Comprehensive Clinical Care Research Articles

G.P.45 - Cautionary tale in Duchenne muscular dystrophy – Opioids in neuromuscular disorders

sites, thus reducing variations in clinical trial outcomes. Centers applying for certification are evaluated based on their ability to provide comprehensive clinical services and care in five domains determined by the TDCI to comprise comprehensive Duchenne care (neuromuscular, cardiac, pulmonary, communication/coordination, endocrine/bone health). The center evaluation is performed via survey completion, site visit, faculty/staff interviews and chart review. Center Metrics, provided annually by certified centers, monitor the center’s continuous improvement in the five domains of care and clinical services. Patients/parents provide additional evaluation via completion of the Clinical Experiences Survey, which mirrors the Center Metrics, and DuchenneConnect, PPMD’s patient-reported outcomes registry. The CDCCP has initiated a network of Certified Duchenne Care Centers. This network is improving patient/family access to standardized, comprehensive care and will provide a framework to support reliable future clinical research and trials.

Non- invasive technique using breath analysis for detection and classification of diabetes

Diabetes, a metabolic disease that is characterized by high glucose level in the blood, is a major problem affecting millions of people today. This disease if left unchecked can create enormous implication on the health of the population. Among the various non-invasive methods of detection, breath analysis presents an easier, more accurate and viable method in providing comprehensive clinical care for the disease. This paper examines the concentration of acetone levels in breath for monitoring blood-glucose levels and thus predicting diabetes. The analysis uses the support vector mechanism to classify the response to healthy and diabetic samples. For the analysis, ten subject samples of acetone levels are taken into consideration and are classified according to three labels, which are healthy, type one diabetic and type two diabetic.

Established disease-modifying treatments in relapsing-remitting multiple sclerosis.

The purpose of this review is to summarize mechanisms of action, efficacy and safety of established disease-modifying treatments (DMTs) that have been widely approved for use in relapsing-remitting multiple sclerosis (RRMS). Established and widely used DMTs for the treatment of RRMS include the interferon-β agents, glatiramer acetate, natalizumab, fingolimod, teriflunomide and dimethyl fumarate. These DMTs have quite different mechanisms of action, efficacy and safety and tolerability profiles, which are summarized concisely in the article below. The treatment algorithm for RRMS is becoming increasingly complex with the ever-expanding armamentarium of DMTs. The choice of DMT will become an increasingly individual decision, based on a number of factors, including disease activity and severity, safety/tolerability profile and patient preference. Neurologists treating patients with multiple sclerosis (MS) will need a thorough knowledge of efficacy, safety and tolerability of the spectrum of DMTs available for treatment of RRMS to provide comprehensive clinical care.

Implementing a Prenatal Oral Health Program Through Interprofessional Collaboration

Interprofessional collaboration has become a critical component of accreditation standards in dentistry and medicine. This article reports on implementation in an academic setting of a prenatal oral health program (pOHP) that addresses coordinated care, accreditation standards, and new clinical practice guidelines. The pOHP is an educational intervention for third-year medical students, residents, and faculty members to deliver preventive oral health information and referral to a dental home for pregnant women. At the same time, senior dental students and faculty members are introduced to prenatal oral health principles and delivery of comprehensive oral health care to pregnant women. A systems-based approach was used to guide the pOHP implementation during the 2012-13 academic year. Participants were 96 third-year medical students (50% of the total in an obstetrics and gynecology clerkship) and all 81 fourth-year dental students. During that academic year, 126 dental referrals were made to the School of Dentistry, and 55 women presented for care, resulting in 50% (n=40) of dental students participating in the clinical experience and delivery of simple to complex oral health procedures. The prenatal period is a frequently missed opportunity to address oral health care. The pOHP is an interprofessional collaboration model designed to educate dental and medical providers and provide a system of referral for comprehensive clinical care of pregnant patients, including educating women about their oral health and that of their children. Such programs can help meet interprofessional accreditation standards and encourage implementation of practice guidelines.

Does ketamine have anti-suicidal properties? Current status and future directions.

