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Generic Substitution of Orphan Drugs for the Treatment of Rare Diseases: Exploring the Potential Challenges.

PubMed

Di Paolo, Antonello; Arrigoni, Elena

2018-03-01

Generic drugs are important components of measures introduced by healthcare regulatory authorities to reduce treatment costs. In most patients and conditions the switch from a branded drug to its generic counterpart is performed with no major complications. However, evidence from complex diseases suggests that generic substitution requires careful evaluation in some settings and that current bioequivalence criteria may not always be adequate for establishing the interchangeability of branded and generic products. Rare diseases, also called orphan diseases, are a group of heterogeneous diseases that share important characteristics: in addition to their scarcity, most are severe, chronic, highly debilitating, and often present in early childhood. Finding a treatment for a rare disease is challenging. Thanks to incentives that encourage research and development programs in rare diseases, several orphan drugs are currently available. The elevated cost of orphan drugs is a highly debated issue and a cause of limited access to treatment for many patients. As patent protection and the exclusivity period of several orphan drugs will expire soon, generic versions of orphan drugs should reach the market shortly, with great expectations about their impact on the economic burden of rare diseases. However, consistent with other complex diseases, generic substitution may require thoughtful considerations and may be even contraindicated in some rare conditions. This article provides an overview of rare disease characteristics, reviews reports of problematic generic substitution, and discusses why generic substitution of orphan drugs may be challenging and should be undertaken carefully in rare disease patients.
Incentivizing Orphan Product Development: United States Food and Drug Administration Orphan Incentive Programs.

PubMed

Le, Tran T

2017-01-01

Over 30 years ago, the United States (US) Congress passed the Orphan Drug Act (ODA) to encourage the development of products for rare diseases or conditions ("orphan products"). The Act provided incentives to sponsors for developing products with orphan designation and established a grant program to fund studies of orphan products. Since its enactment in 1983, the ODA has been credited for bringing more than 590 orphan drugs to the market, inspiring the implementation of orphan legislation globally, and enabling the creation of other programs that extend existing knowledge of the natural history of rare diseases and stimulate the development of medical devices for children and patients with rare diseases. This chapter provides a brief overview of the main features and successes of 5 of the orphan incentive programs administered by the US Food and Drug Administration (FDA): the Orphan Drug Designation Program, the Humanitarian Use Device (HUD) Designation Program, the Orphan Products Clinical Trials Grants Program, the Pediatric Device Consortia (PDC) Grant Program, and the Orphan Products Natural History Grants Program.
The "Teachers Diploma Program" in Zambian Government Schools: A Baseline Qualitative Assessment of Teachers' and Students' Strengths and Challenges in the Context of a School-Based Psychosocial Support Program

ERIC Educational Resources Information Center

Kaljee, Linda; Munjile, Kelvin; Menon, Anitha; Tembo, Stephen; Li, Xiaoming; Zhang, Liying; Malungo, Jacob; Stanton, Bonita; Langhaug, Lisa

2017-01-01

In Zambia, as elsewhere throughout sub-Saharan Africa, orphaned and vulnerable children (OVC) face multiple physical, emotional, social and psychological challenges which often negatively affect opportunities for educational attainment. REPSSI (Regional Psychosocial Support Initiative), in collaboration with, the University of Cape Town and other…
Cultural practices and sexual risk behaviour among adolescent orphans and non-orphans: a qualitative study on perceptions from a community in western Kenya

PubMed Central

2014-01-01

Background This study explored community perceptions of cultural beliefs and practices that may increase sexual risk behaviour of adolescents, to understand more about meaning they hold within the culture and how they expose adolescent orphans and non-orphans to higher risks in a high HIV and teenage pregnancy prevalence context. Methods Using a qualitative descriptive cross-sectional design 14 focus group discussions were conducted with 78 adolescents and 68 parents/guardians purposively selected to represent their communities. Thirteen key informant interviews were also conducted with community leaders, health care and child welfare workers, and adolescents who were also selected purposively. The two methods were used to explore how cultural beliefs and practices predispose adolescent orphans and non- orphans to risky sexual behaviours. Data were analysed through line-by-line coding, grouped into families and retrieved as themes and sub-themes. Results Identified cultural practices that predisposed adolescents orphans and non-orphans to risky sexual behaviours included: adolescent sleeping arrangements, funeral ceremonies, replacing a deceased married daughter with her younger sister in marriage, widow inheritance among boys, early marriage among girls, and preference for boys/sons. Cultural risks perceived to equally affect both orphans and non-orphans were sleeping arrangements, funeral ceremonies, and sister replacement. Factors associated more with orphans than non-orphans were widow inheritance among boys and a preference for boy over girl children. Conclusions Adolescent sexual risk reduction programs should be developed considering the specific cultural context, using strategies that empower communities to challenge the widely accepted cultural norms that may predispose young people in general to sexual risks while targeting those that unequally influence orphans. PMID:24467940
Cultural practices and sexual risk behaviour among adolescent orphans and non-orphans: a qualitative study on perceptions from a community in Western Kenya.

PubMed

Juma, Milka; Askew, Ian; Alaii, Jane; Bartholomew, L Kay; van den Borne, Bart

2014-01-27

This study explored community perceptions of cultural beliefs and practices that may increase sexual risk behaviour of adolescents, to understand more about meaning they hold within the culture and how they expose adolescent orphans and non-orphans to higher risks in a high HIV and teenage pregnancy prevalence context. Using a qualitative descriptive cross-sectional design 14 focus group discussions were conducted with 78 adolescents and 68 parents/guardians purposively selected to represent their communities. Thirteen key informant interviews were also conducted with community leaders, health care and child welfare workers, and adolescents who were also selected purposively. The two methods were used to explore how cultural beliefs and practices predispose adolescent orphans and non- orphans to risky sexual behaviours. Data were analysed through line-by-line coding, grouped into families and retrieved as themes and sub-themes. Identified cultural practices that predisposed adolescents orphans and non-orphans to risky sexual behaviours included: adolescent sleeping arrangements, funeral ceremonies, replacing a deceased married daughter with her younger sister in marriage, widow inheritance among boys, early marriage among girls, and preference for boys/sons. Cultural risks perceived to equally affect both orphans and non-orphans were sleeping arrangements, funeral ceremonies, and sister replacement. Factors associated more with orphans than non-orphans were widow inheritance among boys and a preference for boy over girl children. Adolescent sexual risk reduction programs should be developed considering the specific cultural context, using strategies that empower communities to challenge the widely accepted cultural norms that may predispose young people in general to sexual risks while targeting those that unequally influence orphans.
The role of academic institutions in the development of drugs for rare and neglected diseases.

PubMed

Coles, L D; Cloyd, J C

2012-08-01

There are approximately 7,000 rare disorders, many of which are life-threatening. Diagnosis is often problematic, and therapies are few. Before the passage of the Orphan Drug Act in 1983, neither the pharmaceutical industry nor universities devoted much effort to research on rare diseases. Important changes have occurred within and outside universities that position them to play a significant role in developing orphan drugs. Several models are being employed to promote drug-related research, including disease-focused, discovery-focused, development-focused, and industry-partnership-focused approaches. However, significant barriers challenge universities' ability to fully contribute to orphan drug development. Academic institutions, along with industry, government, and not-for-profit organizations, must address these issues in order to advance the field. New initiatives designed to increase university-based orphan drug research include creating mechanisms to ensure program continuity, building research and regulatory support infrastructure, facilitating commercialization, expanding government support, and developing mutually beneficial partnerships among academe, industry, and government.
Orphans of the Mexican drug war: insights on a public health challenge.

PubMed

Camacho, Salvador; Horstick, Olaf; Sax, Sylvia

2014-08-01

To describe how the Government of Mexico and other direct stakeholders perceive children orphaned by the drug war; to determine the current measures addressing this as a public health problem; and to compare these measures to international frameworks so that relevant recommendations can be identified. This was an exploratory, descriptive case study using qualitative methods. Semi-structured interviews were performed with key informants at the federal, state, and municipal government levels in Mexico, as well as non-governmental organizations, and other institutes working with orphans. Participants were identified with a purposive snowball sample. No official definition of "orphan" was identified; nor was there a shared perception among the key informants of what constitutes being an orphan. An official, collective definition is important because it modifies the quantity of children categorized as such within the target population. Although most of the interviewees perceive that the number of orphans and vulnerable children (OVC) has increased in the last 6 years, they acknowledged there is no reliable data to prove it. The increase, they believe, is due not to the drug war, but to a loss of family cohesion. Stakeholders recommend improving public policies, currently identified as the most difficult barrier to overcome due to a perceived inability to modify existing laws. However, the General Law for Victims was recently passed by the Government of Mexico and addresses many of the challenges identified. When compared to the international frameworks, there are three major issues in Mexico's current situation: coordination among and within stakeholders; emphasis on using community solutions; and putting in place preventive programs. For two of these problems, the General Law of Victims offers solutions.
The real challenges: the orphan generation and employment creation.

PubMed

Whiteside, A

2000-01-01

A baby born to an HIV-positive mother has close to a 100% chance of being orphaned before reaching the age of 10. In South Africa, nearly 1 million children under the age of 15 are projected to lose their mothers by 2005 due to AIDS. These orphans are less likely to receive adequate parenting, education, and nutrition; others will seek to survive on the streets and thus will be more likely to face sexual abuse and exploitation. The long-term impact of HIV/AIDS on both the children and society will be severe. The orphans that AIDS is creating pose serious social, economic, political, and developmental challenges for South Africa. There are two options left for the government: 1) dramatically increasing welfare grants and staffing of welfare departments in order to care for the orphans; 2) find new imaginative measures of meeting the challenge. In addition, provision of employment for its population is another challenge the region is facing. Having the required resources and infrastructure, a potential intervention for South Africa would be training and employing a new cadre of workers to care for AIDS orphans. This type of response would also help build a civil society.
Orphans of the HIV epidemic: the challenges from toddlerhood to adolescence and beyond.

PubMed

Lala, Mamatha M

2014-01-01

This presentation focuses on the challenges and practical issues faced each day by orphans of the HIV epidemic and the holistic care that can be provided, as they continue to grow from toddlerhood to adolescence and beyond. An HIV Research Trust Scholarship enabled me to spend quality time in a sub-Saharan African province worst hit by the HIV epidemic and to interact with local experts and learn from mutual clinical experience. It was an immensely useful exercise as the clinical spectra of the diseases are very similar to ours and they have ongoing active research programs very relevant to our setting. India is arguably home to the largest number of orphans of the HIV epidemic. The responsibility of caring for orphaned children overwhelms and pushes many extended families beyond their ability to cope. Many countries are experiencing large increases in the number of families headed by women and grandparents, or even young children. These households are often unable to meet basic needs, and so the number of children living on the streets is rising. Orphaned children are disadvantaged in many devastating ways. In addition to the trauma of witnessing the sickness and death of one or both parents and perhaps siblings, they lack the necessary parental guidance through crucial life-stages of identity formation and transition into adulthood. They are more likely to suffer damage to their cognitive and emotional development and be subjected to; exploitation in terms of labour, social exclusion, extreme economic uncertainty, physical and sexual abuse, illiteracy, malnutrition and illness. Education remains a distant dream. With stigma and discrimination, they lack legal protection, lose inheritance rights, access to essential services available to other community members and professional help from doctors, teachers and lawyers. The implications for these unfortunate children are extraordinarily grave but governments, international agencies, non-governmental organizations, schools, other community groups and individuals can still alter the course of the crisis. The Committed Communities Development Trust (CCDT) is a voluntary secular Trust, reaching out to 300,000 people annually, focusing intensively on children affected and infected by HIV/AIDS, mainly orphans, child headed families, children living in street situations, brothels, institutions and children at risk of drug addiction, abuse and exploitation in Mumbai. We run several comprehensive HIV/AIDS programmes addressing issues of prevention, care, support, education, awareness, empowerment, training and research through strongly structured home-based care programs, community based programs and temporary residential shelters. The CCDT recognizes and understands the daunting challenges these children face and helps them overcome these as a team by providing comprehensive care and support, giving them an opportunity in life and enabling them to become productive citizens of tomorrow.
Orphan drug: Development trends and strategies

PubMed Central

Sharma, Aarti; Jacob, Abraham; Tandon, Manas; Kumar, Dushyant

2010-01-01

The growth of pharma industries has slowed in recent years because of various reasons such as patent expiries, generic competition, drying pipelines, and increasingly stringent regulatory guidelines. Many blockbuster drugs will loose their exclusivity in next 5 years. Therefore, the current economic situation plus the huge generic competition shifted the focus of pharmaceutical companies from the essential medicines to the new business model — niche busters, also called orphan drugs. Orphan drugs may help pharma companies to reduce the impact of revenue loss caused by patent expiries of blockbuster drugs. The new business model of orphan drugs could offer an integrated healthcare solution that enables pharma companies to develop newer areas of therapeutics, diagnosis, treatment, monitoring, and patient support. Incentives for drug development provided by governments, as well as support from the FDA and EU Commission in special protocols, are a further boost for the companies developing orphan drugs. Although there may still be challenges ahead for the pharmaceutical industry, orphan drugs seem to offer the key to recovery and stability within the market. In our study, we have compared the policies and orphan drug incentives worldwide alongwith the challenges faced by the pharmaceutical companies. Recent developments are seen in orphan drug approval, the various drugs in orphan drug pipeline, and the future prospectives for orphan drugs and diseases. PMID:21180460
Orphan diseases: state of the drug discovery art.

PubMed

Volmar, Claude-Henry; Wahlestedt, Claes; Brothers, Shaun P

2017-06-01

Since 1983 more than 300 drugs have been developed and approved for orphan diseases. However, considering the development of novel diagnosis tools, the number of rare diseases vastly outpaces therapeutic discovery. Academic centers and nonprofit institutes are now at the forefront of rare disease R&D, partnering with pharmaceutical companies when academic researchers discover novel drugs or targets for specific diseases, thus reducing the failure risk and cost for pharmaceutical companies. Considerable progress has occurred in the art of orphan drug discovery, and a symbiotic relationship now exists between pharmaceutical industry, academia, and philanthropists that provides a useful framework for orphan disease therapeutic discovery. Here, the current state-of-the-art of drug discovery for orphan diseases is reviewed. Current technological approaches and challenges for drug discovery are considered, some of which can present somewhat unique challenges and opportunities in orphan diseases, including the potential for personalized medicine, gene therapy, and phenotypic screening.
Fertility among orphans in rural Malawi: challenging common assumptions about risk and mechanisms.

PubMed

Kidman, Rachel; Anglewicz, Philip

2014-12-01

Although a substantial literature suggests that orphans suffer disadvantage relative to nonorphaned peers, the nature of this disadvantage and the mechanisms driving it are poorly understood. Some evidence suggests that orphans experience elevated fertility, perhaps because structural disadvantage leads them to engage in sexual risk-taking. An alternative explanation is that orphans intentionally become pregnant to achieve a sense of normality, acceptance and love. Data from the 2006 wave of the Malawi Longitudinal Study of Families and Health on 1,033 young adults aged 15-25 were used to examine the relationship of maternal and paternal orphanhood with sexual risk indicators and desired and actual fertility. Regression analyses were used to adjust for covariates, including social and demographic characteristics and elapsed time since parental death. Twenty-six percent of respondents had lost their father and 15% their mother. Orphanhood was not associated with sexual risk-taking. However, respondents whose mother had died in the past five years desired more children than did those whose mother was still alive (risk differences, 0.52 among women and 0.97 among men). Actual fertility was elevated among women whose father had died more than five years earlier (0.31) and among men whose mother had died in the past five years (1.06) or more than five years earlier (0.47). The elevations in desired and actual fertility among orphans are consistent with the hypothesis that orphans intentionally become pregnant. Strategies that address personal desires for parenthood may need to be part of prevention programs aimed at orphaned youth.
Fertility Among Orphans in Rural Malawi: Challenging Common Assumptions About Risk and Mechanisms

PubMed Central

Kidman, Rachel; Anglewicz, Philip

2017-01-01

CONTEXT Although a substantial literature suggests that orphans suffer disadvantage relative to nonorphaned peers, the nature of this disadvantage and the mechanisms driving it are poorly understood. Some evidence suggests that orphans experience elevated fertility, perhaps because structural disadvantage leads them to engage in sexual risk-taking. An alternative explanation is that orphans intentionally become pregnant to achieve a sense of normality, acceptance and love. METHODS Data from the 2006 wave of the Malawi Longitudinal Study of Families and Health on 1,033 young adults aged 15–25 were used to examine the relationship of maternal and paternal orphanhood with sexual risk indicators and desired and actual fertility. Regression analyses were used to adjust for covariates, including social and demographic characteristics and elapsed time since parental death. RESULTS Twenty-six percent of respondents had lost their father and 15% their mother. Orphanhood was not associated with sexual risk-taking. However, respondents whose mother had died in the past five years desired more children than did those whose mother was still alive (risk differences, 0.52 among women and 0.97 among men). Actual fertility was elevated among women whose father had died more than five years earlier (0.31) and among men whose mother had died in the past five years (1.06) or more than five years earlier (0.47). CONCLUSION The elevations in desired and actual fertility among orphans are consistent with the hypothesis that orphans intentionally become pregnant. Strategies that address personal desires for parenthood may need to be part of prevention programs aimed at orphaned youth. PMID:25565344
"When the obvious brother is not there": political and cultural contexts of the orphan challenge in northern Uganda.

PubMed

Oleke, Christopher; Blystad, Astrid; Rekdal, Ole Bjørn

2005-12-01

It is estimated that two million of Uganda's children today are orphaned primarily due to AIDS. While recognising the immense impact of HIV/AIDS on the present orphan problem, this article calls for a broader historic and cultural contextualisation to reach an understanding of the vastness of the orphan challenge. The study on which the article is based was carried out among the Langi in Lira District, northern Uganda, with a prime focus on the situation of orphans within the extended family system. The data were collected through ethnographic fieldwork (8 months); in-depth interviews with community leaders (21), heads of households (45) and orphans (35); through focus group discussions (5) with adult men and women caring for orphans, community leaders and with orphans; and also through documentary review. A survey was conducted in 402 households. The findings reveal a transition over the past 30 years from a situation dominated by 'purposeful' voluntary exchange of non-orphaned children to one dominated by 'crisis fostering' of orphans. Sixty-three percent of the households caring for orphans were found to be no longer headed by resourceful paternal kin in a manner deemed culturally appropriate by the patrilineal Langi society, but rather by marginalised widows, grandmothers or other single women receiving little support from the paternal clan. This transition is partly linked to an abrupt discontinuation of the Langi 'widow inheritance' (laku) practice. It is argued that the consequential transformations in fostering practices in northern Uganda must be historically situated through a focus on the effects of armed conflicts and uprooting of the local pastoral and cotton-based economy, which have occurred since the late 1970s. These processes jointly produced dramatic economic marginalisation with highly disturbing consequences for orphans and their caretakers.
Challenges to orphan drugs access in Eastern Europe: the case of Bulgaria.

PubMed

Iskrov, Georgi; Miteva-Katrandzhieva, Tsonka; Stefanov, Rumen

2012-11-01

This article explores how an Eastern European country could deal with orphan drugs access, combining EU policies with its own national settings. The cross-sectional observational study takes the total number of orphan drugs (61) available on EU level by March 2011, and then consecutively filters it through the requirements and criteria of relevant Bulgarian legislation on registration, pricing and reimbursement of medicinal products, obtaining the final number of accessible orphan drugs (16) in Bulgaria. The study further evaluates the average time period from market authorisation to positive reimbursement decision by Bulgarian health authorities (43±29.1 months). Access to orphan drugs should be provided on a reasonable and justified basis. Having in mind the limited availability of resources, it is not a question whether to prioritise rarity, but to create legitimate mechanisms for properly assessing orphan drugs' value and optimally using this value, according to the society's needs and views. The analysis identifies four important challenges to orphan drugs' access in Eastern Europe: (1) elaboration of new orphan drugs pricing approaches, (2) further interaction of cost-effectiveness analysis with medical criteria, (3) active introduction of epidemiological registries for rare diseases, and (4) research of societal preferences and raising public awareness. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.
Challenges and climate of business environment and resources to support pediatric device development.

PubMed

Iqbal, Corey W; Wall, James; Harrison, Michael R

2015-06-01

The incidence of pediatric disease conditions pales in comparison to adult disease. Consequently, many pediatric disorders are considered orphan diseases. Resources for the development of devices targeting orphan diseases are scarce and this poses a unique challenge to the development of pediatric devices. This article outlines these challenges and offers solutions. Copyright © 2015 Elsevier Inc. All rights reserved.
The importance of HIV prevention messaging for orphaned youth in Zimbabwe

PubMed Central

Haney, Erica; Singh, Kavita

2014-01-01

The AIDS epidemic has contributed to a drastic increase in the number of orphans in Zimbabwe. Female adolescent orphans are particularly in jeopardy of contracting HIV due to disadvantages including extreme poverty, low education, and the absent of parental oversight which can lead to higher risk-taking sexual behaviors. By understanding where girls receive education about HIV and who they rely on for information, organizations can effectively modify existing programs to better target this at-risk population. For this study a household survey was conducted which included 216 orphans and 324 non-orphans (n=540), aged 12–17 years old, in the resource-poor setting of Hwange District, Zimbabwe. The aims of this paper were to examine the differences between orphans and non-orphans in HIV prevention message exposure, level of motivation for learning about HIV, and communication with caregivers about safe sex. The household survey revealed that younger orphans, aged 12–15 years old, were more motivated to learn about HIV and had greater HIV messaging exposure in school than non-orphans. These exposure and differences in the levels of motivation between groups dissipated at older ages. Our research also discovered less caregiver communication among orphans than non-orphans. Our findings suggest that HIV programs targeting orphans need to do a better job at keeping older orphans interested in HIV prevention at a time when it matters most. Furthermore, intervention strategies that provide caregiver support are instrumental in effectively delivering prevention messages to girls at home. PMID:22293040
The importance of HIV prevention messaging for orphaned youth in Zimbabwe.

PubMed

Haney, Erica; Singh, Kavita

2012-01-01

The AIDS epidemic has contributed to a drastic increase in the number of orphans in Zimbabwe. Female adolescent orphans are particularly in jeopardy of contracting HIV due to disadvantages including extreme poverty, low education, and the absent of parental oversight which can lead to higher risk-taking sexual behaviors. By understanding where girls receive education about HIV and who they rely on for information, organizations can effectively modify existing programs to better target this at-risk population. For this study a household survey was conducted which included 216 orphans and 324 non-orphans (n=540), aged 12-17 years, in the resource-poor setting of Hwange District, Zimbabwe. The aims of this article were to examine the differences between orphans and non-orphans in HIV prevention message exposure, level of motivation for learning about HIV, and communication with caregivers about safe sex. The household survey revealed that younger orphans, aged 12-15 years, were more motivated to learn about HIV and had greater HIV messaging exposure in school than non-orphans. These exposure and differences in the levels of motivation between groups dissipated at older ages. Our research also discovered less caregiver communication among orphans than non-orphans. Our findings suggest that HIV programs targeting orphans need to do a better job at keeping older orphans interested in HIV prevention at a time when it matters most. Furthermore, intervention strategies that provide caregiver support are instrumental in effectively delivering prevention messages to girls at home.
76 FR 29183 - Exclusion of Orphan Drugs for Certain Covered Entities Under 340B Program

Federal Register 2010, 2011, 2012, 2013, 2014

2011-05-20

... and, if they are, at what price. These covered entities do not know if they can buy these orphan drugs... DEPARTMENT OF HEALTH AND HUMAN SERVICES 42 CFR Part 10 RIN 0906-AA94 Exclusion of Orphan Drugs for... Prices of Drugs Purchased by Covered Entities.'' Section 340B implemented a drug pricing program by which...
Psychosocial Support for Children Orphaned by HIV/AIDS in Zimbabwe

ERIC Educational Resources Information Center

Chitiyo, Jonathan; Chitiyo, Argnue; Chitiyo, Morgan

2016-01-01

Healthy psychosocial development during childhood is a key determinant to the future well-being of all individuals. In many areas of Africa, demand for psychosocial support continues to grow in response to the increasing number of children left orphaned as a result of the HIV/AIDS pandemic. These orphans face various challenges and yet, in most…

Psychological wellbeing of children at public primary schools in Jimma town: An orphan and non-orphan comparative study.

PubMed

Hailegiorgis, Muluken Tigistu; Berheto, Tezera Moshago; Sibamo, Ephrem Lejore; Asseffa, Netsanet Abera; Tesfa, Gashaw; Birhanu, Fitsum

2018-01-01

Orphans face multiple challenges including insufficient food, shelter, schooling, and medical care. Most research on orphans in developing countries concentrates on nutrition and health status. The present study aims to explore the psychological wellbeing of in-school orphaned and non-orphaned children. A comparative cross-sectional study design was used in 370 randomly selected children aged between 10 and 18. Two rosters (one for orphans and one for non-orphans) were created, and then 185 were selected from each roster. Trained field workers used structured questionnaires to obtain information from participants. An adapted Ryff Psychological Wellbeing Scale was used to measure psychological wellbeing. Mean scores were determined for each dimension and for total psychological wellbeing. The mean split was used to divide psychological wellbeing into "high" and "low". Data were coded, entered, cleaned, and analyzed using SPSS version 20. The independent sample t-test was used to determine statistically significant differences in psychological wellbeing between orphaned and non-orphaned children. P values < 0.05 were deemed statistically significant. Of 370 children, 185 (50%) were orphans. Among orphaned children, only 62 (33.5%) scored high on the total psychological wellbeing scale whereas 107 (57.8%) of their non-orphaned peers scored highly. The non-orphaned children had about 10.8 higher mean psychological wellbeing scores than their orphan counterparts (P<0.001). The mean (±SD) psychological wellbeing of the non-orphaned children was 164.0 (17.2) vs. 153.2 (17.2) in the orphaned group. The psychological wellbeing of orphans is significantly lower than their non-orphaned peers. Orphan support projects must consider psychosocial wellbeing in addition to material support.
Psychological wellbeing of children at public primary schools in Jimma town: An orphan and non-orphan comparative study

PubMed Central

Hailegiorgis, Muluken Tigistu; Berheto, Tezera Moshago; Sibamo, Ephrem Lejore; Tesfa, Gashaw; Birhanu, Fitsum

2018-01-01

Introduction Orphans face multiple challenges including insufficient food, shelter, schooling, and medical care. Most research on orphans in developing countries concentrates on nutrition and health status. The present study aims to explore the psychological wellbeing of in-school orphaned and non-orphaned children. Method A comparative cross-sectional study design was used in 370 randomly selected children aged between 10 and 18. Two rosters (one for orphans and one for non-orphans) were created, and then 185 were selected from each roster. Trained field workers used structured questionnaires to obtain information from participants. An adapted Ryff Psychological Wellbeing Scale was used to measure psychological wellbeing. Mean scores were determined for each dimension and for total psychological wellbeing. The mean split was used to divide psychological wellbeing into “high” and “low”. Data were coded, entered, cleaned, and analyzed using SPSS version 20. The independent sample t-test was used to determine statistically significant differences in psychological wellbeing between orphaned and non-orphaned children. P values < 0.05 were deemed statistically significant. Results Of 370 children, 185 (50%) were orphans. Among orphaned children, only 62 (33.5%) scored high on the total psychological wellbeing scale whereas 107 (57.8%) of their non-orphaned peers scored highly. The non-orphaned children had about 10.8 higher mean psychological wellbeing scores than their orphan counterparts (P<0.001). The mean (±SD) psychological wellbeing of the non-orphaned children was 164.0 (17.2) vs. 153.2 (17.2) in the orphaned group. Conclusion The psychological wellbeing of orphans is significantly lower than their non-orphaned peers. Orphan support projects must consider psychosocial wellbeing in addition to material support. PMID:29649248
Depression amongst carers of AIDS-orphaned and other-orphaned children in Umlazi Township, South Africa

PubMed Central

Kuo, Caroline; Operario, Don; Cluver, Lucie

2011-01-01

South Africa faces the challenge of supporting the well-being of adults caring for growing numbers of AIDS-orphaned children. These adults play a critical role in responses to the epidemic but little information exists in regards to their mental health needs. This paper reports on findings from n=1599 adults, recruited through representative household sampling, who serve as primary carers for children in Umlazi Township, a HIV endemic community. Overall, 22% of participants were carers of AIDS-orphaned children, 11% were carers of other-orphaned children, and 67% were carers of non-orphaned children. Prevalence of depression was 30.3%. Orphan carers, regardless of whether they cared for AIDS-orphaned and other-orphaned children, were significantly more likely than carers of non-orphaned children to meet the clinical threshold for depression (35.2% versus 27.9%, p<.01). In multivariate logistic regressions, food insecurity and being a female carer were identified as additional risk factors for greater depression. In contrast, households with access to running water and households dependent on salaries as the main source of income were identified as protective factors for disparities in depression. Mental health interventions are urgently needed to address an increased risk for depression amongst all orphan carers, not just those caring for AIDS-orphaned children. PMID:22081931
Educational Support for Orphans and Vulnerable Children in Primary Schools: Challenges and Interventions

ERIC Educational Resources Information Center

Mwoma, Teresa; Pillay, Jace

2016-01-01

Educational status is an important indicator of children's wellbeing and future life opportunities. It can predict growth potential and economic viability of a state. While this is an ideal situation for all children, the case may be different for orphans and vulnerable children (OVC) due to the challenges they go through on a daily basis. This…
Education status among orphans and non-orphans in communities affected by AIDS in Tanzania and Burkina Faso.

