By Z. Yasmin. Alabama State University.
Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence order 100 mg celebrex fast delivery. European Journal of Clinical Microbiology and Infectious Diseases discount celebrex 100mg free shipping, 2012 buy celebrex without a prescription, 31:919–927 buy generic celebrex from india. Scaling up antiretroviral therapy in resource-limited settings: adapting guidance and meet the challenges. Initiating highly active antiretroviral therapy in sub-Saharan Africa: an assessment of the revised World Health Organization scaling-up guidelines. Immunodeficiency at start of combination antiretroviral therapy in low, middle and high income countries. Effect of highly active antiretroviral therapy on incidence of tuberculosis in South Africa: a cohort study. Proceedings of the National Academy of Sciences of the United States of America, 2010, 107:19485–19489. Antiretroviral Pregnancy Registry international interim report for 1 January 1989 through 31 July 2012. Liver-related deaths in persons infected with the human immunodeficiency virus: the D: A:D study. Liver fibrosis progression in human immunodeficiency virus and hepatitis C virus coinfected patients. Impact of human immunodeficiency virus infection on the course of hepatitis C virus infection: a meta- analysis. Minneaolis, Clinical and Translational Science Institute, University of Minnesota, 2012 (http://apps. Adherence to antiretroviral therapy during and after pregnancy in low-income, middle-income, and high- income countries: a systematic review and meta-analysis. Cross Continents Collaboration for Kids (3Cs4kids) Analysis and Writing Committee. Pretoria, Republic of South Africa National Department of Health 2013 (http://www. Adverse events associated with nevirapine and efavirenz-based first-line antiretroviral therapy: a systematic review and meta-analysis. Safety of efavirenz in the first trimester of pregnancy: an updated systematic review and meta- analysis. 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Simplification of antiretroviral therapy with tenofovir-emtricitabine or abacavir-lamivudine: a randomized, 96-week trial. Conservation of first-line antiretroviral treatment regimen where therapeutic options are limited. Validating clinical and immunological definitions of antiretroviral treatment failure in Malawi. Evaluation of World Health Organization criteria for antiretroviral treatment failure in resource-limited settings. Evaluating patients for second-line antiretroviral therapy in India: the role of targeted viral load testing. Failure of immunologic criteria to appropriately identify antiretroviral treatment failure in Uganda. The role of targeted viral load testing in diagnosing virological failure in children on antiretroviral therapy with immunological failure. Dried blood spots perform well in viral load monitoring of patients who receive antiretroviral treatment in rural Tanzania. Guidelines for the psychosocially assisted pharmacological treatment of opioid dependence. Effect of concomitantly administered rifampin on the pharmacokinetics and safety of atazanavir administered twice daily. Effect of rifampin on steady-state pharmacokinetics of atazanavir with ritonavir in healthy volunteers. Pharmacokinetics of adjusted-dose lopinavir-ritonavir combined with rifampin in healthy volunteers. Resistance in pediatric patients experiencing virologic failure with first- and second-line antiretroviral therapy. Treatment outcomes of patients on second-line antiretroviral therapy in resource-limited settings: a systematic review and meta-analysis. Cardiovascular risk factors in adult Malawians on long-term antiretroviral therapy. Transactions of the Royal Society of Tropical Medicine and Hygiene, 2011, 105:644–649. Length/ height-for-age, weight-for-age, weight-for-length, weight-for-height and body mass index-for-age. 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Challenges in using mobile phones for collection of antiretroviral therapy adherence data in a resource- limited setting. Supporting patient adherence to antiretrovirals using mobile phone reminders: patient responses from South India. Effects of a mobile phone short message service on antiretroviral treatment adherence in Kenya (WelTel Kenya1): a randomised trial. Mobile phone technologies improve adherence to antiretroviral treatment in a resource-limited setting: a randomized controlled trial of text message reminders. Medication diaries do not improve outcomes with highly active antiretroviral therapy in Kenyan children: a randomized clinical trial. Adult patients’ adherence to anti-retroviral treatment: a survey correlating pharmacy refill records and pill counts with immunological and virological indices. Pharmacy adherence measures to assess adherence to antiretroviral therapy: review of the literature and implications for treatment monitoring. Validation of self-report and hospital pill count using unannounced home pill count as methods for determination of adherence to antiretroviral therapy. Adherence to antiretroviral therapy assessed by unannounced pill counts conducted by telephone. Mortality of patients lost to follow-up in antiretroviral treatment programmes in resource-limited settings: systematic review and meta-analysis. Reasons for loss to follow-up among mothers registered in a prevention-of-mother-to-child transmission program in rural Malawi. Transactions of the Royal Soceity of Tropical Medicine and Hygiene, 2008, 102:1195–1200. Block appointments in an overloaded South African health centre: quantitative and qualitative evaluation.