Ketamine, a widely used anesthetic agent, is currently being investigated as a novel therapeutic for depression and suicidality. Ketamine has garnered substantial attention from researchers, clinicians, media outlets, and patients alike, but numerous questions remain. One of the compelling features of ketamine is the rapidity of its antidepressant effects, which peak just 24h after infusion, setting it apart from other existing treatments. Ketamine's rapid time course has inspired research efforts to explore its potential as a life-saving therapy for patients at imminent risk of suicide. In this article, we review current evidence supporting the rapid effects of ketamine on suicidal ideation in the context of unipolar and bipolar depression. We then discuss several future directions that are necessary before ketamine can be considered a viable treatment option for suicidality in clinical settings. These include: testing for a specific anti-suicidal effect-separate from overall antidepressant effects-to ascertain whether ketamine might hold promise for a broader class of suicidal patients; ensuring that acute benefits of ketamine can be prolonged over a clinically meaningful timeframe; and developing a better understanding of the mechanisms by which ketamine might reduce suicide risk. Such efforts will enable the field to more accurately assess the potential of ketamine, as well as its limitations, allowing for appropriate placement within the context of comprehensive clinical care for suicide prevention.

Competent psychopharmacology.

There is little doubt that undergraduate and post-graduate training of physicians, pharmacists, and nurses is insufficient to prepare them to use psychotropics safely and effectively, especially in the context of their expanded off-label uses. Therefore, the development of competencies in psychotropic prescribing needs to be approached as a long-term, practice-based learning commitment. Proposed are the abilities and knowledge components necessary for safe and effective use of psychotropics. Typical challenges in prescribing for chronic and recurrent illnesses include highly variable responses and tolerability, drug interactions, and adverse effects that can be serious, irreversible, and even fatal. Prescribing psychotropics is further complicated by negative public and professional reports and growing patient concerns about the quality of care, and questions about the efficacy, safety, and addictive risks of psychotropics. Increased efforts are needed to enhance clinical training and knowledge in psychopharmacology among trainees and practising clinicians, with more comprehensive and sustained attention to the assessment of individual patients, and greater reliance on patient education and collaboration. Improved competence in psychotropic prescribing should lead to more informed, thoughtful, and better-targeted applications as one component of more comprehensive clinical care.

Terror Attacks Increase the Risk of Vascular Injuries

Objectives: Extensive literature exists about military trauma as opposed to the very limited literature regarding terror-related civilian trauma. However, terror-related vascular trauma (VT), as a unique type of injury, is yet to be addressed.Methods: A retrospective analysis of the Israeli National Trauma Registry was performed. All patients in the registry from 09/2000 to 12/2005 were included. The subgroup of patients with documented VT (N = 1,545) was analyzed and further subdivided into those suffering from terror-related vascular trauma (TVT) and non-terror-related vascular trauma (NTVT). Both groups were analyzed according to mechanism of trauma, type and severity of injury and treatment.Results: Out of 2,446 terror-related trauma admissions, 243 sustained TVT (9.9%) compared to 1302 VT patients from non-terror trauma (1.1%). TVT injuries tend to be more complex and most patients were operated on. Intensive care unit admissions and hospital length of stay was higher in the TVT group. Penetrating trauma was the prominent cause of injury among the TVT group. TVT group had a higher proportion of patients with severe injuries (ISS ≥ 16) and mortality. Thorax injuries were more frequent in the TVT group. Extremity injuries were the most prevalent vascular injuries in both groups; however NTVT group had more upper extremity injuries, while the TVT group had significantly much lower extremity injuries.Conclusion: Vascular injuries are remarkably more common among terror attack victims than among non-terror trauma victims and the injuries of terror casualties tend to be more complex. The presence of a vascular surgeon will ensure a comprehensive clinical care.

