End-of-life in the operational functioning of public healthcare: ethical and legal issues.

BACKGROUND AND AIM: The article aims to outline the current scenario relative to the medical role in end-of-life issues. In order to do this, historical-legal references have been drawn upon relating to technical, legal and scientific thought and doctrine, as it has come down to us in the medical field through the evolution of ethical and philosophical frameworks. METHODS: The authors have conducted a thorough analysis of end-of-life legislative initiatives, in Italy and across the EU, and court rulings to outline possible ways to harmonize and reconcile the current medical ethics frameworks with the needs and rights of all, especially the most vulnerable among us. To that end, the necessary operational choices and adjustments have not yet been made by our legal system, from a technical, as well as moral, standpoint. RESULTS: An operational proposal has therefore been laid out to protect both healthcare providers and patients, in a relationship that goes beyond treatment in the strict sense, which prioritizes mutual needs as an integral part of a common, essential path. CONCLUSIONS: In order for doctors to consider themselves complete, they should in fact deal not only with life, but also with death.

Conscientious objection to abortion: how to strike a legal and ethical balance between conflicting rights?

The Italian Supreme Court ruling no. 18901 of May 13, 2021 has determined that doctors who are opposed to abortion can refuse to perform it on grounds of conscience, but such a refusal does not exempt them from providing assistance to the woman before and after the procedure itself. The legalization of abortion should be considered within a broader strategy to put an end to underground and unsafe abortions, to raise awareness and enhance reproductive education and accessibility to contraceptive methods. The authors have set out to briefly analyze the legal and ethical complexities inherent in the effort to reconcile women's reproductive autonomy and freedom of choice with conscience-based refusal on the part of numerous healthcare professionals. Such an apparent conflict highlights the need for an ethically tenable solution that takes into account the dignity of unborn children, based on the conviction of many healthcare professionals primarily based on moral and religious tenets, that life begins at conception as well as the reproductive freedom and autonomy of women.

Influence of choline chloride-based NADES on the composition of Myristica fragrans Houtt. essential oil.

Natural deep eutectic solvents (NADES) have emerged as green extracting solvents in recent years. In this study, a variety of choline chloride (ChCl)-based natural deep eutectic solvents (NADES) were used as co-solvents for the hydrodistillation of nutmeg with the aim to obtain M. fragrans essential oil (EO) in higher yield and with a lower content of toxic phenylpropenoids (e.g. myristicin and safrole). The influence of ChCl-based NADES as additives in the hydrodistillation process was studied. The results showed that NADES additives improved the yield of the extracted essential oil and influenced its composition leading to a decrease in toxic phenylpropenoids. Best results were achieved by using ChCl-CA NADES ultrasound-assisted pretreatment coupled with traditional 2 â€‹h Clevenger hydrodistillation that increased the yield of the EO from 0.98% (traditional) to 1.41% and a decrease of the phenylpropenoids amount in the essential oil.

New Psychoactive Substances and receding COVID-19 pandemic: really going back to "normal"?