Distribution and quantiﬁcation of polyethyleneimine oligonucleotide complexes in human skin after iontophoretic delivery using confocal scanning laser microscopy celebrex 200mg free shipping. Saturated Anionic Phospholipids enhance transdermal trans- port by electroporation cheap celebrex 100 mg amex. Electroporation and ultradeformable liposomes; human skin barrier repair by phospholipid purchase 200mg celebrex fast delivery. Low frequency sonophoresis: Ultrastructural basis for stratum corneum permeability assessed using quantum dots order 200mg celebrex mastercard. Microfabricated needles for transdermal deliv- ery of macromolecules and nanoparticles: Fabrication methods and transport studies. Liposomes as carriers for dermal delivery of tretinoin: In vitro evaluation of drug permeation and vesicle-skin interaction. Investigation of liposomes as carriers of sodium ascorbyl phosphate for cutaneous photoprotection. Isotretinoin loaded solid lipid nanoparticles with skin targeting for topical delivery. Solid lipid microparticle formulations of the pyrethroid gamma-cyhalothrin-incompatibility of the lipid and the pyrethroid and biological properties of the formulations. Stabilization of all-trans retinol by loading lipophilic antiox- idants in solid lipid nanoparticles. Altered chemical and biological activities of all-trans retinoic acid incorporated in solid lipid nanoparticle powders. Development of a new solid lipid nanoparticle formulation containing retinoic acid for topical treatment of acne. Novel nanoparticulate carrier system based on carnauba wax and decyl oleate for the dispersion of inorganic sunscreens in aqueous media. Fabrication, in vitro degradation and the release behaviours of poly(dl-lactide-co-glycolide) nanospheres containing ascorbic acid. Poly(d,l-lactide) nanoencapsulation to reduce pho- toinactivation of a sunscreen agent. Topical application of liposomally entrapped cyclosporine evaluated by in vitro diffusion studies with human skin. Skin delivery of oestradiol from deformable and traditional liposomes: Mechanistic studies. Skin delivery of 5-ﬂuorouracil from ultrade- formable and standard liposomes in-vitro. Preparation and in vitro evaluation of liposomal/ niosomal delivery systems for antipsoriatic drug dithranol. It is vital that the regulatory process be coherent and avoid mistakes made in developing regulatory frameworks for recent innovations, such as nanotechnology and agricultural biotechnology, to ensure the development of new uses, as well as public conﬁdence (1). Although standards of care have been established, accurate prediction of the effects, both therapeutic and toxic, of a given therapeutic system on a given patient is frustrated by a host of cellular resistance mechanisms that yield disappointing differentials between in vitro predictions and in vivo results (2). Computational models may bridge the gap between the two, producing highly realistic and predictable therapeutic results. The power of such models over in vitro monolayer and even spheroid assays lies in their ability to integrate the complex in vivo interplay of phenomena such as diffusion through lesion, heterogeneous lesion growth, apoptosis, necrosis, and cellular uptake, efﬂux, and target binding. This chapter covers in vitro drug release process from partic- ulate (micro/nano) drug carriers. The discussion is about nanoparticle cell inter- actions; various techniques used for immunoassays are discussed in later parts of this book. In general, drug release rate depends on (i) solubility of drug; (ii) desorption of the surface-bound/adsorbed drug; (iii) drug diffusion through the nanoparticle matrix; (iv) nanoparticle matrix erosion/degradation; and (v) combination of erosion/diffusion process. Thus, sol- ubility, diffusion, and biodegradation of the matrix materials govern the release process. In the case of nanospheres, where the drug is uniformly distributed, the release occurs by diffusion or erosion of the matrix under sink conditions. If the diffusion of the drug is faster than matrix erosion, the mechanism of release is largely controlled by a diffusion process. The rapid initial release or “burst” is mainly due to drug particles over the surface, which diffuse out of the drug polymer matrices (3). Kinetics of Drug Release from Micro/Nanoparticles Kinetics of drug release is an important evaluation parameter. The knowledge of the mechanism and kinetics of drug release from