PubMed

Kürzinger, M L; Pagnier, J; Kahn, J G; Hampshire, R; Wakabi, T; Dye, T D V

2008-07-01

The AIDS pandemic has created an estimated 15 million orphans who may face elevated risk of poor health and social outcomes. This paper compares orphans and non-orphans regarding educational status and delay using data collected in three low-income communities affected by AIDS in Tanzania and Burkina Faso. Orphans were significantly more likely not to attend school than were non-orphans and also to be delayed when in school, though, after controlling for confounders, the risk was borderline and non-significant. Multivariate analysis indicates that variables such as age, religion, family of origin, the relation between the child and the head of household and the dependency ratio of the household better explain differences in education than does orphan status. This study suggests, therefore, that orphans' educational status is relatively equivalent to non-orphans perhaps as a result of family based or community program safety nets.
Exploring Responses to Transformative Group Therapy for Orphaned Children in the Context of Mass Orphaning in Botswana

ERIC Educational Resources Information Center

Thamuku, Masego; Daniel, Marguerite

2013-01-01

In the context of AIDS, the Botswana Government has adopted a group therapy program to help large numbers of orphaned children cope with bereavement. This study explores the effectiveness of the therapy and examines how it interacts with cultural attitudes and practices concerning death. Ten orphaned children were involved in five rounds of data…
An ultra-HTS process for the identification of small molecule modulators of orphan G-protein-coupled receptors.

PubMed

Cacace, Angela; Banks, Martyn; Spicer, Timothy; Civoli, Francesca; Watson, John

2003-09-01

G-protein-coupled receptors (GPCRs) are the most successful target proteins for drug discovery research to date. More than 150 orphan GPCRs of potential therapeutic interest have been identified for which no activating ligands or biological functions are known. One of the greatest challenges in the pharmaceutical industry is to link these orphan GPCRs with human diseases. Highly automated parallel approaches that integrate ultra-high throughput and focused screening can be used to identify small molecule modulators of orphan GPCRs. These small molecules can then be employed as pharmacological tools to explore the function of orphan receptors in models of human disease. In this review, we describe methods that utilize powerful ultra-high-throughput screening technologies to identify surrogate ligands of orphan GPCRs.
Bioinformatics in the orphan crops.

PubMed

Armstead, Ian; Huang, Lin; Ravagnani, Adriana; Robson, Paul; Ougham, Helen

2009-11-01

Orphan crops are those which are grown as food, animal feed or other crops of some importance in agriculture, but which have not yet received the investment of research effort or funding required to develop significant public bioinformatics resources. Where an orphan crop is related to a well-characterised model plant species, comparative genomics and bioinformatics can often, though not always, be exploited to assist research and crop improvement. This review addresses some challenges and opportunities presented by bioinformatics in the orphan crops, using three examples: forage grasses from the genera Lolium and Festuca, forage legumes and the second generation energy crop Miscanthus.
Affordable orphan drugs: a role for not-for-profit organizations.

PubMed

Davies, Elin H; Fulton, Emma; Brook, Daniel; Hughes, Dyfrig A

2017-07-01

The success of the Regulation on Orphan Medicinal Products in the European Union is evidenced by the 127 orphan drugs that have had market authorization since 2000. However, the incentives aimed at stimulating research and development have had the unintended consequence of increasing drug cost, resulting in many orphan drugs not being cost-effective. Orphan drugs command an increasing share of the pharmaceutical market and account for a disproportionate amount of healthcare expenditure. Orphan drug ownership by socially motivated, not-for-profit organizations may facilitate access to more affordable orphan drugs, for the benefit of patients and healthcare systems alike. This study aims to describe opportunities for such organizations to become orphan drug Market Authorization Holders. We reviewed data on the ownership of EMA designated and approved orphan drugs, identified funding opportunities and business models for not-for-profit organizations, and summarised relevant legal and policy documents concerning intellectual property rights and drug regulation. Using repurposed drugs as a paradigm, this narrative review navigates the regulatory hurdles, describes the legal context and identifies funding opportunities, in a bid to facilitate and encourage not-for-profit organizations to lead on the development of affordable orphan drugs. Although the regulatory steps required to obtain an MA for an orphan drug are numerous and challenging, they are not insurmountable and can be achieved by not-for-profit organizations that are socially motivated to reduce the costs of orphan drugs to the payers of healthcare. Opportunities for orphan drug development resulting in affordable products lie mainly with repurposed drugs. © 2017 The British Pharmacological Society.
Peer mentorship program on HIV/AIDS knowledge, beliefs, and prevention attitudes among orphaned adolescents: an evidence based practice

PubMed Central

Nabunya, Proscovia; Ssewamala, Fred M.; Mukasa, Miriam N.; Byansi, William; Nattabi, Jennifer

2015-01-01

Adolescents and young adults in sub-Saharan Africa (SSA) are particularly vulnerable to human immunodeficiency virus (HIV) and acquired immune deficiency syndrome (AIDS) infection. Adolescents orphaned as a direct result of HIV/AIDS are at an elevated risk of acquiring HIV/AIDS and other sexually transmitted infections. However, limited empirical evidence exists on HIV knowledge and prevention programs, especially those designed to address HIV information gaps among adolescents. This study evaluates the effect of a peer mentorship program provided in addition to other supportive services on HIV/AIDS knowledge, beliefs, and prevention attitudes, among school-going orphaned adolescents in southern Uganda. We utilize data from the Bridges to the Future Study, a 5-year longitudinal randomized experimental study funded by the National Institute of Child Health and Human Development. Out of the 1410 adolescents enrolled in the study (average age = 12.7 at study initiation), 855 of them participated in a nine-session, curriculum based peer mentorship program. We analyzed data collected at baseline and 12-months post intervention initiation. The results from bivariate and regression analysis indicate that, controlling for socioeconomic characteristics, adolescents who participated in a peer mentorship program were more likely than non-participants to report increased scores on HIV/AIDS knowledge(b = .86, 95%CI = .47 – 1.3, p ≤ .001); better scores on desired HIV/AIDS-related beliefs (b = .29, 95%CI = .06 – .52, p ≤ .01); and better scores on HIV/AIDS prevention attitudes (b = .76, 95%CI = .16 – 1.4, p ≤ .01). Overall, the study findings point to the potential role a of peer mentorship program in promoting the much-desired HIV/AIDS knowledge, beliefs, and prevention attitudes among orphaned adolescents. Future programs and policies that support AIDS-orphaned adolescents in sub-Saharan Africa should consider incorporating peer mentoring programs that provide correct, age, and culturally appropriate HIV information to help protect orphaned adolescents and reduce the risk of HIV infections. PMID:27042195
Imagining the future: Community perceptions of a family-based economic empowerment intervention for AIDS-orphaned adolescents in Uganda

PubMed Central

Ismayilova, Leyla; Ssewamala, Fred; Mooers, Elizabeth; Nabunya, Proscovia; Sheshadri, Srividya

2012-01-01

AIDS-orphaned children and adolescents in sub-Saharan Africa have inadequate access to basic services, including health and education. Using a qualitative approach, the study explores the meaning of education in rural Uganda, obstacles faced by AIDS-orphaned adolescents and their caregivers to access secondary education, and the potential of an economic empowerment intervention SEED in addressing the challenges of accessing educational opportunities for AIDS-orphaned adolescents. The findings come from 29 semi-structured interviews conducted with eleven adolescents study participants, four caregivers and fourteen community leaders involved in the pilot SEED intervention. Study participants and community members indicated that the savings accounts offer a unique opportunity for orphaned adolescents to stay in school and imagine the future with optimism. PMID:23543861
Integrating A Mentorship Component in Programming for Care and Support of AIDS-Orphaned and Vulnerable Children: Lessons from the Suubi and Bridges Programs in Sub-Saharan Africa.

PubMed

Ssewamala, Fred M; Nabunya, Proscovia; Mukasa, N Miriam; Ilic, Vilma; Nattabi, Jennifer

2014-03-01

We examine a mentorship component within a family-based economic empowerment intervention for AIDS-orphaned children in Uganda. Mentorship was guided by a comprehensive 9-session curriculum. We present themes developed from the mentors' field reports and logs. Findings suggest that mentorship offers AIDS-orphaned children opportunities to develop and strengthen future plans. Moreover, the mentorship process was beneficial to both the mentees and their mentors. The program creates a positive life trajectory for a highly vulnerable group of youth. The findings can be used to understand and design mentorship programs targeted at improving the psychosocial wellbeing of children and adolescents.
Incentives for orphan drug research and development in the United States.

PubMed

Seoane-Vazquez, Enrique; Rodriguez-Monguio, Rosa; Szeinbach, Sheryl L; Visaria, Jay

2008-12-16

The Orphan Drug Act (1983) established several incentives to encourage the development of orphan drugs (ODs) to treat rare diseases and conditions. This study analyzed the characteristics of OD designations, approvals, sponsors, and evaluated the effective patent and market exclusivity life of orphan new molecular entities (NMEs) approved in the US between 1983 and 2007. Primary data sources were the FDA Orange Book, the FDA Office of Orphan Drugs Development, and the US Patent and Trademark Office. Data included all orphan designations and approvals listed by the FDA and all NMEs approved by the FDA during the study period. The FDA listed 1,793 orphan designations and 322 approvals between 1983 and 2007. Cancer was the main group of diseases targeted for orphan approvals. Eighty-three companies concentrated 67.7% of the total orphan NMEs approvals. The average time from orphan designation to FDA approval was 4.0 +/- 3.3 years (mean +/- standard deviation). The average maximum effective patent and market exclusivity life was 11.7 +/- 5.0 years for orphan NME. OD market exclusivity increased the average maximum effective patent and market exclusivity life of ODs by 0.8 years. Public programs, federal regulations, and policies support orphan drugs R&D. Grants, research design support, FDA fee waivers, tax incentives, and orphan drug market exclusivity are the main incentives for orphan drug R&D. Although the 7-year orphan drug market exclusivity provision had a positive yet relatively modest overall effect on effective patent and market exclusivity life, economic incentives and public support mechanisms provide a platform for continued orphan drug development for a highly specialized market.
An Analysis of How Multicultural Adult Orphans Achieve Economic Success

ERIC Educational Resources Information Center

Simonee, Saundra W.

2014-01-01

Successful multicultural adult orphans who were not adopted pose an interesting challenge in their history, their physical, psychological, social emotional and personal identity development. One must understand their journey from orphanhood to adulthood and their current prominent status in life to build a contextualized personal story (Banks,…
Care arrangement, grief, and psychological problems among children orphaned by AIDS in China

PubMed Central

Zhao, Guoxiang; Li, Xiaoming; Fang, Xiaoyi; Zhao, Junfeng; Yang, Hongmei; Stanton, Bonita

2007-01-01

The China Ministry of Health has estimated that there are at least 100,000 AIDS orphans in China. The UNICEF China Office estimates that between 150,000 and 250,000 additional children will be orphaned by AIDS over the next five years. However, limited data are available regarding the socio-demographic characteristics, care arrangement, barriers to appropriate grief resolution and psychological problems among AIDS orphans in China. In this article, we review secondary data and reports from scientific literature, government, non-governmental organizations, and public media regarding children orphaned by AIDS in China to address their living situation, bereavement process, and psychological problems. Our review suggests that AIDS orphans in China are living in a stressful environment with many orphans struggling with psychological problems and unmet basic needs such as food, shelter, education, and medical care. Based on our review, we suggest that future studies should address the psychosocial needs of AIDS orphans in China and develop health promotion programs to mitigate the negative impact of parental death on the physical and psychosocial well-being of these orphans. PMID:18058390
A venture capital view of challenges, opportunities, and innovation in biomedical research.

PubMed

Ratcliffe, L T

2011-02-01

Small biotech companies have been an important source of innovation, pipelines, and new products for the pharmaceutical industry, and are primarily financed by venture capital (VC). The significant changes happening within the VC industry have broad implications for these small companies. This includes a shift to financing later-stage programs with increasing interest in orphan or specialty indications. Nontraditional sources of capital and innovative risk-sharing structures can enable early-stage companies.
Stigma, marginalization and psychosocial well-being of orphans in Rwanda: exploring the mediation role of social support.

PubMed

Caserta, Tehetna Alemu; Pirttilä-Backman, Anna-Maija; Punamäki, Raija-Leena

2016-01-01

Stigma and marginalization are one of the major challenges orphans face in their daily lives, particularly in developing countries, but little is known about their impacts on mental health. This study examines how orphan-related characteristics, stigma and marginalization are associated with psychosocial well-being. It further analyses the role of social support in mediating between stigma and marginalization and mental health, indicated by emotional well-being and mental distress. The participants in this study were 430 Rwandan orphans who were 10-25 years of age, and of whom 179 were females and 251 were males. Results showed that high levels of stigma and marginalization were associated with a lower level of emotional well-being and higher levels of mental distress. A mediation analysis indicated that low level of social support due to stigma and marginalization contributed significantly to low level of emotional well-being. Once stigma, marginalization and social support were fully accounted for, AIDS orphans exhibited higher levels of mental distress than those who were orphaned by genocide or other causes. Future interventions designed to reduce stigma and marginalization for orphans and actions that facilitate social support can significantly improve emotional well-being and reduce mental distress among orphans.
ERRα: a metabolic function for the oldest orphan

PubMed Central

Villena, Josep A.; Kralli, Anastasia

2009-01-01

Estrogen receptor related receptor (ERR)α was one of the first identified (1988) orphan nuclear receptors. Many of the orphan receptors identified after ERRα were deorphanized in a timely manner and appreciated as key transcriptional regulators of metabolic pathways. ERRα, however, remains an orphan. Nevertheless, recent studies have defined regulatory mechanisms and transcriptional targets of ERRα, allowing this receptor to join ranks with other nuclear receptors that control metabolism. Notably, mice lacking ERRα show defects when challenged with stressors that require a ‘shift of gears’ in energy metabolism, such as exposure to cold, cardiac overload or infection. These findings establish the importance of ERRα for adaptive energy metabolism, and suggest that strategies targeting ERRα may be useful in fighting metabolic diseases. PMID:18778951
The extent of community and public support available to families caring for orphans in Malawi.

PubMed

Kidman, Rachel; Heymann, S Jody

2009-04-01

There are an estimated 15 million AIDS orphans worldwide. Families play an important role in safeguarding orphans, but they may be increasingly compromised by the HIV/AIDS epidemic. The international aid community has recognized the need to help families continue caring for orphaned children by strengthening their safety nets. Before we build new structures, however, we need to know the extent to which community and public safety nets already provide support to families with orphans. To address this gap, we analyzed nationally representative data from 27,495 children in the 2004-2005 Malawi Integrated Household Survey. We found that communities commonly assisted orphan households through private transfers; organized responses to the orphan crisis were far less frequent. Friends and relatives provided assistance to over 75% of orphan households through private gifts, but the value of such support was relatively low. Over 40% of orphans lived in a community with support groups for the chronically ill and approximately a third of these communities provided services specifically for orphans and other vulnerable children. Public programs, which form a final safety net for vulnerable households, were more widespread. Free/subsidized agricultural inputs and food were the most commonly used public safety nets by children's households in the past year (44 and 13%, respectively), and households with orphans were more likely to be beneficiaries. Malawi is poised to drastically expand safety nets to orphans and their families, and these findings provide an important foundation for this process.
Affordability Challenges to Value-Based Pricing: Mass Diseases, Orphan Diseases, and Cures.

PubMed

Danzon, Patricia M

2018-03-01

To analyze how value-based pricing (VBP), which grounds the price paid for pharmaceuticals in their value, can manage "affordability" challenges, defined as drugs that meet cost-effectiveness thresholds but are "unaffordable" within the short-run budget. Three specific contexts are examined, drawing on recent experience. First, an effective new treatment for a chronic, progressive disease, such as hepatitis C, creates a budget spike that is transitory because initial prevalence is high, relative to current incidence. Second, "cures" that potentially provide lifetime benefits may claim abnormally high VBP prices, with high immediate budget impact potentially/partially offset by deferred cost savings. Third, although orphan drugs in principle target rare diseases, in aggregate they pose affordability concerns because of the growing number of orphan indications and increasingly high prices. For mass diseases, the transitory budget impact of treating the accumulated patient stock can be managed by stratified rollout that delays treatment of stable patients and prioritizes patients at high risk of deterioration. Delay spreads the budget impact and permits potential savings from launch of competing treatments. For cures, installment payments contingent on outcomes could align payment flows and appropriately shift risk to producers. This approach, however, entails high administrative and incentive costs, especially if applied across multiple payers in the United States. For orphan drugs, the available evidence on research and development trends and returns argues against the need for a higher VBP threshold to incentivize research and development in orphan drugs, given existing statutory benefits under orphan drug legislation. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.

Understanding the strategies employed to cope with increased numbers of AIDS-orphaned children in families in rural settings: a case of Mbeya Rural District, Tanzania.

PubMed

Fauk, Nelsensius Klau; Mwakinyali, Silivano Edson; Putra, Sukma; Mwanri, Lillian

2017-02-07

The purpose of this study was to understand the strategies employed by families that adopt Acquired Immune Deficiency Syndrome (AIDS)-orphaned children (Adoptive families) for coping with and mitigating the impact of AIDS in Mbeya Rural District, Tanzania. High numbers of AIDS-orphaned children aged below 18 years in Mbeya Region have led to increasing the burden of families caring for them. Understanding the coping strategies and impact mitigation activities employed by adoptive families is important in order to develop programmes to help them. This study employed a qualitative method for data collection (one-on-one in-depth interviews). The respondents included 12 male and 8 female heads of families that provide essential care for AIDS-orphaned children in Mbeya Rural District in Tanzania. The framework approach was used to analyse the data that were collected from 15 July to 15 August 2010. The study findings revealed that adoptive families faced several challenges including financial constraints due to increased needs for basic essentials such as health care expenses, school fees and food. Further impacts on adoptive families included shortage of work opportunities and limited time to address these challenges. To mitigate these challenges, adoptive families employed a range of coping strategies including selling family assets and renting out parts of cultivable land for extra cash. Task reallocation which involved the AIDS-orphaned children entering the labour force was also employed as a strategy to mitigate challenges and involved de-enrolling of children from schools so they could take part in income-generating activities in order to earn supplementary family income. The creation of additional income-generating activities such as poultry farming were other coping mechanisms employed, and these received support from both non-governmental organisations (NGOs) and governmental organisations, including the Isangati Agricultural Development Organization (local NGO) and the local government respectively. The current study identified challenges that adoptive families as well as the AIDS-orphaned children themselves faced in Mbeya Rural District, Tanzania. Recognition of these issues highlights the need for targeted interventions to address the underlying social determinants of human immunodeficiency virus or HIV and AIDS in affected populations in order to prevent further imposition of social, cultural and economic disadvantages on families that provide care for AIDS-orphaned children and the children themselves. These findings may prove useful in provoking discussions that may lead to HIV/AIDS prevention and the development of broader mitigation strategies to alleviate the impact of this scourge on families and communities in rural Tanzania, and in similar settings across the world.
What makes orphans in Kigali, Rwanda, non-adherent to antiretroviral therapy? Perspectives of their caregivers.

PubMed

Kikuchi, Kimiyo; Poudel, Krishna C; Muganda, John; Sato, Tomoko; Mutabazi, Vincent; Muhayimpundu, Ribakare; Majyambere, Adolphe; Nyonsenga, Simon P; Sase, Eriko; Jimba, Masamine

2014-01-01

Every year, approximately 260,000 children are infected with HIV in low- and middle-income countries. The timely initiation and high level of maintenance of antiretroviral therapy (ART) are crucial to reducing the suffering of HIV-positive children. We need to develop a better understanding of the background of children's ART non-adherence because it is not well understood. The purpose of this study is to explore the background related to ART non-adherence, specifically in relation to the orphan status of children in Kigali, Rwanda. We conducted 19 focus group discussions with a total of 121 caregivers of HIV-positive children in Kigali. The primary data for analysis were verbatim transcripts and socio-demographic data. A content analysis was performed for qualitative data analysis and interpretation. The study found several contextual factors that influenced non-adherence: among double orphans, there was psychological distance between the caregivers and children, whereas economic burden was the primary issue among paternal orphans. The factors promoting adherence also were unique to each orphan status, such as the positive attitude about disclosing serostatus to the child by double orphans' caregivers, and feelings of guilt about the child's condition among non-orphaned caregivers. Knowledge of orphan status is essential to elucidate the factors influencing ART adherence among HIV-positive children. In this qualitative study, we identified the orphan-related contextual factors that influenced ART adherence. Understanding the social context is important in dealing with the challenges to ART adherence among HIV-positive children.
Psychosocial Support for Orphans and Vulnerable Children in Public Primary Schools: Challenges and Intervention Strategies

ERIC Educational Resources Information Center

Mwoma, Teresa; Pillay, Jace

2015-01-01

Much has been written about orphans and vulnerable children (OVC) with regard to their education and living. However, relatively few studies have documented the psychosocial support provided for OVC in public primary schools to enhance their psychosocial well-being. This study therefore contributes to the understanding of the challenges…
snoSeeker: an advanced computational package for screening of guide and orphan snoRNA genes in the human genome.

PubMed

Yang, Jian-Hua; Zhang, Xiao-Chen; Huang, Zhan-Peng; Zhou, Hui; Huang, Mian-Bo; Zhang, Shu; Chen, Yue-Qin; Qu, Liang-Hu

2006-01-01

Small nucleolar RNAs (snoRNAs) represent an abundant group of non-coding RNAs in eukaryotes. They can be divided into guide and orphan snoRNAs according to the presence or absence of antisense sequence to rRNAs or snRNAs. Current snoRNA-searching programs, which are essentially based on sequence complementarity to rRNAs or snRNAs, exist only for the screening of guide snoRNAs. In this study, we have developed an advanced computational package, snoSeeker, which includes CDseeker and ACAseeker programs, for the highly efficient and specific screening of both guide and orphan snoRNA genes in mammalian genomes. By using these programs, we have systematically scanned four human-mammal whole-genome alignment (WGA) sequences and identified 54 novel candidates including 26 orphan candidates as well as 266 known snoRNA genes. Eighteen novel snoRNAs were further experimentally confirmed with four snoRNAs exhibiting a tissue-specific or restricted expression pattern. The results of this study provide the most comprehensive listing of two families of snoRNA genes in the human genome till date.
“The Luggage that isn’t Theirs is Too Heavy…”:Understandings of Orphan Disadvantage in Lesotho

PubMed Central

Goldberg, Rachel E.; Short, Susan E.

2012-01-01

In Southern Africa, high adult HIV prevalence has fueled concern about the welfare of children losing parents to the epidemic. A growing body of evidence indicates that parental, particularly maternal, death is negatively associated with child outcomes. However, a better understanding of the mechanisms is needed. In addition, the way orphan disadvantage and the mechanisms giving rise to it are understood on the ground is essential for the successful translation of research into policies and programs. This study employs data from 89 in-depth interviews with caregivers and key informants in Lesotho, a setting where approximately one-quarter of adults is infected with HIV, to elaborate understandings of orphan disadvantage. Our analysis focuses on two questions: (i) Do local actors perceive orphans to be disadvantaged compared to non-orphans, and if so, in what ways; and (ii) How do they explain orphans’ differential disadvantage? Analyses suggest that orphans were widely perceived to be disadvantaged; respondents described this disadvantage in material as well as affective domains. Thematic analyses reveal five broad categories of explanation: poverty, love and kin connection, caregiver character, perceptions of orphans, and community norms related to orphan care. These results underscore the need for research and policy to address (i) multiple types of disadvantage, including deficits in kindness and attention; and (ii) the social embeddedness of disadvantage, recognizing that poverty, kinship, and community interact with individual attributes to shape caregiving relationships and child experiences. The findings suggest limited success for programs and policies that do not address the emotional needs of children, or that focus on child or caregiver support to the exclusion of community outreach. PMID:22865946
Psychological distress amongst AIDS-orphaned children in urban South Africa.

