Seasonal and Treatment-Related Variation in 25-Hydroxy Vitamin D Concentration in Patients with Rheumatoid Arthritis.

Background/Objectives: 25-hydroxy vitamin D (25-OH-D) is a fat-soluble compound that plays many essential functions, including bone formation, neuromuscular functions, and prevention of osteoporosis and inflammation. Recent data indicate that its metabolites are associated with rheumatoid arthritis (RA) progression and neuropathic pain in RA patients. We aimed to assess the effect of RA pharmacotherapy and seasonal variation on serum levels of 25-OH-D in RA patients who received treatment with methotrexate (MTX) or leflunomide (LEF) for at least one year. Methods: This study is a retrospective analysis of data collected from 101 patients with RA who received treatment for at least one year. All of them have supplemented 25-OH-D (2000 IU daily) for at least one year. Results: We observed a significant seasonal variation in 25-OH-D concentration (p = 0.004). Moreover, there were significant differences (p = 0.03) between LEF (50.63 ± 17.73 ng/mL) and MTX (34.73 ± 14.04 ng/mL) treatment groups, but only for the summer population. A correlation was observed between 25-OH-D and RA duration-once again, in the summer population (the whole group-r = -0.64; treatment subgroups-r = -0.82 for LEF and -0.61 for MTX). Deficiency of 25-OH-D (below 20 ng/mL) was confirmed in 28.7% of patients, while 18.8% had suboptimal 25-OH-D levels (20-30 ng/mL). Conclusions: Our results showed that both RA pharmacotherapy and seasonal variation affect the serum levels of 25-OH-D in patients with active RA.

Getting them through the door: Social and behavioral determinants of uptake and engagement in an obesity intervention.

Using data from a large-scale screening program (N = 19634), we aimed to prospectively identify factors predicting uptake (i.e. acceptance of the invitation) and engagement (i.e. participation in at least two sessions) in a multi-component-intensive-behavioral-intervention for obesity-management (MBIOM) intervention targeting adolescents (n = 2862; 12-14 years; BMI ≥90th percentile). Approximately one third of adolescents most in need of weight management declined the initial invitation to enter the MBIOM. Poor diet, sedentary behavior, and parental education predicted willingness to enter and stay in the intervention, however measured body mass index did not matter. Perceived family support, instead of initial motivation, facilitated engagement. Our results provide new insights on the importance of regional socio-geographical factors including trust in local authorities.

Fitness, Food, and Biomarkers: Characterizing Body Composition in 19,634 Early Adolescents.

Adolescent obesity persists as a major concern, especially in Central and Eastern Europe, yet evidence gaps exist regarding the pivotal early adolescent years. Our objective was to provide a comprehensive picture using a holistic approach of measured anthropometry in early adolescence, including body composition, cardiorespiratory fitness (CRF), and reported lifestyle characteristics. We aimed to elucidate potential sex/gender differences throughout and associations to biomarkers of disease risk for obese adolescents. Methods: Trained nurses measured 19,634 early adolescents (12−14-year-olds), we collected parental reports, and, for obese adolescents, fasting blood samples in four major Polish cities using a cross-sectional developmental design. Results: 24.7% boys and 18.6% girls were overweight/obese, and 2886 had BMI ≥ 90th percentile. With increasing age, there was greater risk of obesity among boys (p for trend = 0.001) and a decreasing risk of thinness for girls (p for trend = 0.01). Contrary to debate, we found BMI (continuous) was a useful indicator of measured fat mass (FM). There were 38.6% with CRF in the range of poor/very poor and was accounted for primarily by FM in boys, rather than BMI, and systolic blood pressure in girls. Boys, in comparison to girls, engaged more in sports (t = 127.26, p < 0.0001) and consumed more fast food (t = 188.57, p < 0.0001) and sugar-sweetened beverages (167.46, p < 0.0001). Uric acid, a potential marker for prediabetes, was strongly related to BMI in the obese subsample for both boys and girls. Obese girls showed signs of undernutrition. Conclusion: these findings show that overweight/obesity is by far a larger public health problem than thinness in early adolescence and is characterized differentially by sex/gender. Moreover, poor CRF in this age, which may contribute to life course obesity and disease, highlights the need for integrated and personalized intervention strategies taking sex/gender into account.

Pancreatic Injury after COVID-19 Vaccine-A Case Report.