To the Editor, The ongoing rise of New Psychoactive Substances (NPS), i.e. psychotropic molecules devised and synthesized to replicate the effects of traditional drugs of abuse in order to circumvent banned substances schedules, has been posing a challenge of enormous magnitude to substance detection systems and law enforcement worldwide. Still, it would be remiss to ignore the role played by the unprecedented public health emergency relating to the COVID-19 pandemic in the exacerbation of the NPS crisis. The diversion of resources has in fact hindered conventional approaches to drug monitoring, surveillance, control, and public health responses. The dangerous path ahead in our struggle against NPS abuse is best exemplified by the rather recent emergence of isotonitazene, an analogue of a benzimidazole class of analgesic compounds, powerful synthetic opioid and full mu-opioid receptor agonist belonging to the 2-benzylbenzimidazole group of compounds, which comprises the structurally different clonitazene, metonitazene and etonitazene (1). Isonitazene has reportedly been detected on European markets in at least five different forms and could even supplant fentanyl derivatives (2). Currently available data on isonitazene-related abuse and fatalities seem to be emblematic of the volatile, elusive nature of NPS: deaths in which isotonitazene was involved in fact presented substantial differences from casualties arising from synthetic opioids abuse. Case reports have highlighted how flualprazolam was detected in most fatalities associated with isotonitazene whereas flualprazolam was involved in only 8% of other synthetic opioid overdose deaths (3). Rather than rising background use, such a finding seems to suggest likely co-use or co-distribution of flualprazolam and isotonitazene. The key element of polysubstance involvement is rife in synthetic opioid overdose deaths. That being said, significantly more substances were implicated in isotonitazene-related deaths than fatalities linked to other synthetic opioid overdose (4, 5). Such dynamics and mortality patterns further stress the urgency of expanding health services for those suffering from opioid addiction disorders. Fine-tuned and standardized detection mechanisms relying on specialized assays based on sensitive instrumentation are essential for the timely and accurate characterization of such novel synthetic opioids (6-8). Isotonitazene in fact cannot be detected by common fentanyl testing strips (9). Hence, the essential nature of clinical and toxicological cannot be overstated, if we are to effectively deal with the public health risks arising from new substances or classes, along with the healthcare and social costs thereof (10). As new substances appear on illicit markets and are detected, their distinctive traits can only be identified by user experience, in the early stages (11-13). Nonetheless, the pandemic scenario has brought about a profound alteration of substance abuse patterns, and opened up new avenues of supply and demand for which our surveillance/detection systems may not be fully prepared or well-suited. As the pandemic appears to recede and hopefully turn into an endemic context based on coexistence with the SARS-CoV-2 and its less harmful variants, it would be a mistake to take for granted that drug abuse/trafficking dynamics will also get back to where they were before the pandemic. Putting in place policies aimed at monitoring web-based platforms and social media can potentially constitute a valuable tool in terms of keeping in check emerging substances, given how during the COVID-19 pandemic many interactions between traffickers and buyers have moved online (14). After all, social media have been playing an increasingly relevant role as interacting platforms, which users and drug dealers can take advantage of in order to discuss drug prices, substance purity, distinctive traits of the "high" (i.e. desired drug effects) they are seeking, ways of taking the substances, dosages, and characteristics of any new NPS becoming available on such back-alley marketing channels (15). Softwares designed and specifically programmed to sift through and analyze all detectable online information in that regard may prove valuable to figure out evolving dynamics of trafficking, purchases and use. Probing social media users has proven effective tool for public health concerns, e.g. drug checking services which have been harnessed due to their harm reduction potential in places estimated to be at risk, with large crowds gathering (concerts, clubs and the like). Nonetheless, research efforts need to be directed towards the new realm of criminality, the "Dark Web", in which all sorts of illegal exchanges and interactions are known to take place. A 2020 study has highlighted the appalling risks for drug users who choose to pursue that option in order to buy drugs (16). Three dealers were selected on a specific "Dark Web" marketplace, and NPS were ordered through such a channel. All these exchanges were thoroughly documented, and an analysis was undertaken of all the substances thus bought, totaling nine samples, by NMR, HRMS, LC-UV, and two also by x-ray diffraction. It was ultimately concluded that four out of five substances bought had been labeled with NPS names that did not match the actual substance, and two out of three samples of substances sold as new (i.e. unscheduled) NPS were instead found to be already documented substances, mislabeled and peddled under false pretenses. Drug dealers were therefore either deceiving their clients or were unaware as to the actual substances which they were selling. In light of such extremely worrisome findings, it is not hard to understand the implications and the major public health risks that such new trends of trafficking and abuse may entail. It is therefore incumbent upon the scientific community and law enforcement agencies to adapt and strive to meet the new challenges brought by the new criminal ecosystems in terms of drug enforcement, first and foremost the impervious environment known as "Dark Web" relying on untraceable cryptocurrencies for illegal transactions.

Oncofertility and Reproductive Counseling in Patients with Breast Cancer: A Retrospective Study.

