Substitution Therapy Research Articles

Preliminary Investigation of Microbiome and Dietary Differences in Patients with Phenylketonuria on Enzyme Substitution Therapy Compared to Traditional Therapies

BackgroundPhenylketonuria (PKU) is an inborn error of metabolism that impairs the function of the enzyme phenylalanine hydroxylase. Historical treatment includes limiting dietary phenylalanine (Phe) consumption while supplementing with medical food; however, this treatment has been associated with complications, such as nutritional deficiencies and disruptions in the gut microbiota. ObjectiveThe study aim was to compare dietary and gut microbiome differences between adult patients on a traditional PKU diet with those receiving the enzyme substitution therapy Palynziq on a liberalized diet while controlling blood Phe levels to <600 μmol/L (to convert to mg/dL divide by 60.5). DesignA cross-sectional study was conducted comparing patients on a traditional Phe-restricted diet with patients receiving Palynziq eating a liberalized diet. Participants/settingSix patients eating a traditional Phe-restricted diet with medical food and 6 patients on Palynziq eating a liberalized diet without medical food intake for more than 3 years were selected from the University of Kentucky Metabolic Clinic from August to December 2019. Main outcome measuresNutrient intake from 3-day diet records and fecal microbiome taxonomic abundances were analyzed. Statistical analysisMann-Whitney U tests were used for dietary data analysis. Differential abundance analysis for microbiome taxa and pathway data was done using DESeq2 analysis. ResultsDietary data showed patients receiving Palynziq consumed a lower percent of kilocalories from total protein and lower amounts of most micronutrients, but consumed greater amounts of intact protein and cholesterol (P < .05). Microbiome data revealed a greater abundance of the phylum Verrucomicrobia and genus Lachnobacterium in the Traditional group and a greater abundance of the genus Prevotella in the Palynziq group (P < .05). Pathway analysis depicted greater enrichment in carotenoid and amino acid metabolism pathways in the Traditional group (P < .05). Protein (% kcal), dietary fiber (g), fat (% kcal), linolenic acid (% Dietary Reference Intakes), and age were correlated with the underlying microbial community structure for both groups combined. ConclusionsPatients with PKU treated with Palynziq on a liberalized diet manifest significant differences in diet composition compared with those treated with traditional Phe-restricted diets. Several of these dietary differences may affect the microbiome architecture.

Aggression towards clinicians within Opiate Substitution Treatment (OST) services: A survey of service providers

BackgroundHigh levels of aggression towards staff in healthcare settings have been reported. It seems likely that workers in Opioid Substitution Therapy (OST) would be at increased risk of adverse events and their consequences. ObjectivesThis study aimed to establish if practitioners who provide OST are experiencing negative outcomes, specifically aggression, distress, and burnout, and to identify if workload and professional affiliation were associated with these risks. MethodsA survey was conducted of OST practitioners in a single geographical region of New Zealand (population approx. 344,000). The survey asked for demographics (including caseloads), Perception of Patient Aggression Scale New Zealand Revision (POPAS-NZ), Kessler 10 (K10), Short Post-Traumatic Stress Disorder Rating Interview (SPRINT), and Abbreviated Maslach Burnout Inventory (aMBI) and two qualitative questions asking about the best and worst aspects of working in OST. ResultsAll recorded OST workers in the region (n = 181) were invited to participate, 95 practitioners responded to the survey (52.4%). This group included pharmacists, doctors, nurses, social workers and addiction workers. Results indicated aggression, distress, and burnout were being experienced by practitioners. Number of patients seen by a practitioner significantly increased risk of aggression (F(1,90) = 14.14, p < 0.001). Psychiatrists were the most at risk profession (p = 0.016). Burnout responses were high for around 20% of practitioners, with low numbers meeting criteria for distress and PTSD. Positive things about working in OST were relationships with patients, appreciating patient outcomes and positive team environments. Negative aspects were patient behaviours, maintaining empathy, and, administration tasks. ConclusionsAggression was a workplace hazard for OST clinicians. Low rates of distress and PTSD symptoms were reported and some evidence of practitioner burnout. Practitioners reported positive relationships, making a difference and teamwork may have been improving this area of mental health work.

