence.

Effectiveness and feasibility of smoking counselling: a randomized controlled trial in an Italian emergency department.

BACKGROUND: 5A's counselling is recommended for screening and treating patients with smoking addiction. The emergency department (ED) setting might be a suitable environment for conducting interventions for smoking cessation. The present study aims to determine the feasibility and effectiveness on smoking cessation of 5A's counselling administered to ED patients by nurses. METHODS: Parallel group randomized trial assessing 5A's counselling for smoking cessation vs. usual care at a University Hospital in the North of Italy. The primary end-point was prevalence of tobacco-free patients. The secondary outcomes at 6- and 12-month follow-up were (i) consecutive past 30-day smoking abstinence; (ii) past 7-day 50%, or more, decrease in daily tobacco consumption over baseline; and (iii) number of attempts to quit smoking. RESULTS: A total of 480 patients were randomized to intervention (n = 262) or usual care (n = 218). Intention to treat analysis displayed no differences in primary and secondary outcomes between groups. A slight but not statistically significant enhancement in cessation was recorded in the intervention group [relative risk (RR) = 1.04, 95% confidence interval (CI) = 0.58-1.87] at 6 months, whereas a reversed observation at 12 months (RR = 0.86, 95% CI = 0.50-1.47). Similar results were obtained for the secondary outcomes. Per protocol analysis increased the size of the results. Of the 126 smokers receiving counselling, 18 were visited and treated at the local smoking cessation centre, with 12 of them successfully completing the treatment. CONCLUSION: The results of this study indicate that the ED is not a suited environment for 5A's counselling.

Lagrangian Function on the Finite State Space Statistical Bundle.

The statistical bundle is the set of couples ( Q , W ) of a probability density Q and a random variable W such that.

Anti-TNF treatment response in rheumatoid arthritis patients with moderate disease activity: a prospective observational multicentre study (MODERATE).

OBJECTIVES: Rheumatoid arthritis (RA) patients with moderate disease activity show progression of joint damage and have impaired quality of life, physical function, work and daily activities. Little is known about management of patients with moderate RA. The aim of the study was to assess the 1-year response to anti-TNF in biologic-naïve RA patients with moderate (3.2 3.2 and ≤5.1), and were naïve to anti-TNF treatment. RESULTS: Among 157 RA patients, 93 (59%) underwent etanercept, 43 (22%) adalimumab, 26 (17%) certolizumab, 10 golimumab and 2 infliximab; 80% of patients were still in treatment after 12-month observation. One-year clinical remission was achieved by 27 RA patients (21%), reduction of DAS28 score greater than 1.2 was observed in 75 (58%) patients. Moderate and good response according to EULAR criteria was observed in 59 (46%) and 45 (35%) patients, respectively. CONCLUSIONS: Results confirm the efficacy of anti-TNF alpha also in moderate RA patients, who may achieve a substantial decrease of disease activity, and improve their quality of life. The low rate of patients achieving remission may suggest that therapeutic strategies should be more timely and aggressive.

Rheumatoid arthritis affects left ventricular mass: Systematic review and meta-analysis.

BACKGROUND: Cardiovascular disease represents one of the most important extra-articular causes of morbidity and mortality in patients with rheumatoid arthritis (RA). Evidences showed that several cardiac structures can be affected during the course of the disease as well as abnormalities of left ventricular diastolic filling. Contrasting data are available about left ventricular mass (LVM) involvement in patients asymptomatic for cardiovascular disease. The purpose of this systematic review and meta-analysis is to summarize the effects of RA on LVM in rheumatoid arthritis patients without cardiovascular disease. METHODS: A systematic research of the current case-control studies was conducted in Medline on November 20th, 2013. Studies were included if data of measurements of LVM were reported. The pooled mean effect size estimate was calculated according to methods described by Hedges and Olkin. RESULTS: Sixteen eligible studies were included in this meta-analysis. RA determines an increase of absolute and indexed LVM compared with control patients [standardized mean difference (95% CI): 0.41(0.15-0.66) and 0.47(0.32-0.62), respectively]. On the contrary, posterior wall thickness did not show a significant RA effect. Finally, a significant positive effect of RA on interventricular wall thickness was found [standardized mean difference (95% CI): 0.39 (0.07-0.71)]. CONCLUSIONS: Results of this meta-analysis suggest that increased absolute and indexed LVM seem to be characteristic of RA patients with a fundamental clinical significance since they are related to an increased risk of cardiovascular morbidity and mortality. Our data suggest the use of LVM as surrogate end-point for clinical trials involving RA patients.

