Parent–child connectedness and communication in relation to alcohol,tobacco and drug use in adolescence: An integrative review of the literature

Previous reviews have highlighted parent–child connectedness and communication as important protective factors against adolescent substance use. However, these reviews focus on single substances such as alcohol. An integrative review of the literature was conducted to examine which elements of parent–child connectedness and substance-use specific communication are effective across adolescent alcohol, tobacco and drug use. Forty-two English language, peer reviewed articles were reviewed. Open communication occurs within the context of high connectedness between parents and their children. Conversations about health risks are associated with lower levels of substance use while more frequent conversations, those about parents’ own use, permissive messages and consequences of use are associated with higher levels of use. There are disparities regarding conversations about use of each substance: alcohol and tobacco are easier topics of conversation while drug use is rarely discussed. Parental alcohol and tobacco use can influence the credibility of their communication with their child. Parents should be encouraged to have open, constructive, credible, two-sided conversations with their adolescents about substance use. Interventions to improve parents’ communication skills around substance use, particularly drug use, should include the types of approaches and messages highlighted in this review, and, where possible, these interventions should include all family members.     

The use of terpenes and derivatives as a new perspective for cardiovascular disease treatment: a patent review (2008–2018)

Introduction: Terpenes are a class of secondary metabolites that can be found in a variety of animal and plants species. They are considered the most structurally diversified and abundant of all natural compounds. Several studies have shown the application of terpenes, such as carvacrol, linalool, and limonene in many pharmaceutical and medicinal fields, including cardiovascular disorders, the leading cause of death worldwide. Areas covered: In this review, the authors outlined patents from the last 10 years relating to the therapeutic application of terpenes for the treatment and/or prevention of cardiovascular diseases found in different databases, emphasizing the possibility of these compounds becoming new drugs that may help to decrease the burden of these disorders. Expert opinion: There has been a growing awareness over recent years of the therapeutic use of terpenes and their derivatives as new pharmaceutical products. Patents involving the use of terpenes have been especially important in the technological development of new strategies for the treatment of cardiovascular diseases by bringing new scientific knowledge into the pharmaceutical industry. Therefore, the development of biotechnologies using natural products should be encouraged in order to increase the variety of drugs available for the treatment of cardiovascular diseases.     

Small molecules and antibodies for the treatment of psoriasis: a patent review (2010–2015)

Introduction: Psoriasis is a chronic condition whose therapeutic armamentarium is increasingly being discussed, particularly when compared to past decades. The use of biologic agents has profoundly changed the history of this disease, as well as the management of psoriatic patients. Due to the enormous interest in psoriasis, as demonstrated within the scientific community and pharmaceuticals, new therapeutic targets have been identified and novel patented therapeutics are being tested.

Areas covered: This review sought to give an overview of small molecules and antibodies patented in the last five years for the treatment of psoriasis. Therapeutic agents either in the early or advanced phase of development have been described, primarily based on a systematic search using the PubMed Medline database.

Expert opinion: Though the recent introduction of new antipsoriatic agents has facilitated the management of long-term psoriasis, there is still a strong desire for alternative therapeutic options. Indeed, there remain unmet needs regarding safety and efficacy of psoriasis treatment that should be addressed. In this context, recently patented drugs may prove valid, interesting, and promising within the therapeutic paradigm.     

Synthetic drugs for the treatment of vitiligo: a patent review (2010–2015)

Introduction: Vitiligo is one of the most important acquired depigmentation disorders, with an average worldwide prevalence of 0.5–2.0%. The exact etiology of vitiligo is not fully understood, but the principle theories focus on the mechanism responsible for the destruction of melanocytes, which is proposed to be autoimmune, neurogenic, or self-destructive. There is no cure for vitiligo and the results of current treatments vary between individuals, being unsatisfactory in most cases. Despite being a cosmetic disease, the disorder can be psychologically devastating and stigmatizing.

Areas covered: In this review, the authors summarize new synthetic drugs for the treatment of vitiligo developed between 2010 and 2015, which include MC1 R agonists and peptides, as well as considering new approaches and strategies using existing drugs.

