Hypofractionated Concomitant Chemoradiation in Inoperable Locally Advanced Non-small Cell Lung Cancer: A Report on 100 Patients and a Systematic Review.

AIMS: Concomitant chemoradiation is the standard of care in patients with inoperable non-small cell lung cancer. The purpose of this study was to analyse the survival outcome and toxicity data of using hypofractionated chemoradiation. MATERIALS AND METHODS: One hundred patients were treated from June 2011 to November 2016. Treatment consisted of 55 Gy in 20 daily fractions concurrently with split-dose cisplatin vinorelbine chemotherapy over 4 weeks followed by two cycles of cisplatin vinorelbine only. Survival was estimated using Kaplan-Meier and Cox regression was carried out for known prognostic factors. A systematic search of literature was conducted using Medline, Embase and Cochrane databases and relevant references included. RESULTS: In total, 97% of patients completed radiotherapy and 73% of patients completed all four cycles of chemotherapy. One patient died of a cardiac event during consolidative chemotherapy. There were two cases of grade 4 toxicities (one sepsis, one renal impairment). Grade 3 toxicities included nausea/vomiting (17%), oesophagitis (15%), infection with neutropenia (12%) and pneumonitis (4%). Clinical benefit was seen in 86%. Two-year progression-free survival and overall survival rates were 49% and 58%, respectively. The median progression-free survival and overall survival were 23.4 and 43.4 months, respectively. The only significant prognostic factor was the number of chemotherapy cycles received (P = 0.02). The systematic review identified 13 relevant studies; a variety of regimens were assessed with variable reporting of outcomes and toxicity but with overall an improvement in survival over time. CONCLUSION: Our experience compared with the original phase II trial showed improved treatment completion rates and survival with acceptable morbidity. With appropriate patient selection this regimen is an effective treatment option for locally advanced non-small cell lung cancer. This study helps to benchmark efficacy and toxicity rates while considering the addition of new agents to hypofractionated concurrent chemoradiotherapy. The agreement of a standard regimen for assessment in future trials would be beneficial.

Solar-powered oxygen delivery: proof of concept.

SETTING: A resource-limited paediatric hospital in Uganda. OBJECTIVE: Pneumonia is a leading cause of child mortality worldwide. Access to life-saving oxygen therapy is limited in many areas. We designed and implemented a solar-powered oxygen delivery system for the treatment of paediatric pneumonia. DESIGN: Proof-of-concept pilot study. A solar-powered oxygen delivery system was designed and piloted in a cohort of children with hypoxaemic illness. RESULTS: The system consisted of 25 × 80 W photovoltaic solar panels (daily output 7.5 kWh [range 3.8-9.7kWh]), 8 × 220 Ah batteries and a 300 W oxygen concentrator (output up to 5 l/min oxygen at 88% [±2%] purity). A series of 28 patients with hypoxaemia were treated with solar-powered oxygen. Immediate improvement in peripheral blood oxygen saturation was documented (median change +12% [range 5-15%], P < 0.0001). Tachypnoea, tachycardia and composite illness severity score improved over the first 24 h of hospitalisation (P < 0.01 for all comparisons). The case fatality rate was 6/28 (21%). The median recovery times to sit, eat, wean oxygen and hospital discharge were respectively 7.5 h, 9.8 h, 44 h and 4 days. CONCLUSION: Solar energy can be used to concentrate oxygen from ambient air and oxygenate children with respiratory distress and hypoxaemia in a resource-limited setting.

Intellectual and developmental disabilities in Kinshasa, Democratic Republic of the Congo: causality and implications for resilience and support.

This article reports results of a 7-month qualitative study on intellectual and related developmental disabilities in Kinshasa, Democratic Republic of the Congo, particularly as they relate to the causes and meaning of intellectual and developmental disabilities (IDD). This study raises important questions related to the understanding of resilience of persons affected by IDD and the nature and purpose of support they use or desire.

Experiences of housing insecurity among participants of an early childhood intervention programme.

