Substitution Therapy Research Articles

Congenital chloride diarrhea presenting as dilated fetal bowel loops.

Congenital chloride diarrhea presenting as dilated fetal bowel loops.

Clinico-epidemiological Aspects of Cutaneous Lesions in Injecting Drug Users Visiting an Oral Substitution Therapy Centre in Northern India: A Cross-Sectional study.

Drug abuse has been taking a great toll on the health and well-being of the community for the past few decades. Substance abuse can lead to several cutaneous manifestations as direct injuries by the offending drug or the practices of drug usage cause secondary damage to the skin. The early recognition of these signs is of utmost importance to prevent long-term complications. To study the clinical-epidemiological profile of the skin diseases in Injecting Drug Users (IDU) attending an Oral Substitution Therapy (OST) Center in Northern India and to assess the psychological impact of skin conditions in IDUs attending OSTs. This cross-sectional observational study involved 100 IDUs enrolled from the OST center who were subjected to brief history taking and clinical and dermoscopic evaluation of skin lesions. Dermatological quality of life index (DLQI), Depression, Anxiety, Stress Scale (DASS), and WHO-quality of life (QoL) questionnaire were used to evaluate the impact of skin lesions on psycho-social health and QoL of IDUs. Cutaneous lesions ranged from track marks to severe ulcerations and scarring. Mucosal lesions also took a toll on several patients. The patients had varying degrees of anxiety, depression, and mental stress. Injecting Drug Abusers are prone to acquire skin diseases due to injury caused by drugs as well as by drug practices adopted and the degree of neglect may worsen these conditions. These cutaneous lesions hamper QoL and cause psychosocial disturbances.

Organizational attributes and client engagement in community opiate substitute prescribing services

Introduction Little is known about the relationship between treatment organization characteristics and client outcomes or drug-related harms in community opiate substitution therapy. In the absence of sufficient scientific evidence, the organizational configuration of addiction treatment services is often decided on an ad hoc and sometimes politically motivated basis as the evaluation of the impact of policies or practices on clients at the organizational level is limited. The objective of this multi-site cross-sectional study was to identify and understand how client characteristics and staff perceptions of organizational functioning related to client engagement in community-based opiate substitution therapy services in Ireland. Methods This paper reports on a cross-sectional survey of clients (n = 262) and staff (n = 132) questionnaires across 12 discrete community-based prescribing service providers (organizations) in Ireland. Results Measures of client engagement in treatment were shown to be higher in organizations with more positive staff ratings of organizational functioning. In particular, in organizations where staff reported having greater job autonomy, clients reported better overall engagement. Specifically, greater staff autonomy in organizations related to greater levels of treatment participation (p = 0.034), treatment satisfaction (p < 0.001), and better rapport with staff (p < 0.001). Clients who were the longest in treatment expressed significantly poorer rapport with staff (p = 0.44) and were less likely to seek out support from peers (p = 0.023), while those in stable accommodation reported greater participation in treatment (p = 0.009). Levels of peer support were not related to organizational characteristics, but clients with lower levels of education (p = 0.002) and those in early treatment (p = 0.017) were more likely to seek support from peers. Conclusion The findings establish the importance of assessing organizational and client attributes as part of an overall strategy for enhancing the quality of treatment. This paper provides valuable information for policymakers and provides an ample basis for further exploration of how treatment organizations work, and not just that they work. Policymakers and planners need to consider introducing specific interventions for clients or staff in the context of a ‘whole systems’ approach. From an organizational and planning perspective, this should involve further consideration of measures that relate to increasing staff’s sense of autonomy. This paper provides further evidence that the success of policy-making or planning relating to treatment organizations can be successfully measured at the client and organizational levels.

Association of KCNJ6 rs2070995 and methadone response for pain management in advanced cancer at end-of-life

Opioids are the therapeutic agents of choice to manage moderate to severe pain in patients with advanced cancer, however the unpredictable inter-individual response to opioid therapy remains a challenge for clinicians. While studies are few, the KCNJ6 gene is a promising target for investigating genetic factors that contribute to pain and analgesia response. This is the first association study on polymorphisms in KCNJ6 and response to methadone for pain management in advanced cancer. Fifty-four adult patients with advanced cancer were recruited across two study sites in a prospective, open label, dose individualisation study. Significant associations have been previously shown for rs2070995 and opioid response in opioid substitution therapy for heroin addiction and studies in chronic pain, with mixed results seen in postoperative pain. In this study, no associations were shown for rs2070995 and methadone dose or pain score, consistent with other studies conducted in patients receiving opioids for pain in advanced cancer. There are many challenges in conducting studies in advanced cancer with significant attrition and small sample sizes, however it is hoped that the results of our study will contribute to the evidence base and allow for continued development of gene-drug dosing guidelines for clinicians.