The COVID-19 pandemic has caused more than 3 million deaths worldwide. Recently developed genetically engineered vaccines are the most critical solution for controlling the pandemic. Clinical trials on a large number of participants confirmed their safety and efficacy. However, with the growing number of vaccinated people, new infrequent adverse effects have been reported, not described in the medicinal product characteristics. We would like to report a case of acute pancreatic injury that occurred shortly after administering Pfizer BioNTech COVID-19 mRNA vaccine (Comirnaty). The report points out the potential need for close monitoring of patients reporting abdominal pain after vaccination (unresponsive to standard oral painkillers) because such symptom can be associated with acute pancreatitis.

"PoZdro!" as an example of a successful multicenter programme for obesity management and healthy lifestyle promotion in children and adolescents - programme protocol and preliminary results from the first intervention site.

INTRODUCTION: Overweight and obesity rates in children and adolescents increase worldwide for over 30 years, what leads to an increased risk of de-veloping metabolic diseases. AIM OF THE STUDY: Protocol description and preliminary results of the largest to-date obesity management programme for children in Poland - "PoZdro!" MATERIAL AND METHODS: The Programme is based on three main steps: screening, parental engagement and long-term behavioral intervention (medical, dietetic, psychological, physical activity intervention panels) and education activities in secondary schools. Over 30.000 children were screened in four big Polish cities and over 2.000 engaged in the programme. RESULTS: Preliminary results from the first city show that, since 2014, 3998 of the 6346 (63%) eligible students from 24 schools (first grade of the secondary school) were screened. 16% of the children were overweight (body mass index - BMI ≥ 85th < 95th centile) and 4.7% were obese (BMI ≥95th centile). 603 children fulfilling the qualification (QUA) criteria (BMI > 90th centile) were offered the Individual Integrated Care (IIC). 470 (77.94% of QUA) began and 253 (41.96% of QUA, 53.82% of IIC) finished the full interventional pro-gramme with the mean BMI centile decrease of 3.04 in two following years. CONCLUSIONS: "PoZdro!" is a unique obesity prevention and management programme in Poland operating simultaneously in several Polish big cities. The programme incorporates parental engagement and long-term behavioral intervention. Preliminary results show that it may result in meaningful decrease in BMI in two following years. Further data analyses are necessary to show the influence of the programme on metabolic risk in studied group.

Photosensitivity reactions in the elderly population: questionnaire-based survey and literature review.

PURPOSE: Older people are at risk of developing adverse drug reactions, including photosensitivity reactions. Therefore, the aim of the study was to assess the use of potentially photosensitizing medications and photoprotection in the elderly population. PATIENTS AND METHODS: Three hundred and fifty-six respondents (223 [63%] women and 133 [37%] men) aged ≥65 years filled in the original questionnaire concerning photosensitivity reactions to drugs. The diagnosis of drug-induced photosensitivity was based on medical history and clinical examination. RESULTS AND CONCLUSION: We found that drugs potentially causing phototoxic/photoallergic reactions comprised more than one fifth of all drugs used by the participants. The most numerous group was patients treated with 3-5 drugs potentially causing phototoxic/photoallergic reactions simultaneously. Of all drugs, ketoprofen was found to cause the highest number of photosensitivity reactions. Cutaneous adverse reactions were also observed for hydrochlorothiazide, atorvastatin, simvastatin, telmisartan, and metformin. Moreover, it was found that the incidence of photosensitivity reactions can be significantly reduced by using proper photoprotection.

Is it possible to prevent chemotherapy-induced heart failure with cardiovascular drugs - the review of the current clinical evidence.

Cardiovascular diseases and cancer are the most common death causes in the USA and Europe. Moreover, many patients suffer from both of these conditions - a situation which may result from cardiotoxicity of anticancer treatment. In order to reduce the severity of this adverse effect, various methods have been proposed, including the usage of new drug forms and less toxic analogs, omitting the combinations of potentially cardiotoxic drugs and introducing potential cardioprotective agents to the therapy. However, prevention of cardiotoxicity still seems to be insufficient. The article reviews the results of current studies on the use of cardiovascular drugs in the prevention of cardiotoxicity. Based on this knowledge, the most promising cardioprotective drugs seem to be carvedilol, nebivolol, enalapril, and candesartan, as they prevent heart remodeling and correct elevated resting heart rate, which directly affects mortality. Alternatively, in case of adverse reactions, statins might be considered.