these microparticlulate systems indicates their performance and gives proof of adequateness of their design. Drug release data is applied basically for (i) quality con- trol; (ii) understanding of physicochemical aspects of drug delivery systems; (iii) understanding release mechanisms; and (iv) predicting behavior of systems in vivo. However, there are difﬁculties in modeling drug release data, as there is a great diversity in the physical form of micro/nanocapsules/particles with respect to size, shape, arrangement of the core and the coat, properties of core-like solubil- ity, diffusivity, partition coefﬁcient, properties of coat-like porosity, tortuosity, thick- ness, crystallinity, inertness, etc. In addition, there are problems in translating kinet- ics of drug release from “micro” products of perfect geometry to various irregular micro/nanosystems (4). Factors Inﬂuencing Drug Release There are various factors that inﬂuence drug release, discussed as follows: 1. Permeation: It is the process whereby the drug is transported through one or more polymeric membranes corresponding to the coating material which acts as the barrier to drug release. Permeation depends on crystallinity, nature of polymer, degree of polymerization, presence of ﬁllers and plasticizers, matrix properties such as thickness, porosity, tortuosity, diffusion layer, etc. Per- meation may be reduced by the incorporation of dispersed solids, ﬁllers, waxy sealants, and others. Diffusion: It is the movement of drug across concentration gradient until equal- ization takes place. Diffusion coefﬁcient (D) is a measure of the rate of drug movement Diffusion coefﬁcient (6) depends on various factors such as (i) tempera- ture (Arrhenius equation); (ii) molecular weight of the molecule; (iii) radius (for small, electrically neutral, spherical molecules); (iv) plasticizer concentration; (v) size of the penetrant, (vi) position of the drug in the microsphere; and (vii) inter- action between the polymer and the drug. Partition coefﬁcient: Partition coefﬁcient between polymer solvents is referred to as Ko/w. Drug solubility: As diffusion depends on concentration gradient, drug solubility in the penetrant becomes important and then drug release becomes dissolution dependent for sparingly soluble drugs. The Noyes-Whitney equation (8) dC = k(Cs − C dt where dC/dt = amount of drug released per unit time; k = dissolution rate constant; Cs = saturation solubility in solvent; C = concentration in solvent at time t; and Ds A k = (6) Vlb where Ds = diffusion coefﬁcient of the solvent; V = volume of the solution; and lb = boundary layer thickness. By substituting the value of k in equation (5), we get dC Ds A = (Cs − C dt Vlb thus, water-soluble drugs will be released faster than the hydrophobic ones. Si-Nang and Carlier (9) modiﬁed this equation for drug release from micro- capsules dC Ds A K = (8) dt Vlm where A = internal surface area of coating. In this case, the plot of 3 W versus t gives a straight t line and the value of k can be obtained from the slope. For weakly acidic and basic drugs, the inﬂuence of pH on solubility is given by the Handersson-Hasselbach equation: S − S0 For weak acids, pH = pka + log (10) S0 S0 For weak base, pH = pka + log (11) S − S0 where S = saturation solubility of the solute; S0 = intrinsic solubility of the solute. In addition, ﬂux ∝ 1/l; so, as the thickness decreases, ﬂux also increases due to reduced diffusional path length. Other factors include type and amount of matrix material, size and density of the microparticle, presence of additives or adjuvants, extent of polymerization, denaturation, cross-linking or hardening, diffusion temperature, diffusion medium, its polarity, presence of enzymes, etc. Empiric Models of Drug Release Kinetics of drug release from microparticulates can be understood from various models based on their nature. However, simple empiric models are often used in place of complex models, which are discussed in the following text. Exponential Equation Diffusional exponent approach has been given by Peppas and colleagues (11,12). It is applicable for hydrating or eroding systems in which D is not constant, thereby giving anomalous diffusion. Mt n = kt (12) M0 where Mt/M0 = fractional mass of drug released at time t; and n = diffusional expo- nent. The two exponents consist of rapid or burst phase and slow or sustained release phase, respectively. On converting equation (15), we get In Mt 3k1t 1 − =− 2 M0 r which is the equation for a straight line. Nowadays, drug release kinetics are determined and better understood from their nature, depending on whether they are reservoir-, matrix-, or sandwich-type systems. Reservoir-Type Devices (Microcapsules) (14–18) Various equations have been given depending on different situations. Case 1 Assuming that thermodynamic activity of the core material is constant within the microcapsule, which is spherical and has inert homogeneous coating, steady-state release rate is derived from Fick’s ﬁrst law of diffusion.