The Association Between Three Adipocytokines (Adiponectin, Resistin and Visfatin) And Thyroid Status in Patients With Type 2 Diabetes Mellitus and Autoimmune Thyroiditis.

Autoimmune thyroiditis (AIT) and type 2 diabetes mellitus (DM2) are the most common endocrinological diseases worldwide. Relation between these diseases explains several hypotheses. One of them is influence of some adipocytokines. This study evaluated association between three adipocytokines (adiponectin, resistin and visfatin) and thyroid and glycid status in patients with DM2 and AIT compared to the control group (CG). The group consisted of four subgroups: patients with DM2 without thyreopathies, patients with AIT on substitution therapy without diabetes and prediabetes, patients with DM2 and AIT on substitution therapy and healthy subjects as the CG. We investigated parameters of thyroid and glucose metabolism and serum levels of three adipocytokines. The mean level of resistin in the group of patients with diabetes and thyroiditis was significantly higher than in patients with thyroiditis without diabetes and than in the CG. We found a weak negative correlation between visfatin and fasting glucose levels in patients with thyroiditis without diabetes. We detected a weak negative correlation between resistin and glycated haemoglobin and a weak negative correlation between visfatin and thyroid gland volume in patients with diabetes without thyroiditis. In the CG we determined a weak positive correlation between visfatin and free thyroxin. Our results are consistent with several studies, which confirmed association between AIT and adipocytokines.

Еye manifestations of Gaucher’s disease

Gauchers disease is a rare autosomal recessive disease that belongs to the group of sphingolipidoses. This pathology is caused by a lysosomal enzyme glucocerebrosidase deficiency, which leads to its substrate, glucosylceramide, accumulation in macrophages, and leads to damage to the nervous system, parenchymal organs, and the hematopoietic system. The literature reported isolated cases of vision organ damages such as oculomotor function disorders and violations of the structure of the vitreous, retina, cornea, choroid, and conjunctiva. During diagnosis, these clinical symptoms may cause interpretation and, possibly, substitution therapy evaluating difficulties. Retinal changes in Gauchers disease are poorly understood, but they are an important symptom of this disease, which dynamically visualizes and evaluates the substrate deposition in the preretinal and intraretinal layers. The effectiveness of replacement therapy based on the presence of retinal lesions remains controversial.&#x0D; Herein, presented the description of a clinical case of a 10-year-old boy with ocular manifestations of Gauchers disease, a rare orphan disease. The comprehensive ophthalmological examination results revealed preretinal changes in whitish foci in the paramacular zone, microstructural changes in the central retina according to optical coherence tomography, and moderate changes in retinal functions according to electroretinogram, as well as visual field defects and decreased light sensitivity. The revealed changes indicate a violation of metabolic processes in the retinal layers of the eye, which leads to retinal foci (gosher) formation. Noninvasive visualization of these deposits helps assess the disease course and the substitution therapy effectiveness. The management of patients with Gauchers disease requires an interdisciplinary approach with the mandatory involvement of an ophthalmologist.

The inhibition of enkephalin catabolism by dual enkephalinase inhibitor: A novel possible therapeutic approach for opioid use disorders.

Despite the increasing impact of opioid use disorders on society, there is a disturbing lack of effective medications for their clinical management. An interesting innovative strategy to treat these disorders consists in the protection of endogenous opioid peptides to activate opioid receptors, avoiding the classical opioid-like side effects. Dual enkephalinase inhibitors (DENKIs) physiologically activate the endogenous opioid system by inhibiting the enzymes responsible for the breakdown of enkephalins, protecting endogenous enkephalins and increasing their half-lives and physiological actions. The activation of opioid receptors by the increased enkephalin levels, and their well-demonstrated safety, suggests that DENKIs could represent a novel analgesic therapy and a possible effective treatment for acute opioid withdrawal, as well as a promising alternative to opioid substitution therapy minimizing side effects. This new pharmacological class of compounds could bring effective and safe medications avoiding the major limitations of exogenous opioids, representing a novel approach to overcome the problem of opioid use disorders. LINKED ARTICLES: This article is part of a themed issue on Advances in Opioid Pharmacology at the Time of the Opioid Epidemic. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v180.7/issuetoc.