PubMed

Cluver, Lucie; Gardner, Frances; Operario, Don

2007-08-01

South Africa is predicted to have 2.3 million children orphaned by Acquired Immune Deficiency Syndrome (AIDS) by 2020 (Actuarial Society of South Africa, 2005). There is little knowledge about impacts of AIDS-related bereavement on children, to aid planning of services. This study aimed to investigate psychological consequences of AIDS orphanhood in urban township areas of Cape Town, South Africa, compared to control groups of children and adolescents orphaned by other causes, and non-orphans. One thousand and twenty-five children and adolescents (aged 10-19) were interviewed using socio-demographic questionnaires and standardised scales for assessing depression, anxiety, post-traumatic stress, peer problems, delinquency and conduct problems. Controlling for socio-demographic factors such as age, gender, formal/informal dwelling and age at orphanhood, children orphaned by AIDS were more likely to report symptoms of depression, peer relationship problems, post-traumatic stress, delinquency and conduct problems than both children orphaned by other causes and non-orphaned children. Anxiety showed no differences. AIDS-orphaned children were more likely to report suicidal ideation. Compared to Western norms, AIDS-orphaned children showed higher levels of internalising problems and delinquency, but lower levels of conduct problems. Children orphaned by AIDS may be a particularly vulnerable group in terms of emotional and, to a lesser extent, behavioural problems. Intervention programs are necessary to ameliorate the psychological sequelae of losing a parent to AIDS.
SMHASH: Anatomy of the Orphan Stream using RR Lyrae stars

NASA Astrophysics Data System (ADS)

Hendel, David; Scowcroft, Victoria; Johnston, Kathryn V.; Fardal, Mark A.; van der Marel, Roeland P.; Sohn, Sangmo Tony; Price-Whelan, Adrian M.; Beaton, Rachael L.; Besla, Gurtina; Bono, Giuseppe; Cioni, Maria-Rosa L.; Clementini, Gisella; Cohen, Judith G.; Fabrizio, Michele; Freedman, Wendy L.; Garofalo, Alessia; Grillmair, Carl J.; Kallivayalil, Nitya; Kollmeier, Juna A.; Law, David R.; Madore, Barry F.; Majewski, Steven R.; Marengo, Massimo; Monson, Andrew J.; Neeley, Jillian R.; Nidever, David L.; Pietrzyński, Grzegorz; Seibert, Mark; Sesar, Branimir; Smith, Horace A.; Soszyński, Igor; Udalski, Andrzej

2018-06-01

Stellar tidal streams provide an opportunity to study the motion and structure of the disrupting galaxy as well as the gravitational potential of its host. Streams around the Milky Way are especially promising as phase space positions of individual stars will be measured by ongoing or upcoming surveys. Nevertheless, it remains a challenge to accurately assess distances to stars farther than 10 kpc from the Sun, where we have the poorest knowledge of the Galaxy's mass distribution. To address this we present observations of 32 candidate RR Lyrae stars in the Orphan tidal stream taken as part of the Spitzer Merger History and Shape of the Galactic Halo (SMHASH) program. The extremely tight correlation between the periods, luminosities, and metallicities of RR Lyrae variable stars in the Spitzer IRAC 3.6μm band allows the determination of precise distances to individual stars; the median statistical relative distance uncertainty to each RR Lyrae star is 2.5%. By fitting orbits in an example potential we obtain an upper limit on the mass of the Milky Way interior to 60 kpc of 5.6_{-1.1^{+1.2}× 10^{11} M_⊙ }, bringing estimates based on the Orphan Stream in line with those using other tracers. The SMHASH data also resolve the stream in line-of-sight depth, allowing a new perspective on the internal structure of the disrupted dwarf galaxy. Comparing with N-body models we find that the progenitor had an initial dark halo mass of approximately 3.2 × 109 M⊙, placing the Orphan Stream's progenitor amongst the classical dwarf spheroidals.
Economic Modeling Considerations for Rare Diseases.

PubMed

Pearson, Isobel; Rothwell, Ben; Olaye, Andrew; Knight, Christopher

2018-05-01

To identify challenges that affect the feasibility and rigor of economic models in rare diseases and strategies that manufacturers have employed in health technology assessment submissions to demonstrate the value of new orphan products that have limited study data. Targeted reviews of PubMed, the National Institute for Health and Care Excellence's (NICE's) Highly Specialised Technologies (HST), and the Scottish Medicines Consortium's (SMC's) ultra-orphan submissions were performed. A total of 19 PubMed studies, 3 published NICE HSTs, and 11 ultra-orphan SMC submissions were eligible for inclusion. In rare diseases, a number of different factors may affect the model's ability to comply with good practice recommendations. Many products for the treatment of rare diseases have an incomplete efficacy and safety profile at product launch. In addition, there is often limited available natural history and epidemiology data. Information on the direct and indirect cost burden of an orphan disease also may be limited, making it difficult to estimate the potential economic benefit of treatment. These challenges can prevent accurate estimation of a new product's benefits in relation to costs. Approaches that can address such challenges include using patient and/or clinician feedback to inform model assumptions; data from disease analogues; epidemiological techniques, such as matching-adjusted indirect comparison; and long-term data collection. Modeling in rare diseases is often challenging; however, a number of approaches are available to support the development of model structures and the collation of input parameters and to manage uncertainty. Copyright © 2018 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
Ethical imperatives of timely access to orphan drugs: is possible to reconcile economic incentives and patients' health needs?

PubMed

Rodriguez-Monguio, R; Spargo, T; Seoane-Vazquez, E

2017-01-05

More than 6,800 rare diseases and conditions have been identified in the US, which affect 25-30 million Americans. In 1983, the US Congress enacted the Orphan Drug Act (ODA) to encourage the development and marketing of drugs to treat rare diseases and conditions. This study analyzed all orphan designations and FDA approvals since 1983 through 2015, discussed the effectiveness of incentives for the development of treatments for rare diseases, and reflected on the ethical imperatives for timely access to orphan drugs. Study data were derived from the Food and Drug Administration (FDA) Orange Book and the Office of Orphan Drugs Development. A search was conducted to assess literature on the ethical principles and economic incentives for the development of orphan drugs. In the period 1983-2015, the FDA granted 3,647 orphan drug designations and 554 orphan drug approvals. The orphan drug approvals corresponded to 438 different brand names. Cancer was the therapeutic area with the highest number of approvals. The increased number of patients with rare diseases and the growth in the cost of orphan drugs pose a significant economic burden for patients, public programs and private third party payers. Regulatory differences to qualify for orphan designation and various population thresholds employed by the FDA and the European Medicines Agency lead to further unmet health needs for patients with rare diseases and aggravate health inequities. There is no societal consensus on the population and economic thresholds, the drug effectiveness indicator(s), or the societal value to be placed for the approval and reimbursement of orphan drugs. Orphan drug development and marketing in the US concentrate in few therapeutic areas. Despite the increase in the number of FDA approved orphan drugs, the unmet needs of patients with rare diseases evidence that the current incentives are not efficiently stimulating orphan drug development. There is need to balance economic incentives to stimulate the development and marketing of orphan drugs without jeopardizing patients' access to treatment. Thus, aligning pharmaceutical companies' incentives with societal budgetary constraints is necessary and the ethical imperatives of timely access to orphan drugs need to be agreed upon.
Health information, what happens when there isn't any? Information literacy and the challenges for rare and orphan diseases.

PubMed

Spring, Hannah

2014-09-01

This feature looks at the challenges for information literacy in rare and orphan diseases. In particular, it focuses on the information difficulties faced by those living with a rare condition or awaiting a diagnosis, and also those of the health professionals in charge of their care. The feature also highlights some of the key issues that library and information professionals need to be aware of when providing information support in such circumstances. © 2014 The author. Health Information and Libraries Journal © 2014 Health Libraries Group.
Who wants to adopt and who wants to be adopted: a sample of American families and sub-Saharan African orphans.

PubMed

Balding, Christopher; Feng, Yan; Atashband, Armita

2015-12-01

The debate between pro- and anti-international adoption advocates relies heavily on rhetoric and little on data analysis. To better understand the state of orphans and potential adopters in this debate, we utilize the National Survey of Family Growth (NSFG) and the Demographic and Health Surveys (DHS) to study who adopts internationally and the status of orphaned children in sub-Saharan Africa. According to NSFG data adopters are church going, highly educated, stable families aware of the challenges faced by international adoption, with high rates of infertility and rates of child abuse half the population average. According to the DHS data, orphans in sub-Saharan Africa suffer from significantly higher deprivation, reduced schooling and increased levels of stunting and underweight reported than their cohort. Using this data, we estimate conservatively that that 1 50 000 orphans from our sample of sub-Saharan African countries died from their 5-year birth cohort. Given the large number of families seeking to adopt and the high number of orphan deaths, it seems counterproductive to restrict international adoptions given the significantly lower risks faced by children in adopted families compared with remaining orphaned. © The Author 2015; all rights reserved. Published by Oxford University Press in association with The London School of Hygiene and Tropical Medicine.
Household dynamics and socioeconomic conditions in the context of incident adolescent orphaning in KwaZulu-Natal, South Africa

PubMed Central

DeSilva, Mary Bachman; Skalicky, Anne; Beard, Jennifer; Cakwe, Mandisa; Zhuwau, Tom; Quinlan, Tim; Simon, Jonathon L.

2012-01-01

We compared demographics, socioeconomic status, and food insecurity between households with and without recent orphans in a region of high HIV/AIDS mortality in South Africa. We recruited a cohort of 197 recent orphans and 528 non-orphans ages 9–15 and their households using stratified cluster sampling. Households were classified into three groups: orphan-only (N=50); non-orphan-only (N=377); and mixed (N=210). Between September 2004 and May 2007, households were interviewed three times regarding demographics, income and assets, and food insecurity. Baseline bivariate associations were assessed using chi-square- and t-tests. Longitudinal bivariate associations and multivariate models were tested using generalized estimating equations. At baseline, mixed households generally exhibited greater characteristics of vulnerability than orphan and non-orphan households. They were larger, had older, less educated household heads, and reported a much smaller annual per capita income. Orphan households were more likely to report a death in the previous year, and less likely to have an adult employed. These differences persisted over the study. Even non-orphan households exhibited characteristics of vulnerability, with 14% reporting a death one year before baseline, 45% of whom were prime-age adults. At baseline, a much smaller proportion of orphan households reported receiving the child support grant than the other household types, but notably, there were no differences among households in receipt of the grant by Round 3. Household food insecurity was highly prevalent: more than one in five orphan-only and mixed households reported being food insecure in the previous month. These findings suggest that the effects of HIV/AIDS only exacerbate existing high levels of poverty in the district, as virtually all households are vulnerable regardless of orphan status. Community-level programs must help families address a spectrum of needs, including food security, caregiving, and financial support, as well as better target social welfare grants and make them more accessible to vulnerable households. PMID:24223622
Family Economic Strengthening and Parenting Stress Among Caregivers of AIDS-Orphaned Children: Results from a Cluster Randomized Clinical Trial in Uganda.

PubMed

Nabunya, Proscovia; Ssewamala, Fred M; Ilic, Vilma

2014-09-01

This study examines the impact of a family economic strengthening intervention on parenting stress among caregivers of AIDS-orphaned children in Uganda. The study uses data from a 4-year (2008-2012) NIMH randomized clinical trial for AIDS-orphaned children known as Suubi-Maka (N=346 dyads). Child-caregiver dyads from 10 comparable primary schools were randomly assigned to either the control group (n=167 dyads) receiving usual care for school-going orphaned children (such as food aid and scholastic materials) or the treatment group (n=179 dyads) receiving a family economic strengthening intervention (focused on a matched savings account), financial planning and management workshops over and above the usual care. Interviews were conducted at baseline, 12 months and 24 months follow-up. This study uses data from baseline and 24 months post-intervention. We use multivariate regression methods, controlling for socioeconomic characteristics. At 24 months, caregivers in the treatment group reported significantly lower levels of parenting stress compared to caregivers in the control group. Findings from this study point to the potential of a family economic strengthening intervention to improve caregiver's psychosocial wellbeing and that of their families. We conclude that programs and policies aimed at improving the psychosocial wellbeing of families caring for AIDS-orphaned children may consider incorporating economic strengthening components in their programming to help support these kinds of families, caregivers of AIDS-orphaned children especially those residing in developing countries.
Thirty Years of Orphan Drug Legislation and the Development of Drugs to Treat Rare Seizure Conditions: A Cross Sectional Analysis.

PubMed

Döring, Jan Henje; Lampert, Anette; Hoffmann, Georg F; Ries, Markus

2016-01-01

Epilepsy is a serious chronic health condition with a high morbidity impairing the life of patients and afflicted families. Many epileptic conditions, especially those affecting children, are rare disorders generating an urgent medical need for more efficacious therapy options. Therefore, we assessed the output of the US and European orphan drug legislations. Quantitative analysis of the FDA and EMA databases for orphan drug designations according to STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) criteria. Within the US Orphan Drug Act 40 designations were granted delivering nine approvals, i.e. clobazam, diazepam viscous solution for rectal administration, felbamate, fosphenytoin, lamotrigine, repository corticotropin, rufinamide, topiramate, and vigabatrin. Since 2000 the EMA granted six orphan drug designations whereof two compounds were approved, i.e. rufinamide and stiripentol. In the US, two orphan drug designations were withdrawn. Orphan drugs were approved for conditions including Lennox-Gastaut syndrome, infantile spasms, Dravet syndrome, and status epilepticus. Comparing time to approval for rufinamide, which was approved in the US and the EU to treat rare seizure conditions, the process seems faster in the EU (2.2 years) than in the US (4.3 years). Orphan drug development in the US and in the EU delivered only few molecular entities to treat rare seizure disorders. The development programs focused on already approved antiepileptic drugs or alternative pharmaceutical formulations. Most orphan drugs approved in the US are not approved in the EU to treat rare seizures although some were introduced after 2000 when the EU adopted the Orphan Drug Regulation.
Challenges of ligand identification for the second wave of orphan riboswitch candidates.

PubMed

Greenlee, Etienne B; Stav, Shira; Atilho, Ruben M; Brewer, Kenneth I; Harris, Kimberly A; Malkowski, Sarah N; Mirihana Arachchilage, Gayan; Perkins, Kevin R; Sherlock, Madeline E; Breaker, Ronald R

2018-03-04

Orphan riboswitch candidates are noncoding RNA motifs whose representatives are believed to function as genetic regulatory elements, but whose target ligands have yet to be identified. The study of certain orphans, particularly classes that have resisted experimental validation for many years, has led to the discovery of important biological pathways and processes once their ligands were identified. Previously, we highlighted details for four of the most common and intriguing orphan riboswitch candidates. This facilitated the validation of riboswitches for the signaling molecules c-di-AMP, ZTP, and ppGpp, the metal ion Mn 2+ , and the metabolites guanidine and PRPP. Such studies also yield useful linkages between the ligands sensed by the riboswitches and numerous biochemical pathways. In the current report, we describe the known characteristics of 30 distinct classes of orphan riboswitch candidates - some of which have remained unsolved for over a decade. We also discuss the prospects for uncovering novel biological insights via focused studies on these RNAs. Lastly, we make recommendations for experimental objectives along the path to finding ligands for these mysterious RNAs.
What makes orphans in Kigali, Rwanda, non-adherent to antiretroviral therapy? Perspectives of their caregivers

PubMed Central

Kikuchi, Kimiyo; Poudel, Krishna C; Muganda, John; Sato, Tomoko; Mutabazi, Vincent; Muhayimpundu, Ribakare; Majyambere, Adolphe; Nyonsenga, Simon P; Sase, Eriko; Jimba, Masamine

2014-01-01

Introduction Every year, approximately 260,000 children are infected with HIV in low- and middle-income countries. The timely initiation and high level of maintenance of antiretroviral therapy (ART) are crucial to reducing the suffering of HIV-positive children. We need to develop a better understanding of the background of children's ART non-adherence because it is not well understood. The purpose of this study is to explore the background related to ART non-adherence, specifically in relation to the orphan status of children in Kigali, Rwanda. Methods We conducted 19 focus group discussions with a total of 121 caregivers of HIV-positive children in Kigali. The primary data for analysis were verbatim transcripts and socio-demographic data. A content analysis was performed for qualitative data analysis and interpretation. Results The study found several contextual factors that influenced non-adherence: among double orphans, there was psychological distance between the caregivers and children, whereas economic burden was the primary issue among paternal orphans. The factors promoting adherence also were unique to each orphan status, such as the positive attitude about disclosing serostatus to the child by double orphans’ caregivers, and feelings of guilt about the child's condition among non-orphaned caregivers. Conclusions Knowledge of orphan status is essential to elucidate the factors influencing ART adherence among HIV-positive children. In this qualitative study, we identified the orphan-related contextual factors that influenced ART adherence. Understanding the social context is important in dealing with the challenges to ART adherence among HIV-positive children. PMID:25477050
Relationship Between Family Economic Resources, Psychosocial Well-being, and Educational Preferences of AIDS-Orphaned Children in Southern Uganda: Baseline Findings

PubMed Central

Ssewamala, Fred M.; Nabunya, Proscovia; Ilic, Vilma; Mukasa, Miriam N.; Ddamulira, Christopher

2015-01-01

This study examines the relationship between economic resources, psychosocial well-being, and educational preferences of AIDS-orphaned children in southern Uganda. We use baseline data from a sample of 1410 AIDS-orphaned children (defined as children who have lost one or both biological parents to AIDS) enrolled in the Bridges to the Future study, a National Institute of Child Health and Human Development (NICHD) funded study. Analyses from both bivariate and multiple regression analyses indicate the following: 1) despite the well-documented economic and psychosocial challenges AIDS-orphaned children face, many of these children have high educational plans and aspirations; 2) educational aspirations differ by orphanhood status (double orphan vs. single orphan); 3) regardless of orphanhood status, children report similar levels of psychosocial well-being; 4) high levels of family cohesion, positive perceptions of the future, school satisfaction, and lower levels of hopelessness (hopefulness) are associated with high educational aspirations; and 5) reported family economic resources at baseline, all seem to play a role in predicting children's educational preferences and psychosocial well-being. These findings suggest that the focus for care and support of orphaned children should not be limited to addressing their psychosocial needs. Addressing the economic needs of the households in which orphaned children live is equally important. Indeed, in the context of extreme poverty—in which most of the children represented in this study live—addressing structural factors, including poverty, may be a key driver in addressing their psychosocial functioning. PMID:26146601
Exploring responses to transformative group therapy for orphaned children in the context of mass orphaning in Botswana.

PubMed

Thamuku, Masego; Daniel, Marguerite

2013-01-01

In the context of AIDS, the Botswana Government has adopted a group therapy program to help large numbers of orphaned children cope with bereavement. This study explores the effectiveness of the therapy and examines how it interacts with cultural attitudes and practices concerning death. Ten orphaned children were involved in five rounds of data collection during a therapeutic retreat; eight social workers completed questionnaires concerning the effectiveness of the therapy. Most children were able to come to terms with their loss, face problems in their home and school environments, and envision ways of solving problems. All the children described benefits of group formation and the support it would provide when they returned to their home situations.
Health of adults caring for orphaned children in an HIV-endemic community in South Africa.

PubMed

Kuo, Caroline; Operario, Don

2011-09-01

In South Africa, an estimated 2.5 million children have been orphaned by AIDS and other causes of adult mortality. Although there is a growing body of research on the well-being of South African orphaned children, few research studies have examined the health of adult individuals caring for children in HIV-endemic communities. The cross-sectional survey assessed prevalence of general health and functioning (based on Short-Form 36 version 2 scale), depression (based on Center for Epidemiologic Studies-Depression scale), anxiety (using Kessler-10 scale), and post-traumatic stress (using the Harvard Trauma Questionnaire) among a representative community sample of adults caring for children in Umlazi Township, an HIV-endemic community in South Africa. Of 1599 respondents, 33% (n=530) were carers of orphaned children. Results showed that, overall, carers reported poor general health and functioning and elevated levels of depression, anxiety, and post-traumatic stress. Carers of orphaned children reported significantly poorer general health and functioning and higher rates of depression and post-traumatic stress compared with carers of non-orphaned children. In multivariate analyses, orphan carer and non-orphan carer differences in general health were accounted for by age, gender, education, economic assets, and source of income, but differences in depression were independent of these cofactors. Interventions are needed to address physical and mental health of carers in general. Greater health problems among orphan carers appeared to be fully explained by socioeconomic characteristics, which offer opportunities for targeting of programs. More research is needed to understand determinants of mental health disparities among orphan carers, which were not explained by socioeconomic characteristics.
Health of adults caring for orphaned children in an HIV endemic community in South Africa

PubMed Central

Kuo, Caroline; Operario, Don

2011-01-01

In South Africa, an estimated 2.5 million children have been orphaned by AIDS and other causes of adult mortality. Although there is a growing body of research on the well-being of South African orphaned children, few research studies have examined the health of adult individuals caring for children in HIV endemic communities. The cross-sectional survey assessed prevalence of general health and functioning (based on Short-Form 36 version 2 scale), depression (based on Center for Epidemiologic Studies-Depression scale), anxiety (using Kessler-10 scale), and post-traumatic stress (using the Harvard Trauma Questionnaire) among a representative community sample of adults caring for children in Umlazi Township, an HIV endemic community in South Africa. Of 1599 respondents, 33% (n=530) were carers of orphaned children. Results showed that, overall, carers reported poor general health and functioning, and elevated levels of depression, anxiety, and post-traumatic stress. Carers of orphaned children reported significantly poorer general health and functioning and higher rates of depression and post-traumatic stress compared to carers of non-orphaned children. In multivariate analyses, orphan carer and non-orphan carer differences in general health were accounted for by age, gender, education, economic assets, and source of income, but differences in depression were independent of these co-factors. Interventions are needed to address physical and mental health of carers in general. Greater health problems among orphan carers appeared to be fully explained by socioeconomic characteristics, which offer opportunities for targeting of programs. More research is needed to understand determinants of mental health disparities among orphan carers, which were not explained by socioeconomic characteristics. PMID:21480009

Education and nutritional status of orphans and children of HIV-infected parents in Kenya.

PubMed

Mishra, Vinod; Arnold, Fred; Otieno, Fredrick; Cross, Anne; Hong, Rathavuth

2007-10-01

We examined whether orphaned and fostered children and children of HIV-infected parents are disadvantaged in schooling, nutrition, and health care. We analyzed data on 2,756 children aged 0-4 years and 4,172 children aged 6-14 years included in the 2003 Kenya Demographic and Health Survey, with linked anonymous HIV testing, using multivariate logistic regression. Results indicate that orphans, fostered children, and children of HIV-infected parents are significantly less likely to attend school than non-orphaned/non-fostered children of HIV-negative parents. Children of HIV-infected parents are more likely to be underweight and wasted, and less likely to receive medical care for ARI and diarrhea. Children of HIV-negative single mothers are also disadvantaged on most indicators. The findings highlight the need to expand child welfare programs to include not only orphans but also fostered children, children of single mothers, and children of HIV-infected parents, who tend to be equally, if not more, disadvantaged.
Children caring for their "caregivers": exploring the caring arrangements in households affected by AIDS in Western Kenya.

PubMed

Skovdal, Morten

2010-01-01

Reflecting dominant understandings of childhood, many researchers describe orphans as an emotional and financial cost to the households in which they live. This has created a representation of orphans as a burden, not only to their fostering household, but also to society. This article seeks to challenge this representation by exploring children's contributions to their fostering households. Drawing on research from Bondo District in Kenya, this article brings together the views of 36 guardians and 69 orphaned children between the ages of 11 and 17, who articulated their circumstances through photography and drawing. Nearly 300 photos and drawings were selected by the children and subsequently described in writing. An additional 44 in-depth interviews and three focus group discussions were conducted to explore findings further. The data suggest that many fostering households benefit tremendously from absorbing orphaned children. All orphans were found to contribute to their fostering household's income and provide valuable care or support to ageing, ailing or young members of their households. The article concludes that caution should be exercised in using the term "caregiver" to describe foster parents due to the reciprocity, and indeed at times a reversal, of caring responsibilities.
Grief-Processing-Based Psychological Intervention for Children Orphaned by AIDS in Central China: A Pilot Study

ERIC Educational Resources Information Center

Lin, Xiuyun; Fang, Xiaoyi; Chi, Peilian; Li, Xiaoming; Chen, Wenrui; Heath, Melissa Allen

2014-01-01

A group of 124 children orphaned by AIDS (COA), who resided in two orphanages funded by the Chinese government, participated in a study investigating the efficacy of a grief-processing-based psychological group intervention. This psychological intervention program was designed to specifically help COA process their grief and reduce their…
Therapeutic Art Practices with Orphan Children in Bulgaria

ERIC Educational Resources Information Center

Ivanova, Alexandra S.

2004-01-01

This paper presents therapeutic art practices carried out with 60 orphan children in the small town of Ugarchin in northern Bulgaria. In 1999, a group of artists and teachers developed a varied program of art activities for these children. These activities included two 1-week visits and the opening of five art workshops--Art History, Ceramics,…
Strategies for Supporting Orphans and Vulnerable Children: An Exploratory Study of an Exemplary Model of Care in Kenya

ERIC Educational Resources Information Center

Mears, Melynda; Singletary, Jon; Rogers, Rob

2011-01-01

This qualitative study explored the extent to which programs in a religiously affiliated agency in Kenya incorporate 12 internationally sanctioned strategies for supporting orphans and vulnerable children in Sub-Saharan Africa (Olson, Knight, & Foster, 2006). The results indicated that all 12 strategies were being employed, though to varying…
The Burden of Orphans and Vulnerable Children Due to HIV/AIDS in Cameroon

PubMed Central

Nsagha, Dickson S; Bissek, Anne-Cécile ZK; Nsagha, Sarah M; Assob, Jules-Clement N; Kamga, Henri-Lucien F; Njamnshi, Dora M; Njunda, Anna L; Obama, Marie-Thérèse O; Njamnshi, Alfred K

2012-01-01

HIV/AIDS is a major public health problem in Cameroon and Africa, and the challenges of orphans and vulnerable children are a threat to child survival, growth and development. The HIV prevalence in Cameroon was estimated at 5.1% in 2010. The objective of this study was to assess the burden of orphans and vulnerable children due to HIV/AIDS in Cameroon. A structured search to identify publications on orphans and other children made vulnerable by AIDS was carried out. A traditional literature search on google, PubMed and Medline using the keywords: orphans, vulnerable children, HIV/AIDS and Cameroon was conducted to identify potential AIDS orphans publications, we included papers on HIV prevalence in Cameroon, institutional versus integrated care of orphans, burden of children orphaned by AIDS and projections, impact of AIDS orphans on Cameroon, AIDS orphans assisted through the integrated care approach, and comparism of the policies of orphans care in the central African sub-region. We also used our participatory approach working experience with traditional rulers, administrative authorities and health stakeholders in Yaounde I and Yaounde VI Councils, Nanga Eboko Health District, Isangelle and Ekondo Titi Health Areas, Bafaka-Balue, PLAN Cameroon, the Pan African Institute for Development-West Africa, Save the orphans Foundation, Ministry of Social Affairs, and the Ministry of Public Health. Results show that only 9% of all OVC in Cameroon are given any form of support. AIDS death continue to rise in Cameroon. In 1995, 7,900 people died from AIDS in the country; and the annual number rose to 25,000 in 2000. Out of 1,200,000 orphans and vulnerable children in Cameroon in 2010, 300,000(25%) were AIDS orphans. Orphans and the number of children orphaned by AIDS has increased dramatically from 13,000 in 1995 to 304,000 in 2010. By 2020, this number is projected to rise to 350,000. These deaths profoundly affect families, which often are split up and left without any means of support. Similarly, the death of many people in their prime working years hamper the economy. Businesses are adversely affected due to the need to recruit and train new staff. Health and social service systems suffer from the loss of health workers, teachers, and other skilled workers. OVC due to HIV/AIDS are a major public health problem in Cameroon as the HIV prevalence continues its relentless increase with 141 new infections per day. In partnership with the Ministry of Social Affairs and other development organizations, the Ministry of Public Health has been striving hard to provide for the educational and medical needs of the OVC, vocational training for the out-of- school OVC and income generating activities for foster families and families headed by children. A continous multi-sectorial approach headed by the government to solve the problem of OVC due to AIDS is very important. In line with the foregoing, recommendations are proposed for the way forward. PMID:23248738
Pressure for drug development in lysosomal storage disorders - a quantitative analysis thirty years beyond the US orphan drug act.