Between the ages of 10 and 13 she was subjected to regular sexual abuse by an uncle who lived with the family purchase celebrex no prescription. She once told her mother about the abuse but was told to keep it quiet and not tell anyone discount celebrex online visa, as it would bring shame on the family order celebrex 100 mg amex. She did well at school and started work in a local estate agent’s office when she left school purchase genuine celebrex online. Mr Y was a heroin user and eventually she started smoking cigarettes that he gave her. After a few months, she noticed that she felt very unwell if she did not smoke and Mr Y told her that the cigarettes had heroin in them. She had very little antenatal care and avoided the appointments with the social worker, who she only met once. For a few weeks she went back, with her baby, to live with her parents (with the support of social services) and stopped using heroin but the rows with her mother were so bad she eventually left the baby with her mother and went to live with Mr Y in a big city. She came into treatment when Mr Y was arrested for aggravated burglary and went to prison. She was prescribed buprenorphine and managed in an antenatal liaison clinic, where she received antenatal care and drug treatment. Social services were involved from the beginning and found her a place in a local women’s hostel. Ms B was able to stop using heroin and begin to think about some of the problems she had with her abusive relationship and her history of sexual abuse. Her second baby, a little girl, was born at full term and was immediately subject to child protection proceedings and taken into foster care but Ms B had regular contact with the baby. She subsequently went, with the baby, to a mother and baby rehabilitation centre where her parenting could be assessed and she could reduce her buprenorphine. Ms B was clear she wanted to stop using all drugs, keep her daughter and re-establish a relationship with her son and her family. Case study details provided by Dr Emily Finch, a consultant addiction psychiatrist. It is safest to prescribe opiate substitution (see Chapter 8) ‘at a dose that stops or minimises illicit use’. In all pregnant women using or prescribed opioid drugs, particular consideration will also need to be given to their birthing plan, including pain management and the risk of fetal distress at birth. In view of the potential harms to the fetus and to the mother’s health, the pregnant woman should be given support to stop using cocaine during pregnancy. A non-judgemental, sensitive approach, with clear and effective multidisciplinary communication and team working are again essential, addressing the full spectrum of psychosocial and physical health needs. The maximum penalty is life imprisonment for supply of Class A drugs, with seven years for possession, but sentences between two and 14 years are used for possession or supply of Class B or C drugs (see Chapter 1). This has implications for the medical professional, as many illicit drug users first come into contact with the medical profession via the criminal justice system. This can create particular challenges for medical professionals working within the criminal justice setting, which are highlighted throughout this chapter. It offers a valuable opportunity for effective medical treatment of drug use disorder and ultimately the best chance for many dependent drug users to be rehabilitated. A report from the Probation Service explained that she had been picked up by police after having collapsed in the stairwell of a housing estate in east London. It also explained that she was homeless; she had been living in a local authority hostel but had been thrown out of it for taking men back into the hostel for the purpose of prostitution in order to raise funds to feed her drug habit. She was barely conscious at the time that she was found by the police and was high on drugs. She was due to be sentenced for a series of offences, which included attempted robberies of mobile phones from young women whom she had threatened with a knife, and attempts to snatch handbags, also from young women leaving a tube station late at night. The probation report explained that she committed these offences to raise funds to buy drugs and that she was so dependent that, unless she was taken off the streets (and in effect given a lengthy prison sentence), there was a real risk that she would die. The oldest was a six-year-old girl, who had been taken away by the grandmother to Belgium (it was said that she had, in effect, abducted the granddaughter to save her from her mother) and she also had a two-year-old child who was in care. After hearing evidence from the Probation Services, the court imposed a prison sentence at the maximum end of the scale for offences of that nature. The court discussed the possible range of sentences with defence and prosecution counsel and the discussion proceeded upon the basis that it was, in effect, common ground that, for her own good, she needed