Living Under Coronavirus and Injecting Drugs in Bristol (LUCID-B): A qualitative study of experiences of COVID-19 among people who inject drugs.

BackgroundPeople who inject drugs (PWID) are a high-risk group for COVID-19 transmission and serious health consequences. Restrictions imposed in the UK in response to the pandemic led to rapid health and housing service alterations. We aimed to examine PWID experiences of: 1) challenges relating to the COVID-19 public health measures; 2) changes to opioid substitution therapy (OST) and harm reduction services; and 3) perceived effects of COVID-19 on drug use patterns and risk behaviour.MethodsTelephone semi-structured interviews were conducted with 28 PWID in Bristol, Southwest of England. Analysis followed a reflexive thematic analysis.ResultsConcern about COVID-19 and adherence to public health guidance varied. Efforts made by services to continue providing support during the pandemic were appreciated and some changes were preferred, such as less frequent OST collection, relaxation of supervised consumption and needle and syringe programmes (NSP) home delivery. However, remote forms of contact were highlighted as less beneficial and more difficult to engage with than in-person contact. Public health guidance advising people to ‘stay home’ led to increased isolation, boredom, and time to ruminate which impacted negatively on mental health. Lockdown restrictions directly impacted on sources of income and routine. Changes in drug use were explained as a consequence of isolation and fewer interactions with peers, problems accessing drugs, reduced drug purity and reduced financial resources.ConclusionThis study captures the significant impacts and challenges of the COVID-19 pandemic on the lives of PWID. While rapid adaptations to service delivery to help mitigate the risks of COVID-19 were appreciated and some changes such as relaxation of supervised daily OST consumption were viewed positively, barriers to access need further attention. Going forwards there may be opportunities to harness the positive aspects of some changes to services.

Первичная надпочечниковая недостаточность: диагностика и менеджмент (по материалам 17th European Congress of Endocrinology, Dublin, Ireland 16–20 May, 2015)

Первичная надпочечниковая недостаточность (ПНН, болезнь Аддисона) — курабельное заболевание, остающееся потенциально смертельным. ПНН нередко выявляется уже в состоянии надпочечникового криза, при этом своевременная неотложная терапия может предотвратить летальный исход. Для минимизации риска возникновения как надпочечниковых кризов, так и побочных эффектов заместительной терапии при данной патологии чрезвычайно важны индивидуализация схемы лечения (оптимальными являются препараты гидрокортизона в сочетании с флудрокортизоном), выявление сопутствующих аутоиммунных заболеваний, обучение пациентов умению как корректировать ежедневную терапию, так и делать себе инъекции глюкокортикоидов при появлении умеренно выраженных сопутствующих заболеваний. Продолжительность жизни пациентов, получающих адекватную терапию и находящихся под регулярным наблюдением, не отличается от среднестатистической.

Patients'satisfaction and experience in treatment with opioid substitution therapy in Spain. The PREDEPO study.

The aim of this study was to compare patients' satisfaction, experience, objectives, and opinion based on their current opioid substitution therapy (OST) (buprenorphine/naloxone (B/N) or methadone). The PREDEPO study is an observational, cross-sectional, multicentric study performed in Spain. Adult patients diagnosed with opioid use disorder (OUD) receiving OST were included. They were asked to fill in a questionnaire regarding their current OST. A total of 98 patients were enrolled (B/N: 50%, methadone: 50%). Mean age was 47 ± 8 years old and 80% were male. Treatment satisfaction was similar between groups. The most frequently reported factor for being "very/quite satisfied" was "being able to distribute the dose at different times throughout the day" (44% B/N vs. 63% methadone; p = .122). A significantly lower proportion of patients in the B/N group versus the methadone group reported that having to collect the medication daily was "very/quite annoying" (19% vs. 52%, p = .032). Treatment objectives reported by the majority of patients were similar between groups ("not feeling in withdrawal anymore", "reduce/definitely stop drug use", "improve my health", and "stop thinking about using daily") except for "not having money problems anymore" (73% B/N vs. 92% methadone; p = .012). These results suggest there are several unmet expectations regarding current OST. There is a need for new treatments that reduce the burden of OUD, avoid the need for daily dosing, and are less stigmatizing which in turn could improve patient management, adherence and, quality of life.

