Craving variations in patients with substance use disorder and gambling during C

INTRODUCTION

Following the development of the coronavirus disease-2019 (COVID-19) pandemic in Italy, a strict lockdown was imposed from March 9 to May 5, 2020. In the general population, problems such as depression, anxiety, post-traumatic stress symptoms,insomnia, and adjustment disorder symptoms increased[1]. The risks of selfmedication through alcohol or psychoactive substances abuse were also increased, as well as the tendency to adopt pathological behaviors, such as gambling and internet addiction[2,3]. Stressors are essential in the inception and protraction of substance use disorder (SUD). Many stressors are associated with lockdown conditions such as prolonged home confinement, depression and panic related to the disease's uncertainties, working from home, and fear of job loss. People exposed to these stressors may take refuge in addictive substances, increasing SUD incidence among the general population[4] in a post-modern society that is increasingly oriented towards the use of substances, favoring the development of symptoms of psychopathological interest[5]. The COVID-19 pandemic and lockdown are risk conditions for developing internet, videogames, or other addiction, decreased physical activity and related health issues, altered eating habits, and disrupted circadian rhythms. King[6] and Király[7] demonstrated how these behaviors increased during the lockdown, often generated as a coping strategy to stressful situations.

本研究发现，第2代320排螺旋CT机较第1代CT机辐射剂量(CTDI、DLP及ED)显著减小(P<0.01)，降低幅度约46%，更符合利用尽可能低的放射剂量达到临床诊断(as low as reasonably achievable，ALARA)的要求。此外，两代320排螺旋CT机之间的肝脏灌注参数值(PAF、PVF及PI)差异无统计学意义，具有可比性，说明可以用这2台CT机对同一病灶进行动态监测、随访。

In patients with pre-existing mental disorders, the symptomatology may flare up or worsen, generating increased suicidal ideation as a possible consequence[8-10].Substance users and gamblers are groups at risk of developing psychopathological symptoms in a lockdown situation. The phenomenon is likely due to various reasons,including: (1) The limited availability of illegal substances on the black market; (2) the insufficient presence of active treatment programs and the low availability of substitute drugs; and (3) the greater psychopathological susceptibility and lower resilience in a period of reduced economic resources and financial hardship[11,12].

In this study, we evaluated the impact of the COVID-19 pandemic and associated containment measures on craving, a prominent risk factor for relapse[12] in a group of patients suffering from SUD and/or gambling disorder (GD) who were in treatment in outpatient units or in residency programs as inpatients.

MATERIALS AND METHODS

This study was commissioned by the Italian Society of Psychiatry and conducted at the University "Gabriele d'Annunzio" of Chieti-Pescara during the Italian lockdown phase that lasted from March 3 to May 5, 2020. Recruitment centers were randomly chosen among all the structures providing services for SUD and GD patients in regions of Northern (Piemonte, Lombardia), Central (Lazio, Marche), and Southern Italy(Abruzzo, Calabria) (see Appendix A: List of recruitment centers). Randomization procedures were computerized (see Appendix B: Explanation of randomized procedures). Three online meetings were held to train clinicians to the administration of the questionnaire, before the study started. In each recruitment center, a clinician introduced the survey to all the eligible subjects. No compensation was provided for participation in the study. Of the 253 subjects recruited, 153 (mean age 39.8; 77.8%male) gave their consent and anonymously completed the questionnaire. Forty-one subjects completed a pencil and paper questionnaire during the interview. The clinician provided an online questionnaire to 112 patients who had virtual assessments due to lockdown restrictions. Questionnaires were anonymous and each subject was identified through a unique code with no other identifying data. Anonymity was maintained by placing the completed questionnaires in a box by the subject himself, so that the clinician could not associate the subject with his/her questionnaire. All participants provided informed consent. The inclusion criteria were: (1) Diagnosis of SUD or GD according to The Fifth Edition of the Diagnostic and Statistical Manual of Mental Disorders; and (2) being older than 18 years. The exclusion criteria were: (1)Diagnosis of dementia; and (2) refusal to give informed consent.

Our survey was organized into two sections. In the first section, we collected anamnestic and clinical variables (see Appendix C: List of anamnestic and clinical variables). In the second section, using a visual analogue scale (VAS), we asked the subjects to indicate the craving level for the primary substance of abuse and how much their craving and habits have changed from the beginning of lockdown. We chose to use the VAS because of its immediacy and extensive utilization to evaluate craving in addicted patients[13,14]. We investigated changes of: (1) Craving for substances and gambling; and (2) quality of life and life habits (Table 1). A VAS ranging from 0 (I do not use it/I do not do this anymore) to 10 (I use it/I do this much more than before)was employed. To assess changes in quality of life, we utilized a VAS ranging from 0(my life is much worse than before) to 10 (my life is much better than before) (see Appendix D: Questionnaire).