Potential effects of microbial air quality on the number of new cases of diabetes type 1 in children in two regions of Poland: a pilot study.

Aim: The aim of the study was to investigate the relationship between the concentration of psychrophilic bacteria, mesophilic bacteria and mold fungi in bioaerosols, and the number of new cases of type 1 diabetes mellitus (T1DM) in children. Methods: Air samples from the Lubelskie and Pomeranian voivodeships in Poland were collected from January 2015 to December 2016 in winter, spring, summer and autumn. Thirty-three samples were collected in the Pomeranian and 27 in the Lubelskie voivodeship. The air samples were collected on the first day of each month at 1:00 pm for 10 mins at a height of 1.5 m above the ground. The number of mesophilic bacteria was detected after 24-48 hrs incubation at 37°C on tryptone soya agar (TSA; Merck, Darmstadt, Germany). The number of psychrophilic bacteria was detected after 72 hrs incubation at 22°C on TSA. The number of fungi was detected by a 5-day long incubation at 28°C on chloramphenicol yeast glucose agar. Results: In the Lubelskie voivodeship, the mean concentration of psychrophilic bacteria was significantly higher than in the Pomeranian voivodeship (2739 vs 608 CFU/m3, respectively), the mean concentration of mesophilic bacteria was significantly higher (2493 vs 778/m3, respectively) and the concentration of fungi was significantly higher (3840 vs 688 CFU/m3, respectively). We also showed a statistically significant relationship between the number of children with recently diagnosed T1DM and the mean concentration of psychrophilic and mesophilic bacteria in the Pomeranian and Lubelskie voivodeships (P<0.001). Moreover, we found a significant relationship between the number of new cases of T1DM in children and the mean concentration of fungi in bioaerosols in the Lubelskie voivodeship (P<0.001), but not in the Pomeranian voivodeship (P=NS). Conclusion: The results of our research showed that there is a higher concentration of microbial particles in the Lublin voivodeship. Therefore, we recommend changes in climate for children (trips to the sea, mountains, etc) as often as possible.

The association of thyroid-stimulating hormone (TSH) and free thyroxine (fT4) concentration levels with carbohydrate and lipid metabolism in obese and overweight teenagers.

INTRODUCTION: Obesity has increased rapidly among children and adolescents during the last 30 years. Paediatric patients with a BMI above the 85th centile are more often diagnosed with increased TSH levels than are children with proper body weight. MATERIAL AND METHODS: The data of 961 overweight and obese children, aged 13 years, recruited in four cities in Poland as part of PoZdro!, a two-year prophylactic program, were analysed to observe the relationship between serum TSH and fT4 concentration and carbohydrate and lipid metabolism parameters, as well as anthropometric parameters. RESULTS: TSH concentration in the study group was positively correlated, whereas fT4 concentration was negatively correlated with WHR and WHtR values, fasting serum glucose concentrations and one-hour glucose concentration, fasting serum insulin concentrations, one-hour and two-hour insulin concentration, ALT serum activity, as well as total cholesterol, LDL cholesterol, and triglyceride serum concentrations. An increased risk of metabolic syndrome was diagnosed previously in patients with TSH concentrations > 2.5 mUI/L. CONCLUSIONS: TSH concentration in the upper half of the current reference range (> 2.50 mIU/L) is associated with an increased risk of lipid and carbohydrate metabolism disorders and therefore increased chances of developing metabolic syndrome. It seems advisable to regularly monitor thyroid function in overweight and obese paediatric patients.

ANGIOEDEMA AFTER ANGIOTENSIN-CONVERTING ENZYME INHIBITORS.

Angiotensin-converting enzyme inhibitors (ACEI) are one of the most frequently used drugs in the therapy of cardiovascular diseases. Beneficial therapeutic effects may be accompanied by different adverse reactions including angioedema. Recently published data suggest that ACEI-induced angioedema can be life-threatening without emergent intervention, for example due to the respiratory arrest. Monitoring this adverse Jreaction may be especially important for elderly patients who probably receive many different medicines and supplements and thus might be particularly at risk of adverse drug reactions. In the paper we describe two cases of ACEI-induced angioedema in older patients.