Vitamin D Deficiency in Children with Chronic Renal Disease

BACKGROUND: Vitamin D is essential for children and adults for healthy bone growth. Lack of this vitamin in children can cause rickets, and in adults, softening of the bones and an increased risk of fractures. Vitamin D deficiency can cause immune disorders, increased susceptibility to infections, the development of certain types of cancer, diabetes mellitus, and cardiovascular diseases. AIM: The article presents the literature data and the results of our own research on the analysis of the relationship between chronic kidney disease (CKD) and Vitamin D provision in children from 1 to 17 years old. The aim of the study was to establish the level of Vitamin D in children with different stages of CKD. METHODS: Between January 2020 and September 2020, we examined 40 children (16 boys and 24 girls). The patients’ age ranged from 1 to 17 years inclusive. RESULTS: Vitamin D deficiency was found in 62.5% of children with CKD. Vitamin D deficiency was noted in 25% of cases. The prevalence of Vitamin D deficiency correlates with a decrease in glomerular filtration rate. CONCLUSION: Determination of Vitamin D level in children with CKD is important for timely correction and prevention of further progression of CKD. Timely substitution therapy will improve the quality of life of a child with CKD and prevent the development of complications.

Sexual Dysfunction in Males Receiving Buprenorphine-Naloxone Based Opioid Substitution Therapy

Abuse of opioids and related substances have exerted a tremendous economic, social, legal impact apart from its dire consequences on the individual user’s health. Heroin is a quite common illicit opioid that is covertly made available by illegal traders and has a wide client base. The abuser self-administers heroin by two common methods, namely chasing and intravenous injection. Intravenous administration is associated with high risks of contracting parenterally transmitted infections like hepatitis B, hepatitis C, HIV, as well as infective endocarditis, thrombophlebitis etc. The unsafe injecting practices include sharing of needles, syringes, and other paraphernalia. The National Aids Control Programme, currently in its fourth phase (NACP-IV), makes provisions for strategies known as ‘harm reduction’ to prevent transmission of HIV among intravenous drug users. The harm reduction strategies include needle syringe exchange programme (NSEP), behaviour change communication (BCC), outreach, condom promotion, and substitution therapy (1).

Effectiveness of interventions for prevention of common infections in people who use opioids: a protocol for a systematic review of systematic reviews

BackgroundThe North American opioid crisis is driven by opioid-related mortality and morbidity, including opioid use-associated infections (OUAIs), resulting in a substantial burden for society. Users of legal and illegal opioids are at an increased risk of OUAIs compared to individuals not using opioids. As reported for hepatitis C virus (HCV), human immunodeficiency virus (HIV), bacterial, fungal, and other infections, OUAIs transmission and acquisition risks may be modifiable. Several systematic reviews (SRs) synthetized data regarding interventions to prevent infections in persons using drugs (e.g., opioid substitution therapy, needle and syringes exchange programs, psycho-social interventions); however, their conclusions varied. Therefore, SR of published SRs is needed to synthesize the highest level of evidence on the scope and effectiveness of interventions to prevent OUAIs in people using opioids legally or illegally.MethodsWe will comprehensively search for SRs in the PubMed, Embase, PsycINFO, Cochrane Database of Systematic Reviews, Epistemonikos, and Google Scholar databases from inception to November 2020. Data selection and extraction for each SR will be performed independently by two researchers, with disagreements resolved by consensus. All SRs regarding interventions with evaluated effectiveness to prevent OUAI in legal and/or illegal opioid users will be eligible. Risk of bias assessment will be performed using the AMSTAR2 tool. The results will be qualitatively synthesized, and a typology of interventions’ effectiveness with a statement on the strength of evidence for each category will be created.DiscussionOur pilot search of PubMed resulted in 379 SRs analyzing the effectiveness of interventions to prevent HCV and HIV in persons who inject different types of drugs, including opioids. Of these 379 SRs, 8 evaluated primary studies where participants used opioids and would therefore be eligible for inclusion. The search results thus justify the application of SR of SRs approach. Comprehensive data on the scope and effectiveness of existing interventions to prevent OUAIs will help policy-makers to plan and implement preventive interventions and will assist clinicians in the guidance for their patients using opioids.Systematic review registrationRegistered in PROSPERO on 30 July 2020 (#195929).