其次，提请宪法解释的主体不明确。我国现行法律制度中没有关于谁有权提请宪法解释的明确规定，而《立法法》《全国人大常委会议事规则》都规定了特定的立法提案主体，在参考上述规定的前提下，《宪法解释程序法(专家建议稿)》又吸纳了《立法法》关于法律解释提请主体、法规审查提请主体的相关规定，将提请宪法解释的主体规定为各国家机关和武装力量、各政党和社会团体、企业事业单位和个人。提请主体范围较广，对于推动我国宪法解释工作开展具有较强的推动力，但也需避免因提请主体过多，影响宪法的稳定性和权威性问题发生。

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Among 153 subjects that completed the questionnaire, the primary substances of abuse or pathological behavior are reported in Table 1.

Statistical analyses were performed using Statistica version 8.0. Quantitative parameters are presented as the mean ± SD and qualitative parameters as number and percentage per class. The Kolmogorov-Smirnov test was used to check for normality of distributions. Analysis of variance and Duncan post hoc test were employed to analyze differences among subgroup means. The associations between variables were measured using Pearson's correlation. Avalue of < 0.05 was considered significant.

The level of craving was significantly higher (= 4.36;< 0.05) in outpatients (=97; mean = 3.8 ± 3.1) living in their own home during the quarantine compared with inpatients (= 56; mean = 2.8 ± 2.8) in residential programs. Craving for tetrahydrocannabinol was the greatest (4.94,< 0.001) among various preferred substances(Figure 2).

RESULTS

①在立模上用墨线弹出标高线。以人工均匀摊铺，虚铺厚度一般为实际厚度的1.05～1.20倍。摊铺时应找准平整度与排水坡度，施工时对边角处特别注意有无缺料现象，要及时补料进行人工压实。

鼻科医师应该认真对待每一次医学模型中的解剖训练。在模拟标本操作前，鼻科医师应当首先熟练掌握鼻腔鼻窦、鼻颅底、鼻眶相关解剖的理论知识，并仔细阅读鼻鼻窦CT，了解鼻腔鼻窦解剖异常情况，需要充分熟悉鼻内镜鼻窦手术相关的器械特点和性能。具体操作过程中，必须注意规范化鼻内镜技术操作，明确掌握技术要点。我们推荐的鼻内镜鼻窦手术规范化操作步骤如下。

Sixty-seven (43.8%) of the participants reported a comorbid psychiatric condition,especially mood disorders (depression, bipolar disorder) and anxiety. In this subsample, a psychopharmacological treatment was reported by 94% of subjects. The variation in craving between the present and the month before showed VAS-related reductions of craving in 57%, increases in 24%, and no significant change in 19% of the sample (Figure 1).

将拌好的育苗床土装入盘或育苗钵中，新装的盘压在已经装好的盘上，一层层地压，下边压实的再拿到上边压新装土的盘，使育苗床土填实，再利用刮板从穴盘一方刮向另一方，使每个空穴都能平整的装满育苗土。

Patients with a dual diagnosis (= 67; mean craving VAS = 3.9) did not show a significant difference in the levels of craving [(1; 150) = 2.43,> 0.121] with respect to patients without psychiatric comorbidities (= 86; mean craving VAS = 3.1).

Overall, we observed an increased consumption of coffee and cigarettes in about half of the sample. In contrast, symptoms indicative of behavioral addictions and other substances' consumption remained almost stable (Table 2). Changes in life habits are shown in Table 2. Reduced quality of life due to COVID-19 driven by the lockdown was present in 51% of the patients; 25.5% declared no significant changes, and,surprisingly, 23.5% increased quality of life. Low levels of quality of life correlated with high craving scores (= -0.226,= 0.005).

DISCUSSION

One hundred and fifty-three patients completed a structured questionnaire evaluating craving and other behaviors using a visual analogue scale (VAS).Forty-one subjects completed a pencil and paper questionnaire during the interview. The clinician provided an online questionnaire to 112 patients who had virtual assessments due to lockdown restrictions. Statistical analyses were performed using Statistica version 8.0. Quantitative parameters are presented as the mean ± SD and qualitative parameters as number and percentage per class.The Kolmogorov-Smirnov test was used to check for normality of distributions.Analysis of variance and Duncan post hoc test were employed to analyze differences among subgroup means. The associations between variables were measured using Pearson's correlation. Avalue of < 0.05 was considered significant.