Molybdenum Cofactor Deficiency in Humans.

Molybdenum cofactor (Moco) deficiency (MoCD) is characterized by neonatal-onset myoclonic epileptic encephalopathy and dystonia with cerebral MRI changes similar to hypoxic–ischemic lesions. The molecular cause of the disease is the loss of sulfite oxidase (SOX) activity, one of four Moco-dependent enzymes in men. Accumulating toxic sulfite causes a secondary increase of metabolites such as S-sulfocysteine and thiosulfate as well as a decrease in cysteine and its oxidized form, cystine. Moco is synthesized by a three-step biosynthetic pathway that involves the gene products of MOCS1, MOCS2, MOCS3, and GPHN. Depending on which synthetic step is impaired, MoCD is classified as type A, B, or C. This distinction is relevant for patient management because the metabolic block in MoCD type A can be circumvented by administering cyclic pyranopterin monophosphate (cPMP). Substitution therapy with cPMP is highly effective in reducing sulfite toxicity and restoring biochemical homeostasis, while the clinical outcome critically depends on the degree of brain injury prior to the start of treatment. In the absence of a specific treatment for MoCD type B/C and SOX deficiency, we summarize recent progress in our understanding of the underlying metabolic changes in cysteine homeostasis and propose novel therapeutic interventions to circumvent those pathological changes.

Combating illicit fentanyl: Will increased Chinese regulation generate a public health crisis in India?

This study examines how Chinese drug regulations are shifting illicit fentanyl production from China to India. This change has implications for the law, drug enforcement, pharmaceutical industry, and public health, as domestic production increases domestic access to fentanyl, in India. An empirical examination of current trends in fentanyl production and use in the region is conducted, along with an exegesis of the legal and regulatory systems in China and India. There is an accounting of the chemical and pharmaceutical industries, the strengths and weaknesses of drug legislation, and the public health consequences of increased production, distribution, and use of fentanyl in India. This study also details how the Indian government meets this challenge through legislative mechanisms, foremost through class-wide legislative control over fentanyl and its precursors. Class-wide control prohibits the unlawful production and distribution of all current and future fentanyl analogs and their precursors, disincentivizing and disrupting their development and production. The Indian government should also reduce domestic demand by promoting harm reduction measures such as opioid substitution therapy, evidence-based treatment, fentanyl test strip and naloxone distribution, and needle exchange programs.

Long-term analysis of сanagliflozin budget impact in adult patients with type 2 diabetes mellitus and diabetic nephropathy in the Russian Federation

Background. Diabetic nephropathy (DN) is a specific kidney lesion in patients with diabetes mellitus, which leads to the development of endstage kidney disease and requires substitutive renal therapy (dialysis or transplantation). Canagliflozin is a sodium-glucose co-transporter 2 (SGLT2) inhibitor, which exerts a renoprotective effect. According to the published data, the application of canagliflozin in patients with type 2 diabetes mellitus (DM2) and DN could postpone dialysis therapy for almost 13 years.Objective: to perform a long-term analysis of canagliflozin budget impact in adult patients with DM2 and DN from the point of view of the constituent entities of the Russian Federation.Material and methods. A group of comparison for canagliflozin was placebo (no renoprotective pharmacotherapy). The authors proposed a mathematical model for DN progression in groups of patients who received canagliflozin (100 mg orally, daily, long-term) or placebo. The model was based on the extrapolation of the CREDENCE study data. The model was used for the analysis of the direct costs on the lifetime pharmacotherapy and dialysis per one patient. Epidemiologic data from the federal register on the number of adult patients with DM and DN prevalence among these patients were used to evaluate the size of the target population. Based on the clinical recommendations and the medical care standards for patients with DM and the data on the actual state procurement of SGLT2 inhibitors and glucagon-like peptide-1 receptor agonists in 2021, we evaluated the share of patients with DM2+DN who currently do not receive renoprotective therapy but who must be supplied with canagliflozin according to the standards. Among this population, we determined the patients with the glomerular filtration rate within 30–90 ml/min/1.73 m2, which provides the comparability of the target population with patients included in CREDENCE clinical study.Results. Direct medical costs per one patient receiving canagliflozin therapy were 678 108 rubles, which was 52.8% (759,239 rubles) lower than without renoprotective pharmacotherapy (1,437,347 rubles). As a result, considering the modeling period and current practice, the budget costs for pharmacotherapy of patients with DM2+DN were 99.82 billion rubles, in comparison with the proposed practice, which was 47.09 billion rubles (difference in budget costs is 52.73 billion rubles, or 52.8%). The accumulated costs of the regional health care system were lower in patients receiving canagliflozin in comparison with patients without renoprotective pharmacotherapy 11 years after the beginning of treatment.Conclusion. The expansion of canagliflozin application in the therapy for patients with DM2+DN leads to the budget cost cuts in the long run due to the extension of the dialysis-free period.