Trade-offs in Substitution Treatment: A Qualitative Study of an Opioid Substitution Therapy Clinic as an Enabling and a Risk-Environment

This article presents results from a study of clients’ experiences of attending an opioid substitution treatment clinic in Copenhagen, Denmark. The study is part of a research project about the everyday lives of marginalized people who use drugs in Copenhagen, their risk environments, and their access to formal and informal resources. Thirty-eight clients participated in structured interviews, covering topics concerning drug use, income, housing, social relations, violence, and use of health and social services. A risk environment/enabling environment framework was developed to analyze the data. The study highlights the importance of including the drug scene that surrounds the clinic to understand the clinic as both an enabling, constraining, and risky environment affecting the clients’ everyday lives, their safety, health, and well-being. The study shows that the clinic gives the clients access to different material, social and affective resources, but that access to resources often involves different trade-offs. For the clients, such trade-offs include balancing enabling and risky aspects of interaction with other clients or accepting constraints to get access to substitution medicine. Some clients accept such trade-offs, others do not and choose to find other ways to get resources, exposing themselves to potential harm. By paying particular attention to these trade-offs, this study provides a nuanced picture of the clinic’s dual role in both being a source of stability and a place that many clients associate with feeling worried and insecure.

Hemophilia Natural History Study (ATHN 7): Safety of Current Therapies for People with Hemophilia A or B