INTRODUCTION: Improving the prognosis of breast cancer patients is of utmost importance in terms of increasing survival rates. Modern medicine has therefore prioritized better quality of life for patients, even after the disease, through a better management of the potential long-term side effects induced by anticancer treatments. Fertility preservation and family planning are therefore crucial issues to be addressed in all cancer patients of reproductive age. Along those lines, a new branch of medicine with distinct multidisciplinary characteristics has developed over the years: oncofertility. Although both national and international guidelines value reproductive counseling as an essential aspect of the diagnostic-therapeutic pathway, part and parcel of the informed consent process, it is not included within the protocols adopted by the operating units for the care and management of neoplastic diseases. OBJECTIVE: This study aimed to evaluate the activity of the Breast Unit of the Policlinico Umberto I Hospital, Rome, Italy, and the degree of compliance with guidelines. By knowing the strengths and weaknesses of such approaches, the standards of care offered to breast cancer patients can be improved. MATERIALS AND METHODS: A retrospective study based on a review of medical records was conducted between 2014 and 2021. Patients under 40 years of age diagnosed with non-metastatic malignancies were included who received chemotherapy treatment, namely neoadjuvant, adjuvant or adjuvant hormone therapy. RESULTS: The data were extracted from the medical records of 51 patients who met the inclusion criteria, 41% of whom received reproductive counseling, and of these, 43% decided to undertake a path of fertility preservation. Factors such as the absence of children and young age reportedly favored both the interest in counseling proposals by the medical staff and the decision to undertake a path of fertility preservation. CONCLUSIONS: The study shows that there has been growing interest in the topic of oncofertility, especially in light of law 219/2017. Therefore, since 2018, multiple proposals for reproductive counseling have been set forth, but there was not an equally growing demand for fertility preservation practices, which can be explained by the invasive nature of such practices, the patients' concern about their own state of health, and poor or inadequate information. Such impediments highlight the importance of standardized counseling and the need for a multidisciplinary medical team to support the patient in the decision-making process. The study also revealed a drop in the number of patients receiving counseling due to the COVID-19 pandemic, contrary to the positive trend that was recorded prior to the pandemic.

The effects of the COVID-19 pandemic on the use of the performance-enhancing drugs.