Congenital chloride diarrhea

Congenital chloride diarrhea is an autosomal recessive congenital disease caused by a mutation in the SLC26A3 gene mapped to chromosome 7 (locus 7q22-q31). At the beginning of the 21st century, more than 250 cases of congenital chloride diarrhea have been reported, mostly in Finland, Poland, Kuwait, and Saudi Arabia, single cases appear all over the world. SLC26A3 gene encodes an intestinal Cl–/HCO3 – exchanger, а defect of which causes malabsorption of Cl– in the ileum and colon. The disease can be revealed during pregnancy by polyhydramnios, dilated intestinal loops of the fetus on sonography.Most children are born prematurely. Visualization of distended bowel loops and the absence of meconium after birth often leads to unnecessary surgical intervention due to suspected intestinal obstruction or Hirschprung’s disease. The main features of the disease are watery diarrhea, dehydration, failure to thrive, hypochloremia, hyponatremia, hypokalemia and metabolic alkalosis. Fecal chloride excretion is higher than total sodium and potassium excretion. Treatment consists of potassium chloride and sodium chloride replacement therapy. Nowadays patients with adequate treatment reach adulthood but the long-term prognosis is unknown. Therapy stops electrolyte disturbances, but diarrhea persists. Since 2003, we have observed 3 patients with clinical signs of congenital chloride diarrhea with further confi rmation of a mutation in the SLC26A3 gene. All the children were born prematurely, the mothers had polyhydramnios during pregnancy, and the fetus had dilated bowel loops on ultrasound examination in utero. Two patients underwent surgical treatment because of suspected intestinal obstruction or Hirschsprung’s disease in early neonatal period. Before salt substitution therapy, all children had watery diarrhea, failure to thrive and delayed psychomotor development. We have been observing one of our patients for fi ve years from the moment of diagnosis until now. The girl receives therapy with sodium chloride and potassium chloride, her physical and psychomotor development corresponds to her age, there are no electrolyte abnormalities.

Frozen and freeze-dried solvent/detergent treated plasma: Two different pharmaceutical formulations with comparable quality.

OctaplasLG is a frozen solvent/detergent-treated plasma product used for treating complex coagulation factor deficiencies or as substitution therapy in emergency situations where specific factor concentrates are not available. A new freeze-dried (also known as lyophilized) form of OctaplasLG, referred as OctaplasLG Lyo (Octapharma AG, Switzerland) offers rapid reconstitution and more flexible storage conditions, improving logistics and utilization. This study compared the biochemical quality of OctaplasLG Lyo with OctaplasLG and single-donor fresh frozen plasma units. Three batches of OctaplasLG Lyo, manufactured for production process qualification, and 12 batches of OctaplasLG were provided by Octapharma AB (Sweden). Twelve units of fresh frozen plasma were collected by the local FDA-licensed blood provider. All plasma samples were assessed for global coagulation parameters, coagulation factors and protease inhibitors, activation markers of coagulation and fibrinolysis, and important plasma proteins. Quality control assays were conducted in accordance with European Pharmacopeia requirements. Frozen and freeze-dried OctaplasLG demonstrated comparable quality profiles upon thawing or reconstitution. All coagulation factor and protease inhibitor activity parameters were in line with levels mandated by the European Pharmacopeia. Fresh frozen plasma units showed comparable coagulation factor activities, with higher protein S and plasmin inhibitor levels than the OctaplasLG products. Fresh frozen plasma parameters showed high lot-to-lot variations. The two pharmaceutical forms of OctaplasLG (frozen and freeze-dried) have comparable biochemical quality. Key features of OctaplasLG Lyo are rapid reconstitution time and storage flexibility, which may improve logistics and utilization, and have particular advantages in emergency situations and pre-hospital settings.