OBJECTIVES: To understand the barriers to programme success among high-needs families in KidsFirst, an early childhood intervention programme. METHODS: Using a qualitative approach, a secondary analysis was performed using the qualitative data set (111 interviews and focus groups with 242 participants) from the KidsFirst programme evaluation. Data analysis was conducted to identify common experiences among high-needs families in the programme and barriers to programme success. RESULTS: Participants identified housing insecurity as a major factor impeding programme delivery, retention and successful outcomes. Housing insecurity was shown to create or exacerbate ongoing crises among high-needs families. Only after housing insecurity was addressed were families able to benefit from the KidsFirst programme. CONCLUSIONS: The findings of this research suggest that until baseline material security is established for high-needs families, early childhood development (ECD) interventions will be limited in meeting their objectives. In order to have the most effect for those living in poverty, helping families to achieve basic material security, including secure housing, should precede the targeted provision of psychosocial ECD supports. This finding has implications for how ECD intervention programmes could more effectively be designed and whom they should target.

Mitochondrial disease in pregnancy: a systematic review.

Mitochondrial diseases are heterogeneous in clinical presentation and genotype. The incidence of known pathogenic mitochondrial DNA mutations in the general population is 1 in 500. Little is known about the implications of pregnancy for women with mitochondrial disease. We undertook a systematic review of the literature on mitochondrial disease in pregnancy. Ten case reports were identified. The most common complications were threatened preterm labour (5 women) and preeclampsia (4 women). Two women experienced magnesium sulphate toxicity. Pregnancy had a varied effect on mitochondrial disease with some women being asymptomatic; others developing mild symptoms such as exercise intolerance or muscle weakness which resolved postnatally; and others developed more serious, persistent symptoms such as symptomatic Wolff-Parkinson-White syndrome, persistent paraesthesia and focal segmental glomerulosclerosis. Women with mitochondrial disease appear to be at increased risk of complications during pregnancy and labour but further prospective cohort studies are needed.

An issue hiding in plain sight: when are speech-language pathologists special educators rather than related services providers?

PURPOSE: Under the Individuals With Disabilities Education Act (IDEA; as amended, 2004), speech-language pathology services may be either special education or a related service. Given the absence of guidance documents or research on this issue, the purposes of this clinical exchange are to (a) present and analyze the IDEA definitions related to speech-language pathologists (SLPs) and their roles, (b) offer a rationale for the importance of and distinction between their roles, (c) propose an initial conceptualization (i.e., flow chart) to distinguish between when an SLP should function as a related services provider versus a special educator, and (d) suggest actions to develop and disseminate a clearer shared understanding of this issue. METHOD: Federal definitions of special education and related services as related to SLPs are discussed in terms of determining special education eligibility, meeting student needs, ensuring SLPs are following their code of ethics and scope of practice, and facilitating appropriate personnel utilization and service delivery planning. CONCLUSION: Clarifying the distinction between special education and related services should lead to increased likelihood of appropriate services for students with disabilities, improved working conditions for SLPs, and enhanced collaboration among team members. This clinical exchange is meant to promote dialogue and research about this underexamined issue.

Federal family and disability policy: special relevance for developmental disabilities.

The article reviews the federal statutes and relevant decisions of the U.S. Supreme Court that constitute the core concepts of disability policy and their application to persons with disabilities (especially developmental disabilities) and their families.

The Supreme Court, "Our Town," and disability policy: boardrooms and bedrooms, courtrooms and cloakrooms.

In this discussion of recent key disability-related decisions of the U.S. Supreme Court (1995- 2004), we (a) assess whether the Court has supported or undermined certain core concepts of disability policy and (b) examine how the Court balances the comparative rights of those with and those without disabilities. In cases involving employment discrimination, family law, and access to courts and other public decision-making entities, the Court adopts an idealized version of a previous America. We explain the Court's "reverie" for that version, resorting to the constructs known as (a) compelled confrontation and remission to majoritarian processes and (b) advancement of personal relationships.

Access to health care for individuals with developmental disabilities from minority backgrounds.

In this project we examined access to health care by individuals with developmental disabilities in Kansas from low-income populations and from minority backgrounds. Four criteria for determining access were employed: availability, accessibility, affordability, and appropriateness of care. Factors that pose barriers and that facilitate access are described and recommendations are set out, with particular reference to the 2002 Report of the Surgeon General of the United States, related to health status of people with mental retardation.