The coronavirus disease (COVID-19) pandemic has been impacting the whole society in every aspect of the daily life, comprising the sport field. Several restrictive strategies have been implemented by governments in an effort to stem the spread of the disease and salvage public health. Such efforts have severely constrained access to non-essential services, leading to the closure of non-essential points of gathering and business and the enforcement of rigorous social distancing and prolonged lockdowns, in addition to masking and stay-at-home mandates. However necessary, there is no denying that such extremely rigorous, and to most people unprecedented, measures have adversely affected the global economy and the daily lives of everyone of us, including professional and amateur athletes (1). The most important sport events were postponed or cancelled, including the 2020 Tokyo Olympic Games. But how was the phenomenon of performance-enhancing drug (PED) use impacted and how was the most concerning issue affecting the integrity of sport affected by the pandemic control restrictions? The World Anti-doping Agency (WADA) was established in 1999, whereas its code was implemented in 2004 in order to articulate and enforce doping control initiatives and provide educational strategies aimed at preventing PED use (2). Nonetheless, it is worth noting that the prevalence of PED use among athletes is mostly unchanged since the foundation of WADA. Unfortunately, the use of the performance-enhancing drugs is not limited to athletic performances, but it concerns other settings as well. Nowadays, several strategies for doping control are adopted such as education, deterrence, detection, enforcement and rule of law (3), but the most important anti-dissemination strategy is constituted by information campaigns, especially addressed to youngsters, meant to raise awareness as to the serious health risks involved in PED use. Currently, the primary drivers of anabolic androgenic steroids (ASA) use are 1) the determination to improve performances and prevail no matter what the cost may be; 2) the economic benefits, popularity and fame; 3) greater stamina and resistance. This public health issue has raised particular concerns due to the recent ASA market developments, which is somewhat similar to the illicit market of narcotic drugs. Moreover, it has to be considered that the higher stress and psychosocial condition related to pandemic social restrictions has fueled and exacerbated substance use disorders (4). The prevalence of doping in sport causes unfairness and damages the very fabric of our society, especially insofar as it involves children and young adults who look up to athletes as role models. In this concern, the impact of the COVD-19 pandemic may have led to substantial modifications in substance use patterns and an increased risk of substitution, adulteration, contamination, and dilution with a potentially harmful substance (5, 6). During the COVID-19 lockdown, WADA and stakeholders suspended or scaled down doping control programs, testing and other activities. As a consequence, athletes have seen the unexpected opportunity to misuse AAS without the possible risk of testing positive (7). This has been controversial, considering the measures taken by governments to flatten the pandemic curve in order to safeguard public health. Indeed, all the technologies implemented for teleworking, such as teaching students on-line, telehealth applications, prescriptions and referrals, and treating patients in hospitals/care homes via video links can also be applied to enhance and uphold sport integrity. Conversely, anti-doping testing for professional competitive athletes has increased, due to the lockdown raising suspicion about doping opportunities. The U.S. Anti-doping Agency has put in place novel measures to combat the lack of anti-doping testing during the pandemic: these include a "in-home self-test" that requires athletes to provide urine and small blood samples at home to be tested in the anti-doping laboratory, under supervision provided by video-conference (8). As such, reports from forensic science and toxicology laboratories are crucial for the early detection and response to such events. Furthermore, toxicology laboratories should assure their continue effort in providing new methods and technologies designed to tackle the consumption of illicit substances and to monitor the constantly changing illegal drug markets (9). The most recent WADA code revision has certainly brought about important progress in the ongoing fight against PED abuse. Indeed, it has introduced the possibility to store the samples for 10 years after the first analysis, maintaining the same legal value if re-tested and use for prosecution purposes (10). In that regard, the prospect of re-testing the same sample with newly developed analytical methods based on innovative technologies may represent a strong deterrent for doping users, since anti-doping research rapidly evolves (6), largely by implementing the same approaches used to fight new psychoactive substances (NPS) use (11,12). It is worth noting that the NPS phenomenon bears several similarities with doping, especially due to the constant emergence of new substances and methods aimed at circumventing current legal restrictions. In Italy, the National Antidoping Organization (NADO-Italia) is in charge of guaranteeing compliance with WADA rules and the transposition of the List of Prohibited Substances and Methods. However, the gap between elite athletes and amateur athletes is still broad and unaddressed, since non-professional sport competitions are not adequately overseen, and neither are the competing athletes . This difference may give rise to an important public health issue, on account of the adverse effects of uncontrolled doping agents consumption. In this concern, the Italian anti-doping law created the "Section of the Technical Health Committee for Supervision and Control on Doping and for Health Protection in Sport Activities", that carries out, among its other tasks, the following activities on amateur sport: 1) updating each year the list of banned substances and practices, adapting it to the WADA list; 2) determining cases, criteria and methodologies for anti-doping controls; 3) promoting research projects and information/training campaigns meant to protect health in sports and tackle doping (13). In conclusion, regarding the highly complex dynamics triggered by the pandemic, new and unexpected challenges have come to the fore in the ongoing fight against substance abuse in its every aspect, such as NPS (14), ASA consumption by amateur athletes, or other substance abuse settings, e.g. driving under the influence of psychotropic substances (15). The current Italian antidoping approach for amateur athletes seems to be a promising strategy to bridge the gap between professional sports and amateur sports. Moreover, youngsters should be thoroughly educated as to the threats posed by such substances, so that they can realize how profoundly and severely drug abuse can affect not only their sport career, but their health and well-being overall.

The March 2021 Italian constitutional court ruling on surrogacy: a prelude to common European legislation for the sake of reproductive health?

PURPOSE: Surrogacy is an arrangement by which a surrogate mother bears a child for another couple or person, and is often thought of as a form of 'treatment' for couples (or even individuals) with fertility or sterility issues. Still, surrogacy entails ethical issues related to gender, fundamental human rights, exploitation and inequality. MATERIALS AND METHODS: Starting from the Italian state of affairs, the authors have set out to briefly expound upon such complexities, taking into account relevant jurisprudence on the subject, with a particular focus on inter-country surrogacy and second-parent adoption, which can themselves engender significant legal dilemmas. When residents of countries where surrogacy is banned travel abroad and hire a surrogate, that may lead to considerable legal hurdles as well. RESULTS: In Italy and elsewhere, the courts have all too often had to fill the vacuum left by the lack of targeted legislation. The Italian Constitutional Court has recently urged lawmakers to enact new legislation to uphold the minor's best interests. In fact, while some countries recognise the surrogate as the legal parent, others ascribe parenthood to the commissioning parents. That discrepancy can lead to a 'clash of laws', resulting in children ending up stateless and unable to maintain an already established family relationship. CONCLUSIONS: Just like fundamental protection of human rights and public health, the regulation of revolutionary technologies that change the very notion of reproduction, parenthood, and human identity needs to be governed by uniform standards, shared at least by nations which espouse common core values.