Coenzyme Q10 - A new player in the treatment of heart failure?

Coenzyme Q10 is the only endogenously synthesized lipid with a redox function which exhibits broad tissue and intracellular distribution in mammals. Beneficial effects of Coenzyme Q10 supplementation were observed in several age-related diseases including heart failure. CoQ10 (coenzyme Q10) level is significantly decreased in patients with this disease, which correlates with severity of clinical symptoms. Supplementation with various pharmaceutical formulations of CoQ10 improves impaired cardiac function and clinical course of heart failure. Current data from clinical trials indicate that CoQ10 can significantly reduce morbidity and mortality of heart failure patients in addition to guideline recommended pharmacotherapy.

Polycystic ovary syndrome and diabetes mellitus type 1 in adult and adolescent females.

INTRODUCTION: The growing prevalence of type 1 diabetes mellitus (T1DM) and polycystic ovary syndrome (PCOS; the most frequent cause of anovulatory infertility) results in their growing comorbidity. OBJECTIVE: To review the available data on comorbidity of type 1 diabetes mellitus and the polycystic ovary syndrome and their relations, especially in the adolescent group. MATERIALS AND METHODS: The available medical databases have been searched to identify relevant bibliography; then analysis and synthesis of the available data have been conducted. RESULTS: At present, the prevalence of comorbid T1DM and PCOS in girls has not been established. CONCLUSION: The available data on T1DM and PCOS comorbidity in adult women suggest the need for early diagnostic investigations to detect their comorbidity and for early therapeutic interventions. Further research to investigate their coprevalence is necessary. In female adolescents, either with or without T1DM, PCOS should be diagnosed not earlier that two years after menarche or when at age of 16 menarche is still absent, with all of the three Rotterdam criteria met. In time between menarche and the end of second year of menstruation high/medium risk of PCOS can be identified. After the fourth year of menstruating, the patient should be treated as an adult. Such approach will eliminate differences in diagnosis resulting from different law definition of adulthood in various countries. In girls with T1DM treatment should be started for any individual component of PCOS to reduce the risk of progression of the syndrome.

[Addiction to benzodiazepines - analysis of patients of Independent Public Hospital for Mental Diseases Patients in Miedzyrzecz].

Benzodiazepines (BZD) are substances with proven anxiolytic, sedative, hypnotic, muscle relaxant, and anticonvulsant effect whose activity targets a macromolecular complex comprising GABAA receptors, benzodiazepine receptors and chloride channels. Broad spectrum of action of benzodiazepines affects their more and more frequent consumption by the patients, despite the reports on their addictive potential. The aim of the study was to analyze patients addicted to benzodiazepines, taking into account factors that may increase the risk of addiction. Material and Methods: The study was based on medical records of 52 patients (27 women, 25 men) of Independent Public Hospital for Mental Diseases Patients in Miedzyrzecz from January 2013 to June 2015. The initial diagnosis of admitted patients included psychiatric and behavioral disorders due to taking hypnotics and sedatives (substance withdrawal). We analyzed the amount and time of use of benzodiazepines, alcohol consumption, as well as previous therapies due to alcohol abuse or alcohol dependence. Results: Among the 52 patients (27 women, 25 men aged 26 to 68 years), the majority of city dwellers was working with secondary education Average time of benzodiazepine use was 16 years, 60% of the patients were addicted to 1 benzodiazepine, 20% to two, 10% to three, and nearly 10% to 4. Clonazepam, alprazolam and diazepam were among the most frequently abused benzodiazepines. Conclusions: More and more often observed too long term treatment with benzodiazepines poses the risk of dependence on this group of drugs.

Current approach for detection of sub-clinical left ventricular dysfunction associated with chemotherapy.

The article describes the current knowledge concerning approaches for detection of sub-clinical left ventricular dysfunction associated with chemotherapy. The authors focused on the problem of defining cardiotoxicity as well as diagnostic methods, which may be useful in predicting the occurrence of such complications. Currently, cardiac biomarkers measurement (troponin, NT-proBNP), tissue Doppler-based strain imaging and peak systolic longitudinal strain rate are most useful for detection of early myocardial changes during therapy, whereas speckle tracking echocardiography (STE) and peak systolic global longitudinal strain (GLS) appear to be the best measure. The problem of cardiotoxicity requires close cooperation between oncologists and cardiologists, particularly in light of the growing number of cancer cases.