PubMed

Mechler, Konstantin; Mountford, William K; Hoffmann, Georg F; Ries, Markus

2015-04-18

Lysosomal storage disorders are a heterogeneous group of approximately 50 monogenically inherited orphan conditions. A defect leads to the storage of complex molecules in the lysosome, and patients develop a complex multisystemic phenotype of high morbidity often associated with premature death. More than 30 years ago the Orphan Drug Act of 1983 passed the United States legislation intended to facilitate the development of drugs for rare disorders. We directed our efforts in assessing which lysosomal diseases had drug development pressure and what distinguished those with successful development and approvals from diseases not treated or without orphan drug designation. Analysis of the FDA database for orphan drug designations through descriptive and comparative statistics. Between 1983 and 2013, fourteen drugs for seven conditions received FDA approval. Overall, orphan drug status was designated 70 times for 20 conditions. Approved therapies were enzyme replacement therapies (N = 10), substrate reduction therapies (N = 1), small molecules facilitating lysosomal substrate transportation (N = 3). FDA approval was significantly associated with a disease prevalence higher than 0.5/100,000 (p = 0.00742) and clinical development programs that did not require a primary neurological endpoint (p = 0.00059). Orphan drug status was designated for enzymes, modified enzymes, fusion proteins, chemical chaperones, small molecules leading to substrate reduction, or facilitating subcellular substrate transport, stem cells as well as gene therapies. Drug development focused on more common diseases. Primarily neurological diseases were neglected. Small clinical trials with either somatic or biomarker endpoints were successful. Enzyme replacement therapy was the most successful technology. Four factors played a key role in successful orphan drug development or orphan drug designations: 1) prevalence of disease 2) endpoints 3) regulatory precedent, and 4) technology platform. Successful development seeded further innovation.
Access to orphan drugs in the Middle East: Challenge and perspective

PubMed Central

Almalki, Ziyad S.; Alahmari, Abdullah K.; Guo, Jeff J.; Kelton, Christina M.L.

2012-01-01

Summary An orphan drug is a drug developed specifically to treat a rare medical condition. With a combined population of less than 400 million, about 2.8 million patients are estimated to be suffering from a rare disease in the Middle East. Some disorders such as hemoglobinopathy, glucose-6-phosphate dehydrogenase deficiency, autosomal recessive syndromes, and several metabolic disorders have a presence throughout the Middle East. In order to promote the treatment of these diseases, Middle Eastern governments need to facilitate education and training of healthcare personnel; develop and execute a method for obtaining and paying for orphan drugs; and, finally, provide tax, marketing, and other incentives to domestic and international firms to develop drugs specifically for the diseases of most importance to Middle Eastern patients. PMID:25343087
Food security and nutritional outcomes among urban poor orphans in Nairobi, Kenya.

PubMed

Kimani-Murage, Elizabeth W; Holding, Penny A; Fotso, Jean-Christophe; Ezeh, Alex C; Madise, Nyovani J; Kahurani, Elizabeth N; Zulu, Eliya M

2011-06-01

The study examines the relationship between orphanhood status and nutritional status and food security among children living in the rapidly growing and uniquely vulnerable slum settlements in Nairobi, Kenya. The study was conducted between January and June 2007 among children aged 6-14 years, living in informal settlements of Nairobi, Kenya. Anthropometric measurements were taken using standard procedures and z scores generated using the NCHS/WHO reference. Data on food security were collected through separate interviews with children and their caregivers, and used to generate a composite food security score. Multiple regression analysis was done to determine factors related to vulnerability with regards to food security and nutritional outcomes. The results show that orphans were more vulnerable to food insecurity than non-orphans and that paternal orphans were the most vulnerable orphan group. However, these effects were not significant for nutritional status, which measures long-term food deficiencies. The results also show that the most vulnerable children are boys, those living in households with lowest socioeconomic status, with many dependants, and female-headed and headed by adults with low human capital (low education). This study provides useful insights to inform policies and practice to identify target groups and intervention programs to improve the welfare of orphans and vulnerable children living in urban poor communities.
Proposed 'grant-and-access' program with price caps could stimulate development of drugs for very rare diseases.

PubMed

Valverde, Ana M; Reed, Shelby D; Schulman, Kevin A

2012-11-01

The 1983 Orphan Drug Act created incentives for the development of orphan drugs. Despite its successes, including a substantial increase in new drugs, approved orphan drugs still treat fewer than 5 percent of registered rare diseases. In addition, concerns have arisen about the high prices of many of these therapies, which can cost hundreds of thousands of dollars per patient each year. In this article, we propose a new "grant-and-access pathway," in which drug developers could opt to compete for federal grants to subsidize the costs of clinical testing. In return for the grant funding, companies would no longer claim orphan drug tax credits and would agree to price caps for marketed products based on the duration and costs associated with drug development, expected market size, and target rate of return. We identify scenarios in which such a policy could provide a net benefit to society.
Asset Ownership and Health and Mental Health Functioning Among AIDS-Orphaned Adolescents: Findings From a Randomized Clinical Trial in Rural Uganda

PubMed Central

Han, Chang-Keun; Neilands, Torsten B

2010-01-01

This study evaluated an economic empowerment intervention designed to promote life options, health and mental health functioning among AIDS-orphaned adolescents in rural Uganda. The study used an experimental design in which adolescents (N=267) were randomly assigned to receive an economic empowerment intervention or usual care for orphaned children. The study measured mental health functioning using 20 items of the Tennessee Self-Concept Scale (TSCS: 2)—a standardized measure for self-esteem—and measured overall health using a self-rated health measure. Data obtained at 10-month follow-up revealed significant positive effects of the economic empowerment intervention on adolescents’ self-rated health and mental health functioning. Additionally, health and mental health functioning were found to be positively associated with each other. The findings have implications for public policy and health programming for AIDS-orphaned adolescents. PMID:19520472
School performance and school behavior of children affected by AIDS in China

PubMed Central

Tu, Xiaoming; Lv, Yunfei; Li, Xiaoming; Fang, Xiaoyi; Zhao, Guoxiang; Lin, Xiuyun; Hong, Yan; Zhang, Liying; Stanton, Bonita

2009-01-01

It is generally recognized that the AIDS epidemic will have a negative effect on the orphans’ school education. However, few studies have been carried out to examine the school performance and school behavior of AIDS orphans and vulnerable children (children living with HIV-infected parents). Using both self-report and teacher evaluation data of 1625 children from rural central China, we examined the impact of parental HIV/AIDS on children's school performances (academic marks, educational expectation, and student leadership) and school behaviors (e.g., aggression, shy/anxious and assertive social skills). Results indicate that AIDS orphans and vulnerable children had disadvantages in school performances in comparison to their peers from the same community who did not experience AIDS-related death and illness in their family (comparison children). AIDS orphans had the lowest academic marks based on the reports of both children and teachers. Educational expectation was significantly lower among AIDS orphans and vulnerable children than comparison children from teacher's perspective. AIDS orphans were significantly more likely to demonstrate aggressive, impulsive and anxious behaviors than non-orphans. Moreover, orphans have more learning difficulties. Vulnerable children were also at a disadvantage on most measures. The data suggest that a greater attention is needed to the school performance and behavior of children affected by AIDS. The findings also indicate that AIDS relief and assistance program for children should go beyond the school attendance and make efforts to improve their school performance and education aspiration. PMID:20107622
Mapping the extent of thinned continental crust across the Orphan Basin, offshore Newfoundland, Canada, using a combination of vintage and new seismic refraction/wide-angle reflection data

NASA Astrophysics Data System (ADS)

Welford, J. Kim; Dehler, Sonya; Funck, Thomas

2017-04-01

The SIGNAL (Seismic Investigations off Greenland, Newfoundland and Labrador) 2009 cruise was undertaken by the Geological Survey of Canada (GSC) and the Geological Survey of Denmark and Greenland (GEUS), with scientific contributions from Dalhousie University, to collect refraction/wide-angle reflection (RWAR) profiles as part of each country's continental shelf program under UNCLOS (United Nations Convention on the Law of the Sea) Article 76. Line 1 extended from the Bonavista Platform off Newfoundland, across the Orphan Basin, to Orphan Knoll and beyond into oceanic crust. The line followed the same track as an earlier seismic refraction line and ocean-bottom seismometer (OBS) locations were chosen to complement and to extend the original station coverage. The final crustal velocity model across Orphan Basin shows thinned continental crust (15 to 20 km thick) beneath most of the basin with thinner crust (10 km thick) immediately outboard of the Bonavista Platform, interpreted as a failed rift zone. Seaward of the failed rift, the velocity structure of the thinned continental crust is generally uniform over 250 km toward Orphan Knoll. Immediately outboard of Orphan Knoll, the crust thins to 8 km and exhibits a velocity structure consistent with oceanic crust. The results from modelling of the combined refraction/wide-angle reflection dataset support an extension of Canada's continental shelf beyond the seaward limits of the Orphan Basin.
Drug development for exceptionally rare metabolic diseases: challenging but not impossible.

PubMed

Putzeist, Michelle; Mantel-Teeuwisse, Aukje K; Wied, Christine C Gispen-de; Hoes, Arno W; Leufkens, Hubert G M; de Vrueh, Remco L A

2013-11-15

We studied to what extent the level of scientific knowledge on exceptionally rare metabolic inherited diseases and their potential orphan medicinal products is associated with sponsors deciding to apply for an orphan designation at the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA). All metabolic diseases with a genetic cause and prevalence of less than 10 patients per 1 million of the population were selected from the 'Orphanet database of Rare diseases'. The outcome of interest was the application for an orphan designation at FDA or EMA. The level of publicly available knowledge of the disease and drug candidate before an orphan designation application was defined as whether the physiological function corresponding with the pathologic gene and initiation of the pathophysiological pathway was known, whether an appropriate animal study was identified for the disease, whether preclinical proof of concept was ascertained and the availability of data in humans. Other determinants included in the study were metabolic disease class, the prevalence of the disease, prognosis and time of first description of the disease in the literature. Univariate relative risks (RRs) and 95% confidence intervals (CIs) of an orphan designation application were calculated for each of these determinants. In addition, a multivariate Cox regression analysis was conducted (Forward LR). In total, 166 rare metabolic genetic diseases were identified and included in the analysis. For only 42 (25%) of the diseases an orphan designation application was submitted at either FDA or EMA before January 2012. The multivariate analysis identified preclinical proof of concept of a potential medicinal product as major knowledge related determinant associated with an orphan designation application (RRadj 3.9, 95% CI 1.9-8.3) and confirmed that prevalence of the disease is also associated with filing an application for an orphan designation (RRadj 2.8, 95% CI 1.4-5.4). For only one out of four known exceptionally rare metabolic inherited diseases sponsors applied for an orphan designation at FDA or EMA. These applications were found to be associated with the prevalence of the rare disease and the level of available scientific knowledge on the proof of concept linking possible drug candidates to the disease of interest.
The founder of the Friends Foundation--Tessie Soi.

PubMed

Topurua, Ore

2013-01-01

Tessie Soi is well known in Papua New Guinea and beyond for her work with HIV/AIDS (human immunodeficiency virus/acquired immune deficiency syndrome) patients, including through the Friends Foundation, an organization that focuses on helping families affected by HIV and AIDS. This article explores Tessie's early life and childhood, providing insight into some of the values she learned from her parents. Providing details about the Friends Foundation and the Orphan Buddy Systems program, a program Tessie established to support AIDS orphans, the article offers insight into Tessie's beliefs and compassion, simultaneously highlighting the value she places on her family.
Challenges in orphan drug development and regulatory policy in China.

PubMed

Cheng, Alice; Xie, Zhi

2017-01-18

While regulatory policy is well defined for orphan drug development in the United States and Europe, rare disease policy in China is still evolving. Many Chinese patients currently pay out of pocket for international treatments that are not yet approved in China. The lack of a clear definition and therefore regulatory approval process for rare diseases has, until now, de-incentivized pharmaceutical companies to pursue rare disease drug development in China. In turn, many grassroots movements have begun to support rare disease patients and facilitate drug discovery through research. Recently, the Chinese FDA set new regulatory guidelines for drugs being developed in China, including an expedited review process for life-saving treatments. In this review, we discuss the effects of these new policy changes on and suggest potential solutions to innovate orphan drug development in China.
Psychosocial challenges and protective influences for socio-emotional coping of HIV+ adolescents in South Africa: a qualitative investigation.

PubMed

Petersen, I; Bhana, A; Myeza, N; Alicea, S; John, S; Holst, H; McKay, M; Mellins, C

2010-08-01

While the roll-out of antiretroviral therapy in South Africa should lead to a reduction in mother to child transmission, mortality and orphaning, it will also be accompanied by a large number of children entering adolescence and adulthood with a chronic infectious disease. Adolescence is a particularly vulnerable period for HIV-infected people in relation to mental health problems and engagement in high-risk behaviours, including non-compliance with medical treatment. The goal of this qualitative study was to develop an understanding of the psychosocial challenges as well as protective influences promoting socio-emotional coping in HIV+ adolescents in order to inform mental health promotion and HIV prevention programming for this population in South Africa. In-depth qualitative interviews were conducted with HIV+ adolescents (25) and caregivers of HIV+ children (15) at a large HIV/AIDS Clinic in South Africa. Data were analysed thematically using NVivo8 software. Psycho-social challenges for adolescents included dealing with loss of biological parents in the case of orphans; coming to terms with their HIV+ status including identity difficulties; external stigma and discrimination; and disclosure difficulties. For caregivers, disclosure and lack of financial, family and social support emerged as key challenges. Medication, HIV information, a future orientation and social support was identified as important for coping and general well-being of adolescents, with financial and social support emerging as key for promoting supportive caregiving contexts. While HIV+ adolescents in South Africa experience similar concerns to those in high-income countries, socio-emotional coping may be compromised by increased levels of loss due to the late roll-out of ARVS and challenges to caregiving contexts including poverty, stigma and minimally supported foster care arrangements. There is a need for mental health promotion programmes for adolescents to adopt an ecological approach, strengthening protective influences at the individual, interpersonal, community and policy levels.
38 CFR 21.4020 - Two or more programs.

Code of Federal Regulations, 2010 CFR

2010-07-01

...) VOCATIONAL REHABILITATION AND EDUCATION Administration of Educational Assistance Programs General § 21.4020...) Title II of the Veterans' Readjustment Assistance Act of 1952; (3) The War Orphans' Educational...
38 CFR 21.4020 - Two or more programs.

Code of Federal Regulations, 2011 CFR

2011-07-01

...) VOCATIONAL REHABILITATION AND EDUCATION Administration of Educational Assistance Programs General § 21.4020...) Title II of the Veterans' Readjustment Assistance Act of 1952; (3) The War Orphans' Educational...
Neuro-psychopharmacological perspective of Orphan receptors of Rhodopsin (class A) family of G protein-coupled receptors.

PubMed

Khan, Muhammad Zahid; He, Ling

2017-04-01

In the central nervous system (CNS), G protein-coupled receptors (GPCRs) are the most fruitful targets for neuropsychopharmacological drug development. Rhodopsin (class A) is the most studied class of GPCR and includes orphan receptors for which the endogenous ligand is not known or is unclear. Characterization of orphan GPCRs has proven to be challenging, and the production pace of GPCR-based drugs has been incredibly slow. Determination of the functions of these receptors may provide unexpected insight into physiological and neuropathological processes. Advances in various methods and techniques to investigate orphan receptors including in situ hybridization and knockdown/knockout (KD/KO) showed extensive expression of these receptors in the mammalian brain and unmasked their physiological and neuropathological roles. Due to these rapid progress and development, orphan GPCRs are rising as a new and promising class of drug targets for neurodegenerative diseases and psychiatric disorders. This review presents a neuropsychopharmacological perspective of 26 orphan receptors of rhodopsin (class A) family, namely GPR3, GPR6, GPR12, GPR17, GPR26, GPR35, GPR39, GPR48, GPR49, GPR50, GPR52, GPR55, GPR61, GPR62, GPR63, GPR68, GPR75, GPR78, GPR83, GPR84, GPR85, GPR88, GPR153, GPR162, GPR171, and TAAR6. We discussed the expression of these receptors in mammalian brain and their physiological roles. Furthermore, we have briefly highlighted their roles in neurodegenerative diseases and psychiatric disorders including Alzheimer's disease, Parkinson's disease, neuroinflammation, inflammatory pain, bipolar and schizophrenic disorders, epilepsy, anxiety, and depression.

The government of Kenya cash transfer for orphaned and vulnerable children: cross-sectional comparison of household and individual characteristics of those with and without

PubMed Central

2014-01-01

Background The ‘Cash Transfer to Orphans and Vulnerable Children’ (CT-OVC) in Kenya is a government-supported program intended to provide regular and predictable cash transfers (CT) to poor households taking care of OVC. CT programs can be an effective means of alleviating poverty and facilitating the attainment of an adequate standard of living for people’s health and well-being and other international human rights. The objective of this analysis was to compare the household socioeconomic status, school enrolment, nutritional status, and future outlook of orphaned and separated children receiving the CT compared to those not receiving a CT. Methods This project analyzes baseline data from a cohort of orphaned and separated children aged <19 years and non-orphaned children living in 300 randomly selected households (HH) in 8 Locations of Uasin Gishu County, Kenya. Baseline data were analyzed using multivariable logistic and Poisson regression comparing children in CT-HH vs. non-CT HH. Odds ratios are adjusted (AOR) with 95% confidence intervals (CI) for guardian age and sex, child age and sex, and intra-HH correlation. Results Included in this analysis were data from 1481 children and adolescents in 300 HH (503 participants in CT, 978 in non-CT households). Overall there were 922 (62.3%) single orphans, 324 (21.9%) double orphans, and 210 (14.2%) participants had both parents alive and were living with them. Participants in CT-HH were less likely to have ≥2 pairs of clothes compared to non-CT HH (AOR: 0.32, 95% CI: 0.16-0.63). Those in CT HH were less likely to have missed any days of school in the preceding month (AOR: 0.62, 95% CI: 0.42-0.94) and those aged <1-18 years in CT-HH were less likely to have height stunting for their age (AOR: 0.65, 95% CI: 0.47-0.89). Participants aged at least 10 years in CT-HH were more likely to have a positive future outlook (AOR: 1.72, 95% CI: 1.12-2.65). Conclusions Children and adolescents in households receiving the CT-OVC appear to have better nutritional status, school attendance, and optimism about the future, compared to those in households not receiving the CT, in spite of some evidence of continued material deprivation. Consideration should be given to expanding the program further. PMID:25239449
Towards a definition of orphaned and vulnerable children.

PubMed

Skinner, Donald; Tsheko, N; Mtero-Munyati, S; Segwabe, M; Chibatamoto, P; Mfecane, S; Chandiwana, B; Nkomo, N; Tlou, S; Chitiyo, G

2006-11-01

The HIV epidemic presents challenges including orphans and a large mass of children rendered vulnerable by the epidemic and other societal forces. Focus on orphaned and vulnerable children (OVC) is important, but needs accurate definition. Twelve focus group interviews of service providers, leaders in these communities, OVC and their caretakers were conducted at six project sites across Botswana, South Africa and Zimbabwe to extend this definition. The loss of a parent through death or desertion is an important aspect of vulnerability. Additional factors leading to vulnerability included severe chronic illness of a parent or caregiver, poverty, hunger, lack of access to services, inadequate clothing or shelter, overcrowding, deficient caretakers, and factors specific to the child, including disability, direct experience of physical or sexual violence, or severe chronic illness. Important questions raised in this research include the long-term implications for the child and community, and the contribution of culture systems.
Functional profiles of orphan membrane transporters in the life cycle of the malaria parasite

PubMed Central

Kenthirapalan, Sanketha; Waters, Andrew P.; Matuschewski, Kai; Kooij, Taco W. A.

2016-01-01

Assigning function to orphan membrane transport proteins and prioritizing candidates for detailed biochemical characterization remain fundamental challenges and are particularly important for medically relevant pathogens, such as malaria parasites. Here we present a comprehensive genetic analysis of 35 orphan transport proteins of Plasmodium berghei during its life cycle in mice and Anopheles mosquitoes. Six genes, including four candidate aminophospholipid transporters, are refractory to gene deletion, indicative of essential functions. We generate and phenotypically characterize 29 mutant strains with deletions of individual transporter genes. Whereas seven genes appear to be dispensable under the experimental conditions tested, deletion of any of the 22 other genes leads to specific defects in life cycle progression in vivo and/or host transition. Our study provides growing support for a potential link between heavy metal homeostasis and host switching and reveals potential targets for rational design of new intervention strategies against malaria. PMID:26796412
Microeconomic loans and health education to families in impoverished communities: implications for the HIV pandemic.

PubMed

Sherer, Renslow D; Bronson, John D; Teter, Caroline J; Wykoff, Randolph F

2004-01-01

Poverty is among the root causes of death and poor health worldwide. Project HOPE's Village Health Bank (VHB) program is a public health intervention that combines integrated microcredit lending and health education. Groups of 18 to 25 women receive small loans, and biweekly, one-hour health education sessions. Since 1993, about 50,000 women in 949 VHBs have participated in seven countries in the Americas, Africa, and Southeast Asia, receiving more than US$25 million in loans and 8,445 hours of health education. Members of VHBs are charged modest interest rates that enable them to become self-sufficient (eg, able to cover all operating charges, including the costs of the health education staff, and the necessary loan capital to continue without infusion of outside resources). The VHB program produces substantial economic improvements for individuals and groups, and benefits in health knowledge and behaviors, including increased utilization of healthcare services. Data from Guatemala, Malawi, and Thailand demonstrate that VHBs in countries with high HIV prevalence have been comparably successful in spite of the enormous added burdens of chronic illness, deaths, and orphans in need of support. For example, in 2004, 48 percent of 266 VHB members in Malawi experienced at least one death in their household in the preceding year, and 67 percent housed one or more orphans with an average of two orphans per household. Because of the unique combination of increased household economic stability and improved health knowledge, the VHB program is now being adapted to families of people affected by HIV/AIDS, including orphans.
Effects of a Large-Scale Unconditional Cash Transfer Program on Mental Health Outcomes of Young People in Kenya.

PubMed

Kilburn, Kelly; Thirumurthy, Harsha; Halpern, Carolyn Tucker; Pettifor, Audrey; Handa, Sudhanshu

2016-02-01

This study investigates the causal effect of Kenya's unconditional cash transfer program on mental health outcomes of young people. Selected locations in Kenya were randomly assigned to receive unconditional cash transfers in the first phase of Kenya's Cash Transfer Program for orphans and Vulnerable Children. In intervention locations, low-income households and those with orphans and vulnerable childrens began receiving monthly cash transfers of $20 in 2007. In 2011, 4 years after program onset, data were collected on the psychosocial status for youth aged 15-24 years from households in intervention and control locations (N = 1960). The primary outcome variable was an indicator of depressive symptoms using the 10-question Center for Epidemiologic Studies Depression Scale. Secondary outcomes include an indicator for hopefulness and physical health measures. Logistic regression models that adjusted for individual and household characteristics were used to determine the effect of the cash transfer program. The cash transfer reduced the odds of depressive symptoms by 24 percent among young persons living in households that received cash transfers. Further analysis by gender and age revealed that the effects were only significant for young men and were larger among men aged 20-24 years and orphans. This study provides evidence that poverty-targeted unconditional cash transfer programs, can improve the mental health of young people in low-income countries. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
Drug development for exceptionally rare metabolic diseases: challenging but not impossible

PubMed Central

2013-01-01

Background We studied to what extent the level of scientific knowledge on exceptionally rare metabolic inherited diseases and their potential orphan medicinal products is associated with sponsors deciding to apply for an orphan designation at the US Food and Drug Administration (FDA) or the European Medicines Agency (EMA). Methods All metabolic diseases with a genetic cause and prevalence of less than 10 patients per 1 million of the population were selected from the ‘Orphanet database of Rare diseases’. The outcome of interest was the application for an orphan designation at FDA or EMA. The level of publicly available knowledge of the disease and drug candidate before an orphan designation application was defined as whether the physiological function corresponding with the pathologic gene and initiation of the pathophysiological pathway was known, whether an appropriate animal study was identified for the disease, whether preclinical proof of concept was ascertained and the availability of data in humans. Other determinants included in the study were metabolic disease class, the prevalence of the disease, prognosis and time of first description of the disease in the literature. Univariate relative risks (RRs) and 95% confidence intervals (CIs) of an orphan designation application were calculated for each of these determinants. In addition, a multivariate Cox regression analysis was conducted (Forward LR). Results In total, 166 rare metabolic genetic diseases were identified and included in the analysis. For only 42 (25%) of the diseases an orphan designation application was submitted at either FDA or EMA before January 2012. The multivariate analysis identified preclinical proof of concept of a potential medicinal product as major knowledge related determinant associated with an orphan designation application (RRadj 3.9, 95% CI 1.9-8.3) and confirmed that prevalence of the disease is also associated with filing an application for an orphan designation (RRadj 2.8, 95% CI 1.4-5.4). Conclusion For only one out of four known exceptionally rare metabolic inherited diseases sponsors applied for an orphan designation at FDA or EMA. These applications were found to be associated with the prevalence of the rare disease and the level of available scientific knowledge on the proof of concept linking possible drug candidates to the disease of interest. PMID:24237580
Applying a Family-Level Economic Strengthening Intervention to Improve Education and Health-Related Outcomes of School-Going AIDS-Orphaned Children: Lessons from a Randomized Experiment in Southern Uganda.