Medically assisted procreation in times of COVID-19: what impact on health care system organization and the reproductive rights of couples?

BACKGROUND AND AIM: The emergency caused by the spread of COVID-19 has overwhelmed health care facilities and required the reorganization of health systems in many nations worldwide. A year after its appearance, measures aimed at further containing disease transmission through massive vaccination campaigns. In pregnancy, vaccination should be administered with caution, in light of the lack of reliable data, since pregnant women have been excluded from experimentation. The pandemic has had a significant impact on assisted reproduction procedures in Italy. Methods: The authors have set out to analyze the measures issued by the Italian government in order to counter the spread of COVID-19, in addition to the national and international guidelines on assisted reproduction. DISCUSSION: The purpose of these documents is precautionary in nature: such measures are based on the principles of responsibility and solidarity, essential to stave off the saturation of health systems, curb contagion, but also to lay out a set of rules to starting a pregnancy while preserving the health of couples, operators and newborns. The authors also expound upon the rights claimed by couples seeking access to MAP (i.e. the right to become a parent, the couple's right to health, interest in demographic development). Conclusions: The coronavirus disease 2019 (COVID-19) has had a major impact on infertile couples. Since the pandemic broke out, Italy, like most European countries, has interrupted most ordinary activities of the centers operating in the field of assisted fertilization. We believe that access to assisted fertilization techniques by sterile and infertile couples should be part of the right to health rather than of the supposed right to become parents or the increase in the birth rate, also evoked as the COVID-19 pandemic unfolded. The current system of compensation and reimbursements needs to be reconfigured in order to prevent any form of discrimination.

Does the EU COVID Digital Certificate Strike a Reasonable Balance between Mobility Needs and Public Health?

The need to fight a highly aggressive virus such as SARS-CoV-2 has compelled governments to put in place measures, which, in the name of health protection, have constrained many freedoms we all enjoy, including freedom of movement, both nationally and within the European Union. In order to encourage and facilitate the return to free movement, the European Parliament has launched a "COVID-19 digital certificate". A spirited debate centered around the use of this certificate is still ongoing among scholars, many of whom have pointed out the uncertainties relative to COVID-19 immunity, privacy issues and the risk of discriminatory effects. The authors, while highlighting some critical aspects, argue that the COVID digital certificate in its current approved version can effectively help prevent the spread of the infection and promote free movement, while upholding the right to health as much as possible. However, they also stress the need for a thorough information campaign to illustrate the advantages and limitations of this document in order to avoid creating a false sense of security in the public opinion, who may wrongly assume that the emergency has been overcome for good.

Posthumous sperm retrieval: a procreative revolution.

Aim Postmortem sperm retrieval with consequent artificial insemination has become a technically possible option for future use in assisted reproductive technology (ART). The authors have set out to discuss the social and ethical significance of posthumous sperm retrieval, and the laws currently in force in Italy, the United States and elsewhere. Methods International literature from 1997 to 2020 has been reviewed from Pubmed database, Google Scholar and Scopus, drawn upon American, Italian and international sources (an ethically acceptable solution can only be achieved through an overhaul of the laws currently in effect). One of the most contentious issues was about donor consent. In Italy, a donor's will to retrieve his sperm in the event of premature disappearance can be proven according to the Law 219/2017, through advance health care directives. Results A substantial increase, both in requests and protocols, was documented in the United States. In Italy, over the last two years, three rulings were issued concerning posthumous insemination. However, no official standardized protocols, guidelines or targeted legislation exist at the national level to regulate medical activity in that realm, whereas established laws often set implicit limitations. Conclusion Current legal frameworks appear to be inadequate, because in most cases they were conceived under conditions that have radically changed. The need for newly-updated regulatory frameworks to promptly bridge that gap is increasingly clear, if current social needs related to reproductive rights are to be met in the foreseeable future.