The challenge of using the rheumatoid arthritis diagnostic criteria in clinical practice.

The new 2010 ACR/EULAR (American College of Rheumatology/European League Against Rheumatism) criteria of Rheumatoid Arthritis recently published, have been released to classify and identify patients with early RA who could benefit from early therapy. They recommend anti-citrullinated protein antibody (ACPA) testing as an alternative criterion to Rheumatoid Factor (RF) and ACPA that were introduced together with the other classic criteria in a scoring system. We previously criticized these new criteria because of unavailable specificity and sensibility in the first paper, and the use of ACPA as dichotomous criterion (presence/absent) and alternatives to rheumatoid factor. Our previous work promoted discussion and fostered new research on this issue. By the light of new data, in an effort to improve clinical reasoning, we suggest a more practical probabilistic point of view. In this regard, we analyze the sensitivity and specificity of the diagnostic studies that evaluate the performance of the 2010 classification criteria. Then, we compare the old and the new classification criteria. Subsequently, we describe the use of likelihood ratios applied to the classification criteria and different cutoff levels of ACPA for decision-making in different setting. Moreover, we define some properties of likelihood ratios and their use for diagnosing or excluding rheumatoid arthritis. We want to share this kind of knowledge within the scientific community because we believe that it can help general practitioners and specialists to recognize early arthritis patients implementing a more efficient probabilistic clinical reasoning.

Heart involvement in rheumatoid arthritis: systematic review and meta-analysis.

OBJECTIVE: The aim of our study was to conduct a systematic review with meta-analysis of the current case-control studies about the valvular and pericardial involvement in patients with Rheumatoid Arthritis (RA), asymptomatic for cardiovascular diseases. METHODS: Case-control studies were identified by searching PubMed (1975-2010) and the Cochrane Central Register of Controlled Trials (CENTRAL) (1975-2010). Participants were adult patients with RA asymptomatic for cardiovascular diseases, and the outcome measure was the presence of cardiac involvement. RESULTS: Quantitative synthesis included 10 relevant studies out of 2326 bibliographic citations that had been found. RA resulted significantly associated to pericardial effusion (OR 10.7; 95% CI 5.0-23.0), valvular nodules (OR 12.5; 95% CI 2.8-55.4), tricuspidal valve insufficiency (OR 5.3; 95% CI 2.4-11.6), aortic valve stenosis (OR 5.2; 95% CI 1.1-24.1), mitral valve insufficiency (OR 3.4; 95% CI 1.7-6.7), aortic valve insufficiency (OR 1.7; 95% CI 1.0-2.7), combined valvular alterations (OR 4.3; 95% CI 2.3-8.0), mitral valve thickening and/or calcification (OR 5.0; 95% CI 2.0-12.7), aortic valve thickening and/or calcification (OR 4.4; 95% CI 1.1-17.4), valvular thickening and/or calcification (OR 4.8; 95% CI 2.2-10.5), and mitral valve prolapse (OR 2.2; 95% CI 1.2-4.0). CONCLUSIONS: Our systematic review pointed out the strength and the grade of both pericardial and cardiac valvular involvement in RA patients. Our findings underscore the importance of an echocardiographic assessment at least in clinical research when RA patients are involved. Moreover, further research is needed to understand the possible relationship of our findings and the increased cardiovascular mortality.

Polymyalgia rheumatica and vertebral fractures: a 1-year pilot controlled study.

No data exist about the possibility that vertebral fracture in PMR patients could be independent of steroid therapy. For this reason, we aimed to investigate this topic by a case cohort study with a 1-year follow-up for each patient. We selected ten consecutive patients who experienced vertebral fractures (VF-group) during the first month of 1-year follow-up period and without any other significant associated condition. As a control group we studied ten control patients, without vertebral fractures and with a follow-up of 1 year, randomly selected among a larger group of patients affected by polymyalgia rheumatica. The following data were analysed: eritrosedimention rate (ESR), visual analogical scale score (VAS), methyprednisolone daily dosage. Each patient had been monthly evaluated by the aforementioned clinical and laboratoristic parameters during the 1-year follow-up period. The VF-group resulted with a higher and statistically significant median corticosteroid 12-month total dosage [mean 3,480 mg (95%CI 2,805-3,030) vs. 2,760 mg (2,666.25-3,247.5)]. The VF-group had statistically significant higher ESR and VAS AUC when compared to control group (median ESR AUC, 484.75 vs. 288.25; P = 0.0001; median VAS AUC, 70.75 vs. 43.5 P < 0.0001); ESR at the baseline (cut-off >80 mm) showed a specificity of 90% (95%CI 56-100) and sensitivity of 70% (95%CI 35-93). VAS difference from first to second month (cut-off