New horizons in the pathogenesis, assessment and management of delirium

Delirium is one of the foremost unmet medical needs in healthcare. It affects one in eight hospitalised patients and is associated with multiple adverse outcomes including increased length of stay, new institutionalisation, and considerable patient distress. Recent studies also show that delirium strongly predicts future new-onset dementia, as well as accelerating existing dementia. The importance of delirium is now increasingly being recognised, with a growing research base, new professional international organisations, increased interest from policymakers, and greater prominence of delirium in educational and audit programmes. Nevertheless, the field faces several complex research and clinical challenges. In this article we focus on selected areas of recent progress and/or uncertainty in delirium research and practice. (i) Pathogenesis: recent studies in animal models using peripheral inflammatory stimuli have begun to suggest mechanisms underlying the delirium syndrome as well as its link with dementia. A growing body of blood and cerebrospinal fluid studies in humans have implicated inflammatory and stress mediators. (ii) Prevention: delirium prevention is effective in the context of research studies, but there are several unresolved issues, including what components should be included, the role of prophylactic drugs, and the overlap with general best care for hospitalised older people. (iii) Assessment: though there are several instruments for delirium screening and assessment, detection rates remain dismal. There are no clear solutions but routine screening embedded into clinical practice, and the development of new rapid screening instruments, offer potential. (iv) Management: studies are difficult given the heterogeneity of delirium and currently expert and comprehensive clinical care remains the main recommendation. Future studies may address the role of drugs for specific elements of delirium. In summary, though facing many challenges, the field continues to make progress, with several promising lines of enquiry and an expanding base of interest among researchers, clinicians and policymakers.

Assessing the impact of intensive programme utilisation on HIV and sexually transmitted infection prevalence among a high-risk population in urban settings of Karnataka: evidence from three cross-sectional surveys, 2005–12

BackgroundWe evaluate the impact since 2003 of the Bill & Melinda Gates Foundation's Indian AIDS initiative, Avahan, in four districts of Karnataka, south India. The programme involved comprehensive outreach, clinical care, and other services to reduce the risk of HIV and other sexually transmitted infections (STIs) among high-risk women and men by promoting behavioural changes. Though there were reviews of the programme performance through periodic cross-sectional surveys, the actual impact of the programme could not be assessed in the absence of a suitable control group. MethodsUsing three rounds of biobehavioural assessment data gathered between 2005 and 2012 in four districts of Karnataka, south India, we used the propensity score matching (PSM) method to demonstrate the true effect of different components of programme exposure on HIV/STI prevalence and consistent condom use with different sexual partners. This method creates a contrafactual group of control individuals who were not exposed to the programme intensively and compares the outcome measures with each respective case that was intensively exposed to the programme. Principal component analysis was used to generate a composite indicator of intensity of programme exposure. FindingsOf the 7071 study individuals, 6364 (90%) received any services from the programme; however, only 4455 (63%) utilised the programme intensively. The PSM analysis indicated that intensive programme utilisation could account for an 18, 11, and 5 percentage point increase in self-efficacy in condom use with clients (p<0·0001), regular partners (p=0·023), and with all partners (p=0·035), respectively, compared with programme utilisation that was not intensive. There was a reduction of 2% (95% CI 1·02–2·34) to 5% (4·86–5·93) prevalence in STIs and about 2% (0·96–2·74) in prevalence of HIV among those who utilised the programme intensively. InterpretationPSM has methodologically gained importance in programme evaluation studies. Findings clearly conclude that programme utilisation could bring effective behavioural change; nevertheless, emphasis should also be placed on intensity of programme utilisation. FundingAvahan, the India AIDS Initiative of the Bill & Melinda Gates Foundation.

HIV testing: the danger of keeping secrets

How has stigma and lack of trust been allowed to overshadow information sharing and comprehensive clinical care within the NHS? Results of HIV tests performed by sexual health services are not routinely communicated to primary care. The rationale for this is to protect patient confidentiality and encourage people to attend for testing if they feel they may be at risk. I find this disquieting on several levels. GPs deal with huge amounts of sensitive data regarding all aspects of their patients’ lives. …

A Unifying Ontology to Integrate Histological and Clinical Observations for Drug-Induced Liver Injury