Expert opinion: In conclusion, we found significant advancement in this field of research, demonstrating the growing interest of academic and industrial groups in developing successful products for the treatment of vitiligo. New therapeutic options could contribute to improving the quality of life of patients and advance the search for a truly effective treatment of vitiligo.     

Usnic acid and its derivatives for pharmaceutical use: a patent review (2000–2017)

Introduction: Usnic acid (UA) is a lichen-derived secondary metabolite with a unique dibenzofuran skeleton and is commonly found in lichenized fungi of the genera Usnea and Cladonia. Usnic acid has been incorporated for years in cosmetics, perfumery, and traditional medicines. It has a wide range of bioactivities, including antimicrobial, antiviral, anticancer, anti-inflammatory properties.

Areas covered: This review covers patents on therapeutic activities of UA and its synthetic derivatives published during the period 2000–2017.

Expert opinion: UA demonstrates excellent anticancer and antimicrobial properties. However, its application was withdrawn due to acute liver toxicity reported with chronic consumption. The broad spectrum of its biological activity indicates high the variability of UA’s binding preferences. The main idea to be addressed in the future should include the synthesis of UA derivatives because these might possess increased bioactivity, bioavailability and decreased toxicity. It is noteworthy that UA derivatives possessed better antibacterial, antitubercular, and anticancer activity than the parent compound . Most importantly, UA and its analogs (to a greater extent than UA) can be useful in cancer drug treatment. They have the potential for joint application with other anticancer drugs in order to overcome drug resistance.     

2-Indolinone a versatile scaffold for treatment of cancer: a patent review (2008–2014)

Introduction: 2-Indolinone is a well-known aromatic heterocyclic organic compound. A lot of work has been done on this bicyclic structure by academic and company researchers to synthesize compounds directed to a plethora of molecular targets in order to discover new drug leads. This review presents up-to-date information in the field of cancer therapy research based on this small building block.

Areas covered: The present review gives an account of the recent patent literature (2008–2014) describing the discovery of 2-indolinone derivatives with selected therapeutic activities. In this period, a large amount of patents were published on this topic. We have limited the analysis to 37 patents on 2-indolinone derivatives having potential clinical application as chemotherapeutic agents. In this review, the therapeutic applications of 2-indolinone derivatives for the treatment of cancer reported in international patents have been discussed.

Expert opinion: 2-Indolinone is the scaffold of the compounds considered from a medicinal chemistry perspective. Many of them have been developed and marketed for therapeutic use. In cancer chemotherapy, progress has been made in designing selective 2-indolinone derivatives. Some of them show preclinical efficacy. However, 2-indolinone has not exhausted all of its potential in the development of new compounds for clinical applications and remains a great tool for future research.     

Mind–body practices: An alternative,drug-free treatment for smoking cessation? A systematic review of the literature

Objective

The limited success of current smoking cessation therapies encourages research into new treatment strategies. Mind–body practices such as yoga and meditation have the potential to aid smoking cessation and become an alternative drug-free treatment option. The aim of this article is to assess the efficacy of yoga and other meditation-based interventions for smoking cessation, to identify the challenges of clinical trials applying mind–body treatments, and to outline directions for future research on these types of therapies to assist in smoking cessation.

Methods

A systematic review of the scientific literature.

Results

Fourteen clinical trials met the inclusion criteria defined for this review. Each article was reviewed thoroughly, and evaluated for quality, design, and methodology. Although primary outcomes differed between studies, the fourteen articles, most with limitations, reported promising effects supporting further investigation of the use of these practices to improve smoking cessation.

Conclusions

The literature supports yoga and meditation-based therapies as candidates to assist smoking cessation. However, the small number of studies available and associated methodological problems require more clinical trials with larger sample sizes and carefully monitored interventions to determine rigorously if yoga and meditation are effective treatments.     

Innovative strategies in the diagnosis and treatment of tuberculosis: a patent review (2014–2017)

Introduction: Tuberculosis (TB) is a disease caused due to an infection of Mycobacterium tuberculosis (M TB) bacilli affecting millions of people worldwide. It is the ninth leading cause of death and ranks above the HIV/AIDS. The unique intracellular life cycle, more dangerous drug-resistant forms of bacilli, and insufficient investments in the TB research and development hindered the occurrence of optimum diagnostic, preventive, and treatment strategy against this disease.