A Comparative Study to Assess the Mental Health Problems, Quality of Life, Work Ability and Social Adjustments Among OST and Non-OST Drug Users in Chandigarh

Introduction: Injectable drug use is a cause of disease burden and a contributor to blood-borne virus transmission and health-related problems. It is one of the serious problems of our country. The best suitable strategy of treatment for opioid dependence is ‘opioid substitution therapy’ (OST). It is beneficial for the injectable drug users (IDUs) in reduction in the behaviour of injecting and opioid use, which helps in reducing criminal activities, domestic violence, enhancing ties within the family and improving productivity. Objective: To assess the mental health problems, quality of life, work ability and social adjustability among OST and non-OST IDUs. Materials and Methods: The descriptive study was conducted among 100 male IDUs (50 in the OST group and 50 in the non-OST group), registered with the two selected non-governmental organizations (NGOs) of Chandigarh selected by using the consecutive sampling technique. The OST group was contacted during their visit to the centre for receiving the daily dose of OST, while the non-OST group was contacted during their visit to the NGO centres for getting fresh syringes in exchange with used syringes under the syringe exchange programme. The data were collected by interviewing the study subjects by using the interview schedule comprising of the (a) socio-demographic profile, (b) health problems, (c) substance-use-related problems scale, (d) work ability and social adjustability scale, (e) the depression, anxiety and stress scale-21 and (f) World Health Organization Quality-of-Life BREF (WHOQOL BREF) Scale. All the tools were standardized and available in the open domain. Results: The study subjects were in the age group of 18–58 years with the mean age of 27.52 ± 6.67 years. Significantly lesser problems in the OST group study participants related to health, occupation, finance, legal, family, marital and social status were reported than those in the non-OST group participants ( t-test, p &lt; 0.01). A significantly higher percentage of the study participants in the non-OST group had depression, anxiety and stress than that in the OST group. Quality of life of IDUs in the OST group was significantly better than that of IDUs in the non-OST group, as per the WHOQOL BREF Scale (Mann–Whitney U test, p &lt; 0.05). Conclusion: IDUs on OST therapy (OST group) were having lesser problems in the area of health (physical and mental), occupational, financial, legal, family, marital, social and better quality of life than those in the non-OST group.

To what extent does opioid substitution therapy reduce hepatitis C transmission in adults with intravenous opioid use disorder?

To what extent does opioid substitution therapy reduce hepatitis C transmission in adults with intravenous opioid use disorder?

Real-world treatment, dosing, and discontinuation patterns among patients treated with pegvaliase for phenylketonuria: Evidence from dispensing data

BackgroundPhenylketonuria (PKU) is an inborn metabolic error characterized by a deficiency of the enzyme required for the metabolism of phenylalanine, an essential amino acid found in most protein-containing foods. Pegvaliase (Palynziq®) is an enzyme substitution therapy approved for adults with PKU who have inadequate blood phenylalanine control (≥600 μmol/L) on existing management. ObjectiveTo characterize the treatment, discontinuation, and dosing patterns in patients treated with pegvaliase in real-world practice settings in the United States following commercial availability in 2018. Study designRetrospective cohort study using BioMarin's proprietary drug dispense database associated with the pegvaliase REMS program. MethodsSample construction identified all patients who properly initiated pegvaliase in real world settings (‘full cohort’) and a subset of patients (‘extended follow-up cohort’) with ≥12 months between first dispense of maximum dose and last pegvaliase dispense. Key outcomes were quantified across patients in both cohorts: maximum daily dose; time to maximum daily dose; maximum daily syringes; and dose escalation over time. The overall dose at discontinuation and time to discontinuation were calculated. Patients who subsequently reinitiated therapy were identified. For the extended follow-up cohort, 12-month changes in dose and syringes and dispensing gaps during the 12 months after maximum dose were quantified across all patients and were further stratified by maximum dose. ResultsOverall, 1596 patients associated with 33,814 dispenses were reflected in the pegvaliase dispense dataset during the study period from July 9, 2018, through December 31, 2021; 1280 patients associated with 25,973 dispenses met inclusion criteria for the full cohort, with 19.9 dispenses each on average. Of these patients, 483 patients associated with 15,149 dispenses also met the extended follow-up criteria, with an average of 31.4 dispenses.Average treatment duration in the full cohort was 82.2 weeks, including 50.8 weeks after maximum daily dose was achieved. The average maximum daily dose was 30 mg with an average time to maximum dose of 31.8 weeks: 43.0% of patients had a maximum dose of 20 mg, 31.3% a maximum dose of 40 mg, and 12.0% a maximum dose of 60 mg. At data cut-off, 289 patients (22.6%) had discontinued; within this group, 126 patients (43.6%) discontinued within the first 6 months of treatment initiation.The overall average treatment duration for patients in the extended follow up cohort at data cut off was 131.2 weeks, including 98.6 weeks after maximum dose was achieved. The average maximum daily dose across the cohort was 32.9 mg: 42.4% of patients had a maximum dose of 20 mg, 41.0% a maximum dose of 40 mg, and 11.2% a maximum dose of 60 mg. At 12 months after achieving maximum dose, 35% of patients had down-dosed, with a 46.8% decrease (on average) from their maximum dose. ConclusionsReal-world use of pegvaliase reflects longer titration periods than in the dosing schedule based on trial experience. Over time, a substantial number of patients are able to reduce their daily dose by titrating down from their maximum dose, a finding of great interest to clinicians and patients alike.