Drug-induced liver injury (DILI) may present any morphologic characteristic of acute or chronic liver disease with no standardized terminology in place. Defining lexemes of DILI histopathology would allow the development of advanced knowledge discovery and data mining tools for across comparisons of publicly available information. For these purposes, a DILI ontology (DILIo) was developed by using the Unified Medical Language System tool and the standardized terminology of the Systematized Nomenclature of Medicine-Clinical Terms (SNOMED CT). The DILIo was entrained on findings of 114 US Food and Drug Administration-approved drugs by extracting all clinically DILI-related histopathologic descriptions for 1082 liver biopsy samples, which were then analyzed using the Unified Medical Language System MetaMap and subsequently mapped to the SNOMED CT. The DILIo provides a standard means to describe and organize liver injury induced by drugs, enabling comparative analysis of drugs within and across histopathologic terms. The analysis showed that flutamide, troglitazone, diclofenac, isoniazid, and tamoxifen were reported to have the most diverse histopathologic observations in liver biopsy. Necrosis, cholestasis, fatty degeneration, fibrosis, infiltrate, and hepatic necrosis were the most frequent terms used as descriptors of histopathologic features of DILI. In conclusion, DILIo entrains different algorithms for an efficient meta-analysis of published findings for an improved understanding of mechanisms and clinical characteristics of DILI.

A Clinical Approach to Inherited Hypertrophy

Left-ventricular hypertrophy is a common finding in clinical practice and the end result of a number of different disease processes. As such, distinguishing hypertrophy attributable to athletic training or chronic hypertension from more rare and potentially life-threatening genetic conditions, including hypertrophic cardiomyopathy (HCM), is of utmost clinical importance. This is true not only for the individual patient but also for the patient’s family members, who may be at risk when the cause is a heritable disease. We review how family history can be used in identifying inherited cardiac hypertrophy and in guiding ongoing management of the patient and the rest of the family. An in-depth, multigenerational family history has the potential to enhance every aspect of care, from establishing a diagnosis to devising a genetic testing strategy, interpreting genetic test results, and providing ongoing risk assessment for sudden cardiac death (SCD). We review that family history is not simply a static account of preexisting deaths and diagnoses, but a dynamic ongoing process incorporating new and valuable insights from family medical records, clinical cardiology evaluations, genetic testing, and visual analysis of the patient’s family tree. Such insights enable comprehensive clinical care for families affected by HCM. Scientific understanding of inherited cardiac hypertrophy dates back to 1958, when British forensic pathologist Donald Teare1 published an evocative series of case histories. Several sudden deaths in unrelated young adults had revealed, on autopsy, asymmetrical left-ventricular (LV) hypertrophy accompanied by a bizarre and disorganized myocardium: the disease known today as HCM. In a brief addendum, Teare1 described a family with multiple afflicted members, including a sister and brother who had each died suddenly, one while running for a bus and the other while riding a bicycle. Teare and his colleagues2 would later devote an entire publication to this family, tracing its history …

Hyperbare Oxygenation bei nekrotisierenden Weichteilinfektionen: Kontra

Hyperbaric oxygen therapy (HBOT) is discussed as an adjuvant option to treat necrotizing soft tissue infections (NSTI). While the Federal Joint Committee decided in 2007 not to support HBOT for the indication necrotizing fasciitis and Fournier's gangrene, it was decided to accept HBOT for treatment of clostridial myonecrosis for the German health insurance. Thus, in Germany necrotizing fasciitis (NF) is not a confirmed indication for HBOT. Against this background the cons of the clinical benefits of HBOT should be formulated. A literature search (MEDLINE/EMBASE/COCHRANE/manual search) using the keywords "necrotizing fasciitis", "Fournier's gangrene", "necrotizing cellulitis", "necrotizing soft tissue infections" as well as "hyperbaric medicine", "hyperbaric therapy" and "hyperbaric treatment" was carried out. An analysis of the spatial distribution of German hyperbaric oxygen chambers enabling intensive care (HOC-IC) was made. A total of 250 articles with n=2,556 NSTI patients (n=993 treated by HBOT) was found and 50% of the articles were case reports or series. There were only ten retrospective studies comparing the effects of HBOT with non-HBO treatment and none of them verified the benefit of HBOT in NF patients. In Germany only nine hyperbaric oxygen chambers (HOC-IC) enable intensive care. Currently, patient data are not included in scientific studies or multicenter studies, while studies assessing the benefit with higher evidence levels have been required for more than 15 years. The previously published human clinical studies do not confirm any therapeutic benefit of HBOT in NF patients. Any time delay in the start of surgical therapy by HBOT would not be acceptable. In Germany a comprehensive clinical care with HOC is not possible. On average the additional costs of HBO treatment for NF patients is approximately 8,000-25,000<euro>/patient which is not generally reimbursed by health insurance companies. Initializing a register study to assess the benefit of HBOT in NF patients appears feasible and is urgently needed.