PubMed

Ssewamala, Fred M; Karimli, Leyla; Torsten, Neilands; Wang, Julia Shu-Huah; Han, Chang-Keun; Ilic, Vilma; Nabunya, Proscovia

2016-01-01

Children comprise the largest proportion of the population in sub-Saharan Africa. Of these, millions are orphaned. Orphanhood increases the likelihood of growing up in poverty, dropping out of school, and becoming infected with HIV. Therefore, programs aimed at securing a healthy developmental trajectory for these orphaned children are desperately needed. We conducted a two-arm cluster-randomized controlled trial to evaluate the effectiveness of a family-level economic strengthening intervention with regard to school attendance, school grades, and self-esteem in AIDS-orphaned adolescents aged 12-16 years from 10 public rural primary schools in southern Uganda. Children were randomly assigned to receive usual care (counseling, school uniforms, school lunch, notebooks, and textbooks), "bolstered" with mentorship from a near-peer (control condition, n = 167), or to receive bolstered usual care plus a family-level economic strengthening intervention in the form of a matched Child Savings Account (Suubi-Maka treatment arm, n = 179). The two groups did not differ at baseline, but 24 months later, children in the Suubi-Maka treatment arm reported significantly better educational outcomes, lower levels of hopelessness, and higher levels of self-concept compared to participants in the control condition. Our study contributes to the ongoing debate on how to address the developmental impacts of the increasing numbers of orphaned and vulnerable children and adolescents in sub-Saharan Africa, especially those affected by HIV/AIDS. Our findings indicate that innovative family-level economic strengthening programs, over and above bolstered usual care that includes psychosocial interventions for young people, may have positive developmental impacts related to education, health, and psychosocial functioning.
Applying a Family-Level Economic Strengthening Intervention to Improve Education and Health-Related Outcomes of School-going AIDS-Orphaned Children: Lessons from a Randomized Experiment in Southern Uganda

PubMed Central

Ssewamala, Fred M.; Leyla, Karimli; Neilands, Torsten; Julia Shu-Huah, Wang; Chang-Keun, Han; Vilma, Ilic; Proscovia, Nabunya

2015-01-01

Children comprise the largest proportion of the population in sub-Saharan Africa. Of these, millions are orphaned. Orphanhood increases the likelihood of growing up in poverty, dropping out of school, and becoming infected with HIV. Therefore, programs aimed at securing a healthy developmental trajectory for these orphaned children are desperately needed. We conducted a two-arm cluster-randomized controlled trial to evaluate the effectiveness of a family-level economic strengthening intervention with regard to school-attendance, school grades, and self-esteem in AIDS-orphaned adolescents aged 12–16 years from 10 public rural primary schools in southern Uganda. Children were randomly assigned to receive usual care (counseling, school uniforms, school lunch, notebooks and textbooks), “bolstered” with mentorship from a near-peer (control condition, n=167), or to receive bolstered usual care plus a family-level economic strengthening intervention in the form of a matched Child Savings Account (Suubi-Maka treatment arm, n = 179). The two groups did not differ at baseline, but 24-months later, children in the Suubi-Maka treatment arm reported significantly better educational outcomes, lower levels of hopelessness, and higher levels of self-concept compared to participants in the control condition. Our study contributes to the ongoing debate on how to address the developmental impacts of the increasing numbers of orphaned, and vulnerable children and adolescents in sub-Saharan Africa, especially those affected by HIV/AIDS. Our findings indicate that innovative family-level economic strengthening programs, over and above bolstered usual care that includes psychosocial interventions for young people, may have positive developmental impacts related to education, health, and psychosocial functioning. PMID:26228480
Orphan Gpr182 suppresses ERK-mediated intestinal proliferation during regeneration and adenoma formation

PubMed Central

Kechele, Daniel O.; Blue, R. Eric; Zwarycz, Bailey; Espenschied, Scott T.; Mah, Amanda T.; Siegel, Marni B.; Perou, Charles M.; Ding, Shengli; Magness, Scott T.; Lund, P. Kay

2017-01-01

Orphan GPCRs provide an opportunity to identify potential pharmacological targets, yet their expression patterns and physiological functions remain challenging to elucidate. Here, we have used a genetically engineered knockin reporter mouse to map the expression pattern of the Gpr182 during development and adulthood. We observed that Gpr182 is expressed at the crypt base throughout the small intestine, where it is enriched in crypt base columnar stem cells, one of the most active stem cell populations in the body. Gpr182 knockdown had no effect on homeostatic intestinal proliferation in vivo, but led to marked increases in proliferation during intestinal regeneration following irradiation-induced injury. In the ApcMin mouse model, which forms spontaneous intestinal adenomas, reductions in Gpr182 led to more adenomas and decreased survival. Loss of Gpr182 enhanced organoid growth efficiency ex vivo in an EGF-dependent manner. Gpr182 reduction led to increased activation of ERK1/2 in basal and challenge models, demonstrating a potential role for this orphan GPCR in regulating the proliferative capacity of the intestine. Importantly, GPR182 expression was profoundly reduced in numerous human carcinomas, including colon adenocarcinoma. Together, these results implicate Gpr182 as a negative regulator of intestinal MAPK signaling–induced proliferation, particularly during regeneration and adenoma formation. PMID:28094771
"We Are Like Orphans": Exploring Narratives of Lao Doctoral Alumni Educated in Sweden

ERIC Educational Resources Information Center

Silfver, Ann-Louise; Berge, Britt-Marie

2016-01-01

In this article, we explore the narratives of 10 doctoral alumni from Lao People's Democratic Republic (PDR) who underwent graduate training in Sweden. The narratives identify challenges encountered by the alumni but more importantly reveal the agency by which these challenges were overcome. The most important strategy was that of collaborative…
78 FR 20665 - Pediatric Device Consortia Grant Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-04-05

... population (neonates, infants, children, and adolescents) includes patients who are 21 years of age or... of the Office of Orphan Products Development (OOPD) Pediatric Device Consortia (PDC) Grant Program. The goal of the PDC Grant Program is to facilitate the development, production, and distribution of...
What HIV programs work for adolescent girls?

PubMed

Hardee, Karen; Gay, Jill; Croce-Galis, Melanie; Afari-Dwamena, Nana Ama

2014-07-01

Adolescent girls face unique challenges in reducing their risk of acquiring HIV because of gender inequalities, but much of HIV programming and evaluation lacks a specific focus on female adolescents. This article, based on a review of 150 studies and evaluations from 2001 to June 2013, reviews evidence on programming for adolescents that is effective for girls or could be adapted to be effective for girls. The evidence suggests specific interventions for adolescent girls across 3 critical areas: (1) an enabling environment, including keeping girls in school, promoting gender equity, strengthening protective legal norms, and reducing gender-based violence; (2) information and service needs, including provision of age-appropriate comprehensive sex education, increasing knowledge about and access to information and services, and expanding harm reduction programs for adolescent girls who inject drugs; and (3) social support, including promoting caring relationships with adults and providing support for adolescent female orphans and vulnerable children. Numerous gaps remain in evidence-based programming for adolescent girls, including a lack of sex- and age-disaggregated data and the fact that many programs are not explicitly designed or evaluated with adolescents in mind. However, evidence reinforces bolstering critical areas such as education, services, and support for adolescent girls. This article contributes to the growing body of literature on HIV and adolescent girls and reviews the vulnerabilities of girls, articulates the challenges of programming, develops a framework for addressing the needs of girls, and reviews the evidence for successful programming for adolescent girls.
Family Contexts and Schooling Disruption among Orphans in Post-Genocide Rwanda

PubMed Central

2014-01-01

This study examines the relationship between orphan status and schooling disruption in post-genocide Rwanda. The results indicate that while non-orphans have more favorable schooling outcomes in two-parent than in single-parent families, the reverse is true among Rwandan orphans. In single-mother households, paternal orphans, i.e. orphans with only a living mother, have better outcomes than their orphan and non-orphan counterparts. In contrast, paternal orphans have worse outcomes than other children in two-parent households, especially in households headed by males. Maternal orphans are more likely to experience schooling disruptions than non-orphans regardless of family structure. The maternal-orphan disadvantage is nevertheless greater in female-headed than in male-headed households. As expected, non-related orphans are more disadvantaged than orphans related to their household heads. However, non-related orphans have a greater disadvantage in two-parent than in single-parent households. The results also suggest that within households, the provision of childcare to children below schooling age is an impediment to orphan’s schooling. These impediments are, however, greater for double-orphans than paternal or maternal orphans. PMID:25035526
Review of 11 national policies for rare diseases in the context of key patient needs.

PubMed

Dharssi, Safiyya; Wong-Rieger, Durhane; Harold, Matthew; Terry, Sharon

2017-03-31

Rare diseases collectively exert a global public health burden in the severity of their manifestations and the total number of people they afflict. For many patients, considerable barriers exist in terms of access to appropriate care, delayed diagnosis and limited or non-existing treatment options. Motivated by these challenges, the rare disease patient community has played a critical role, elevating the patient voice and mobilizing legislation to support the development of programs that address the needs of patients with rare diseases.The US Orphan Drug Act of 1983 served as a key milestone in this journey, providing a roadmap for other countries to introduce and implement similar orphan drug legislation; more recently, the European Union (EU) has gone further to encourage the widespread adoption and implementation of rare disease plans or strategies designed to more adequately address the comprehensive needs of patients with rare diseases. Despite these legislative efforts and the growing contributions of patient advocacy groups in moving forward implementation and adoption of rare disease programs, gaps still exist across the policy landscape for several countries. To gain deeper insights into the challenges and opportunities to address key needs of rare disease patients, it is critical to define the current status of rare disease legislation and policy across a geographically and economically diverse selection of countries. We analyzed the rare disease policy landscape across 11 countries: Germany, France, the United Kingdom, Canada, Bulgaria, Turkey, Argentina, Mexico, Brazil, China, and Taiwan. The status and implementation of policy was evaluated for each country in the context of key patient needs across 5 dimensions: improving coordination of care, diagnostic resources, access to treatments, patient awareness and support, and promoting innovative research. Our findings highlight the continuing role of the patient community in driving the establishment and adoption of legislation and programs to improve rare disease care. Further, we found that while national rare disease plans provide important guidance for improving care, implementation of plans is uneven across countries. More research is needed to demonstrate the effect of specific elements of rare disease plans on patient outcomes.
Using constitutive activity to define appropriate high-throughput screening assays for orphan g protein-coupled receptors.

PubMed

Ngo, Tony; Coleman, James L J; Smith, Nicola J

2015-01-01

Orphan G protein-coupled receptors represent an underexploited resource for drug discovery but pose a considerable challenge for assay development because their cognate G protein signaling pathways are often unknown. In this methodological chapter, we describe the use of constitutive activity, that is, the inherent ability of receptors to couple to their cognate G proteins in the absence of ligand, to inform the development of high-throughput screening assays for a particular orphan receptor. We specifically focus on a two-step process, whereby constitutive G protein coupling is first determined using yeast Gpa1/human G protein chimeras linked to growth and β-galactosidase generation. Coupling selectivity is then confirmed in mammalian cells expressing endogenous G proteins and driving accumulation of transcription factor-fused luciferase reporters specific to each of the classes of G protein. Based on these findings, high-throughput screening campaigns can be performed on the already miniaturized mammalian reporter system.
A Universal Method for Fishing Target Proteins from Mixtures of Biomolecules using Isothermal Titration Calorimetry

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zhou, X.; Sun, Q; Kini, R

2008-01-01

The most challenging tasks in biology include the identification of (1) the orphan receptor for a ligand, (2) the ligand for an orphan receptor protein, and (3) the target protein(s) for a given drug or a lead compound that are critical for the pharmacological or side effects. At present, several approaches are available, including cell- or animal-based assays, affinity labeling, solid-phase binding assays, surface plasmon resonance, and nuclear magnetic resonance. Most of these techniques are not easy to apply when the target protein is unknown and the compound is not amenable to labeling, chemical modification, or immobilization. Here we demonstratemore » a new universal method for fishing orphan target proteins from a complex mixture of biomolecules using isothermal titration calorimetry (ITC) as a tracking tool. We took snake venom, a crude mixture of several hundred proteins/peptides, as a model to demonstrate our proposed ITC method in tracking the isolation and purification of two distinct target proteins, a major component and a minor component. Identities of fished out target proteins were confirmed by amino acid sequencing and inhibition assays. This method has the potential to make a significant advancement in the area of identifying orphan target proteins and inhibitor screening in drug discovery and characterization.« less
African Orphan Crops under Abiotic Stresses: Challenges and Opportunities.

PubMed

Tadele, Zerihun

2018-01-01

A changing climate, a growing world population, and a reduction in arable land devoted to food production are all problems facing the world food security. The development of crops that can yield under uncertain and extreme climatic and soil growing conditions can play a key role in mitigating these problems. Major crops such as maize, rice, and wheat are responsible for a large proportion of global food production but many understudied crops (commonly known as "orphan crops") including millets, cassava, and cowpea feed millions of people in Asia, Africa, and South America and are already adapted to the local environments in which they are grown. The application of modern genetic and genomic tools to the breeding of these crops can provide enormous opportunities for ensuring world food security but is only in its infancy. In this review, the diversity and types of understudied crops will be introduced, and the beneficial traits of these crops as well as their role in the socioeconomics of Africa will be discussed. In addition, the response of orphan crops to diverse types of abiotic stresses is investigated. A review of the current tools and their application to the breeding of enhanced orphan crops will also be described. Finally, few examples of global efforts on tackling major abiotic constraints in Africa are presented.
African Orphan Crops under Abiotic Stresses: Challenges and Opportunities

PubMed Central

2018-01-01

A changing climate, a growing world population, and a reduction in arable land devoted to food production are all problems facing the world food security. The development of crops that can yield under uncertain and extreme climatic and soil growing conditions can play a key role in mitigating these problems. Major crops such as maize, rice, and wheat are responsible for a large proportion of global food production but many understudied crops (commonly known as “orphan crops”) including millets, cassava, and cowpea feed millions of people in Asia, Africa, and South America and are already adapted to the local environments in which they are grown. The application of modern genetic and genomic tools to the breeding of these crops can provide enormous opportunities for ensuring world food security but is only in its infancy. In this review, the diversity and types of understudied crops will be introduced, and the beneficial traits of these crops as well as their role in the socioeconomics of Africa will be discussed. In addition, the response of orphan crops to diverse types of abiotic stresses is investigated. A review of the current tools and their application to the breeding of enhanced orphan crops will also be described. Finally, few examples of global efforts on tackling major abiotic constraints in Africa are presented. PMID:29623231
Prioritization of orphan disease-causing genes using topological feature and GO similarity between proteins in interaction networks.

PubMed

Li, Min; Li, Qi; Ganegoda, Gamage Upeksha; Wang, JianXin; Wu, FangXiang; Pan, Yi

2014-11-01

Identification of disease-causing genes among a large number of candidates is a fundamental challenge in human disease studies. However, it is still time-consuming and laborious to determine the real disease-causing genes by biological experiments. With the advances of the high-throughput techniques, a large number of protein-protein interactions have been produced. Therefore, to address this issue, several methods based on protein interaction network have been proposed. In this paper, we propose a shortest path-based algorithm, named SPranker, to prioritize disease-causing genes in protein interaction networks. Considering the fact that diseases with similar phenotypes are generally caused by functionally related genes, we further propose an improved algorithm SPGOranker by integrating the semantic similarity of GO annotations. SPGOranker not only considers the topological similarity between protein pairs in a protein interaction network but also takes their functional similarity into account. The proposed algorithms SPranker and SPGOranker were applied to 1598 known orphan disease-causing genes from 172 orphan diseases and compared with three state-of-the-art approaches, ICN, VS and RWR. The experimental results show that SPranker and SPGOranker outperform ICN, VS, and RWR for the prioritization of orphan disease-causing genes. Importantly, for the case study of severe combined immunodeficiency, SPranker and SPGOranker predict several novel causal genes.
Aviation-Academic Orphan Looking for a Home.

ERIC Educational Resources Information Center

Smith, Hubert C.

1979-01-01

Aviation programs at many colleges and universities have been viewed by administrators in all sorts of perspectives, from very favorable to complete nuisances. As a result, these programs have ended up being located in a wide variety of academic structures. (Author/RE)

Depressive symptoms among older caregivers raising children impacted by HIV/AIDS in the Omusati Region of Namibia.

PubMed

Kalomo, Eveline; Lee, Kyoung Hag; Besthorn, Fred

2017-12-01

The study of depressive symptoms among caregivers raising HIV/AIDS-orphans is emerging as an important area of research. However, it has not been explored at length in generational and cultural contexts. In this study, the authors explore the role of financial strain, raising a HIV-infected and/or impacted child, and caregiver knowledge on the depressive symptoms of 89-older caregivers raising HIV/AIDS-orphans in Namibia, Africa. In this study, we found elevated levels of depressive symptoms among this population. Using hierarchical regression, a significant positive association between financial strain and depressive symptoms was found. A significant negative association between caring for an HIV-infected orphan and depression was shown. Our work suggests the need for economic assistance programs and psychosocial interventions for older caregivers.
Recovering Radioactive Materials with ORSP Team

ScienceCinema

LANL

2017-12-09

The National Nuclear Security Administration sponsors a program, executed by Los Alamos National Laboratory, to recover radioisotopes used by industry and academia and no longer needed. Called the "Offsite Source Recovery Program (OSRP), it has recovered more than 16,000 orphan sources as of 2008.
An enumeration of orphans and analysis of the problems and wishes of orphans: the case of Kariba, Zimbabwe.

PubMed

Mangoma, Jaqualine; Chimbari, Moses; Dhlomo, Elmon

2008-09-01

In southern Africa, HIV and AIDS accounts for the largest proportion of orphans. Very often the orphaned children become destitute, and young girls in particular become more vulnerable to HIV and AIDS as they try to fend for the rest of the family. This paper reports on the number of orphans in Kariba, Zimbabwe, describing their problems, coping strategies and wishes. The study was carried out in Nyamhunga and Mahombekombe high-density residential areas of Kariba, Zimbabwe. All households in the study area were visited, and a semi-structured questionnaire aimed at enumerating orphans and obtaining information regarding general problems of orphans was administered to heads of households present. In addition, information on the plight, coping strategies and survival wishes of orphans were collected through 15 focus group discussions held with orphans, care givers, community leaders and stakeholders. The prevalence of orphans in Kariba, based on a sample of 3 976 households, was found to be very high (56%) with most of the orphans in the age group 6-12 years. The majority of the orphans were paternal and under maternal care. Over 30% of the orphans of school-going age were not in school, and some young girl orphans became involved in commercial sex work. The survival wish list of the orphans included school fees, accommodation, health care provision, adequate food and income-generating projects. However, suggestions on orphan care and needs given by community members were somewhat divergent from the orphans' wish list, indicating that community interventions may not be sensitive to the wishes of those affected. Although the study did not categorise orphans according to cause of death of parents, there are indications that most of the orphans are accounted for by HIV and AIDS.
Program for Institutionalized Children, 1974-75.

ERIC Educational Resources Information Center

Ramsay, James G.

This program for institutionalized children, funded under the Elementary Secondary Education Act of 1965, involved approximately 2181 children in 35 institutions in the New York City metropolitan area. Children were institutionalized for a variety of reasons: they were orphaned, neglected, dependent, in need of supervision, or emotionally…
Exploring impacts of multi-year, community-based care programs for orphans and vulnerable children: a case study from Kenya.

PubMed

Larson, Bruce A; Wambua, Nancy; Masila, Juliana; Wangai, Susan; Rohr, Julia; Brooks, Mohamad; Bryant, Malcolm

2013-01-01

The Community-Based Care for Orphans and Vulnerable Children (CBCO) program operated in Kenya during 2006-2010. In Eastern Province, the program provided support to approximately 3000 orphans and vulnerable children (OVC) living in 1500 households. A primary focus of the program was to support savings and loan associations composed of OVC caregivers (typically elderly women) to improve household and OVC welfare. Cross-sectional data were collected in 2011 from 1500 randomly selected households from 3 populations: program participants (CBCO group, n=500), households in the same villages as program participants but not in the program (the local-community-group = Group L, n=300), and households living in nearby villages where the program did not operate (the adjacent-community-group, Group A, n=700). Primary welfare outcomes evaluated are household food security, as measured by the Household Food Insecurity Access instrument, and OVC educational attainment. We compared outcomes between the CBCO and the subset of Group L not meeting program eligibility criteria (L-N) to investigate disparities within local communities. We compared outcomes between the CBCO group and the subset of Group A meeting eligibility criteria (A-E) to consider program impact. We compared outcomes between households not eligible for the program in the local and adjacent community groups (L-N and A-N) to consider if the adjacent communities are similar to the local communities. In May-June 2011, at the end of the OVC program, the majority of CBCO households continued to be severely food insecure, with rates similar to other households living in nearby communities. Participation rates in primary school are high, reflecting free primary education. Among the 18-22 year olds who were "children" during the program years, relatively few children completed secondary school across all study groups. Although the CBCO program likely provided useful services and benefits to program participants, disparities continued to exist in food security and educational outcomes between program participants and their non-OVC peers in the local community. Outcomes for CBCO households were similar to those observed for OVC households in adjacent communities.
Exploring impacts of multi-year, community-based care programs for orphans and vulnerable children: A case study from Kenya

PubMed Central

Larson, Bruce A.; Wambua, Nancy; Masila, Juliana; Wangai, Susan; Rohr, Julia; Brooks, Mohamad; Bryant, Malcolm

2013-01-01

The Community-Based Care for Orphans and Vulnerable Children (CBCO) program operated in Kenya during 2006–2010. In Eastern Province, the program provided support to approximately 3000 orphans and vulnerable children (OVC) living in 1500 households. A primary focus of the program was to support savings and loan associations composed of OVC caregivers (typically elderly women) to improve household and OVC welfare. Cross-sectional data were collected in 2011 from 1500 randomly selected households from 3 populations: program participants (CBCO group, n = 500), households in the same villages as program participants but not in the program (the local-community-group = Group L, n = 300), and households living in nearby villages where the program did not operate (the adjacent-community-group, Group A, n = 700). Primary welfare outcomes evaluated are household food security, as measured by the Household Food Insecurity Access instrument, and OVC educational attainment. We compared outcomes between the CBCO and the subset of Group L not meeting program eligibility criteria (L-N) to investigate disparities within local communities. We compared outcomes between the CBCO group and the subset of Group A meeting eligibility criteria (A-E) to consider program impact. We compared outcomes between households not eligible for the program in the local and adjacent community groups (L-N and A-N) to consider if the adjacent communities are similar to the local communities. In May-June 2011, at the end of the OVC program, the majority of CBCO households continued to be severely food insecure, with rates similar to other households living in nearby communities. Participation rates in primary school are high, reflecting free primary education. Among the 18–22 year olds who were “children” during the program years, relatively few children completed secondary school across all study groups. Although the CBCO program likely provided useful services and benefits to program participants, disparities continued to exist in food security and educational outcomes between program participants and their non-OVC peers in the local community. Outcomes for CBCO households were similar to those observed for OVC households in adjacent communities. PMID:23745629
Issues surrounding orphan disease and orphan drug policies in Europe.

PubMed

Denis, Alain; Mergaert, Lut; Fostier, Christel; Cleemput, Irina; Simoens, Steven

2010-01-01

An orphan disease is a disease with a very low prevalence. Although there are 5000-7000 orphan diseases, only 50 orphan drugs (i.e. drugs developed to treat orphan diseases) were marketed in the EU by the end of 2008. In 2000, the EU implemented policies specifically designed to stimulate the development of orphan drugs. While decisions on orphan designation and the marketing authorization of orphan drugs are made at the EU level, decisions on drug reimbursement are made at the member state level. The specific features of orphan diseases and orphan drugs make them a high-priority issue for policy makers. The aim of this article is to identify and discuss several issues surrounding orphan disease and drug policies in Europe. The present system of orphan designation allows for drugs for non-orphan diseases to be designated as orphan drugs. The economic factors underlying orphan designation can be questioned in some cases, as a low prevalence of a certain indication does not equal a low return on investment for the drug across its indications. High-quality evidence about the clinical added value of orphan drugs is rarely available at the time of marketing authorization, due to the low number of patients. A balance must be struck between ethical and economic concerns. To this effect, there is a need to initiate a societal dialogue on this issue, to clarify what society wants and accepts in terms of ethical and economic consequences. The growing budgetary impact of orphan drugs puts pressure on drug expenditure. Indications can be extended for an orphan drug and the total prevalence across indications is not considered. Finally, cooperation needs to be fostered in the EU, particularly through a standardized approach to the creation and use of registries. These issues require further attention from researchers, policy makers, health professionals, patients, pharmaceutical companies and other stakeholders with a view to optimizing orphan disease and drug policies in Europe.
Supporting Adolescent Orphan Girls to Stay in School as HIV Risk Prevention: Evidence From a Randomized Controlled Trial in Zimbabwe

PubMed Central

Cho, Hyunsan; Rusakaniko, Simbarashe; Iritani, Bonita; Mapfumo, John; Halpern, Carolyn

2011-01-01

Objectives. Using a randomized controlled trial in rural eastern Zimbabwe, we tested whether comprehensive support to keep orphan adolescent girls in school could reduce HIV risk. Methods. All orphan girls in grade 6 in 25 primary schools were invited to participate in the study in fall 2007 (n = 329). Primary schools were randomized to condition. All primary schools received a universal daily feeding program; intervention participants received fees, uniforms, and a school-based helper to monitor attendance and resolve problems. We conducted annual surveys and collected additional information on school dropout, marriage, and pregnancy rates. We analyzed data using generalized estimating equations over 3 time points, controlling for school and age at baseline. Results. The intervention reduced school dropout by 82% and marriage by 63% after 2 years. Compared with control participants, the intervention group reported greater school bonding, better future expectations, more equitable gender attitudes, and more concerns about the consequences of sex. Conclusions. We found promising evidence that comprehensive school support may reduce HIV risk for orphan girls. Further study, including assessment of dose response, cost benefit, and HIV and herpes simplex virus 2 biomarker measurement, is warranted. PMID:21493943
FACTORS ASSOCIATED WITH INTERNALISING PROBLEMS IN ORPHANS AND THEIR CAREGIVERS IN RURAL MOZAMBIQUE.

PubMed

Libombo, P; Baker-Henningham, H; Grantham-McGregor, S

2012-01-01

To compare internalising problems reported by orphans and their caregivers with that of non-orphans and their caregivers. Case control study. Cahora-Bassa District of Tete, Mozambique Seventy-six maternal or double orphans (aged 10-14 years) and their caregivers were compared with seventy-four non-orphans and their caregivers living in the same neighbourhood. children were interviewed with a semi-structured questionnaire concerning their internalising problems, family structure, school attendance, daily experiences and perceived problems. The children's primary caregivers were also interviewed concerning their depressive symptoms, available social support, socio-economic conditions and perceived problems. Orphans lived in poorer households than non-orphans and reported more internalising symptoms and more economic and psychosocial disadvantages. Orphan caregivers were more depressed and had less social support than non-orphan caregivers. Child internalising symptoms were independently associated with bullying (B = 8.04, 95% CI: 0.24,15.85), perceived undeserved punishment (B = 11.98, 95% CI: S.98,17.98) and orphan status (B = 33.36, 95% CI: 26.67, 40.05). The effect of punishment was stronger for orphans than non-orphans. Frequency of hunger affected internalising symptoms only in orphans. Caregiver depression was independently associated with low social support (B = -0.35, 95% CI: -0.51, -0.18), few possessions (B = -2.10, 95% CI: -3.42, -0.79) an orphan status (B = 4.54, 95% CI: 3.30, 5.78) and possessions had a stronger effect in orphan caregivers. Quality of housing caused depression only in caregivers of orphans. Both orphans and their caregivers were more depressed than the non-orphans and their caregivers. They were exposed to more economic and psychosocial disadvantages and were more vulnerable to risks.
Pharmaceutical expenditure on drugs for rare diseases in Canada: a historical (2007-13) and prospective (2014-18) MIDAS sales data analysis.