Relationship between work fatigue and manual dexterity in dental professionals: observational study.

BACKGROUND: Neuro-muscular fatigue (ANM) in the upper limbs can cause impaired coordination and dexterity. The main purpose of the study was to investigate whether ANM induced by a working day produced a reduction in digital dexterity in a population of dental health workers (OSD). Secondary objective was to investigate whether there were relationships between any reductions in dexterity and independent socio-demographic variables (gender, age and profession). METHODS: A cohort of OSD was assessed before and at the end of a working day of at least 7 hours using the Functional Dexterity Test (FDT). The effects of ANM (time), of the tested limb (dominance), and of their interaction on dexterity were investigated using two-way ANOVA. A multiple linear regression model was applied to explore the relationship between dexterity performance and independent variables. RESULTS: A total of 50 OSDs were included. The net time of the FDT at the end of the day was always higher than in the morning. The ANOVA showed a significant difference for time (p <0.001) and side (p <0.001), but an effect from the interaction between the two factors was not identified (p = 0.428). The worsening of manual dexterity appears to be weakly correlated with age on both sides, and with the profession in the dominant limb. CONCLUSION: The ANM appears to have negatively affected the dexterity of both hands in the sample examined. The results of this study may be useful for planning the OSD's work agenda more carefully.

Relationship between nerve conduction studies and the Functional Dexterity Test in workers with carpal tunnel syndrome.

BACKGROUND: Dexterity impairments caused by carpal tunnel syndrome (CTS) make working and daily activities challenging. We aimed to investigate: i) the relationship between dexterity and nerve conduction studies (NCS) in workers with classic symptoms presentation; ii) the ability of the Functional Dexterity Test (FDT) to discriminate different levels of CTS severity as classified by NCS; iii) the diagnostic accuracy of a clinical battery composed of the FDT, Phalen's test and Tinel's sign. METHODS: In a convenience sample of individuals diagnosed with CTS, we correlated FDT net scores with the NCS-based classification by means of Spearman's (rho) test. Discriminative ability of the FDT was assessed by ANOVA, and a ROC curve determined cutoff thresholds. Sensitivity, specificity, and likelihood ratios (LRs) were used to investigate the diagnostic accuracy of the clinical battery. RESULTS: Data from 180 hands were collected. The FDT was significantly correlated (rho = 0.25, p <  0.001) with NCS. The FDT was able to discriminate subjects with severe/extreme NCS findings, and two thresholds (0.29-0.36) were identified. Adding the FDT to the provocative tests improved the overall diagnostic accuracy (specificity: 0.97, CI95% 0.83-0.99; LR+: 14.49, CI95% 2.09-100.53). CONCLUSIONS: Sensorimotor impairments related to CTS can affect hand dexterity. The FDT discriminated patients with severe NCS involvement. Positive results on the clinical battery (Phalen, Tinel, and FDT) could help to confirm the CTS diagnosis, showing a very high specificity and LR+. On the contrary, the low sensitivity is not able to rule out CTS in individuals with negative results.

Rehabilitation strategies for low anterior resection syndrome. A systematic review.

OBJECTIVE: To summarize the evidence in the literature about rehabilitative treatments that reduce low anterior resection syndrome (LARS) symptoms in patients who underwent surgery for colorectal cancer. METHODS: We have search in PubMed, Cochrane Central Register of Controlled Trials, Cumulative Index of Nursing and Allied Health and Scopus databases. Studies selected were limited to those including only patient undergone low rectal resection with sphincter preservation and with pre-post assessment with a LARS score. Five articles fit the criteria. RESULTS: The percutaneous tibial nerve stimulation demonstrated moderate results and sacral nerve stimulation was found to be the best treatment with greater symptom improvement. Only one study considered sexual and urinary problems in the outcomes assessment. CONCLUSIONS: In clinical practice patients should evaluate with the LARS and other score for evaluation of urinary and sexual problems. Future research must be implemented with higher quality studies to identify the least invasive and most effective treatment/s.