Perspectives of physicians, families, and case managers concerning access to health care by individuals with developmental disabilities.

This study of the status of medical care for Kansans with developmental disabilities consists of reports from physicians, service providers, and family members. Overall, these three groups indicated satisfaction with medical care across the four criteria of availability, accessibility, appropriateness, and affordability. The bases for these results are outlined, and suggestions for improving satisfaction with health care are presented.

A brief overview of special education law with focus on autism.

This article reviews the provisions of Individuals with Disabilities Education Act as they apply particularly to students with autism. It also refers to the antidiscrimination provisions of the Rehabilitation Act Amendments (Sec. 504) and to their relevance to students with autism. It attempts to answer specific questions posed by the National Academy of Science.

Estrogen deficiency causes central leptin insensitivity and increased hypothalamic neuropeptide Y.

OBJECTIVE: Altered fat distribution is a consequence of menopause, but the mechanisms responsible are unknown. Estrogen insufficiency in humans can be modeled using ovariectomized rats. We have shown that increased adiposity in these rats is due to reduced physical activity and transient hyperphagia, and can be reversed with 17beta-estradiol treatment. The aims of this study were to examine whether this altered energy balance is associated with circulating leptin insufficiency, central leptin insensitivity, decreased hypothalamic leptin receptor (Ob-Rb) expression, and/or increased hypothalamic neuropeptide Y (NPY). METHODS: Plasma leptin levels, adipose tissue ob gene expression, energy balance responses to i.c.v. leptin, hypothalamic Ob-Rb expression and NPY concentration in five separate hypothalamic regions were measured in adult female rats after either ovariectomy or sham operations. RESULTS: Obesity was not associated with hypoleptinemia or decreased ob gene expression in ovariectomized rats; however, it was associated with insensitivity to central leptin administration. Food intake was less suppressed and spontaneous physical activity was less stimulated by leptin. This was not due to decreased hypothalamic Ob-Rb expression. NPY concentration in the paraventricular nucleus of the hypothalamus was elevated in the ovariectomized rats, consistent with leptin insensitivity; however this effect was transient and disappeared as body fat and leptin levels increased further and hyperphagia normalized. CONCLUSION: Impaired central leptin sensitivity and overproduction of NPY may contribute to excess fat accumulation caused by estrogen deficiency.

Perspectives of dentists, families, and case managers on dental care for individuals with developmental disabilities in Kansas.

The status of dental care for individuals with developmental disabilities in Kansas was examined. Dentists, family members, and case managers reported general, but partial, satisfaction with the availability, accessibility, appropriateness, and affordability of such care. Reasons for the results and recommendations for further improvement are discussed.

Cloning of leptin cDNA and assignment to the long arm of chromosome 5 in the marsupial Sminthopsis crassicaudata.

We have isolated and sequenced full-length cDNA clones for leptin in the dasyurid marsupial Sminthopsis crassicaudata (fat-tailed dunnart). Southern and in situ hybridisation data indicated a single leptin gene in the S. crassicauda- ta genome, localised to arbitrary chromosome bands 5q24--> q31 on the long arm of chromosome 5, the short-arm terminus of which bears the only nucleolar organising region. The nucleotide sequence of the cDNAs revealed that the primary translation product of S. crassicaudata leptin is composed of 167 amino acid residues, with a potential signal peptide of 21 residues. The mature protein of 146 amino acids is 82% similar to both the mouse and human proteins and is predicted to have a molecular weight of 16.26 kDa. Northern blot analysis revealed that the corresponding mRNA is approximately 3.9 kb in size and is expressed only in white adipose tissue of this marsupial species. Evolutionary analyses indicate that S. crassicaudata leptin cDNA has evolved at a significantly faster rate than cDNAs from eutherian mammals.

Peripheral administration of CRF and urocortin: effects on food intake and the HPA axis in the marsupial Sminthopsis crassicaudata.