Cost-effectiveness of pharmacy-led versus conventionally delivered antiviral treatment for hepatitis C in patients receiving opioid substitution therapy: An economic evaluation alongside a pragmatic cluster randomised trial

Elimination targets for hepatitis C have been set across the world. In the UK almost 90% of infections are in people who inject drugs. Evidence shows community case-finding is effective at identifying and treating undiagnosed patients. The aim of this analysis was to assess, from a healthcare provider perspective, the cost-effectiveness of a new pharmacist-led test and treat pathway for hepatitis C in opioid agonist treatment (OAT) patients attending community pharmacies compared to conventional care. In a cluster randomised controlled trial, pharmacies were randomised to the pharmacist-led or conventional care pathway. Mean cost per OAT patient and per patient initiating treatment was identified for each pathway. A Markov model tracking disease progression was developed, with a 50-year time horizon and 3·5% time discount rate, to estimate the incremental cost-effectiveness ratio (ICER) per quality-adjusted life-year (QALY) gained and the probability of being cost-effective at a £30,000 per QALY willingness-to-pay threshold. Probabilistic sensitivity analysis was performed for a range of drug discounts, re-infection rates, and model assumptions. Mean cost per OAT patient (£3,674 vs £1,965) and per patient initiating treatment (£863 vs £404) was higher in the pharmacist-led pathway, due to higher uptake of testing and pharmacist time requirements. Over a 50-year time horizon the ICER per QALY gained was £31,612 at NHS indicative price for treatment (£38,979 for 12 weeks) and 12·1/100 person-years re-infection rate, reducing to £21,027/£10,220/-£501 per QALY gained with 30%/60%/90% drug price discounts and £25,373/£21,738/£14,912 per QALY gained at re-infection rates of 8/5/2 per 100 person-years. At 30%/60%/90% drug discount rates, the pharmacist-led pathway has an 80%/98%/100% probability of being cost-effective. The pharmacist-led pathway is effective at increasing testing and treatment uptake, with cost-effectiveness being highly dependent on drug price discounts. Trial funding provided by the Scottish Government, Gilead Sciences, and Bristol-Myers Squibb.

Bone Turnover in Relation to Thyroid-Stimulating Hormone in Hypothyroid Patients on Thyroid Hormone Substitution Therapy.