[Efficacy of alcohol withdrawal syndrome therapy in patients from Independent Public Hospital for Mental Diseases in Miedzyrzecz]. / Skutecznosc leczenia alkoholowego zespofu abstynencyjnego u pacjentów Samodzielnego Publicznego Szpitala dla Nerwowo i Psychicznie Chorych w Miedzyrzeczu.

Consumption of alcohol is a serious social problem. Research on alcohol addicts prove that its consumption affects the physical and mental health of drinking person, his/her family and the social dimension (eg. crime, unemployment, poverty). The aim of this study was to evaluate the effectiveness of the treatment of alcohol withdrawal syndrome (AW) in patients of 2417 Unit of Treatment of Alcohol Withdrawal Syndromes of Independent Public Hospital for Mental Diseases (SPSNPCH) in Miedzyrzecz. The study was conducted in 122 of 24/7 Unit of Treatment of Alcohol Withdrawal Syndromes (SPSNPCH) treated from January to March 2015. Patients during hospitalization were subjected to intensive pharmacotherapy of AW (Stage I) and cognitive-behavioral therapy (Stage II). Of the group of 122 people starting treatment Stage I was completed by 112 patients (90%); 10 patients (8%) have been discharged at their own request. The participation in Stage II was consented only by 54 patients, of which 6 (4%) withdrew from this form of therapy. Full two-stage treatment consisting of pharmacotherapy of AWS and then psychotherapy was completed only by 48 (39%) patients.

How does autoimmune thyroiditis in children with type 1 diabetes mellitus influence glycemic control, lipid profile and thyroid volume?

AIM: To investigate whether autoimmune thyroiditis (AIT) in children with type 1 diabetes mellitus (DM1) has any influence on glycemic control, lipid profile or thyroid volume. METHODS: A total of 330 patients with DM1 and AIT (DM1+AIT group) were compared with 309 children with DM1 without AIT (control group). Patients were treated in four Polish academic pediatric diabetes centers from 2008 to 2012: Warsaw, Lodz, Katowice and Gdansk. All patients underwent measurements of thyroid-stimulating hormone (TSH), free thyroxine, anti-thyroid peroxidase (anti-TPO) antibody, anti-thyroglobulin (anti-TG) antibody and HbA1c levels, and thyroid ultrasound examination. RESULTS: Among AIT+DM1 patients, 62% (n=205) were female, whereas in the control group 60.8% (n=188) were male (p<0.0001). Children with AIT+DM1 had lower a BMI-SDS (mean difference of -0.5, 95% CI -0.68 to -0.33; p<0.0001), had a higher SDS thyroid volume (0.27, 95% CI 0.03-0.51; p=0.014) and needed less insulin (-0.15, 95% CI -0.20 to -0.11 U/kg body weight per day; p<0.0001) in comparison with the control group. AIT patients had higher HbA1c levels (0.66, 95% CI 0.36%-0.96%, p<0.0001), lower HDL-cholesterol levels (-3.68, 95% CI -1.41 to -5.94 mg/dL, p=0.002) and higher triglyceride levels (7.16, 95% CI 1.22-13.10 mg/dL, p=0.02). Patients with positive anti-TPO and anti-TG antibodies were older (by 1.95 years, 95% CI 0.98-2.92 years, p=0.006) and had longer DM1 duration (by 1.64 years, 95% CI 0.76-2.52 years, p=0.006). Presence of anti-TPO antibodies was associated with higher TSH levels (odds ratio 2.34, 95% CI 1.36-4.04; p=0.007). CONCLUSION: AIT accompanying DM1 is associated with worse glycemic control and lipid profile as well as a lower daily insulin requirement. The female gender is more likely to develop AIT and hypothyroidism.

[Analysis of the problem of addiction in the elderly]. / Analiza problemu uzaleznien w grupie osób w wieku podeszlym.