to be given a custodial sentence of the longest duration that was proper in the circumstances. This would give the defendant the best chance of receiving drug treatment in prison. The case was unusual in that the Probation Service was able to make enquiries about which prison the defendant would be sent to, and about the availability of drug treatment courses in that prison. This was exceptional, since it is very rare indeed for a sentencing judge to know anything about the prison to which a defendant is to be sent, or about the availability of drug rehabilitation courses in that prison. While drug treatment programmes delivered in a controlled prison environment may offer some prisoners the opportunity to be rehabilitated, rates of drug use during incarceration remain high. Analysis of the findings of the 1997 National Survey found that over a quarter of the men who had used heroin reported first initiating use in prison. Care planning is integral to the process; this is an agreed plan of action between the service user and the Criminal Justice Intervention Team worker, which involves setting goals based on the individual needs identified. This plan documents and enables routine review of the service user’s needs, goals and progress across four key domains: • drug and alcohol use • physical and psychosocial health • offending • social functioning (including housing, employment and relationships). The different levels/tiers of treatment reflected their intensity and ranged from non-specialist general healthcare through open drugs treatment and community-based drug treatment to residential drug treatment. This requirement is one of a menu of 12 requirements to which offenders can be sentenced. There are three levels of intensity of contact, which include, but do not entirely consist of, medical treatment. Before making the requirement, the court must be satisfied that: • the offender is dependent on or has a propensity to use any controlled drug • he or she would benefit from treatment • the necessary arrangements can be made for the treatment • the offender agrees to comply with the requirement. Arrangements for treatment are available through the Probation Trusts, which operate at a local level. There is provision for the court to review the progress of the offender during the order, and to agree changes in the treatment. The treatment can be residential or non-residential, which is decided by the court, and must be supervised by a suitably qualified person. A review of the National Drug Rehabilitation Requirement found a variation in treatment delivery across England and Wales. Sessions were set aside in existing magistrates’ courts for dedicated panels of magistrates or particular district judges to sit for sentencing. Appropriate sanctions and other rehabilitation services that could be included in community sentences were available to all courts in England and Wales. In January 2011, the Ministry of Justice published The Dedicated Drug Courts Pilot Evaluation Process Study. It also leads to a blurring of the distinction between judicial and therapeutic strategies, with the result that a drug user may view the doctor treating them as part of the judicial system and be confused about whether they are being punished, or treated as a patient. Effective communication is essential to ensure that those undergoing treatment fully understand their rights as outlined in Section 10. Issues that arise for health professionals include the following: • high rates of illiteracy and learning disability in offenders, often coupled with a lack of time and/or privacy for consultations, which raise serious questions about their freedom to give informed consent • the perception of offenders that the doctor is not impartial but is working for the police or prison • the ethics of providing treatment when the patient has effectively been coerced to consent. It has been estimated that the value of illicit drugs within prison is about £100 million. There is disagreement as to which of the routes of illicit supply is the most prominent. A Policy Exchange report in 2010 contends that the majority of drug dealing within prison is highly organised and involves the collusion of around 1,000 corrupt staff, which equates to around seven prison officers per prison. It is important that medical professionals are able to make independent clinical and ethical decisions about the most appropriate treatment for individuals in prison, in exactly the same way as for those living in the community outside prison. Treatment with methadone in prison has been shown to significantly reduce heroin use among those treated. Treatment options will include continued opioid prescribing or slow reduction or detoxification if appropriate, with regular reviews, and clinical decisions based on a careful and full assessment, including risk assessment, in collaboration with the full team and the patient. There is a paucity of research evaluating the most effective treatment for opiate detoxification in prisons.