Fast recovery with etanercept in patients affected by polymyalgia rheumatica and decompensated diabetes: a case-series study.

We enrolled nine consecutive patients affected by newly diagnosed polymyalgia rheumatica and decompensated diabetes mellitus. All patients were treated with etanercept (25 mg twice weekly) and prednisone and were followed up to 1 year. At the sixth-month follow-up, etanercept and prednisone were withdrawn. Patients were seen at regular intervals (days 0, 30, 60, 90, 150, 180) and the following variables determined: erythrocytes sedimentation rate, C-reactive protein, fasting serum glucose, pain measured by visual analog scale, and the Health Assessment Questionnaire. Our results indicate that etanercept might have some steroid-sparing effects, but controlled investigations are needed to support etanercept use in clinical practice for this kind of patients.

Safety of etanercept therapy in rheumatoid patients undergoing surgery: preliminary report.

This is a preliminary report on a case-series of rheumatoid patients that underwent various kinds of elective surgery but did not withdraw etanercept therapy in spite of physician advise. Elective surgery consisted of right knee surgical prosthesis, bilateral cataract, bilateral hallux valgus, right hip prosthesis, bladder stone by cystoscopy and left inguinal hernia. All the patients had a regular healing rate. During follow-up (6-12 months) no one of these patients were suffering from infective complications after surgery. According to same recent literature results, our data suggest that it is the time to value rheumatoid patient preferences through a correct information about cost-benefit of this treatment to establish together with patients if etanercept therapy has to be discontinued before and after elective surgery. Finally, we think that adverse drug reaction surveillance has to be boosted, and editors of leading scientific journal should publish more papers on case-series about drug safety and tolerability in particular conditions.

Effects of L-acetylcarnitine on cirrhotic patients with hepatic coma: randomized double-blind, placebo-controlled trial.

Multiple therapeutic modalities have been used to treat hepatic encephalopathy. L: -Acetylcarnitine (LAC) is a physiologically active substance that improves both the energetic and the neurotransmission profiles. LAC is able to cross the hematoencephalic barrier and reach the cerebral regions, where the acetylic group may be utilized. The aim of this work was to evaluate the efficacy of LAC in the treatment of hepatic coma in cirrhotic patients. Twenty-four suitably selected patients were enrolled in the study and, following randomization, received either LAC (n=13) or placebo (n=11). Statistically significant differences in neurological findings, as evaluated by the Glasgow Scale, as well as in ammonia serum levels and BUN were found following LAC treatment. In the placebo group we observed two cases of improved neurological findings as well as one case of improved EEG grading. In the other group we observed an improvement of neurological findings and of EEG grade in 10 and 8 subjects, respectively. Noteworthily, seven (54%) patients went from grade 4 down to grade 3, and one from grade 4 down to grade 1. The improvement in the neurological picture was evident at between 1 and 4 hr after the end of treatment, remaining until 24 hr after. No side effects were observed in our study series. Our study demonstrates that LAC administration improved neurological and biohumoral symptoms in selective cirrhotic patients with hepatic coma.

Serum carnitine levels in patients with tumoral cachexia.