Areas covered: The aim of this review is to provide an update and overview of the current trends in the diagnosis, prevention, and treatment of the disease. It summarizes a recent patent literature (2014–2017) available on the same.

Expert opinion: Some questions like ‘why most of these inventions do not reach up to the market for public use? Are these inventions being explored only to get a financial return to a particular industry or do they have any societal benefit?’ emphatically come to mind. Together with the efforts taken by various governmental and nongovernmental organizations, a public awareness about the recent advancements in the diagnosis and treatment of the disease is of the highest importance to make ‘the end of TB’ from the universe.     

Approaches to Ras signaling modulation and treatment of Ras-dependent disorders: a patent review (2007 – present)

Introduction: Ras proteins are small GTPases molecular switches that cycle through two alternative conformational states, a GDP-bound inactive state and a GTP-bound active state. In the active state, Ras proteins interact with and modulate the activity of several downstream effectors regulating key cellular processes including proliferation, differentiation, survival, senescence, migration and metabolism. Activating mutations of RAS genes and of genes encoding Ras signaling members have a great incidence in proliferative disorders, such as cancer, immune and inflammatory diseases and developmental syndromes. Therefore, Ras and Ras signaling represent important clinical targets for the design and development of pharmaceutically active agents, including anticancer agents.

Areas covered: The authors summarize methods available to down-regulate the Ras pathway and review recent patents covering Ras signaling modulators, as well as methods designed to kill specifically cancer cells bearing activated RAS oncogene.

Expert opinion: Targeted therapy approach based on direct targeting of molecules specifically altered in Ras-dependent diseases is pursued with molecules that down-regulate expression or inhibit the biological function of mutant Ras or Ras signaling members. The low success rate in a clinical setting of molecules targeting activated members of the Ras pathway may require development of novel approaches, including combined and synthetic lethal therapies.     

A combined,bioidentical, oral, 17β-estradiol and progesterone capsule for the treatment of moderate to severe vasomotor symptoms due to menopause

ABSTRACT

Introduction: Many women seek treatment to alleviate menopausal vasomotor symptoms (VMS). Numerous women use combination compounded hormone therapy (CHT) to achieve the benefits of estrogen/progesterone for endometrial protection. TX-001HR is a combination of bioidentical 17β-estradiol (E2) and progesterone (P4) in a single capsule designed for continuous daily use to treat moderate to severe VMS.

Areas covered: This drug profile describes the efficacy and safety of 4 doses of this E2/P4 (mg/mg: 1/100, 0.5/100, 0.5/50, 0.25/50) for treating moderate to severe VMS in menopausal woman with a uterus.

Expert opinion: In REPLENISH (NCT01942668), the two highest doses of TX-001HR significantly reduced VMS frequency and severity at 4 and 12 weeks versus placebo (co-primary endpoints); all doses met the primary endpoint of endometrial safety. Rates of amenorrhea were high and improved over time; the Menopause Quality of Life and Medical Outcomes Study-Sleep instruments improved with E2/P4. TX-001HR was well tolerated and had no clinically significant impact on vital signs, metabolic or coagulation parameters, or breast safety. The combination bioidentical E2/P4 capsule (1 mg/100 mg dose was FDA-approved as Bijuva in October 2018) may provide a safe, effective, rigorously studied alternative for women with a uterus who prefer CHT for relief of VMS.     