The hypothalamic peptides corticotrophin releasing factor (CRF) and urocortin (UCN) decrease food intake and increase energy expenditure when administered either centrally or peripherally to rodents. The effects of CRF and UCN on food intake in other mammals (for example marsupials), however, are not known. Peripherally administered CRF induced cortisol release in the marsupial Sminthopsis crassicaudata via the CRF1 receptor, and central CRF administration potently decreased food intake, as in rodents. When peripherally administered, both CRF and UCN decreased food intake in S. crassicaudata, but UCN was considerably more potent ( approximately 50 fold) in this regard. The anorectic effects of CRF and UCN were not blocked by the CRF1 receptor antagonist antalarmin, suggesting that the peripheral effects of CRF and UCN on food intake are mediated primarily by the CRF2 receptor.

The effect of ovarian steroids and photoperiod on body fat stores and uncoupling protein 2 in the marsupial Sminthopsis crassicaudata.

To determine the effects of photoperiod and ovarian steroids on fat stores in the marsupial S. crassicaudata, animals were ovariectomised (OVX) or sham operated, and maintained under either short-day (SD) or long-day (LD) photoperiods for 104 days. Photoperiod had no effect on body weight in the sham animals. In the LD OVX animals, body weight fell and remained below baseline for about 45 days, whereafter it returned to baseline. In contrast, body weight of SD OVX animals increased over the first 45 days then returned to baseline. Tail width (a reflection of body fat stores) increased in both sham and OVX animals exposed to SD. When exposed to LD, tail width increased only in the OVX animals. There was no effect of either photoperiod or OVX on total cumulative energy intake. Leptin mRNA expression was increased in the LD OVX animals compared to the shams. Photoperiod had no effect on UCP2 mRNA expression in any tissue; however, OVX decreased UCP2 mRNA expression in muscle. These data indicate that in S. crassicaudata: (a) fat mass increases in response to both SD photoperiod and OVX and they have additive effects; (b) the effects of photoperiod on fat mass are mediated by both gonadal steroid dependent and independent mechanisms; (c) alterations in UCP2 mRNA expression may mediate the effect of OVX, but not photoperiod; and (d) UCP2 mRNA is differentially regulated in muscle and fat.

Kinetics of duck hepatitis B virus infection following low dose virus inoculation: one virus DNA genome is infectious in neonatal ducks.

Using pooled serum from congenitally duck hepatitis B virus (DHBV)-infected ducks as inoculum, we examined the effect of virus dose on the incubation period of infection and on the patterns of spread of virus infection in the liver. The pooled serum inoculum contained 9.5 x 10(9) DHBV genomes per milliliter and had an infectivity titre (ID50) in newly hatched ducks of 1.5 x 10(10) per milliliter with a 95% confidence interval of 3.0 x 10(9) to 6.3 x 10(10) ID50/ml, indicating the equivalence between one DHBV genome and one infectious unit within the limits of the assays. The incubation period of infection was inversely related to the dose of inoculum and the onset of viraemia ranged from Day 6 with the highest dose to Day 14 or 29 with the lowest dose inoculum. To study the spread of virus infection from a low percentage of initially infected cells we inoculated newly hatched ducks intravenously with sufficient DHBV (1.5 x 10(3) ID50) to infect only approximately 0.0001% of total liver cells. DHBV infection first reached detectable levels on Day 4 postinoculation (p.i.) and was detected in approximately 0.035% of hepatocytes, most of which occurred as single cells or pairs of cells, indicating that a number of rounds of infection had occurred with the spread of virus both to adjoining cells, i.e., by cell-to-cell spread, and to cells located in other parts of the liver lobule. Despite some bird-to-bird variation in timing, the percentage of infected hepatocytes increased exponentially with a mean doubling time of 16 hr from Day 4 to Day 14 p.i., by which time replication was seen in > 95% of hepatocytes. This rapid dissemination from a small number of infected hepatocytes suggests that, in neonatal ducks, there are no major delays in virus replication within the liver, that any innate and adaptive defence mechanisms operating during the first 10 to 14 days of infection are insufficient to contain virus spread, and that even a small number of infected hepatocytes produce enough progeny to rapidly infect the remaining hepatocytes.