A Framework for Elimination of Perinatal Transmission of HIV in the United States

The availability of effective interventions to prevent mother-to-child HIV transmission and the significant reduction in the number of HIV-infected infants in the United States have led to the concept that elimination of mother-to-child HIV transmission (EMCT) is possible. Goals for elimination are presented. We also present a framework by which elimination efforts can be coordinated, beginning with comprehensive reproductive health care (including HIV testing) and real-time case-finding of pregnancies in HIV-infected women, and conducted through the following: facilitation of comprehensive clinical care and social services for women and infants; case review and community action; allowing continuous quality research in prevention and long-term follow-up of HIV-exposed infants; and thorough data reporting for HIV surveillance and EMCT evaluation. It is emphasized that EMCT will not be a one-time accomplishment but, rather, will require sustained effort as long as there are new HIV infections in women of childbearing age.

Inclusion of medical genetics in primary health care: report of a pilot project in Brazil

Over the past few decades, several advances have been made in our knowledge of the genetic basis of diseases, prompting particular attention to the prevention and control of this determinant and to the adequate management of those affected or at risk of developing genetic conditions. The causes of genetic disease are manifold, and a variety of approaches are thus required for their prevention and to ensure better care of patients and families. In 2000, the World Health Organization (WHO) proposed that interventions for prevention and control of genetic disorders and congenital malformations should be added to the primary health care (PHC) framework (WHO 2000). The main characteristic of PHC is its status as the first contact to the health system, providing comprehensive, continuous care over time and coordinating the care received by individuals and families at the various points of care throughout the health system. Other defining characteristics of PHC include its family- and community-oriented nature and cultural competence (Starfield 1992). At the interface between genetics and PHC is the field of community genetics. In 1998, Leo ten Kate defined community genetics as “bringing genetic services to the community as a whole.” (ten Kate 1998) The author later expanded this definition, describing community genetics as “the art and science of the responsible and realistic application of health and disease-related genetics and genomics knowledge and technologies in human populations and communities to the benefit of individuals therein. Community genetics is multi-, inter- and transdisciplinary and aims to maximize benefits while minimizing the risk of harm, respecting the autonomy of individuals and ensuring equity” (ten Kate et al. 2010). Within this context, several efforts have been made in the direction of integrating basic knowledge of genetics into the framework of PHC. Education is viewed as the key for preparing primary care providers for a reality in which genetics will be present in the daily routine of health care and disease prevention (Khoury 2003). Genetic diseases contribute significantly to the population-wide disease burden, and primary care providers have an important role to play in their prevention and in the identification of patients that could benefit from referral to medical genetics services, as they will remain responsible for the care of these patients throughout the life course (Burke and Emery 2002). In 2009, the Brazilian government published its national policy for comprehensive clinical genetics care (Brasil 2009). This policy includes both specialty medical genetics care and primary care. In the latter setting, the policy provides for identification and follow-up of families with conditions related to congenital anomalies and genetically determined diseases. The objective of this study was to ascertain whether implementation of a medical genetics education program produced for primary care providers could contribute to the integration of concepts and attitudes related to the identification, management, and prevention of congenital malformations and genetic diseases into the care provided at primary health care units.

My Journey From India to APA

My Journey From India to APA

Molecular Spectrum of β-Thalassemia Mutations in the admixed Venezuelan population, and their linkage to β-Globin Gene Haplotypes