PubMed

Divino, Victoria; DeKoven, Mitch; Kleinrock, Michael; Wade, Rolin L; Kim, Tony; Kaura, Satyin

2016-05-21

Health Canada has defined rare diseases as life-threatening, seriously debilitating, or serious chronic conditions affecting a very small number of patients (~1 in 2,000 persons). An estimated 9 % of Canadians suffer from a rare disease. Drugs treating rare diseases (DRDs) are also known as orphan drugs. While Canada is currently developing an orphan drug framework, in the United States (US), the Orphan Drug Act (ODA) of 1983 established incentives for the development of orphan drugs. This study measured total annual expenditure of orphan drugs in Canada (2007-13) and estimated future (2014-18) orphan drug expenditure. Orphan drugs approved by the US Food and Drug Administration (FDA) in the US were used as a proxy for the orphan drug landscape in Canada. Branded, orphan drugs approved by the FDA between 1983 through 2013 were identified (N = 356 unique products). Only US orphan drugs with the same orphan indication(s) approved in Canada were included in the analysis. Adjustment via an indication factoring was applied to products with both orphan and non-orphan indications using available data sources to isolate orphan-indication sales. The IMS Health MIDAS database of audited biopharmaceutical sales was utilized to measure total orphan drug expenditure, calculated annually from 2007-2013 and evaluated as a proportion of total annual pharmaceutical drug expenditure (adjusted to 2014 CAD). Between 2007 and 2013, expenditure was measured for a final N = 147 orphan drugs. Orphan drug expenditure totaled $610.2 million (M) in 2007 and $1,100.0 M in 2013, representing 3.3- 5.6 % of total Canadian pharmaceutical drug expenditure in 2007-2013, respectively. Future trend analysis suggests orphan drug expenditure will remain under 6 % of total expenditure in 2014-18. While the number of available orphan drugs and associated expenditure increased over time, access remains an issue, and from the perspectives of society and equity, overall spending on orphan drugs is lower relative to the number of patients affected with an orphan disease in Canada. The overall budget impact of orphan drugs is small and fairly stable relative to total pharmaceutical expenditure. Concerns that growth in orphan drug expenditure may lead to unsustainable drug expenditure do not appear to be justified.
Influence of school support on early marriage experiences and health services utilization among young orphaned women in Zimbabwe.

PubMed

Luseno, Winnie Kavulani; Zhang, Lei; Iritani, Bonita J; Hartman, Shane; Rusakaniko, Simbarashe; Hallfors, Denise Dion

2017-03-01

School support programs reduce school dropout, early marriage, and early pregnancy for a majority of young orphaned women. We used a mixed-methods approach to examine why these programs are less effective for a significant minority by exploring their influence on marriage and health services utilization. Participants were from a randomized controlled trial testing school support as HIV prevention. Half as many intervention as control participants had been married; married intervention participants had 1 more year of education compared with married control participants. Receiving school support did not appear to improve health-related factors. Pregnancy was among the most common reasons for marriage across both groups. The greatest benefit of school support appears to be in delaying marriage and pregnancy while increasing educational attainment.
Growing up without parents: socialisation and gender relations in orphaned-child-headed households in rural Zimbabwe.

PubMed

Francis-Chizororo, Monica

2010-01-01

The most distressing consequences of the HIV/AIDS pandemic's impact on children has been the development of child-headed households (CHHs). Child 'only' households challenge notions of the ideal home, family, and 'normal' childhood, as well as undermining international attempts to institute children's rights. The development of these households raises practical questions about how the children will cope without parental guidance during their childhood and how this experience will affect their adulthood. Drawing on ethnographic research with five child heads and their siblings, this article explores how orphaned children living in 'child only' households organise themselves in terms of household domestic and paid work roles, explores the socialisation of children by children and the negotiation of teenage girls' movement. Further, it examines whether the orphaned children are in some way attempting to 'mimic' previously existing family/household gender relations after parental death. The study showed that all members in the CHHs irrespective of age and gender are an integral part of household labour including food production. Although there is masculinisation of domestic chores in boys 'only' households, roles are distributed by age. On the other hand, households with a gender mix tended to follow traditional gender norms. Conflict often arose when boys controlled teenage girls' movement and sexuality. There is a need for further research on CHHs to better understand orphans' experiences, and to inform policy interventions.
Physical and sexual abuse in orphaned compared to non-orphaned children in sub-Saharan Africa: A systematic review and meta-analysis

PubMed Central

Nichols, J.; Embleton, L.; Mwangi, A.; Morantz, G.; Vreeman, R.; Ayaya, S.; Ayuku, D.; Braitstein, P.

2013-01-01

This systematic review assessed the quantitative literature to determine whether orphans are more likely to experience physical and/or sexual abuse compared to non-orphans in sub-Saharan Africa (SSA). It also evaluated the quality of evidence and identified research gaps. Our search identified 10 studies, all published after 2005, from Zimbabwe, South Africa, Kenya and Uganda. The studies consisted of a total 17,336 participants (51% female and 58% non-orphans). Of those classified as orphans (n = 7,315), 73% were single orphans, and 27% were double orphans. The majority of single orphans were paternal orphans (74%). Quality assessment revealed significant variability in the quality of the studies, although most scored higher for general design than dimensions specific to the domain of orphans and abuse. Combined estimates of data suggested that, compared to non-orphans, orphans are not more likely to experience physical abuse (combined OR = 0.96, 95% CI [0.79, 1.16]) or sexual abuse (combined OR = 1.25, 95% CI [0.88, 1.78]). These data suggest that orphans are not systematically at higher risk of experiencing physical or sexual abuse compared to non-orphans in sub-Saharan Africa. However, because of inconsistent quality of data and reporting, these findings should be interpreted with caution. Several recommendations are made for improving data quality and reporting consistency on this important issue. PMID:24210283
Early social deprivation negatively affects social skill acquisition in chimpanzees (Pan troglodytes).

PubMed

van Leeuwen, Edwin J C; Mulenga, Innocent Chitalu; Chidester, Diana Lisensky

2014-03-01

In a highly social species like chimpanzees, the process by which individuals become attuned to their social environment may be of vital importance to their chances of survival. Typically, this socialization process, defined by all acquisition experiences and fine-tuning efforts of social interaction patterns during ontogeny, occurs in large part through parental investment. In this study, we investigated whether maternal presence enhances the socialization process in chimpanzees by comparing the social interactions of orphaned and mother-reared individuals at the Chimfunshi Wildlife Orphanage Trust in Zambia. As response variables, we selected social interactions during which an elaborate level of fine-tuning is assumed to be necessary for sustaining the interaction and preventing escalation: social play. Comparing orphaned (n = 8) to sex- and age-matched mother-reared juvenile chimpanzees (n = 9), we hypothesized that the orphaned juveniles would play less frequently than the mother-reared and would be less equipped for fine-tuning social play (which we assayed by rates of aggression) because of the lack of a safe and facilitating social environment provided by the mother. First, contrary to our hypothesis, results showed that the orphaned juveniles engaged in social play more frequently than the mother-reared juveniles, although for significantly shorter amounts of time. Second, in support of our hypothesis, results showed that social play of the orphaned juveniles more often resulted in aggression than social play of the mother-reared juveniles. In conjunction, these results may indicate that, just like in humans, chimpanzee mothers provide their offspring with adequate social skills that might be of pivotal importance for future challenges like successful group-living and securing competitive fitness advantages.
Comparative analysis of the scope of European Union paediatric investigation plans with corresponding orphan designations.

PubMed

Ecker, Andrea; Mariz, Segundo; Naumann-Winter, Frauke; Norga, Koenraad; Barisic, Ingeborg; Girard, Thomas; Tomasi, Paolo; Mentzer, Dirk; Sepodes, Bruno

2018-05-01

Market forces may not be sufficient to stimulate research and development of medicines for small patient populations, such as children and patients with rare diseases. Both the European Union Orphan and Paediatric Regulations were introduced to address the unmet public health needs of these smaller patient populations through the use of incentives, rewards and obligations. Developers for new medicines for rare diseases must agree a paediatric investigation plan (PIP) or waiver with the European Medicines Agency's (EMA) Paediatric Committee (PDCO), and can also apply for an orphan designation (OD) from the EMA's Committee of Orphan Medicinal Products (COMP). The scope of both the OD and the PIP (or waiver) is defined by the agreed condition. The aim of this study was to analyse the approach of PDCO and COMP in defining the appropriate condition for a PIP or OD, respectively, in order to investigate potential challenges in the paediatric development of orphan medicines which have to meet the requirements of both legislations. A comparative analysis of PIP conditions and OD conditions was performed for medicines that have been reviewed by both Committees. We found that in the substantial majority of cases there is no divergence between the conclusions of COMP and PDCO with regard to the condition for which a medicine is to be developed. These findings demonstrate that a collaborative approach allows both Regulations to work synergistically to foster pharmaceutical development for rare diseases in childhood. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2018. All rights reserved. No commercial use is permitted unless otherwise expressly granted.
The use of rites of passage in strengthening the psychosocial wellbeing of orphaned children in Botswana.

PubMed

Thamuku, Masego; Daniel, Marguerite

2012-10-01

Children who have been bereaved in the context of AIDS may experience many challenges to their psychosocial wellbeing. Programmes to help orphaned children are usually anchored in child rights. As the individual focus of rights-based approaches is inept in African collectivist culture, NGOs tend to make use of group approaches in psychosocial support programmes. One orphan-strengthening programme in Botswana, called the Ark for Children, uses rites of passage and rites of affirmation as part of a therapeutic retreat. This study explored how rites of passage and rites of affirmation contribute to psychosocial strengthening of orphaned children in Botswana. Ten orphaned children were involved in five rounds of data collection during a 16-day therapeutic retreat; and eight social workers answered questions on the effectiveness of the therapy. A supplementary document analysis was also completed, which included retreat reports since 2001 and correspondence from community-based support workers and graduates of the programme. Participants reported that the rites used during the retreat helped them to commit to therapeutic transformation. During a retreat, all the participants witness and support each individual going through each rite - a process reported to foster and strengthen group formation. It was documented that the symbols used as part of the themed rites of affirmation are used by participants for years afterwards as reminders of their transformation and commitment to the group. We conclude that rites of passage can provide a powerful tool to help children commit to therapeutic transformation, build the supportive group, and enable the community to recognise and affirm that the children return as changed individuals and members of the group.
Dealing with Uncertainty and Accounting for Social Value Judgments in Assessments of Orphan Drugs: Evidence from Four European Countries.

PubMed

Nicod, Elena; Berg Brigham, Karen; Durand-Zaleski, Isabelle; Kanavos, Panos

To better understand the reasons for differences in reimbursement decisions for orphan drugs in four European countries that were not readily apparent from health technology assessment (HTA) reports and operating procedures. Semistructured interviews with representatives of HTA bodies in England, Scotland, Sweden, and France were conducted. An interview topic guide was developed on the basis of findings from a systematic comparison of HTA decisions for 10 orphan drugs. Qualitative thematic data analysis was applied to the interview transcripts using the framework approach. Eight representatives from the four HTA bodies were interviewed between March and June 2015. Evidentiary requirements and approaches to dealing with imperfect or incomplete evidence were explored, including trial design and duration, study population and subgroups, comparators, and end points. Interviewees agreed that decisions regarding orphan drugs are made in a context of lower quality evidence, and the threshold of acceptable uncertainty varied by country. Some countries imposed higher evidentiary standards for greater clinical claims, which may be more challenging for orphan diseases. The acceptability of surrogate end points was not consistent across countries nor were the validation requirements. The most common social value judgments identified related to innovation, disease severity, and unmet need. Differences were seen in the way these concepts were defined and accounted for across countries. Although agreement was seen in evidentiary requirements or preferences, there were subtle differences in the circumstances in which uncertain evidence may be considered acceptable, possibly explaining differences in HTA recommendations across countries. Copyright © 2017 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
The US Orphan Drug Act: rare disease research stimulator or commercial opportunity?

PubMed

Wellman-Labadie, Olivier; Zhou, Youwen

2010-05-01

This study investigates issues associated with the United States Orphan Drug Act. A comprehensive orphan drug database was compiled from FDA data and corporate annual reports of major pharmaceutical companies. Analysis allowed the generation of a descriptive orphan drug portrait as well as documentation of orphan drugs along their lifecycle. Currently, 2002 products have obtained orphan drug designation with 352 drugs obtaining FDA approval. Approximately 33% of orphan drugs are oncology products. On average, products obtain 1.7 orphan designations with approximately 70% obtaining a single designation. At least 9% of orphan drugs have reached blockbuster status with two-thirds having two or more designations. An additional 25 orphan drugs had sales exceeding US$ 100 million in 2008 alone. Since 1983, at least 14 previously discontinued products have been recycled as orphan drugs. The United States Orphan Drug Act has created issues which, in some cases, have led to commercial and ethical abuses. Orphan Drug Act reform is necessary but current incentives, including 7 year market exclusivity, should be maintained in order to favour patients as well as economic prosperity. Suggested reforms include price regulation, subsidy paybacks for profitable drugs and the establishment of an International Orphan Drug Office. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.
Persisting mental health problems among AIDS-orphaned children in South Africa.

PubMed

Cluver, Lucie D; Orkin, Mark; Gardner, Frances; Boyes, Mark E

2012-04-01

By 2008, 12 million children in sub-Saharan Africa were orphaned by AIDS. Cross-sectional studies show psychological problems for AIDS-orphaned children, but until now no longitudinal study has explored enduring psychological effects of AIDS-orphanhood in the developing world. A 4-year longitudinal follow-up of AIDS-orphaned children with control groups of other-orphans and non-orphans. 1021 children (M = 13.4 years, 50% female, 98% isiXhosa-speaking) were interviewed in 2005 and followed up in 2009 with 71% retention (49% female, M = 16.9 years), in poor urban South African settlements. Children were interviewed using sociodemographic questionnaires and well-validated standardised scales for assessing depression, anxiety, and post-traumatic stress. Data were analysed using mixed-design ANOVA and backward-stepping regression. AIDS-orphaned children showed higher depression, anxiety, and post-traumatic stress disorder (PTSD) scores in both 2005 and 2009 when compared with other-orphans and non-orphans. Backward-stepping regression, controlling for baseline mental health, and sociodemographic cofactors such as age, gender, and type of bereavement, revealed that being AIDS-orphaned in 2005 was associated with depression, anxiety, and PTSD scores in 2009. This was not the case for other-orphaned or non-orphaned children. Age interacted with orphan status, such that there was a steep rise in psychological distress in the AIDS-orphaned group, but no rise with age amongst other-orphans and non-orphans. Negative mental health outcomes amongst AIDS-orphaned children are maintained and worsen over a 4-year period. It is important that psychosocial support programmes are sustained, and focus on youth as well as young children. © 2011 The Authors. Journal of Child Psychology and Psychiatry © 2011 Association for Child and Adolescent Mental Health.
Insurance Companies’ Perspectives on the Orphan Drug Pipeline

PubMed Central

Handfield, Robert; Feldstein, Josh

2013-01-01

Background Rare diseases are of increasing concern to private and public healthcare insurance plans. Largely neglected by manufacturers before the 1983 passing of the Orphan Drug Act (ODA), orphan drugs have become a commercialization target of steadily increasing importance to the healthcare industry. The ODA mandates the coverage of rare diseases, which are defined in research communities as diseases that are so infrequent that there is no reasonable expectation of a drugmaker recovering the cost of developing that drug. Objectives To determine the views of leading commercial US payers regarding providing access to and coverage for orphan drugs; to assess whether and to what degree cost-effectiveness analysis (CEA) is viewed by payers as relevant to rare disease coverage. Methods The study sample was identified through a call for action sent by America's Health Insurance Plans to its members, resulting in 4 interviews conducted and 3 completed surveys from a total of 7 companies. These 7 US health insurance companies represent approximately 75% of the US private insurance market by revenue and include approximately 157 million covered lives (using self-reported data from insurance companies). Representatives of 3 companies responded to the survey, and representatives of 4 companies were interviewed via the phone. The interviews were conducted with subject matter experts at each company and included 2 senior vice presidents of a pharmacy program, 1 chief medical director, and 1 head of pharmacoeconomics. The surveys were completed by 1 vice president of clinical pharmacy strategy, 1 chief pharmacy director, and 1 medical director. Results Based on the responses in this study, approximately 67% of US private insurance companies are concerned about orphan drugs, but only approximately 17% have developed meaningful strategies for addressing the cost of orphan drugs. Of the companies who do have such a strategy, 100% are unsure how to determine the best economic assessment tools to control orphan drug costs, and two thirds are relying on prior authorization as a means to control costs. More than 80% of the companies are not using cost-effectiveness methodologies with regard to rare diseases, generally because of a lack of the availability of medicines to facilitate such comparisons. CEA is used by less than 20% of our study sample of payers in dealing with orphan drug policies. Conclusions Evaluating cost-effectiveness is a valuable strategy for payers seeking to facilitate appropriate access and coverage decision-making related to orphan drugs, but it is not well understood or adapted by private insurance companies. Health economists, along with providers and payers, must work together to design rational methodologies to evaluate the value of orphan drugs, perhaps by adopting cost-effectiveness methodologies to consider a compound's total research and development and commercialization demands relative to its cost-effectiveness. PMID:24991385

Insurance companies' perspectives on the orphan drug pipeline.

PubMed

Handfield, Robert; Feldstein, Josh

2013-11-01

Rare diseases are of increasing concern to private and public healthcare insurance plans. Largely neglected by manufacturers before the 1983 passing of the Orphan Drug Act (ODA), orphan drugs have become a commercialization target of steadily increasing importance to the healthcare industry. The ODA mandates the coverage of rare diseases, which are defined in research communities as diseases that are so infrequent that there is no reasonable expectation of a drugmaker recovering the cost of developing that drug. To determine the views of leading commercial US payers regarding providing access to and coverage for orphan drugs; to assess whether and to what degree cost-effectiveness analysis (CEA) is viewed by payers as relevant to rare disease coverage. The study sample was identified through a call for action sent by America's Health Insurance Plans to its members, resulting in 4 interviews conducted and 3 completed surveys from a total of 7 companies. These 7 US health insurance companies represent approximately 75% of the US private insurance market by revenue and include approximately 157 million covered lives (using self-reported data from insurance companies). Representatives of 3 companies responded to the survey, and representatives of 4 companies were interviewed via the phone. The interviews were conducted with subject matter experts at each company and included 2 senior vice presidents of a pharmacy program, 1 chief medical director, and 1 head of pharmacoeconomics. The surveys were completed by 1 vice president of clinical pharmacy strategy, 1 chief pharmacy director, and 1 medical director. Based on the responses in this study, approximately 67% of US private insurance companies are concerned about orphan drugs, but only approximately 17% have developed meaningful strategies for addressing the cost of orphan drugs. Of the companies who do have such a strategy, 100% are unsure how to determine the best economic assessment tools to control orphan drug costs, and two thirds are relying on prior authorization as a means to control costs. More than 80% of the companies are not using cost-effectiveness methodologies with regard to rare diseases, generally because of a lack of the availability of medicines to facilitate such comparisons. CEA is used by less than 20% of our study sample of payers in dealing with orphan drug policies. Evaluating cost-effectiveness is a valuable strategy for payers seeking to facilitate appropriate access and coverage decision-making related to orphan drugs, but it is not well understood or adapted by private insurance companies. Health economists, along with providers and payers, must work together to design rational methodologies to evaluate the value of orphan drugs, perhaps by adopting cost-effectiveness methodologies to consider a compound's total research and development and commercialization demands relative to its cost-effectiveness.
HTA programme response to the challenges of dealing with orphan medicinal products: Process evaluation in selected European countries.

PubMed

Nicod, Elena; Annemans, Lieven; Bucsics, Anna; Lee, Anne; Upadhyaya, Sheela; Facey, Karen

2017-03-28

Challenges commonly encountered in HTA of orphan medicinal products (OMPs) were identified in Advance-HTA. Since then, new initiatives have been developed to specifically address issues related to HTA of OMPs. This study aimed to understand why these new HTA initiatives in England, Scotland and at European-level were established and whether they resolve the challenges of OMPs. The work of Advance-HTA was updated with a literature review and a conceptual framework of clinical, regulatory and economic challenges for OMPs was developed. The new HTA programmes were critiqued against the conceptual framework and outstanding challenges identified. The new programmes in England and Scotland recognise the challenges identified in demonstrating the value of ultra-OMPs (and OMPs) and that they require a different process to standard HTA approaches. Wider considerations of disease and treatment experiences from a multi-stakeholder standpoint are needed, combined with other measures to deal with uncertainty (e.g. managed entry agreements). While approaches to assessing this new view of value of OMPs, extending beyond cost/QALY frameworks, differ, their criteria are similar. These are complemented by a European initiative that fosters multi-stakeholder dialogue and consensus about value determinants throughout the life-cycle of an OMP. New HTA programmes specific to OMPs have been developed but questions remain about whether they sufficiently capture value and manage uncertainty in clinical practice. Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.
Outcome of anti-retroviral treatment in HIV-infected orphans and non-orphans at an ART centre in North India.

PubMed

Bhattacharya, Malobika; Saxena, Romit

2012-01-01

Few Indian studies have reported the long-term efficacy of anti-retroviral treatment (ART) in children and in orphaned, HIV-infected children in particular. To study differences in outcome of ART in HIV-infected orphans compared with non-orphans. A retrospective study of 87 HIV-infected children who commenced ART in the period January 2006 to August 2007. The main measures were orphan status, absolute CD4 count and weight-for-height (WHZ) and height-for-age (HAZ) Z-scores. Median follow-up was 33 months. Forty (45·9%) children were orphaned. Orphans and non-orphans had similar baseline median WHZ and HAZ (-2·48 vs -2·63, P = 0·65 and -2·78 vs -2·91, P = 0·77, respectively). The two groups were similar in terms of WHO clinical stage and frequency of severe immunosuppression at presentation (P = 0·88 and 0·25, respectively). After ART initiation, the median absolute CD4 count increased progressively in both groups. Median WHZ and HAZ increased throughout the study period in the orphans and reached -1 at 27 and 39 months of ART, respectively. In the non-orphans, WHZ remained below that of the orphan group, the difference becoming statistically significant from 18 months of ART. The increment in HAZ in the non-orphan group was at par with the orphan group until 12 months of follow-up, after which it fell between 18 and 30 months. Subsequently, HAZ rose but remained below that of the orphan group. Both WHZ and HAZ failed to reach -1 in the non-orphan group. In both groups, 85% reported 100% adherence to ART. The outcome of ART is not affected by orphan status with the extended family adequately supporting orphaned children. Growth of children whose parents are HIV-infected may be constrained despite ART if there is inadequate family support.
The correlation between HTA recommendations and reimbursement status of orphan drugs in Europe.

PubMed

Kawalec, Paweł; Sagan, Anna; Pilc, Andrzej

2016-09-06

The aim of this study was to review and compare types of reimbursement recommendations for orphan drugs issued by eight European health technology assessment (HTA) agencies and the reimbursement status of these drugs in the corresponding countries. Separate calculations were also performed for three sub-groups: ultra-orphan drugs, oncology orphan drugs and other (non-ultra, non-oncology) orphan drugs. We reviewed drugs authorized by the European Medicine Agency (EMA) between 1 November 2002 and 30 September 2015. Among these, we identified 101 orphan drugs. Seventy-nine of them were assessed by eight European HTA agencies. The average rates of positive, conditional and negative reimbursement recommendations issued by these agencies were 55.7 %, 15.3 % and 29.0 %, respectively. On average, 21.2 % of EMA-authorized orphan drugs were reimbursed in the eight European countries studied: 49.0 % of those with positive, 53.6 % of those with conditional, and 16.0 % of those with negative reimbursement recommendations. In addition, 5.4 % of orphan drugs that had not been assessed by any of the eight HTA agencies were also reimbursed. The shares of oncology, ultra, and other orphan drugs that were assessed by HTA agencies were similar, with the lowest share observed in ultra-orphan drugs (72 %) and the highest in other orphan drugs (80 %). In terms of reimbursement, 20 % of oncology orphan drugs, 25 % of ultra-orphan drugs and 21 % of other orphan drugs were reimbursed. Reimbursement of orphan drugs does not always correspond to the type of HTA recommendation. While the highest rate of reimbursement is observed (unsurprisingly) among drugs with positive or conditional recommendation, a high rate of reimbursement (11 %) is also observed among ultra-orphan drugs that had never been assessed by any HTA agency.
Shining a light in the black box of orphan drug pricing

PubMed Central

2014-01-01

Background The pricing mechanism of orphan drugs appears arbitrary and has been referred to as a “black box”. Therefore, the aim of this study is to investigate how drug- and disease-specific variables relate to orphan drug prices. Additionally, we aim to explore if certain country-specific pricing and reimbursement policies affect the price level of orphan drugs. Methods Annual treatment costs per indication per patient were calculated for 59 orphan drugs with a publicly available price in Belgium, the Netherlands, Czech Republic, France, Italy and the United Kingdom. A multiple linear regression model was built with 14 drug- and disease-specific variables. A Mann-Whitney U test was used to explore whether there is a correlation between annual treatment costs of orphan drugs across countries with different pricing and reimbursement policies. Results Repurposed orphan drugs, orally administered orphan drugs or orphan drugs for which an alternative treatment is available are associated with lower annual treatment costs. Orphan drugs with multiple orphan indications, for chronic treatments or for which an improvement in overall survival or quality-of-life has been demonstrated, are associated with higher annual treatment costs. No association was found between annual treatments cost of orphan drugs across countries and the different pricing and reimbursement systems. Conclusions This study has shown that prices of orphan drugs are influenced by factors such as the availability of an alternative drug treatment, repurposing, etc. Current debate about the affordability of orphan drugs highlights the need for more transparency in orphan drug price setting. PMID:24767472
EU orphan regulation--ten years of application.

PubMed

Michaux, Geneviève

2010-01-01

In April 2000, European Regulation (EC) No 141/2000 on Orphan Medicinal Products, which, following the U.S. example, had been adopted to boost the research, development, and marketing of medicinal products for rare diseases, became effective. Ten years later, figures prove that, with an average of more than 70 orphan designations per year, the European orphan regulation is a success. To date, the key issue is no longer research and development but effective market access. Less than 10% of the orphan designated products are approved for marketing and even less products are actually placed on the European national markets due to pricing and reimbursement obstacles. The article examines the European orphan regime, focusing on its two cornerstones--orphan designation and exclusivity--and highlighting the concepts that are still unclear and the issues that have not yet been addressed. The European Orphan Regulation has been proved to work well, but it would be even more successful if orphan designation was easier and orphan incentives were more attractive. The article concludes on the changes to be made to the European orphan legal regime that would encourage even more the research and development of orphan products.
Neglect and perceived stigmatization impact psychological distress of orphans in Tanzania.

PubMed

Hermenau, Katharin; Eggert, Ina; Landolt, Markus A; Hecker, Tobias

2015-01-01

Research has shown that orphans in sub-Saharan Africa are at increased risk for mental health problems. Exposure to maltreatment and HIV/AIDS-related stigmatization are related to orphans' psychological distress. Yet, researchers stress the need for more research in low-income countries to identify which factors of being an orphan may lead to psychological distress. The present study aims to systematically investigate orphans' experiences of maltreatment and stigmatization to identify factors that relate to their psychological distress. In total, 89 Tanzanian children who had lost at least one parent were compared to 89 matched non-orphans (mean age: 11 years; 51% boys). We measured exposure to maltreatment and perceived stigmatization as an orphan. Mental health was assessed using the Strengths and Difficulties Questionnaire, the Children's Depression Inventory, the UCLA PTSD Index for Children, and the Reactive-Proactive Questionnaire. Orphans reported significantly more experiences of neglect, but not of abuse. A group comparison revealed more depressive symptoms, posttraumatic stress symptoms, and aggressive behavior among orphans. Neglect, abuse, and stigmatization correlated with orphans' internalizing and externalizing problems, yet only neglect and stigmatization were related to orphans' depression severity. Perceived stigmatization moderated the relationship between neglect and depression. Our findings suggest that orphans in Tanzania are at increased risk of experiencing neglect. Maltreatment and perceived stigmatization may play a role in orphans' psychological distress. Culturally appropriate and evidence-based interventions may help to prevent maltreatment and stigmatization of orphans.
Influence of school support on early marriage experiences and health services utilization among young orphaned women in Zimbabwe

PubMed Central

Luseno, Winnie K.; Zhang, Lei; Iritani, Bonita J.; Hartman, Shane; Rusakaniko, Simbarashe; Hallfors, Denise Dion

2017-01-01

School support programs reduce school dropout, early marriage and early pregnancy for a majority of young orphaned women. We used a mixed methods approach to examine why these programs are less effective for a significant minority by exploring their influence on marriage and health services utilization. Participants were from a randomized controlled trial (RCT) testing school support as HIV prevention. Half as many intervention as control participants had been married; married intervention participants had one more year of education compared to married control participants. Receiving school support did not appear to improve health-related factors. Pregnancy was among the most common reasons for marriage across both groups. The greatest benefit of school support appears to be in delaying marriage and pregnancy while increasing educational attainment. PMID:27211856
The use of the United States FDA programs as a strategy to advance the development of drug products for neglected tropical diseases.