INTRODUCTION: The recent introduction of new therapies for people with hemophilia A and B (HA and HB) mandates careful monitoring of the safety of these treatments. The primary aim of ATHN 7: A Natural History Study of the Safety, Effectiveness, and Practice of Treatment for People with Hemophilia (NCT03619863) is to monitor the safety of current hemophilia therapies.METHODS: ATHN 7 is a longitudinal, prospective cohort study being conducted at 26 American Thrombosis and Hemostasis Network (ATHN)-affiliated sites. The study is approved by central and local institutional review boards. Any person with a diagnosis of congenital hemophilia A or B (factor VIII or IX activity < 50%) who receives care at a participating site is eligible for inclusion. Participants and/or a parent/guardian sign informed consent and assent prior to participation. Adverse events, including those events designated by the European Haemophilia Safety Surveillance group as well as other adverse events of special interest, are recorded and monitored. Demographic and clinical information are collected at baseline and at least quarterly through participant interview and medical record review. Descriptive statistics of medical history and demographic data as well as longitudinal data are used to characterize the study population.RESULTS: As of June 2021, a total of 391 participants had enrolled in ATHN 7. The median age of participants was 22.5 ± 17.8 years. Males represented 97.7% (382/391) of participants. Eighty-five percent (333/391) were not Hispanic. White participants comprised 82.6% (323/391) of the study population, while 7.9% (31/391) were Black/African American, 3.8% (15/391) were Asian, 1.8% (7/391) were of mixed race, and 3.8% (15/391) were of other or unknown race. The primary diagnosis of participants included 70.1% (274/391) with severe HA, 15.3% (60/391) with moderate HA, 7.2% (28/391) with mild HA, 4.1% (16/391) with severe HB, 2.0% (8/391) with moderate HB, and 1.0% (4/391) with mild HB. Nineteen percent (71/391) of participants had a documented history of an inhibitor at the time of enrollment with a mean peak inhibitor titer of 96.7 ± 214.3 Bethesda Units. Substitution therapy with a non-factor molecule was the primary medication for 43.4% (162/391) participants, while 4.3% (16/391) utilized a plasma-derived clotting factor concentrate, 28.4% (196/391) utilized a standard half-life, recombinant factor concentrate, 18.3% (126/391) utilized an extended half-life recombinant factor concentrate, 4.1% (28/391) utilized a bypassing agent, and 19.3% (133/391) utilized some other hemostatic agent. Continuous prophylaxis was the primary regimen for 79.1% (295/391) participants. The remaining 19.6% (73/391) of participants were on episodic therapy. Within the cohort of 391 participants, a total of 14 adverse events have been reported in 8 participants. No adverse events of special interest were reported. Redness or rash at injection site accounted for 64.2% (9/14) of the reported adverse events, all in participants receiving emicizumab. Two participants experienced bruising or bleeding while on emicizumab. Two participants on emicizumab were diagnosed with malignancy, neither found to be attributed to their therapy. One participant developed an allergic reaction to their standard half-life recombinant factor concentrate.DISCUSSION: Open to enrollment in January 2019, ATHN 7 has now collected 18 months of longitudinal safety data for therapies used to treat HA and HB in 391 participants, an addition of 12 months and 24 participants since our last report. As the study was designed to enhance representation of those utilizing substitution therapy, almost half of the participants were on emicizumab for prophylaxis of bleeding. Adverse events attributable to hemophilia therapy was limited to minor skin reactions. As previously reported, a single participant experienced delayed bleeding after closed head trauma (despite factor replacement and normal intracranial imaging at the time of the event), providing potentially important information on the risk of delayed bleeding from significant trauma in those receiving emicizumab. Over the coming year, participants in ATHN 7 will be transitioned to ATHN's new longitudinal natural history study, ATHN TRANSCENDS (NCT04398628). DisclosuresBuckner: Pfizer: Honoraria; Takeda: Honoraria; Bayer: Honoraria; Sanofi: Honoraria; Spark: Honoraria; Genetech: Honoraria; CSL Behring: Honoraria; Novo Nordisk: Honoraria; Tremeau Pharmaceuticals: Consultancy, Honoraria; BioMarin: Consultancy, Honoraria; uniQure: Consultancy, Honoraria; American Thrombosis: Membership on an entity's Board of Directors or advisory committees; Hemostasis Network: Membership on an entity's Board of Directors or advisory committees. Carpenter: Hemophilia and Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees; Kedrion Pharmaceuticals: Honoraria; Genentech: Honoraria; Novo Nordisk: Honoraria. Raffini: Genentech: Consultancy; CSL Behring: Consultancy; HEMA Biologics: Consultancy; XaTek: Consultancy; Bayer: Consultancy. Zia: Takeda: Consultancy; Hemophilia and Thrombosis Research Society: Membership on an entity's Board of Directors or advisory committees. Recht: Hema Biologics: Consultancy; Kedrion: Consultancy; Novo Nordisk: Consultancy; Octapharma: Consultancy; Pfizer: Consultancy; Sanofi: Consultancy; Takeda: Consultancy; uniQure: Consultancy; Foundation for Women and Girls with Blood Disorders, Partners in Bleeding Disorders: Speakers Bureau; American Thrombosis and Hemostasis Network: Current Employment; Oregon Health & Science University: Current Employment; Genentech: Consultancy; CSL Behring: Consultancy; Catalyst Biosciences: Consultancy.

Infected deep vein thrombophlebitis in people who inject drugs: missed opportunities and potential for alternative antimicrobial approaches

Infected deep vein thrombophlebitis (i-DVT) in people who inject drugs (PWID) is a clinically challenging but poorly characterised disease. We undertook a retrospective observational study of 70 PWID presenting acutely with i-DVT to improve the clinical and microbiological characterisation of this disease. i-DVT was frequently associated with bacteraemia (59.1% patients with blood cultures obtained), groin abscesses (in 34.3%; of which 54.2% required surgical drainage), and septic pulmonary emboli (38.6%) requiring anticoagulation. Network analysis identified a cluster of patients presenting with respiratory symptoms but lacking typical DVT symptoms, more likely to have septic pulmonary emboli. A microbiologic diagnosis was frequently achieved (70%). Causative pathogens were predominantly gram-positive (S. aureus and streptococci, especially anginosus group), whereas gram-negative pathogens were identified very infrequently (in 6.1% of microbiological diagnoses). This suggests routine empiric therapy against gram-negative bacteria, though commonly administered, is not required. High rates of clinical cure (88.6%) were observed despite the complex nature of infections and independently of the highly variable intravenous and total antimicrobial durations received. There exists a rationale to devise pragmatic approaches to implement novel individualised treatment plans utilising oral antimicrobial therapy for i-DVT. Despite frequent healthcare interactions, opportunities to address HCV treatment and opioid substitution therapy were frequently missed during these acute admissions.