Demographic changes observed in recent decades around the world lead to the aging of societies at a rapid rate. The increasing number of elder people is a result of extending the average length of human life. Elder people are struggling with many problems--loneli- ness, disability or financial problems. The problem can also be addiction, usually suspected in young people. The aim of the study was to evaluate the prevalence of addiction--smoking, drinking alcohol, use of medicines and drugs, watching television or using the Internet--in the elderly. Additional objective was to assess the problem of sleep disorders and the purchase of OTC drugs, dietary supplements and vitamin preparations in this population. Examined group consisted of 104 people aged over 65 years, of whom only 23 were smokers and 86 were consumers of various alcohols. None of the respondents confirmed any contact with drugs and the use of addiction treatment. Only 4 respondents did not watch any TV programs and 37 did not use the Internet (nor themselves nor with the help of others). 94 respondents used drugs and non-prescription preparations. 57 responders did not experienced sleep disorders.

[Safety of nicotine addiction treatment]. / Bezpieczenstwo terapii uzaleznien od nikotyny.

Not all smoking addicts can succeed in quitting smoking with willpower only. These people may use nicotine replacement therapy (patches, gums, lozenges, sublingual tablets, inhalers), medicines (bupropion, varenicline and cytisine) and psychological aid. Each drug, besides its therapeutic effect, creates the risk of adverse reactions which number and severity is not always accepted by the patient. The aim of the study was to analyze adverse effects of bupropion, varenicline and cytisine formulations reported by patients. From July 2011 to June 2013 Regional Centre for Monitoring Adverse Drug Reactions (Department of Clinical Pharmacology, Department of Cardiology, Poznan University of Medical Sciences) recorded 32 suspected adverse reactions to the use of drugs for the treatment of nicotine addiction (12 after the preparation of cytisine and varenicline, 8 after preparations of bupropion). High determination caused that none of the patients withdrew from the therapy because of adverse effects.

L-thyroxine stabilizes autoimmune inflammatory process in euthyroid nongoitrous children with Hashimoto's thyroiditis and type 1 diabetes mellitus.

OBJECTIVE: To investigate if L-thyroxine (T4) treatment may influence the clinical course of autoimmune thyroiditis (AIT) or prevent progression to subclinical or overt hypothyroidism in euthyroid nongoitrous pediatric patients with type 1 diabetes mellitus (T1DM) and AIT. METHODS: The study was performed in four Polish pediatric diabetes centers. Of 330 children with T1DM and AIT followed between 2008 and 2012, 101 received L-T4 and 160 underwent clinical observation for 24 months. Thyroid stimulating hormone (TSH), free T4 (fT4), anti thyroid peroxidase antibody (anti-TPO), anti thyroglobulin antibody (anti-TG), glycosylated hemoglobin (HbA1c) levels, and lipid profile were assessed in all patients. Ultrasonographic evaluation was also performed in all children at each examination. RESULTS: Patients treated with thyroid hormones had higher TSH levels (3.99; interquantile 3.5 to 4.52 vs. 2.09 mIU/L; interquantile 1.55 to 3.06; pp<0.0001). A fall in TSH level (0.87 mIU/L 95% CI 0.43-1.30; pp<0.0001) was documented after the first year of treatment. FT4 level did not differ between the groups at baseline (p=0.7434), but rose in the treatment group and fell in the control group [mean difference 0.78 95% CI-0.22-1.53 pmol/L (p=0.02) after 12 months and 0.98 95% CI 0.04-1.76 (p=0.005) after 24 months]. Higher levels of anti-TPO were initially found in the treated patients (pp<0.0001) and significantly decreased over the 24-month period (pp<0.0001). Children in the treatment group had higher anti-TG levels (pp<0.0001), which showed a borderline decrease (p=0.08) in time. In the control group, anti-TG levels rose marginally (p=0.06) during the study. CONCLUSIONS: The data demonstrate that treatment with L-T4 in euthyroid pediatric patients with T1DM and AIT stabilizes autoimmune inflammation in the thyroid gland and is to be recommended as soon as the diagnosis is established.

[The attitude of the patients with mixed addictions towards the cigarette smoking]. / Stosunek pacjentów z uzaleznieniem mieszanym do nalogu palenia.

The nicotine addiction is an important problem of people also addicted from psychoactive substances and with behavioral addictions. Therefore the article tries to answers question concerning the attitude of patients with mixed addictions (including nicotine) to cigarette smoking. The surveys were carried out in Private Psychological Clinic. Among 20 patients, 17 were addicted to alcohol, 2 to drugs and 1 to internet. All patients with mixed addictions were also treated for the habit of smoking as an addiction. The results of this study suggested that addiction to psychoactive substances and internet is strictly associated with smoking.