In order to establish the spectrum of β-thalassemia (β-thal) mutations in the Venezuelan population for the first time, 127 unrelated subjects either with a suspicion of β-thal trait or with a clinically recognized β-thal syndrome of different degrees of severity, were studied. DNA from these subjects was analyzed by a polymerase chain reaction (PCR)-based reverse dot-blot method or amplification refractory mutation system (ARMS). Prototype β-globin gene sequencing of relevant DNA was performed to confirm the mutations. Fifteen different mutations were identified accounting for 92.0% of the mutant alleles explored, revealing a significant genetic heterogeneity at the β-globin gene locus in this population. The most frequent mutations were codon 39 (C >T) 34.1%, IVS-I-1 (G >A) 11.1%, IVS-I-6 (T > C) 6.6%, IVS-I-110 (G >A) 6.6%, IVS-II-849 (A >G) 6.6%, −88 (C >T) 6.0%, −29 (A >G) 5.2%, followed by the less common IVS-I-5 (G >A) 3.7%, the 1,393 bp deletion 3.0%, IVS-II-1 (G >A) 3.0%, −86 (C >G) 2.2%, IVS-II-1 (G >T) 1.5%, codons 41/42 (–TCTT) 1.5%, IVS-II-745 (C >G) 0.7% and deletional δβ-thal 0.7%. Overall, these data demonstrate that the major sources of β-thal alleles in Venezuela, as expected, are of Mediterranean and African origins. This is the first large study defining the molecular spectrum of β-thal in the highly admixed population of Venezuela and lays the foundation for genetic counseling as well as implementing comprehensive clinical care programs. Diversity of haplotypes associated with some of the β-thal mutations can be explained by in situ recombination events in Venezuela.

Editorial introductions

Editorial introductions

Prophylactic Feeding Tubes for Patients with Locally Advanced Head-and-Neck Cancer Undergoing Combined Chemotherapy and Radiotherapy—Systematic Review and Recommendations for Clinical Practice

This work aimed to determine the benefits and risks of prophylactic feeding tubes for adult patients with squamous cell carcinoma of the head and neck who receive combined chemotherapy and radiotherapy with curative intent and to make recommendations on the use of prophylactic feeding tubes and the provision of adequate nutrition to this patient population. A national multidisciplinary panel conducted a systematic review of the evidence and formulated recommendations to guide clinical decision-making. The draft evidence summary and recommendations were distributed to clinicians across Canada for their input. No randomized controlled trials have directly addressed this question. Evidence from studies in the target population was limited to seven descriptive studies: two with control groups (one prospective, one retrospective) and five without control groups. Results from ten controlled studies in patients treated with radiotherapy alone were also reviewed. The available evidence was insufficient to draw definitive conclusions about the effectiveness of prophylactic feeding tubes in the target patient population or to support an evidence-based practice guideline. After review of the evidence, of guidelines from other groups, and of current clinical practice in Canada, the multidisciplinary panel made consensus-based recommendations regarding comprehensive interdisciplinary clinical care before, during, and after cancer treatment. The recommendations are based on the expert opinion of the panel members and on their understanding of best clinical practice.

Survival Outcomes of Pediatric Intestinal Failure Patients: Analysis of Factors Contributing to Improved Survival Over the Past Two Decades

Intestinal failure (IF) is associated with significant and life-threatening complications. Recent studies suggest that treatments for IF in the pediatric population are improving over time. Based on this, we examined whether pediatric IF survival rates have improved in our patient population over the past two decades, and secondarily examined which aspects of patient care contributed to changes in survival. We conducted a retrospective chart review of all pediatric patients with IF at our children's hospital from 1990 through 2009. Cox regression analyses were used to determine change in survival rates over time (5-y cohorts), and we examined multiple covariates to determine their potential influence on survival rates over time. A significant improvement in survival of 171 children with IF was noted over the past two decades. Children with an onset of IF in the 1990-1994 cohort had significantly decreased survival compared with children in all subsequent cohorts (P = 0.011). The only intervention that was identified between this time period and future periods was the establishment of a comprehensive intestinal failure clinical care team. While the latter three cohorts were not significantly different, progressively increased survival was noted. Ability to wean off parenteral nutrition (PN) and small bowel length greater than 10% of the expected length were significantly associated with improved survival over this time period (P < 0.01). Other tested covariates, including the more recent use of ethanol lock therapy (to prevent catheter sepsis) and lipid reduction strategies (to treat PN-associated cholestasis) failed to show a significant impact on improved survival. Despite a striking improvement in survival of children with IF over the past two decades, the only identified intervention that significantly impacted survival was establishment of a comprehensive care team. These findings emphasize the need for multi-disciplinary efforts to care for such complex and challenging children.