BACKGROUND: Cachexia is a serious complication of many cancers that is common in cancer and AIDS patients. However, the key factors and mechanisms involved in the development of cachexia are not yet understood. There is little data currently available regarding carnitine metabolism in patients with neoplasm and cachexia. METHODS: Forty-six neoplastic patients with different localizations of their primary disease gave signed, informed consent before enrolling in the present study. They underwent routine laboratory investigation, including examination of the levels of the various forms of carnitine present in serum (i.e., long-chain acylcarnitine, short-chain acylcarnitine, soluble acid acylcarnitine, free carnitine, and total carnitine). These values were compared with those found in 30 cancer patients in good nutritional status as well as with those of 30 healthy control subjects. RESULTS: In the comparison of serum plasma carnitine of cachectic patients versus controls, the difference in free carnitine was - 8.20 micromol/L (p=0.000); the difference in short-chain acylcarnitine - 2.60 micromol/L (p=0.029); the difference in soluble acid carnitine - 10.80 micromol/L (p=0.000); the difference in long-chain acylcarnitine - 0.40 micromol/L (p=0.036); and the difference in total carnitine -11.20 micromol/L (p=0.000). In the comparison of serum plasma carnitine of cachectic versus neoplastic patients in good nutritional status, the difference in free carnitine was -5.80 micromol/L (p=0.006); the difference in soluble acid carnitine - 7.20 micromol/L (p=0.000); and the difference in total carnitine - 7.50 micromol/L (p=0.000). CONCLUSION: Our study showed that, in the multifactorial pathogenesis of cachexia, the low serum levels of carnitine in terminal neoplastic patients, which are due to a decreased dietary intake as well as to an impaired endogenous synthesis of this substance, could play an important role. These low serum carnitine levels may also contribute to the development of cachexia in cancer patients.

Effects of L-carnitine in patients with hepatic encephalopathy.

AIM: To evaluate the influence of L-carnitine on mental conditions and ammonia effects on patients with hepatic encephalopathy (HE). METHODS: One hundred and fifty patients (10 patients with alcoholism, 41 patients with hepatitis virus B infection, 78 patients with hepatitis C virus infection, 21 patients with cryptogenetic cirrhosis) meeting the inclusion criteria were randomized into group A receiving a 90-d treatment with L-carnitine (2 g twice a day) or into group B receiving placebo in double blind. RESULTS: At the end of the study period, a significant decrease in NH4 fasting serum levels was found in patients with hepatic encephalopathy (P<0.05) after the treatment with levocarnitine (LC). Significant differences were also found between symbol digit modalities test and block design in patients with hepatic encephalopathy (P<0.05). CONCLUSION: Results of our study suggest an important protective effect of L-carnitine against ammonia-precipitated encephalopathy in cirrhotic patients.

Interleukin-2 plus ribavirin versus interferon-alpha-2b plus ribavirin in patients with chronic hepatitis C who did not respond to previous interferon-alpha-2b treatment.

BACKGROUND: Interferon (IFN)-alpha-2b therapy has been shown to improve clinical conditions of patients with chronic hepatitis C. Several studies showed that the addition of ribavirin to IFNalpha-2b greatly improved the biochemical as well as the virologic and histological response rate in patients with chronic hepatitis C. The aim of this study was to evaluate biochemical, virologic, and histological responses as well as adherence to a treatment employing ribavirin plus low doses of recombinant interleukin (IL-2) or IFNalpha-2b in subjects with chronic active hepatitis C, which relapsed or did not respond to previous treatment with interferon alone. PATIENTS AND METHODS: We evaluated all 75 consecutive adult patients with chronic hepatitis C admitted to our department, who were previously treated with one course of recombinant or lymphoblastoid IFNalpha-2b (3 million to 6 million IU three times a week for at least 4 months), and either relapsed or did not respond to this treatment. Sixty patients met the inclusion criteria for enrollment in our study. Randomization was performed on the basis of a computer-generated list. The treatment schedule was based on subcutaneous administration of recombinant IFNalpha-2b (Intron A) at a dosage of 3 million IU every day, or IL-2 (aldesleukin) at a dose of 1 million IU every day, with oral ribavirin administered 400 mg twice daily (morning and night) [for patients weighing <75 kg] or 500 mg twice daily (for those weighing > or = 75 kg). The planned treatment period was 6 months. RESULTS: Both IFN and IL-2 treatment groups achieved a significant biochemical response with respect to baseline values at the end of the treatment (p < 0.0001 for both) and at the end of the follow up (p < 0.001 for both). The differences between the two groups at the end of treatment and at the end of the follow up were significant (p < 0.04 and p < 0.003 respectively) in favor of IL-2-treatment. The virologic response rate for IL-2-treated patients was significantly higher than for IFN-treated patients at months 3 (p < 0.05) and 6 (p < 0.05) of the treatment. Both groups showed significant improvement in histological activity index with respect to baseline values, but the difference between the groups was not significant. No withdrawals have been registered. CONCLUSION: The combination of IL-2 and ribavirin seems to increase the probability of a sustained biochemical and virologic response in patients with chronic hepatitis C that is unresponsive to IFN. Our study showed that IL-2 plus ribavirin may provide a clinically important option that appears to be well tolerated and effective in patients with chronic hepatitis C virus infection.