Changes in the profile and therapeutic care of people who use drugs with HCV mono-infection: a retrospective study between 2015 and 2019 from a monocentric tertiary referent center in France.

People who use drugs (PWUDs) are the main group at risk for hepatitis C virus (HCV) transmission and a key population for hepatitis C elimination. Multidisciplinary team (MDT) meetings were set up in France in December 2014 within regional reference centers to supervise the prescriptions and delivery of direct-acting antivirals (DAAs) to optimize the management of HCV infection. The aim of this retrospective study was to analyze the changes in the profile and therapeutic care of PWUDs with HCV mono-infection according to the evolution of MDT meetings in a regional tertiary reference center. Between 2015 and 2019, overall 1912 HCV-infected patients presented at the MDT meetings, 547 were PWUDs with HCV mono-infection treated with DAAs. Five periods were defined according to the evolution of MDT meetings. The profile and management of PWUDs were compared among these five periods. Over time, the frequency of advanced stage of fibrosis decreased from 90.8 to 36.3% (P < 0.001), whereas the therapeutic care of the patients in primary addictology centers and networks of general practitioners increased from 17.4 to 55% (P < 0.001). The frequency of excessive alcohol consumption varied between 9.1 and 30% (P = 0.003) and that of opioid substitution therapy between 42.5 and 70% (P < 0.001). The Sustained virologic response assessed 12 weeks after the end of treatment rate was above 95% for the five periods. Between 2015 and 2019, the changes in the profile and management of PWUDs have followed the evolution of MDT meetings concerning patients with less advanced fibrosis and more therapeutic hepatitis C care made by the primary care centers.

Dual Cancer in a Patient with Type 1 Gaucher Disease: Case Report and Literature Review

Gaucher Disease (GD) is a rare inherited lysosomal storage disease caused by biallelic mutations in the gene encoding the lysosomal enzyme acid β-glucocerebrosidase, with progressive accumulation of the sphingolipid glucosylceramide in the lysosomes of macrophages, mainly in the liver, spleen, bone, and bone marrow. It is characterized by anemia, thrombocytopenia, hepatosplenomegaly, sometimes severe bone involvement and, in certain forms, neurological involvement. We present the case of a 77-year-old male, diagnosed in 2006, at 63, with GD type1. At the onset, the patient presented fatigue, asthenia, upper abdominal discomfort, skin pallor and minor bone pain. During follow-up, CT was performed and displayed an enlarged spleen (25 cm) and a well-defined mass in the kidney cortex, but it could not establish whether it was malignant or not. Considering the patient refused surgery at that moment, a new CT exam was performed six months later, and the kidney tumor significantly increased in size. Nephrectomy and necessity splenectomy were performed, and recovery was uneventful. The histopathological examination revealed clear cell renal cell carcinoma, grade 2 Fuhrman. Enzyme substitution therapy with Imiglucerasum was initiated in 2012 with favorable evolution. Seven years later, during a routine ultrasound follow-up, a 4/3.8 cm hyperechoic mass was found in the eighth liver segment. The biological tests revealed a high value of alpha-fetoprotein (AFP-185.2 ng/mL). Considering the patient’s history, possible diagnoses of the newly found focal liver lesion were: gaucheroma, metastasis secondary to kidney cancer, or a primitive liver tumor. Core biopsy was performed, and it was suggestive of a poorly differentiated hepatocellular carcinoma G3. A non-anatomical resection of liver segments VII and VIII with partial resection of inferior vena cava was performed, followed by full post-operative recovery. A histopathological examination confirmed the initial diagnosis. Currently, one month postoperatively, the patient in good clinical condition, continues the enzyme replacement treatment and is undergoing oncological follow-up. We presented a complex case of GD, diagnosed at an advanced age, who responded well to substitution therapy in regard to hematologic and bone symptoms, but who unfortunately developed two types of cancer managed aggressively despite the advanced age.