Background Bone turnover markers (BTMs) have emerged as a useful tool for monitoring bone remodeling activity in the skeleton, and their serum levels correlate with bone loss rates in osteoporotic and normal individuals. Whether the same holds for other metabolic bone diseases is still subject to discussion. Methods We analyzed the relation between levels of BTMs and TSH in 79 females on thyroid hormone substitution therapy for hypothyroidism. Based on the reference range for TSH (0.2–4.0 mU/L) in our lab, we assessed BTMs in five different groups of patients based on the following criteria: (1) hypothyroidism (TSH >4.0); (2) TSH in the high normal range (1.0–4.0); (3) TSH in the low normal range (0.2–1.0); (4) TSH below the normal range (0.01–0.2); (5) TSH undetectable (<0.01). We studied the relationship between TSH and four different bone markers: procollagen type 1 N-terminal propeptide (PINP), C-terminal cross-linking telopeptide of type 1 collagen (CTX), osteocalcin (OC), and bone specific alkaline phosphatase (BSAP). In a subgroup of patients, bone mineral density was assessed by a DXA scan. Results PINP emerged as the most sensitive and dynamic BTM for assessment of bone turnover in this patient group, achieving significant rho values on nonparametric correlation analysis for both TSH (rho −0.47; p=0.0001) and FT4 (rho 0.27; p=0.018). CTX and OC also revealed significant correlations to TSH, albeit with lower rho values (−0.37 and −0.24, respectively). Categorical analysis showed that bone turnover increased significantly, albeit with pronounced interindividual variability for TSH values below the lower limit of normal (0.2 mU/l), with the most severe affected being women exhibiting suppression of TSH. Further analysis of loss rates by DXA in a limited subgroup of patients showed that this was accompanied by accelerated bone loss. Conclusion PINP is the most sensitive marker of bone turnover in thyroid disorders. TSH values below the lower limit of normal are associated with increased bone turnover and accelerated bone loss, however, with pronounced interindividual variations. Assessment of PINP may be a valuable tool in cases where there is concern about possible adverse effects of thyroid hormone substitution therapy on bone.

Diamorphine assisted treatment in Middlesbrough: a UK drug treatment case study

ABSTRACT Introduction Diamorphine Assisted Treatment (DAT) is a treatment offer for individuals with Opioid Dependency (OD), who have failed to benefit from standard treatment model (Opioid Substitution Therapy [OST]). In the Middlesbrough DAT service, self-administered injectable synthetic heroin (diacetylmorphine) is offered to participants, twice daily under the supervision of medical staff in a controlled and safe environment. This case report evidences outcomes from the first operational DAT service in England outside of a research trial. Method Descriptive quantitative data from participants who engaged within the first year of operation of DAT (n=14) is presented detailing engagement, harm reduction, and psychosocial outcomes, and criminality of the cohort. Results The DAT service was associated with high engagement, a large reduction in positive toxicology screens for street heroin, reduced homelessness, increased engagement with psychosocial interventions and a substantial reduction of criminal offences. Poly-drug use (specifically the consumption of street tablets) impacted treatment engagement for a proportion of the sample. Conclusions We present this work as an example of bottom-up policy making within the context of UK drug treatment and implications for practice discussed.

Menorrhagia as main presentation sign of severe hypothyroidism in a pediatric patient: a case report

BackgroundThe relative high frequency of menstrual irregularities in the first two–three years after menarche may lead to the risk of underestimation of associated pathological conditions, which are always to be accurately researched with careful examination and anamnesis. The association between menstrual irregularities and hypothyroidism is described in literature but the available data are scarce and mainly based on adult case series. It is described that low plasma levels of thyroid hormone can shift the hemostatic system towards a hypocoagulable and hyperfibrinolytic state and seem to lead to an increased bleeding risk.Case presentationThis case report describes the case of a thirteen years old girl who presented to our Emergency Department complaining of menorrhagia for the last fifteen days, leading to severe anemia. The objective examination revealed clinical signs of hypothyroidism and a severe short stature, lower than mid-parental height, with stunting of growth and a significant bone age delay. Blood exams and thyroid ultrasound were consistent with the diagnosis of severe hypothyroidism in autoimmune thyroiditis with acquired von Willebrand syndrome, growth hormone deficiency. Magnetic resonance showed pituitary functional hyperplasia.The substitutive therapy with levothyroxine led to the resolution of heavy bleeding after five days and following normalization of coagulative parameters and pituitary hyperplasia.ConclusionsHypothyroidism usually presents with unspecific symptoms, with consequent risk of diagnostic delay. It can influence the coagulation system and it seems to be associated to increased risk of menstrual irregularities.We underline the importance of a regular follow up of the pubertal development, including height measurements, thyroid palpation and menstrual anamnesis to intercept red flags findings for hypothyroidism.

Personality dysfunction in opiate addicts on opioid substitution treatment and the risk of HCV infection.