Feasibility of adding everolimus to carboplatin and paclitaxel,with or without bevacizumab,for treatment-naive,advanced non–small cell lung cancer

Introduction One standard of care for advanced non–small cell lung cancer (NSCLC) is paclitaxel plus carboplatin?±?bevacizumab. This two-step phase I study evaluated the feasibility of adding everolimus to paclitaxel plus carboplatin?±?bevacizumab for advanced NSCLC. Methods Adults with advanced NSCLC naive to systemic therapy were enrolled. A Bayesian dose-escalation model was used to identify feasible daily or weekly everolimus doses given with paclitaxel (200 mg/m² q21 days) and carboplatin (AUC 6 mg/mL/min q21 days) (step 1) and paclitaxel (200 mg/m² q21 days), carboplatin (AUC 6 mg/mL/min q21 days), and bevacizumab (15 mg/kg q21 days) (step 2). Primary endpoint was end-of-cycle 1 dose-limiting toxicity (DLT) rate. Secondary endpoints included safety; relative dose intensities of paclitaxel, carboplatin, and bevacizumab; pharmacokinetics; and tumor response. Results Fifty-two patients were enrolled and received everolimus 5 mg/day plus carboplatin and paclitaxel (step 1 daily; n?=?13); everolimus 30 mg/week plus carboplatin and paclitaxel (step 1 weekly; n?=?13); everolimus 5 mg/day plus carboplatin, paclitaxel, and bevacizumab (step 2 daily; n?=?13); or everolimus 30 mg/week plus carboplatin, paclitaxel, and bevacizumab (step 2 weekly; n?=?13). End-of-cycle 1 DLT rate was 16.7 % (step 1 daily), 30.8 % (step 1 weekly), 30.0 % (step 2 daily), and 16.7 % (step 2 weekly). Cycle 1 DLTs were grade 3 neutropenia, anal abscess, diarrhea, and thrombocytopenia and grade 4 myalgia, cellulitis, neutropenia, febrile neutropenia, pulmonary embolism, and thrombocytopenia. The most common adverse events were neutropenia, fatigue, anemia, and thrombocytopenia. One patient (step 2 daily) experienced complete response, 10 patients partial response. Conclusions The feasible everolimus doses given with carboplatin and paclitaxel?±?bevacizumab were 5 mg/day and 30 mg/week. Neither schedule was very well tolerated in this unselected NSCLC population.     

A rapid review of the impacts of “Big Events ” on risks,harms, and service delivery among people who use drugs: Implications for responding to COVID-19

Background“Big Events” are major disruptions to physical, political, and economic environments that can influence vulnerability to drug-related harms. We reviewed the impacts of Big Events with relevance to the COVID-19 pandemic on drug-related risk and harms and access to drug treatment and harm reduction services.MethodsWe conducted a rapid review of quantitative, qualitative, and mixed methods literature relating to the following Big Events: respiratory infection pandemics, natural disasters, financial crises, and heroin shortages. Included studies reported data on changes to risks, harms, and/or service provisioning for people who use illicit drugs (other than cannabis) in the context of these Big Events. Searches were conducted in PubMed in May 2020, and two reviewers screened studies for inclusion. Peer-reviewed studies published in English or French were included. We used a narrative synthesis approach and mapped risk pathways identified in the literature.ResultsNo studies reporting on respiratory infection pandemics were identified. Twelve studies reporting on natural disaster outcomes noted marked disruption to drug markets, increased violence and risk of drug-related harm, and significant barriers to service provision caused by infrastructure damage. Five studies of the 2008 global financial crisis indicated increases in the frequency of drug use and associated harms as incomes and service funding declined. Finally, 17 studies of heroin shortages noted increases in heroin price and adulteration, potentiating drug substitutions and risk behaviors, as well as growing demand for drug treatment.ConclusionCurrent evidence reveals numerous risk pathways and service impacts emanating from Big Events. Risk pathway maps derived from this literature provide groundwork for future research and policy analyses, including in the context of the COVID-19 pandemic. In light of the findings, we recommend responding to the pandemic with legislative and financial support for the flexible delivery of harm reduction services, opioid agonist treatment, and mental health care.     

Progress in acetylcholinesterase reactivators and in the treatment of organophosphorus intoxication: a patent review (2006–2016)

Introduction: organophosphorus compounds act as irreversible inhibitors of the vital enzyme acetylcholinesterase (AChE). this leads in the accumulation of acetylcholine (ACh) leading to cholinergic crisis and death. The main therapeutic approach is based on immediate administration of an ache reactivator as an antidote enabling recovery of the ache function.