Mitragynine improves cognitive performance in morphine-withdrawn rats.

The treatment of opiate addiction is an unmet medical need. Repeated exposure to opiates disrupts cognitive performance. Opioid substitution therapy, with, e.g., methadone, may further exacerbate the cognitive deficits. Growing evidence suggests that mitragynine, the primary alkaloid from the Kratom (Mitragyna speciosa) leaves, may serve as a promising alternative therapy for opiate addiction. However, the knowledge of its health consequences is still limited. We aimed to examine the cognitive effects of mitragynine substitution in morphine-withdrawn rats. Furthermore, we asked whether neuronal addiction markers like the brain-derived neurotrophic factor (BDNF) and Ca2+/calmodulin-dependent kinase II alpha (αCaMKII) might mediate the observed effects. Male Sprague-Dawley rats were given morphine at escalating doses before treatment was discontinued to induce a spontaneous morphine withdrawal. Then, vehicle or mitragynine (5mg/kg, 15mg/kg, or 30mg/kg) substitution was given for 3days. A vehicle-treated group was used as a control. Withdrawal signs were scored after 24h, 48h, and 72h, while novel object recognition (NOR) and attentional set-shifting (ASST) were tested during the substitution period. Discontinuation of morphine significantly induced morphine withdrawal signs and cognitive deficit in the ASST. The substitution with mitragynine was able to alleviate the withdrawal signs. Mitragynine did not affect the recognition memory in the NOR but significantly improved the reversal learning deficit in the morphine-withdrawn rats. These data support the idea that mitragynine could be used as safe medication therapy to treat opiate addiction with beneficial effects on cognitive deficits.

Impact of opioid-induced constipation on opioid substitution therapy management: the patient perspective.

BackgroundAlthough opioid-induced bowel dysfunction is a well-known and frequent adverse event correlated with opioids, it is scarcely investigated in patients on opioid substitution treatment (OST) and no standard of care is currently available for this population. We aimed to explore the opinion of patients on the impact of constipation on the management of OST and quality of life (QoL).MethodsWe performed a survey that was directed to opioid-dependent patients treated with OST and followed-up in a Service for Addiction Treatment in Italy. The questionnaire included questions about sociodemographic characteristics, the experience of constipation, general QoL, OST management, interference of opioid-induced constipation (OIC) with opioid management, the experience of OIC treatment in the health system, and risk factors for constipation.ResultsConstipation at the moment of the survey (n=105) was reported by 81% of patients and was the most frequent adverse event of OST; 73% of respondents reported at least one severe or very severe symptom of constipation in the last 2 weeks. OIC was reported to hinder adherence to OST by 33% of respondents and 38% of them felt that control of craving had been more difficult since initiation of constipation. Overall, 34% of patients interfered with their OST by changing the schedule on their own in an attempt to improve constipation. Patients were proactive in looking for a solution for constipation but reported poor help from the healthcare system.ConclusionOur patient-based survey suggests that careful and efficient management of constipation could increase adherence to OST and improve patient satisfaction and QoL.

Sexual Dysfunction in Males Receiving Buprenorphine-naloxone-based Opioid Substitution Therapy

Sexual Dysfunction in Males Receiving Buprenorphine-naloxone-based Opioid Substitution Therapy

Opiates Possibly Boosted Human Civilization

: Testosterone is a fundamental biological drive for human survival. Evidence documents an association between the evolutionary suppression of testosterone and the civilization processes, especially their socialization and family colonization abilities, among early humans. Interestingly, opiates suppress testosterone as a side effect. However, in clinical practice, clients undergoing opioid substitution therapy have subnormal, normal, or even above-normal testosterone. This paper discusses a possibility indicating that opiates promoted civilization processes among early humans. We further suggest that modern humans might have inherited the positive impact of opiates on early humans as a biological propensity for using opioids. Some users may use opioids for self-medication to decrease their extraordinarily high testosterone levels.