BackgroundImpulsivity, affective instability, and neglect of oneself and other people's safety as symptoms of personality dysfunction are associated with risky behaviors regarding the transmission of infectious diseases either sexually or by intravenous drug abuse.ObjectiveThe aim of this study was to analyze the association between hepatitis C virus (HCV) infection and personality dysfunction in opiate addicts on opioid substitution treatment.MethodsThis was a cross-sectional, observational investigation of patients over 18 years of age who were actively participating in opioid substitution treatment at five centers in Bosnia and Herzegovina. The occurrence of HCV infection was the primary study outcome, and personality functioning, the main independent variable, was assessed using the Severity Indices of Personality Problems (SIPP−118) questionnaire. The association between scores of personality functioning domains items and HCV infection status was determined by binary logistic regression analysis.ResultsPatients on opioid substitution therapy with HCV infection more frequently had personality disorders (OR 2.168, 95% CI 1.161–4.05) and were treated longer than patients without HCV infection (OR 1.076, 95% CI 1.015–1.14). HCV infection was associated with lower self-respect (OR 0.946, 95% CI 0.906–0.988), decreased capacity to have enduring relationships with other people (OR 0.878, 95% CI 0.797–0.966), and lower capability to cooperate with others (OR 0.933, 95%CI 0.888–0.98). On the other hand, except for self-respect, other elements of the Identity Integration domain (enjoyment, purposefulness, stable self-image, and self-reflexive functioning), when more functional, increased the risk of HCV infection.ConclusionsOur study demonstrates that opiate addicts on opioid substitution treatment have a higher risk of HCV infection if their personality is dysfunctional, especially in the aspects of self-respect, enduring relationships, and cooperativity. The risk is even higher in addicts who have an established diagnosis of any kind of personality disorder.

An Exploration of Organizational Characteristics and Training Adoption in Irish Community Drug Treatment Services.

Changes in patterns of drug use and population needs necessitate the adoption of new technologies. Despite high failure rates in adopting new technologies acquired in training, little is known about the process that can support successful change. This study explores the impact that staff and service characteristics have on the process of training adoption in Irish opiate substitution therapy services, with a specific focus on the concept of organizational readiness to change. A cross-sectional survey was conducted on a convenience sample of 132 staff members across 12 services in Ireland. The relationship between staff demographics, their perceptions of organizational readiness to change, burnout, and a four-stage process of training adoption were considered. Discipline, job tenure, and educational levels are important predictors of engagement in the adoption process. Staff in services with higher institutional needs, greater pressures for change, and poorer resources were less likely to be exposed to, or adopt, training. Having lower levels of stress and more influence with peers was associated with better adoption of training. Planners and service managers need to carefully consider the composition or dynamics of services when initiating change. Organizational readiness to change and staff characteristics as measured by instruments used in this study are important determinants of the process of innovation or training adoption and provide a good basis for developing further understanding of how treatment services work. This article expands on results from previous studies conducted in the United States to a European context.

Opioid substitution in pregnancy a narrative review: contemporary evidence for use of methadone and buprenorphine in pregnancy

ABSTRACT Illicit opioid use is a growing public health emergency and is associated with adverse medical and social outcomes. Opioid use in the pregnant population is increasing globally, and optimal management incorporates opioid substitution programs with improved concurrent engagement in medical care. The two main drugs used in opioid substitution programs are methadone and buprenorphine. Methadone has been used since the 1970s and provides treatment stability leading to improved engagement with obstetric services. Buprenorphine is a newer treatment, has greater dosing flexibility, and may be associated with fewer neonatal adverse effects. Direct comparisons of methadone and buprenorphine treatments are limited but suggest that buprenorphine is associated with less severe neonatal withdrawal; however, it is not universally well-tolerated and tends to be prescribed to less severely affected mothers. Given the lack of clear evidence to support one opioid substitution therapy over another, the principal aim of therapy should be to stabilize treatment and promote more comprehensive engagement with multidisciplinary services.

Immunoglobulin-Substitutionstherapie bei hämatologischen Patienten mit sekundärem Antikörpermangel

Immunglobulin Substitution Therapy in Hematological Patients with secondary Antibody Deficiency Abstract. Hematological malignancies and immunochemotherapy are frequently associated with secondary cellular and humoral immunodeficiencies. Due to the growing application of effective therapeutic antibodies, and cellular therapies specifically targeting and hence depleting antibody producing cells (B- and plasma cells) the incidence of secondary antibody deficiencies in the daily practice is increasing. This article will provide a short overview of the etiology of secondary antibody deficiencies in hematological patients. Then, it will discuss the efficacy and indication of immunoglobulin substitution therapy in these patients and finally address the choice of the respective preparation.