PubMed

Sachs-Barrable, Kristina; Conway, Jocelyn; Gershkovich, Pavel; Ibrahim, Fady; Wasan, Kishor M

2014-11-01

Neglected tropical diseases (NTDs) are infections which are endemic in poor populations in lower- and middle-income countries (LMIC). Approximately one billion people have now or are at risk of getting an NTD and yet less than 5% of research dollars are focused on providing treatments and prevention of these highly debilitating and deadly conditions. The United States Food and Drug Administration (FDA) Orphan Drug Designation program (ODDP) provides orphan status to drugs and biologics, defined as those intended for the safe and effective treatment, diagnosis or prevention of rare diseases and/or disorders that affect fewer than 200 000 people in the United States, or that affect more than 200 000 persons but are not expected to recover the costs of developing and marketing a treatment drug. These regulations have led to the translation of rare disease knowledge into innovative rare disease therapies. The FDA Guidance for Industry on developing drugs for the treatment and prevention of NTDs describes the following regulatory strategies: Orphan Product Designation, Fast Track Designation, Priority Review Designation, Accelerated Approval and Tropical Disease Priority Review Voucher. This paper will discuss how these regulations and especially the ODDP can improve the clinical development and accessibility of drug products for NTDs.
Depression among AIDS-orphaned children higher than among other orphaned children in southern India

PubMed Central

2014-01-01

Background Systematic data on mental health issues among orphaned children are not readily available in India. This study explored depression and its associated risk factors among orphaned children in Hyderabad city in south India. Methods 400 orphaned children drawn equally from AIDS and non-AIDS orphan groups aged 12–16 years residing in orphanages in and around Hyderabad city in southern India were recruited to assess depression and associated risk factors using the Center for Epidemiologic Studies-Depression Scale (CES-DC). Variation in the intensity of depression was assessed using multiple classification analysis (MCA). Results 397 (99%) orphans provided complete interviews in the study of whom 306 (76.5%) were aged 12 to 14 years, and 206 (51.8%) were paternal orphans. Children orphaned by AIDS were significantly more likely to report being bullied by friends or relatives (50.3%) and report experiencing discrimination (12.6%) than those orphaned due to other reasons (p < 0.001). The overall prevalence of depression score >15 with CES-DC was 74.1% (95% CI 69.7-78.4) with this being significantly higher for children orphaned by AIDS (84.4%, 95% CI 79.4 – 89.5) than those due to other reasons (63.6%, 95% CI 56.9 – 70.4). Mean depression score was significantly higher for children orphaned by AIDS (34.6) than the other group (20.6; p < 0.001). Among the children orphaned by AIDS, the bulk of depression score was clustered in 12–14 years age groups whereas in the children orphaned by other reasons it was clustered in the 15–16 years age group (p = 0.001). MCA analysis showed being a child orphaned by AIDS had the highest effect on the intensity of depression (Beta = 0.473). Conclusions Children orphaned by AIDS had significantly higher depressive symptoms than the other orphaned children. These findings could be used for further planning of mental health interventions to meet the mental health needs of orphaned children, that could include preventive, diagnostic and treatment services. PMID:24708649
Anatomy of the Orphan Stream using RR Lyrae Stars

NASA Astrophysics Data System (ADS)

Hendel, David; Johnston, Kathryn; Scowcroft, Victoria; SMHASH

2018-01-01

Stellar tidal streams provide an opportunity to study the motion and structure of the disrupting galaxy as well as the gravitational potential of its host. Streams around the Milky Way are especially promising as new datasets make additional phase space dimensions available as constraints. We present observations of 32 stars thought to be RR Lyrae in the Orphan tidal stream as part of the {\\it Spitzer} Merger History and Shape of the Galactic Halo (SMHASH) program. The extremely tight correlation between the periods, luminosities, and metallicities of RR Lyrae variable stars in the {\\it Spitzer} IRAC $3.6\\mu$m band allows the determination of precise distances to individual stars; the median statistical distance uncertainty in this sample is $2.5\\%$. By fitting orbits in an example potential we obtain an upper limit on the mass of the Milky Way interior to 60 kpc of $\\mathrm{3.9_{-0.8}^{+1.2}\\times 10^{11} M_\\odot}$, bringing estimates based on the Orphan stream in line with those using other tracers. The SMHASH data also resolves the stream in line-of-sight depth, allowing unprecedented access its internal structure. Comparing this structure with n-body models we find that Orphan had an initial dark halo mass $\\sim \\mathrm{3 \\times 10^{9} M_\\odot}$, placing the progenitor amongst the classical dwarf spheriodals.
SOCIAL SUPPORT DISPARITIES FOR CAREGIVERS OF AIDS-ORPHANED CHILDREN IN SOUTH AFRICA

PubMed Central

Kuo, Caroline; Fitzgerald, Jane; Operario, Don; Casale, Marisa

2012-01-01

Drawing upon a sample of 1,599 adults caring for children in HIV-endemic Umlazi Township in South Africa, this cross-sectional survey investigated whether perceived social support varied among caregivers of AIDS-orphaned children (n=359) as compared to caregivers of children orphaned by other causes (n=171) and caregivers of non-orphaned children (n=1,069). Results of multivariate linear regressions indicate that caregivers of AIDS-orphaned children reported significantly lower levels of social support compared to caregivers of other-orphaned children and non-orphaned children independent of socio-demographic covariates. Caregivers of other-orphaned and non-orphaned children reported similar levels of social support. In terms of sources of support, all caregivers were more likely to draw support from family and significant others rather than friends. These findings indicate a need to develop interventions that can increase levels of social support for caregivers of AIDS-orphaned children, particularly networks that include friends and significant others. PMID:22904575
New and evolving rare diseases research programs at the National Institutes of Health.

PubMed

Groft, S C; Rubinstein, Y R

2013-01-01

Research emphasis on rare diseases and orphan products remains a major focus of the research Institutes and Centers of National Institutes of Health (NIH). NIH provides more than USD 31 billion annually in biomedical research and research support. This research is the basis of many of the health advances in rare and common diseases. Numerous efforts and a major emphasis by the public and private sector initiatives have resulted in an increase of interventions and diagnostics for rare diseases. Newer translational research programs provide a more systematic and coordinated approach to rare diseases research and orphan products development. The approach that is offered requires extensive public-private partnerships with the pharmaceutical industry, contract research organizations, philanthropic foundations, medical and scientific advisory boards, patient advocacy groups, the academic research community, research and regulatory scientists, government funding agencies, and the public. Each program is unique and requires lengthy planning and collaborative efforts to reach programmatic goals. © 2013 S. Karger AG, Basel.
Estimating the budget impact of orphan medicines in Europe: 2010 - 2020.

PubMed

Schey, Carina; Milanova, Tsveta; Hutchings, Adam

2011-09-27

Orphan drugs are a growing issue of importance to European healthcare policy makers. The success of orphan drug legislation in Europe has resulted in an increasing number of licensed medicines for rare diseases, and many more yet unlicensed products have received orphan drug designation. Increasingly the concerns amongst policy makers relate to issues of patient access and affordability, yet few studies have sought to estimate the future budget impact of orphan drugs. The aim of this study was to predict the total cost of orphan medicines in Europe between 2010 and 2020 as a percentage of total European pharmaceutical expenditure. A disease-based epidemiological model was created based upon trends in the designation and approval of new orphan medicines, prevalence estimates for orphan diseases, and historical price and sales data for orphan drugs in Europe (defined as Eurozone + UK). The analysis incorporated two stages: 1) Predicting the number of diseases for which new orphan drugs will be approved over the next decade, based on an analysis of trends from the EU registry of orphan medicines; 2) Estimating the average ex-factory drug cost across an orphan disease life cycle, from the year in which the first orphan medicine is launched to the point where the first medicine loses marketing exclusivity. The two sets of information were combined to quantify the annual cost of orphan drugs from 2010 through 2020. The results from the model predicted a steady increase in the cumulative number of diseases for which an orphan drug is approved, averaging just over 5 new diseases per year over the next 10 years. The annual per patient cost of existing orphan drugs was seen to vary between €1,251 and €407,631, with the median cost being €32,242 per year. The share of the total pharmaceutical market represented by orphan drugs is predicted to increase from 3.3% in 2010 to a peak of 4.6% in 2016 after which it is expected to level off through 2020, as growth falls into line with that in the wider pharmaceutical market. In sensitivity analysis peak-year orphan drug budget impact ranged between 3% - 6.6%. Although European orphan drug legislation has led to an increase in the number of approved orphan drugs, the growth in cost, as a proportion of total pharmaceutical expenditure, is likely to plateau over the next decade as orphan growth rates converge on those in the broader pharmaceutical market. Given the assumptions and simplifications inherent in such a projection, there is uncertainty around the base case forecast and further research is needed to monitor how trends develop. However, fears that growth in orphan drug expenditure will lead to unsustainable cost escalation do not appear to be justified. Furthermore, based on the results of this budget impact forecast, the European orphan drug legislation is not leading to a disproportionate impact on pharmaceutical expenditure.
Estimating the budget impact of orphan medicines in Europe: 2010 - 2020

PubMed Central

2011-01-01

Background Orphan drugs are a growing issue of importance to European healthcare policy makers. The success of orphan drug legislation in Europe has resulted in an increasing number of licensed medicines for rare diseases, and many more yet unlicensed products have received orphan drug designation. Increasingly the concerns amongst policy makers relate to issues of patient access and affordability, yet few studies have sought to estimate the future budget impact of orphan drugs. The aim of this study was to predict the total cost of orphan medicines in Europe between 2010 and 2020 as a percentage of total European pharmaceutical expenditure. Methods A disease-based epidemiological model was created based upon trends in the designation and approval of new orphan medicines, prevalence estimates for orphan diseases, and historical price and sales data for orphan drugs in Europe (defined as Eurozone + UK). The analysis incorporated two stages: 1) Predicting the number of diseases for which new orphan drugs will be approved over the next decade, based on an analysis of trends from the EU registry of orphan medicines; 2) Estimating the average ex-factory drug cost across an orphan disease life cycle, from the year in which the first orphan medicine is launched to the point where the first medicine loses marketing exclusivity. The two sets of information were combined to quantify the annual cost of orphan drugs from 2010 through 2020. Results The results from the model predicted a steady increase in the cumulative number of diseases for which an orphan drug is approved, averaging just over 5 new diseases per year over the next 10 years. The annual per patient cost of existing orphan drugs was seen to vary between €1,251 and €407,631, with the median cost being €32,242 per year. The share of the total pharmaceutical market represented by orphan drugs is predicted to increase from 3.3% in 2010 to a peak of 4.6% in 2016 after which it is expected to level off through 2020, as growth falls into line with that in the wider pharmaceutical market. In sensitivity analysis peak-year orphan drug budget impact ranged between 3% - 6.6%. Conclusions Although European orphan drug legislation has led to an increase in the number of approved orphan drugs, the growth in cost, as a proportion of total pharmaceutical expenditure, is likely to plateau over the next decade as orphan growth rates converge on those in the broader pharmaceutical market. Given the assumptions and simplifications inherent in such a projection, there is uncertainty around the base case forecast and further research is needed to monitor how trends develop. However, fears that growth in orphan drug expenditure will lead to unsustainable cost escalation do not appear to be justified. Furthermore, based on the results of this budget impact forecast, the European orphan drug legislation is not leading to a disproportionate impact on pharmaceutical expenditure. PMID:21951518
Orphan care in Botswana's working households: growing responsibilities in the absence of adequate support.

PubMed

Miller, Candace M; Gruskin, Sofia; Subramanian, S V; Rajaraman, Divya; Heymann, S Jody

2006-08-01

Botswana has one of the world's highest HIV-prevalence rates and the world's highest percentages of orphaned children among its population. We assessed the ability of income-earning households in Botswana to adequately care for orphans. We used data from the Botswana Family Health Needs Study (2002), a sample of 1033 working adults with caregiving responsibilities who used public services, to assess whether households with orphan-care responsibilities encountered financial and other difficulties. Thirty-seven percent of respondents provided orphan care, usually to extended family members. We applied logistic regression models to determine the factors associated with experiencing problems related to orphan caregiving. Nearly half of working households with orphan-care responsibilities reported experiencing financial and other difficulties because of orphan care. Issues of concern included caring for multiple orphans, caring for sick adults and orphans simultaneously, receiving no assistance, and low income. The orphan crisis is impoverishing even working households, where caregivers lack sufficient resources to provide basic needs. Neither the public sector nor communities provide adequate safety nets. International assistance is critical to build capacity within the social welfare infrastructure and to fund community-level activities that support households. Lessons from Botswana's orphan crisis can provide valuable insights to policymakers throughout sub-Saharan Africa.
Access to Orphan Drugs: A Comprehensive Review of Legislations, Regulations and Policies in 35 Countries.

PubMed

Gammie, Todd; Lu, Christine Y; Babar, Zaheer Ud-Din

2015-01-01

To review existing regulations and policies utilised by countries to enable patient access to orphan drugs. A review of the literature (1998 to 2014) was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country. Fifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country's legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35) had in place orphan drug legislation. Access to orphan drugs depends on individual country's pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access. Overall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases.
Caregivers' and non-caregivers' knowledge regarding HIV/AIDS and attitude towards HIV/AIDS and orphans in Nigeria.

PubMed

Ohnishi, Mayumi; Nakamura, Keiko; Kizuki, Masashi; Seino, Kaoruko; Inose, Tomoko; Takano, Takehito

2008-09-01

Nigeria has an estimated 930,000 AIDS orphans, which has a marked impact on family and community. This study was performed to characterise caregivers' knowledge regarding HIV/AIDS and their attitude towards HIV/AIDS, orphans in general and AIDS orphans in particular. Caregivers and non-caregivers aged 25-70 years in Nigeria were interviewed from January and March 2003, and logistic regression analysis was used to determine associations between caregivers' knowledge regarding HIV/AIDS and attitudes towards HIV/AIDS, orphans and AIDS orphans, and demographic characteristics and background status regarding HIV/AIDS and orphans. A total of 824 interviewees participated in the survey (82.4% response rate), of whom 290 (35.2%) were current caregivers of orphans. The mean number of orphans per current caregiver was 1.8 (standard deviation 1.4). Factors related to higher knowledge level regarding HIV/AIDS were female gender [odds ratio (OR) = 3.49; 95% confidence interval (CI): 2.33, 5.22] and belief that AIDS is a common disease (OR = 3.39; 95% CI: 2.19, 5.26). Factors associated with positive attitudes towards HIV/AIDS, orphans in general and AIDS orphans in particular were age 35-44 years (OR = 1.73; 95% CI: 1.11, 2.69), Koranic schooling (OR = 8.69; 95% CI: 2.42, 31.19), polygamy (OR = 1.76; 95% CI: 1.17, 2.62), belief that there are increasing numbers of orphans in the community (OR = 2.59; 95% CI: 1.32, 5.08) and having relatives or friends with HIV/AIDS (OR = 2.88; 95% CI: 1.61, 1.58). There was a slight correlation (r = 0.17, P < 0.001) between caregivers' knowledge regarding HIV/AIDS and positive attitudes towards HIV/AIDS, orphans and AIDS orphans. Demographic characteristics and personal experience should be taken into consideration to improve attitudes and behaviour related to HIV/AIDS and caring for orphans and AIDS orphans.
State Agency Programs for Handicapped, Delinquent and Neglected Children.

ERIC Educational Resources Information Center

Ohio State Dept. of Education, Columbus.

Originally designed to improve the education of disadvantaged children in the public schools, Title I of the Elementary and Secondary Education Act was amended in 1966 to include children in state institutions who are handicapped, orphaned, neglected, or delinquent. In this collection of brief essays, educators from programs in various parts of…
Market uptake of orphan drugs--a European analysis.

PubMed

Picavet, E; Annemans, L; Cleemput, I; Cassiman, D; Simoens, S

2012-12-01

Variations in market uptake of an orphan drug have important implications with respect to access to care and inequality of treatment. Therefore, the aim of this study was to quantify both the sales and volume uptake of orphan drugs in Europe and to assess whether a country's gross domestic product (GDP) and/or health technology assessment (HTA) influences the orphan drugs' market uptake. We analysed the numbers of orphan drugs launched and the sales and volume uptake for 17 orphan drugs in 23 European countries from 2001 until the beginning of 2010 using the IMS Health database. Countries were clustered based on GDP and the availability of a formal HTA-organization. The uptake of orphan drugs varied across European countries. The highest volumes and contributions of orphan drugs in the first year occurred in countries with a high GDP (and implicitly, a higher budget for healthcare), independently of the existence of an HTA-organization. In contrast, in countries with a low GDP, orphan drugs were less available when there was a formal HTA-organization. There, budgetary restrictions can cause the exclusion of less cost-effective orphan drugs. We observed substantial variation in the market uptake of orphan drugs. Such variation may have important implications with respect to access to care and inequality of treatment. The uptake of orphan drugs could be promoted through the clinical added value of orphan drugs (CAVOD) project and various conditional pricing and reimbursement mechanisms. © 2012 Blackwell Publishing Ltd.

HIV infection and sexual risk behaviour among youth who have experienced orphanhood: systematic review and meta-analysis

PubMed Central

2011-01-01

Background Previous research has suggested that orphaned children and adolescents might have elevated risk for HIV infection. We examined the state of evidence regarding the association between orphan status and HIV risk in studies of youth aged 24 years and younger. Methods Using systematic review methodology, we identified 10 studies reporting data from 12 countries comparing orphaned and non-orphaned youth on HIV-related risk indicators, including HIV serostatus, other sexually transmitted infections, pregnancy and sexual behaviours. We meta-analyzed data from six studies reporting prevalence data on the association between orphan status and HIV serostatus, and we qualitatively summarized data from all studies on behavioural risk factors for HIV among orphaned youth. Results Meta-analysis of HIV testing data from 19,140 participants indicated significantly greater HIV seroprevalence among orphaned (10.8%) compared with non-orphaned youth (5.9%) (odds ratio = 1.97; 95% confidence interval = 1.41-2.75). Trends across studies showed evidence for greater sexual risk behaviour in orphaned youth. Conclusions Studies on HIV risk in orphaned populations, which mostly include samples from sub-Saharan Africa, show nearly two-fold greater odds of HIV infection among orphaned youth and higher levels of sexual risk behaviour than among their non-orphaned peers. Interventions to reduce risk for HIV transmission in orphaned youth are needed to address the sequelae of parental illness and death that might contribute to sexual risk and HIV infection. PMID:21592368
The availability and affordability of orphan drugs for rare diseases in China.

PubMed

Gong, Shiwei; Wang, Yingxiao; Pan, Xiaoyun; Zhang, Liang; Huang, Rui; Chen, Xin; Hu, Juanjuan; Xu, Yi; Jin, Si

2016-02-27

Orphan drugs are intended to treat, prevent or diagnose rare diseases. In recent years, China healthcare policy makers and patients have become increasingly concerned about orphan drug issues. However, very few studies have assessed the availability and affordability of orphan drugs for rare diseases in China. The aim of this study was to provide an overview of the availability and affordability of orphan drugs in China and to make suggestions to improve patient access to orphan drugs. Two components of the availability of orphan drugs were examined. Market availability was assessed by the extent to which orphan drugs were marketed in China with a comparison to orphan drugs in international markets, such as the U.S., EU and Japan. We conducted surveys and collected data from 24 tertiary public hospitals in China to measure hospital-level availability of orphan drugs. The affordability of orphan drugs was calculated using hospital dispensary prices and was expressed as days of average daily income required for the cost of a course of treatment. Affordability was also analyzed under the Chinese basic medical insurance system. Orphan drugs approved in the U.S., EU and Japan had 37.8%, 24.6% and 52.4% market availability in China, respectively. Median availability of 31 orphan drugs surveyed at the 24 tertiary public hospitals was 20.8% (very low). Within a periodic treatment course, the average treatment cost of 23 orphan drugs is approximately 4, 843. 5 USD, which equates to 505.6 days of per capita net income for an urban resident with a middle income (187.4 days for a high-income urban resident) or 1,582.8 days's income for a rural resident with a middle income (657.2 days for a high-income rural resident). Except for homoharringtonine, 22 orphan drugs for 14 rare diseases were unaffordable for the most of residents in China. With 5% out-of-pocket expenses, only three generics could be afforded by middle-income residents, whereas seven drugs for high-income urban residents. The Chinese government can take more responsibility for improving the availability and affordability of orphan drugs through setting up incentive policies and public platforms for sharing of orphan drug information. Control of the high price of orphan drugs, combined with a joint funding model from both government and private enterprise can efficiently reduce the economic burden of affected patients in China.
Access to Orphan Drugs: A Comprehensive Review of Legislations, Regulations and Policies in 35 Countries

PubMed Central

Gammie, Todd

2015-01-01

Objective To review existing regulations and policies utilised by countries to enable patient access to orphan drugs. Methods A review of the literature (1998 to 2014) was performed to identify relevant, peer-reviewed articles. Using content analysis, we synthesised regulations and policies for access to orphan drugs by type and by country. Results Fifty seven articles and 35 countries were included in this review. Six broad categories of regulation and policy instruments were identified: national orphan drug policies, orphan drug designation, marketing authorization, incentives, marketing exclusivity, and pricing and reimbursement. The availability of orphan drugs depends on individual country’s legislation and regulations including national orphan drug policies, orphan drug designation, marketing authorization, marketing exclusivity and incentives such as tax credits to ensure research, development and marketing. The majority of countries (27/35) had in place orphan drug legislation. Access to orphan drugs depends on individual country’s pricing and reimbursement policies, which varied widely between countries. High prices and insufficient evidence often limit orphan drugs from meeting the traditional health technology assessment criteria, especially cost-effectiveness, which may influence access. Conclusions Overall many countries have implemented a combination of legislations, regulations and policies for orphan drugs in the last two decades. While these may enable the availability and access to orphan drugs, there are critical differences between countries in terms of range and types of legislations, regulations and policies implemented. Importantly, China and India, two of the largest countries by population size, both lack national legislation for orphan medicines and rare diseases, which could have substantial negative impacts on their patient populations with rare diseases. PMID:26451948
Sexual risk among orphaned adolescents: is country-level HIV prevalence an important factor?

PubMed Central

Robertson, Laura; Gregson, Simon; Garnett, Geoff P.

2010-01-01

Previous studies from sub-Saharan Africa have found that orphans experience increased sexual risk compared to non-orphans. We developed a theoretical framework for the investigation of determinants of HIV risk and used it to generate specific hypotheses regarding the effect of country-level HIV prevalence on the sexual risk experience of orphans. We expected that countries with high HIV prevalence would experience a higher prevalence of orphanhood. We further hypothesised that orphans in countries with high HIV prevalence would experience increased sexual risk, compared to non-orphans, due to pressure on the extended family network, which is primarily responsible for the care of orphans in sub-Saharan Africa, resulting in poorer standards of care and guidance. We used hierarchical logistic regression models to investigate this hypothesis using cross-sectional, Demographic and Health Survey data from 10 sub-Saharan African countries. We found that countries with high HIV prevalence did indeed have higher prevalence of orphanhood. We also found that, amongst female adolescents, maternal and double orphans were significantly more likely to have started sex than non-orphans in countries with high HIV prevalence but were not at increased risk in low HIV prevalence countries. This effect of country-level HIV prevalence on the sexual risk of orphans was not explained by household level factors such as wealth, overcrowding or age of the household head. The same pattern of risk was not observed for male adolescents — male orphans were not more likely to have started sex than non-orphans. This suggests that orphaned adolescent women are an important target group for HIV prevention and that efforts should be made to integrate prevention messages into existing support programmes for orphans and vulnerable children. PMID:20552462
21 CFR 316.24 - Granting orphan-drug designation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Granting orphan-drug designation. 316.24 Section 316.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.24 Granting orphan-drug designation...
21 CFR 316.24 - Granting orphan-drug designation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false Granting orphan-drug designation. 316.24 Section 316.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.24 Granting orphan-drug designation...
21 CFR 316.24 - Granting orphan-drug designation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Granting orphan-drug designation. 316.24 Section 316.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.24 Granting orphan-drug designation...
21 CFR 316.24 - Granting orphan-drug designation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false Granting orphan-drug designation. 316.24 Section 316.24 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.24 Granting orphan-drug designation...
The needs of health promoters on a health promotion programme for families with adolescents orphaned by HIV and AIDS.

PubMed

Mthobeni, Maseapo P; Peu, Mmapheko D

2013-02-01

The South African communities has shown to have a challenge in accessing health services especially in rural areas; hence the national strategic objective 1.7 aimed at strengthening community systems to expand access to services using the community-based care programmes (NSP 2012-2016). The programmes enhance access to health services whilst promoting health and educating the community to improve health knowledge and work towards attaining a healthy living (NSP 2012-2016). However, the health promoters from the rural Hammanskraal region in the North West Province of South Africa often found themselves rendering the health promotion services in their communities with limited resources. This study aimed at exploring and describing the challenges faced by health promoters in implementing health promotion programmes for families with adolescents orphaned by HIV and AIDS. The study followed a qualitative design. Data was collected using focus group interviews. Participants were purposely selected by the social worker and the health promotion coordinator working at Hammanskraal. The process of data analysis was adapted from the eight steps of Tesch method of data analysis where categories, sub-categories and themes were isolated. The following categories emerged as the needs of health promoters on health promotion programmes for families with adolescents orphaned by HIV and AIDS, (1) financial needs, (2) resources, (3) basic life needs, (4) educational needs and (5) health promoter's needs. It is therefore recommended that equal distribution of resources: including medicine, equipment and finances, should be maintained in order to ensure non-interrupted services.
Pricing and reimbursement of orphan drugs: the need for more transparency

PubMed Central

2011-01-01

Pricing and reimbursement of orphan drugs are an issue of high priority for policy makers, legislators, health care professionals, industry leaders, academics and patients. This study aims to conduct a literature review to provide insight into the drivers of orphan drug pricing and reimbursement. Although orphan drug pricing follows the same economic logic as drug pricing in general, the monopolistic power of orphan drugs results in high prices: a) orphan drugs benefit from a period of marketing exclusivity; b) few alternative health technologies are available; c) third-party payers and patients have limited negotiating power; d) manufacturers attempt to maximise orphan drug prices within the constraints of domestic pricing and reimbursement policies; and e) substantial R&D costs need to be recouped from a small number of patients. Although these conditions apply to some orphan drugs, they do not apply to all orphan drugs. Indeed, the small number of patients treated with an orphan drug and the limited economic viability of orphan drugs can be questioned in a number of cases. Additionally, manufacturers have an incentive to game the system by artificially creating monopolistic market conditions. Given their high price for an often modest effectiveness, orphan drugs are unlikely to provide value for money. However, additional criteria are used to inform reimbursement decisions in some countries. These criteria may include: the seriousness of the disease; the availability of other therapies to treat the disease; and the cost to the patient if the medicine is not reimbursed. Therefore, the maximum cost per unit of outcome that a health care payer is willing to pay for a drug could be set higher for orphan drugs to which society attaches a high social value. There is a need for a transparent and evidence-based approach towards orphan drug pricing and reimbursement. Such an approach should be targeted at demonstrating the relative effectiveness, cost-effectiveness and economic viability of orphan drugs with a view to informing pricing and reimbursement decisions. PMID:21682893
Pricing and reimbursement of orphan drugs: the need for more transparency.