Areas covered: This review covers the development of AChE reactivators in order to introduce a new efficient drug that will overcome significant failures of common antidotes. Further options together with methods of detection are also discussed in order to assure a complete insight into the treatment of intoxication.

Expert opinion: Since organophosphates belong to the most toxic chemical warfare agents, efficient antidotes are a matter of importance. The solution of how to limit the basic drawbacks of clinically used reactivators remained a spotlight for many researches worldwide. Recent strategies of the treatment of OP exposure bring us new possibilities which may overcome classic antidotes. The importance of detection of OP also has to be taken into consideration. Especially, with the fast spreading toxic effect when death can occur within minutes.     

What has been achieved in HIV prevention,treatment and care for people who inject drugs, 2010–2012? A review of the six highest burden countries

ObjectiveIn 2010 the international HIV/AIDS community called on countries to take action to prevent HIV transmission among people who inject drugs (PWID). To set a baseline we proposed an “accountability matrix”, focusing upon six countries accounting for half of the global population of PWID: China, Malaysia, Russia, Ukraine, Vietnam and the USA. Two years on, we review progress.DesignWe searched peer-reviewed literature, conducted online searches, and contacted experts for ‘grey’ literature. We limited searches to documents published since December 2009 and used decision rules endorsed in earlier reviews.ResultsPolicy shifts are increasing coverage of key interventions for PWID in China, Malaysia, Vietnam and Ukraine. Increases in PWID receiving antiretroviral treatment (ART) and opioid substitution treatment (OST) in both Vietnam and China, and a shift in Malaysia from a punitive law enforcement approach to evidence-based treatment are promising developments. The USA and Russia have had no advances on PWID access to needle and syringe programmes (NSP), OST or ART. There have also been policy setbacks in these countries, with Russia reaffirming its stance against OST and closing down access to information on methadone, and the USA reinstituting its Congressional ban on Federal funding for NSPs.ConclusionsPrevention of HIV infection and access to HIV treatment for PWID is possible. Whether countries with concentrated epidemics among PWID will meet goals of achieving universal access and eliminating new HIV infections remains unknown. As long as law enforcement responses counter public health responses, health-seeking behaviour and health service delivery will be limited.     

Co-occurrence of tobacco product use,substance use,and mental health problems among youth: Findings from wave 1 (2013–2014) of the population assessment of tobacco and health (PATH) study

IntroductionCigarette use is associated with substance use and mental health problems among youth, but associations are unknown for non-cigarette tobacco product use, as well as the increasingly common poly-tobacco use.MethodsThe current study examined co-occurrence of substance use and mental health problems across tobacco products among 13,617 youth aged 12–17 years from Wave 1 (2013–2014) of the nationally representative Population Assessment of Tobacco and Health (PATH) Study. Participants self-reported ever cigarette, e-cigarette, smokeless tobacco, traditional cigar, cigarillo, filtered cigar, hookah, and other tobacco product use; alcohol, marijuana, and other drugs; and lifetime substance use, internalizing and externalizing problems.ResultsIn multivariable regression analyses, use of each tobacco product was associated with substance use, particularly cigarillos and marijuana (AOR = 18.9, 95% CI: 15.3–23.4). Cigarette (AOR = 14.7, 95% CI: 11.8–18.2) and cigarillo (AOR = 8.1, 95% CI: 6.3–10.3) use were strongly associated with substance use problems and tobacco users were more likely to report internalizing (AOR = 1.6, 95% CI: 1.4–1.8) and externalizing (AOR = 1.4, 95% CI: 1.3–1.6) problems. Female tobacco users were more likely to have internalizing problems than male tobacco users. Poly-tobacco users were more likely than exclusive users to use substances (AOR = 3.4, 95% CI: 2.7–4.3) and have mental health (AOR = 1.2, 95% CI: 1.0–1.5) and substance use (AOR = 4.7, 95% CI: 3.4–6.6) problems.ConclusionsRegardless of the tobacco product used, findings reveal high co-occurrence of substance use and mental health problems among youth tobacco users, especially poly-tobacco users. These findings suggest the need to address comorbidities among high risk youth in prevention and treatment settings.