In order to explain this controversial data, we propose the hypothesis of a perceived lack of availability of substances and gambling areas. Practical difficulties in sources of supply, such as the unavailability of the usual dealing spaces, may have interrupted the development of the craving priming. Craving is usually determined by the possibility to obtain a substance. When external measures limit this possibility, cravingitself could be dramatically reduced, as the case of the strict lockdown. Second, we hypothesize the presence of decreased social pressure on a group of subjects who are usually excluded and stigmatized. Social exclusion is indeed a psychosocial stress factor[22] that can increase craving and drug use[23]. As social identification is the self-definition of a person in terms of group membership[10], the period of lockdown because of the COVID-19 pandemic can favor personal feelings of being part of a group facing a common danger and sharing a common fate. Therefore, this new social identity might overshadow the sense of exclusion and rejection in the abuser,ultimately with the positive outcome of reducing craving and substance abuse. This possibility is consistent with data from a survey released by the Israel Democracy Institute that showed how the sense of belonging and unity increased during the COVID-19 outbreak among groups usually sidelined[24]. In this direction, the use of a specific strategy such as telepsychiatry acquires great importance for careful monitoring of the patient’s clinical and psychopathological conditions, in order to prevent relapses and to promote social integration[25].

Our data also indicates that residential treatment in containment facilities during the quarantine is an effective procedure that positively impacts craving levels,probably reinforcing the first hypothesis regarding the unavailability of the substance as a means to reduce craving.

In line with other studies, our data showed an increase in the consumption of coffee and cigarettes. Increased cigarette use could be explained as a natural response to stressful events, especially as a consequence of depressive symptoms; the consumption of coffee could be determined by the tendency towards sugary foods and drinks, in order to find quick relief in stressful times[26,27].

It is also interesting to note that a relevant part of the sample reported reduced quality of life during the strict lockdown, with a negative correlation between craving and perceived quality of life. This data leads us to hypothesize that despite a substantial reduction in the perceived quality of life, the levels of craving have in any case been reduced, as a counter-proof of how much the unavailability of the substance and the increase in social integration may have had a direct positive effect on the reduction of craving.

Limitations

The main limitation of our study is the high prevalence of cocaine abusers. This demographic feature is different from other treatment-seeking cohorts where alcohol is generally the main substance of abuse. This discrepancy is probably because our recruitment centers are specialized in the treatment of cocaine use disorder. Another limitation of the study is the use of a VAS instead of validated scales. We chose to use VAS because of its immediacy to homogenize and accelerate the completion of the questionnaire, making it suitable also online during the virtual assessments due to lockdown restrictions. Our results are difficult to generalize because of the brief time of observation, and further studies are needed.

CONCLUSION

Our data suggest that craving was globally reduced in a period that could be highly stressogenic. This unexpected result may be explained by: (1) A perceived lack of availability of substances and gambling areas that interrupted the development of the craving priming; and (2) the presence of a decreased social pressure. Our results can lay the groundwork for future treatment policies in the direction of strategies that limit the availability of the substance and in parallel towards strategies that aim at greater social integration of subjects affected by addiction disorders.

好好给我捻船，我一分钱都不亏你，从今天起，每天给你加一百。王鲶鱼说着，嘴里刁着一颗软中华，脚下喀嚓喀嚓几声，就消失在码头那边的阳光里。

Our data suggest that craving, regardless of whether determined by substances or behaviors, was globally reduced in a period that could be highly stressogenic. This data leads us to hypothesize that despite a substantial reduction in the perceived quality of life, the levels of craving have in any case been reduced, as a counter-proof of how much the unavailability of the substance and the increase in social integration may have had a direct positive effect on the reduction of craving.

Our results can lay the groundwork for future treatment policies in the direction of strategies that limit the availability of the substance and in parallel towards strategies that aim at greater social integration of subjects affected by addiction disorders.

APS-C单反都可以使用同品牌全画幅单反的镜头，但反过来却不一定可以。佳能的EF-S系列镜头只能在旗下的APS-C机身上使用，而尼康的全画幅相机则可以使用DX系列镜头，但相机会自动切换到DX模式。无反相机的卡口与单反不同，但可通过转接环转接其他系统的镜头。

The authors wish to dedicate this manuscript in memory of Dr. Sepede. Her energy and scientific keenness will continue to be a reference model for us. The authors also wish to thank the “CO-dip group” for the help in carrying out the study: Ceci Franca,Lucidi Lorenza, Picutti Elena, Di Carlo Francesco, Corbo Mariangela, Vellante Federica, Fiori Federica, Tourjansky Gaia, Catalano Gabriella, Carenti Maria Luisa,Concetta Incerti Chiara, Bartoletti Luigi, Barlati Stefano, Romeo Vincenzo Maria, and Valchera Alessandro.