Elevated plasma total homocysteine in centenarians.

Homocysteine (Hcy) is a sulfur-containing metabolite of methionine and is an emerging independent risk factor for atherosclerosis. Previous studies have shown that age, gender, renal function and folic acid intake are the main factors influencing total plasma Hcy levels in humans. A unique approach to the science of human longevity is the natural model of centenarians. The objective of this study was to verify whether the previously determined risk factors for atherosclerosis and atherosclerosis-related diseases change with age and, finally, to establish the vitamin nutritional status role. We studied 54 centenarians (14 males and 40 females) aged between 100-107 years (mean age 102.6+/-1.8 years) living in Sicily (Italy), recruited via the Registry Office, and compared them with three control groups composed of subjects with different age ranges. Total plasma Hcy, folate, vitamin B12 and pyridoxal phosphate (PLP) levels were compared between the groups by the Student's t test. The comparison between centenarians and <65-year old, randomly selected individuals showed that in centenarians the mean value of serum creatinine levels was 18 micromol/l (p=0.000) higher, the mean total Hcy value was 22 micromol/l higher (p=0.000), the mean PLP value was 17.9 nmol/l lower (p=0.000), the mean folate level was 2.1 nmol/l lower (p<0.001) and vitamin B12 was 70.5 pmol/l lower (p=0.000). The comparison between centenarians and >65-year old, randomly selected individuals showed that in centenarians the mean value of serum creatinine levels was 8 micromol/l higher (p=0.037), the mean total Hcy value was 11.6 micromol/l higher (p=0.000) and the mean PLP value was 4.2 nmol/l higher (p=0.000). It seems that centenarians are protected by some mechanism (maybe genetic) that allows them a long survival despite the high value of homocysteinemia. On the other hand, it can by hypothesized that good vitamin intake is essential to live over 100 years.

Ultrasound evaluation of centenarians' gallbladder.

Background: Ultrasound (US) examination of gallbladder is considered to be reliable, both in morphological and functional evaluation. We used US to study the gallbladder of a series of centenarians in order to show the characteristics of this organ in these subjects. We then compared the data obtained with two control populations omposed of elderly and adult subjects, respectively. Methods: US examination was done after an overnight fast and after emptying the gallbladder at 15-min intervals for a period of 90 min. To induce emptying of the gallbladder, we chose a semisolid meal with a small caloric value (370 kcal). The following parameters were evaluated: fasting gallbladder volume (in milliliters) before administration of the meal (considered to be 100%); gallbladder emptying (according to the formula: fasting gallbladder volume minus post-meal gallbladder volume at 10-min intervals divided by fasting gallbladder volume: the result of this operation was multiplied by 100); gallbladder motor functions, such as ejection volume (ml), is considered as the difference between fasting gallbladder volume and residual volume; ejection fraction (%), considered as the difference between fasting gallbladder volume and residual volume, is expressed as percentage fasting volume; and ejection rate (%/min) is calculated by dividing ejection fraction by time requested to reach the residual volume. Results: We found a common bile duct diameter that was significantly higher in centenarians than in the elderly and adults. Gallbladder wall thickness was significantly higher in centenarians than in adults. We also found substantially significant differences between centenarians with and without gallstones and elderly and adult subjects in the following parameters: mean gallbladder volume (reduced), residual volume (reduced), ejection volume (reduced) and ejection rate (reduced). The differences were not significant for the ejection fraction, and they were slightly reduced in centenarians compared to the other groups. There was a negative correlation between age and axial length (transverse diameter), age and width and age and common bile duct (CBD) diameter in the elderly group only. Conclusions: The study of gallbladder function in elderly people and centenarians is important because this parameter is related to the quality of digestion and absorption of many alimentary substances as well as to the formation of cholesterol gallstones. We found that gallbladder functions in centenarians are almost normal with respect to the elderly and adults. Contractility was higher than in our elderly sample. This fact ensures a correct concentration of bile salts and a good intestinal transit rate. It may represent one of the factors allowing for good digestive function in these subjects, which contributes to their health status.