PubMed

Simoens, Steven

2011-06-17

Pricing and reimbursement of orphan drugs are an issue of high priority for policy makers, legislators, health care professionals, industry leaders, academics and patients. This study aims to conduct a literature review to provide insight into the drivers of orphan drug pricing and reimbursement. Although orphan drug pricing follows the same economic logic as drug pricing in general, the monopolistic power of orphan drugs results in high prices: a) orphan drugs benefit from a period of marketing exclusivity; b) few alternative health technologies are available; c) third-party payers and patients have limited negotiating power; d) manufacturers attempt to maximise orphan drug prices within the constraints of domestic pricing and reimbursement policies; and e) substantial R&D costs need to be recouped from a small number of patients. Although these conditions apply to some orphan drugs, they do not apply to all orphan drugs. Indeed, the small number of patients treated with an orphan drug and the limited economic viability of orphan drugs can be questioned in a number of cases. Additionally, manufacturers have an incentive to game the system by artificially creating monopolistic market conditions. Given their high price for an often modest effectiveness, orphan drugs are unlikely to provide value for money. However, additional criteria are used to inform reimbursement decisions in some countries. These criteria may include: the seriousness of the disease; the availability of other therapies to treat the disease; and the cost to the patient if the medicine is not reimbursed. Therefore, the maximum cost per unit of outcome that a health care payer is willing to pay for a drug could be set higher for orphan drugs to which society attaches a high social value. There is a need for a transparent and evidence-based approach towards orphan drug pricing and reimbursement. Such an approach should be targeted at demonstrating the relative effectiveness, cost-effectiveness and economic viability of orphan drugs with a view to informing pricing and reimbursement decisions.
Access to orphan drugs despite poor quality of clinical evidence

PubMed Central

Dupont, Alain G; Van Wilder, Philippe B

2011-01-01

AIM We analysed the Belgian reimbursement decisions of orphan drugs as compared with those of innovative drugs for more common but equally severe diseases, with special emphasis on the quality of clinical evidence. METHODS Using the National Health Insurance Agency administrative database, we evaluated all submitted orphan drug files between 2002 and 2007. A quality analysis of the clinical evidence in the orphan reimbursement files was performed. The evaluation reports of the French ‘Haute Autorité de Santé’, including the five-point scale parameter ‘Service Médical Rendu (SMR), were examined to compare disease severity. Chi-squared tests (at P < 0.05 significance level) were used to compare the outcome of the reimbursement decisions between orphan and non-orphan innovative medicines. RESULTS Twenty-five files of orphan drugs and 117 files of non-orphan drugs were evaluated. Twenty-two of 25 (88%) submissions of orphan drugs were granted reimbursement as opposed to 74 of the 117 (63%) non-orphan innovative medicines (P = 0.02). Only 52% of the 25 orphan drug files included a randomized controlled trial as opposed to 84% in a random control sample of 25 non-orphan innovative submissions (P < 0.01). The duration of drug exposure was in most cases far too short in relation to the natural history of the disease. CONCLUSIONS Orphan drug designation predicts reimbursement despite poor quality of clinical evidence. The evidence gap at market authorization should be reduced by post-marketing programmes, in which the centralized regulatory and the local reimbursement authorities collaborate in an efficient way across the European Union member states. PMID:21395641
Orphaned female elephant social bonds reflect lack of access to mature adults.

PubMed

Goldenberg, Shifra Z; Wittemyer, George

2017-10-31

Compensatory social behavior in nonhuman animals following maternal loss has been documented, but understanding of how orphans allocate bonding to reconstruct their social networks is limited. Successful social integration may be critical to survival and reproduction for highly social species and, therefore, may be tied to population persistence. We examined the social partners involved in affiliative interactions of female orphans and non-orphans in an elephant population in Samburu, northern Kenya that experienced heightened adult mortality driven by drought and intense ivory poaching. We contrasted partners across different competitive contexts to gain insight to the influence of resource availability on social interactions. Though the number of partners did not differ between orphans and non-orphans, their types of social partners did. Orphans interacted with sisters and matriarchs less while feeding than did non-orphans, but otherwise their affiliates were similar. While resting under spatially concentrated shade, orphans had markedly less access to mature adults but affiliated instead with sisters, bulls, and age mates. Orphan propensity to strengthen bonds with non-dominant animals appears to offer routes to social integration following maternal loss, but lack of interaction with adult females suggests orphans may experience decreased resource access and associated fitness costs in this matriarchal society.
The impact of the global economic crisis on HIV and AIDS programmes directed at women and children in Zambia.

PubMed

Serieux, John; Njelesani, Mwansa; Chompolola, Abson; Sepehri, Ardeshir; Guliani, Harminder

2015-01-01

This investigation sought to ascertain the extent to which the global economic crisis of 2008-2009 affected the delivery of HIV/AIDS-related services directed at pregnant and lactating mothers, children living with HIV and children orphaned through HIV in Zambia. Using a combined macroeconomic analysis and a multiple case study approach, the authors found that from mid-2008 to mid-2009 the Zambian economy was indeed buffeted by the global economic crisis. During that period the case study subjects experienced challenges with respect to the funding, delivery and effectiveness of services that were clearly attributable, directly or indirectly, to the global economic crisis. The source of funding most often compromised was external private flows. The services most often compromised were non-medical services (such as the delivery of assistance to orphans and counselling to HIV-positive mothers) while the more strictly medical services (such as antiretroviral therapy) were protected from funding cuts and service interruptions. Impairments to service effectiveness were experienced relatively equally by (HIV-positive) pregnant women and lactating mothers and children orphaned through HIV. Children living with AIDS were least affected because of the primacy of ARV therapy in their care.
21 CFR 316.30 - Annual reports of holder of orphan-drug designation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Annual reports of holder of orphan-drug... SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.30 Annual reports of holder of orphan-drug designation. Within 14 months after the date on which a drug was designated...
Orphan status, HIV risk behavior, and mental health among adolescents in rural Kenya.

PubMed

Puffer, Eve S; Drabkin, Anya S; Stashko, Allison L; Broverman, Sherryl A; Ogwang-Odhiambo, Rose A; Sikkema, Kathleen J

2012-09-01

To examine orphan status, mental health, social support, and HIV risk among adolescents in rural Kenya. Randomly selected adolescents aged 10-18 years completed surveys assessing sexual activity, sex-related beliefs and self-efficacy, mental health, social support, caregiver-child communication, time since parental death, and economic resources. Analysis of covariance and regression analyses compared orphans and nonorphans; orphan status was tested as a moderator between well-being and HIV risk. Orphans reported poorer mental health, less social support, and fewer material resources. They did not differ from nonorphans on HIV risk indicators. Longer time since parental death was associated with poorer outcomes. In moderator analyses, emotional problems and poorer caregiver-youth communication were more strongly associated with lower sex-related self-efficacy for orphans. Orphans are at higher risk for psychosocial problems. These problems may affect orphans' self-efficacy for safer sex practices more than nonorphans. Decreased HIV risk could be one benefit of psychosocial interventions for orphans.
Migration, Household Configurations, and the Well-Being of Adolescent Orphans in Rwanda

PubMed Central

2014-01-01

This study uses data from the 2002 Rwandan census to situate the discourse on migration and orphan well-being within the context of the household. According to its findings, migrant orphans are less likely than non-migrant orphans to live in households with less favorable structural characteristics such as single-parent households. Significant differences are also found in the implied gains to living standards and schooling associated with migration among paternal, maternal, and double-orphans. However, the higher living standards and schooling attainment of orphan migrants relative to their non-migrant counterparts disappear within child-headed household contexts. More generally, the results indicate that the higher living standards of migrant orphans are in part driven by the fact that they mostly live in households with migrant household-heads or migrant spouses. Yet the analysis also suggests that orphans living within these contexts experience higher levels of intra-household discrimination in investments in their schooling, relative to their orphan counterparts who live in non-migrant households. PMID:25009364
A Peer-to-Peer Health Education Program for Vulnerable Children in Uganda

ERIC Educational Resources Information Center

Falk, Diane S.; Pettet, Kristen; Mpagi, Charles

2016-01-01

In this paper, children attending a U.S.-sponsored private primary school serving orphaned and vulnerable children in Uganda were interviewed in focus groups about their participation in a peer-to-peer health education program in which they used music, dance, poetry, art, and drama to convey health information. The children reported enhanced…
Program of Adaptation Assistance in Foster Families and Particular Features of Its Implementation

ERIC Educational Resources Information Center

Zakirova, Venera G.; Gaysina, Guzel I.; Zhumabaeva, Asia

2015-01-01

Relevance of the problem stated in the article, conditioned by the fact that the successful adaptation of orphans in a foster family requires specialized knowledge and skills, as well as the need of professional support. Therefore, this article aims at substantiation of the effectiveness of the developed pilot program psycho-pedagogical support of…
Assessing the general health of diagnostic orphans using the Short Form Health Survey (SF-12v2): a latent variable modelling approach.

PubMed

McBride, Orla; Adamson, Gary; Bunting, Brendan P; McCann, Siobhan

2009-01-01

Research has demonstrated that diagnostic orphans (i.e. individuals who experience only one to two criteria of DSM-IV alcohol dependence) can encounter significant health problems. Using the SF-12v2, this study examined the general health functioning of alcohol users, and in particular, diagnostic orphans. Current drinkers (n = 26,913) in the National Epidemiologic Survey on Alcohol and Related Conditions were categorized into five diagnosis groups: no alcohol use disorder (no-AUD), one-criterion orphans, two-criterion orphans, alcohol abuse and alcohol dependence. Latent variable modelling was used to assess the associations between the physical and mental health factors of the SF-12v2 and the diagnosis groups and a variety of background variables. In terms of mental health, one-criterion orphans had significantly better health than two-criterion orphans and the dependence group, but poorer health than the no-AUD group. No significant differences were evident between the one-criterion orphan group and the alcohol abuse group. One-criterion orphans had significantly poorer physical health when compared to the no-AUD group. One- and two-criterion orphans did not differ in relation to physical health. Consistent with previous research, diagnostic orphans in the current study appear to have experienced clinically relevant symptoms of alcohol dependence. The current findings suggest that diagnostic orphans may form part of an alcohol use disorders spectrum severity.

21 CFR 316.23 - Timing of requests for orphan-drug designation; designation of already approved drugs.

Code of Federal Regulations, 2010 CFR

2010-04-01

...) A sponsor may request orphan-drug designation at any time in the drug development process prior to... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Timing of requests for orphan-drug designation..., DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan...
HIV seroprevalence among orphaned and homeless youth: no place like home.

PubMed

Hillis, Susan D; Zapata, Lauren; Robbins, Cheryl L; Kissin, Dmitry M; Skipalska, Halyna; Yorick, Roman; Finnerty, Erin; Marchbanks, Polly A; Jamieson, Denise J

2012-01-02

We evaluated the combined influences of orphaned status and homelessness on HIV seroprevalence and risk among street-involved Ukrainian youth in 2008. Systematic, multicity, community-based, cross-sectional assessment. Time-location sampling was used to identify eligible youth aged 15-24 after city-wide mapping of 91 sites where street-involved youth gathered in Odessa, Kiev, and Donetsk. Universal sampling identified 961 youth in 74 randomly selected sites; 97% consented. Youth reporting one or both parents dead were classified as orphaned; those without a stable residence or sleeping outside their residence at least two nights per week were classified as homeless. Trained staff provided HIV counseling and rapid testing via mobile vans. Adjusted odds ratios (AORs) were calculated using logistic regression, accounting for intracluster homogeneity. We found 32% (300 of 929) were both orphaned and homeless; 48% either (but not both) homeless [37% (343 of 929)] or orphaned [11% (104 of 929)]; and [20% (182 of 929)] neither orphaned nor homeless. HIV seroprevalences were 7% for neither orphaned/homeless; 16 and 17%, respectively, for either orphaned/homeless; 28% for both orphaned/homeless (P for trend <0.0001). AORs for HIV infection were 1 for neither; 2.3 and 2.4 for either homeless [95% confidence interval (CI) 1.7-2.9] or orphaned (CI 1.8-3.3); 3.3 for both orphaned/homeless (CI 2.3-4.4). Ever-use of injection drugs increased from 15 to 32 to 48% for those who neither, either, or both orphaned and homeless, respectively (P for trend <0.0001). One of four youths who were both homeless and orphaned was HIV-infected; these youths were significantly more likely to be HIV infected and to report injection drug use than those with adequate housing and living parents.
Impact of orphan drugs on Latvian budget.

PubMed

Logviss, Konstantins; Krievins, Dainis; Purvina, Santa

2016-05-11

Number of orphan medicinal products on the market and number of rare disease patients, taking these usually expensive products, are increasing. As a result, budget impact of orphan drugs is growing. This factor, along with the cost-effectiveness of orphan drugs, is often considered in the reimbursement decisions, directly affecting accessibility of rare disease therapies. The current study aims to assess the budget impact of orphan drugs in Latvia. Our study covered a 5-year period, from 2010 to 2014. Impact of orphan drugs on Latvian budget was estimated from the National Health Service's perspective. It was calculated in absolute values and relative to total pharmaceutical market and total drug reimbursement budget. A literature review was performed for comparison with other European countries. Orphan drug annual expenditure ranged between EUR 2.065 and 3.065 million, with total 5-year expenditure EUR 12.467 million. It constituted, on average, 0.84 % of total pharmaceutical market and 2.14 % of total drug reimbursement budget, respectively. Average annual per patient expenditures varied widely, from EUR 1 534 to EUR 580 952. The most costly treatment was enzyme replacement therapy (Elaprase) for MPS II. Glivec had the highest share (34 %) of the total orphan drug expenditure. Oncological drugs represented more than a half of the total orphan drug expenditure, followed by drugs for metabolic and endocrine conditions and medicines for cardiopulmonary diseases. Three indications: Ph+ CML, MPS II, and PAH accounted for nearly 90 % of the total orphan drug expenditure. Budget impact of orphan drugs in Latvia is very small. It increased slightly over a period of five years, due to the slight increase in the number of patients and the number of orphan drugs reimbursed. Current Latvian drug reimbursement system is not sufficient for most orphan drugs.
The influence of the European paediatric regulation on marketing authorisation of orphan drugs for children

PubMed Central

2014-01-01

Background Drug development for rare diseases is challenging, especially when these orphan drugs (OD) are intended for children. In 2007 the EU Paediatric Drug Regulation was enacted to improve the development of high quality and ethically researched medicines for children through the establishment of Paediatric Investigation Plans (PIPs). The effect of the EU Paediatric Drug Regulation on the marketing authorisation (MA) of drugs for children with rare diseases was studied. Methods Data on all designated orphan drugs, their indication, MA, PIPs and indication group (adult or child) were obtained from the European Medicines Agency (EMA). The outcome and duration of the process from orphan drug designation (ODD) to MA, was compared, per indication, by age group. The effect of the Paediatric Drug Regulation, implemented in 2007, on the application process was assessed with survival analysis. Results Eighty-one orphan drugs obtained MA since 2000 and half are authorised for (a subgroup of) children; another 34 are currently undergoing further investigations in children through agreed PIPs. The Paediatric Drug Regulation did not significantly increase the number of ODDs with potential paediatric indications (58% before vs 64% after 2007 of ODDs, p = 0.1) and did not lead to more MAs for ODs with paediatric indications (60% vs 43%, p = 0.22). ODs authorised after 2007 had a longer time to MA than those authorised before 2007 (Hazard ratio (95% CI) 2.80 (1.84-4.28), p < 0.001); potential paediatric use did not influence the time to MA (Hazard ratio (95% CI) 1.14 (0.77-1.70), p = 0.52). Conclusions The EU Paediatric Drug Regulation had a minor impact on development and availability of ODs for children, was associated with a longer time to MA, but ensured the further paediatric development of drugs still off-label to children. The impact of the Paediatric Drug Regulation on research quantity and quality in children through PIPs is not yet clear. PMID:25091201
The influence of the European paediatric regulation on marketing authorisation of orphan drugs for children.

PubMed

Kreeftmeijer-Vegter, Annemarie Rosan; de Boer, Anthonius; van der Vlugt-Meijer, Roselinda H; de Vries, Peter J

2014-08-05

Drug development for rare diseases is challenging, especially when these orphan drugs (OD) are intended for children. In 2007 the EU Paediatric Drug Regulation was enacted to improve the development of high quality and ethically researched medicines for children through the establishment of Paediatric Investigation Plans (PIPs). The effect of the EU Paediatric Drug Regulation on the marketing authorisation (MA) of drugs for children with rare diseases was studied. Data on all designated orphan drugs, their indication, MA, PIPs and indication group (adult or child) were obtained from the European Medicines Agency (EMA). The outcome and duration of the process from orphan drug designation (ODD) to MA, was compared, per indication, by age group. The effect of the Paediatric Drug Regulation, implemented in 2007, on the application process was assessed with survival analysis. Eighty-one orphan drugs obtained MA since 2000 and half are authorised for (a subgroup of) children; another 34 are currently undergoing further investigations in children through agreed PIPs. The Paediatric Drug Regulation did not significantly increase the number of ODDs with potential paediatric indications (58% before vs 64% after 2007 of ODDs, p = 0.1) and did not lead to more MAs for ODs with paediatric indications (60% vs 43%, p = 0.22). ODs authorised after 2007 had a longer time to MA than those authorised before 2007 (Hazard ratio (95% CI) 2.80 (1.84-4.28), p < 0.001); potential paediatric use did not influence the time to MA (Hazard ratio (95% CI) 1.14 (0.77-1.70), p = 0.52). The EU Paediatric Drug Regulation had a minor impact on development and availability of ODs for children, was associated with a longer time to MA, but ensured the further paediatric development of drugs still off-label to children. The impact of the Paediatric Drug Regulation on research quantity and quality in children through PIPs is not yet clear.
DRUG EVALUATION AND DECISION MAKING IN CATALONIA: DEVELOPMENT AND VALIDATION OF A METHODOLOGICAL FRAMEWORK BASED ON MULTI-CRITERIA DECISION ANALYSIS (MCDA) FOR ORPHAN DRUGS.

PubMed

Gilabert-Perramon, Antoni; Torrent-Farnell, Josep; Catalan, Arancha; Prat, Alba; Fontanet, Manel; Puig-Peiró, Ruth; Merino-Montero, Sandra; Khoury, Hanane; Goetghebeur, Mireille M; Badia, Xavier

2017-01-01

The aim of this study was to adapt and assess the value of a Multi-Criteria Decision Analysis (MCDA) framework (EVIDEM) for the evaluation of Orphan drugs in Catalonia (Catalan Health Service). The standard evaluation and decision-making procedures of CatSalut were compared with the EVIDEM methodology and contents. The EVIDEM framework was adapted to the Catalan context, focusing on the evaluation of Orphan drugs (PASFTAC program), during a Workshop with sixteen PASFTAC members. The criteria weighting was done using two different techniques (nonhierarchical and hierarchical). Reliability was assessed by re-test. The EVIDEM framework and methodology was found useful and feasible for Orphan drugs evaluation and decision making in Catalonia. All the criteria considered for the development of the CatSalut Technical Reports and decision making were considered in the framework. Nevertheless, the framework could improve the reporting of some of these criteria (i.e., "unmet needs" or "nonmedical costs"). Some Contextual criteria were removed (i.e., "Mandate and scope of healthcare system", "Environmental impact") or adapted ("population priorities and access") for CatSalut purposes. Independently of the weighting technique considered, the most important evaluation criteria identified for orphan drugs were: "disease severity", "unmet needs" and "comparative effectiveness", while the "size of the population" had the lowest relevance for decision making. Test-retest analysis showed weight consistency among techniques, supporting reliability overtime. MCDA (EVIDEM framework) could be a useful tool to complement the current evaluation methods of CatSalut, contributing to standardization and pragmatism, providing a method to tackle ethical dilemmas and facilitating discussions related to decision making.
Posttraumatic stress symptoms among adults caring for orphaned children in HIV-endemic South Africa.

PubMed

Kuo, Caroline; Reddy, Madhavi K; Operario, Don; Cluver, Lucie; Stein, Dan J

2013-06-01

There is growing evidence that mental health is a significant issue among families affected by AIDS-related parental deaths. The current study examined posttraumatic stress symptoms and identified risk factors among adults caring for AIDS-orphaned and other-orphaned children in an HIV-endemic South African community. A representative community sample of adults caring for children (N = 1,599) was recruited from Umlazi Township. Of the 116 participants who reported that a traumatic event was still bothering them, 19 % reported clinically significant posttraumatic stress symptoms. Of the 116 participants, caregivers of AIDS-orphaned and other-orphaned children were significantly more likely to meet threshold criteria for PTSD (28 %) compared to caregivers of non-orphaned children (10 %). Household receipt of an old age pension was identified as a possible protective factor for PTSD symptoms among caregivers of orphaned children. Services are needed to address PTSD symptoms among caregivers of orphaned children.
Posttraumatic Stress Symptoms among Adults Caring for Orphaned Children in HIV-endemic South Africa

PubMed Central

Kuo, Caroline; Reddy, Madhavi K.; Operario, Don; Cluver, Lucie; Stein, Dan J.

2013-01-01

There is growing evidence that mental health is a significant issue among families affected by AIDS-related parental deaths. The current study examined posttraumatic stress symptoms and identified risk factors among adults caring for AIDS-orphaned and other-orphaned children in an HIV-endemic South African community. A representative community sample of adults caring for children (N = 1,599) was recruited from Umlazi Township. Of the 116 participants who reported that a traumatic event was still bothering them, 19% reported clinically significant posttraumatic stress symptoms. Of the 116 participants, caregivers of AIDS-orphaned and other-orphaned children were significantly more likely to meet threshold criteria for PTSD (28%) compared to caregivers of non-orphaned children (10%). Household receipt of an old age pension was identified as a possible protective factor for PTSD symptoms among caregivers of orphaned children. Services are needed to address PTSD symptoms among caregivers of orphaned children. PMID:23539187
Points to consider: efficacy and safety evaluations in the clinical development of ultra-orphan drugs.

PubMed

Maeda, Kojiro; Kaneko, Masayuki; Narukawa, Mamoru; Arato, Teruyo

2017-08-23

The unmet medical needs of individuals with very rare diseases are high. The clinical trial designs and evaluation methods used for 'regular' drugs are not applicable in the clinical development of ultra-orphan drugs (<1000 patients) in many cases. In order to improve the clinical development of ultra-orphan drugs, we examined several points regarding the efficient evaluations of drug efficacy and safety that could be conducted even with very small sample sizes, based on the review reports of orphan drugs approved in Japan. The clinical data packages of 43 ultra-orphan drugs approved in Japan from January 2001 to December 2014 were investigated. Japanese clinical trial data were not included in the clinical data package for eight ultra-orphan drugs, and non-Japanese clinical trial data were included for six of these eight drug. Japanese supportive data that included retrospective studies, published literature, clinical research and Japanese survey results were clinical data package attachments in 22 of the 43 ultra-orphan drugs. Multinational trials were conducted for three ultra-orphan drugs. More than two randomized controlled trials (RCTs) were conducted for only 11 of the 43 ultra-orphan drugs. The smaller the number of patients, the greater the proportion of forced titration and optional titration trials were conducted. Extension trials were carried out for enzyme preparations and monoclonal antibodies with high ratio. Post-marketing surveillance of all patients was required in 36 of the 43 ultra-orphan drugs. For ultra-orphan drugs, clinical endpoints were used as the primary efficacy endpoint of the pivotal trial only for two drugs. The control groups in RCTs were classified as follows: placebo groups different dosage groups, and active controls groups. Sample sizes have been determined on the basis of feasibility for some ultra-orphan drugs. We provide "Draft Guidance on the Clinical Development of Ultra-Orphan Drugs" based on this research. The development of ultra-orphan drugs requires various arrangements regarding evidence collection, data sources and the clinical trial design. We expect that this draft guidance is useful for ultra-orphan drugs developments in future.
Nutritional status, psychological well-being and the quality of life of AIDS orphans in rural Henan Province, China.

PubMed

He, Zhonghu; Ji, Chengye

2007-10-01

To assess the influence of orphanhood due to AIDS on children's nutritional status, psychological well-being and life quality, and to explore appropriate intervention strategies in China. In 2005, 186 children aged 8-15 years (93 AIDS orphans and 93 non-orphans) from a rural area of Henan Province were surveyed in a cross-sectional and matched pairs study on nutritional status, psychological health and life quality. We found no compelling evidence for poorer nutritional status in orphans. The nutritional status of both orphans and non-orphans was extremely poor according to the prevalence of stunting, underweight, wasting and anaemia. Depression, low self-esteem and lower quality of life were more frequent in orphans. These differences mainly existed in boys' groups. No significant differences were found between paternal, maternal and double orphans, or orphans in orphanages or extended families. Regression analysis revealed that orphanhood leads to low self-esteem and more depression which contributes to lower quality of life and mediates the association between orphanhood and quality of life. The high prevalence of poor nutritional status indicates that basic material needs of children, including AIDS orphans, are not met in rural China. Psychological problems were prominent among orphans and had become the most important contributor of lower life quality. Boys were at least as vulnerable as girls. The living conditions of all children in rural China must be improved; school-based care and support are crucial and would be a cost-effective way to improve the overall life quality of AIDS orphans.
Is orphan drug status beneficial to tropical disease control? Comparison of the American and future European orphan drug acts.

PubMed

Trouiller, P; Battistella, C; Pinel, J; Pecoul, B

1999-06-01

OBJECTIVES To quantify past outcomes of tropical pharmacology research and development (R & D) and to assess past benefits of the American orphan drug act and potential benefits of the future European orphan drug regulation on tropical diseases. This paper presents two analyses: a 1983-97 retrospective study of the United States Orphan Drug Act concerning rare diseases and a prospective study of the European Proposal for a Regulation Concerning Orphan Drugs and its possible impact on tropical diseases. Different programmes have in the past tried to stimulate R & D in this area, but results remain limited. Of 1450 new chemical entities marketed between 1972 and 1997, 13 were specifically for tropical diseases and considered as essential drugs. Between 1983 & 1997, the US Orphan Drug Act approved 837 drugs and marketing of 152 new molecular entities (NMEs). Three NMEs have been designated for malaria and human African trypanosomiasis. Seven others, already commonly used in tropical diseases, received either orphan designation or an orphan approval for another indication. Pharmaceutical companies benefit from the US framework only when the US market exclusivity clause was applicable. Future European orphan drug regulation appears to be similar to the US Orphan Drug Act. CONCLUSION The orphan drug programmes relating to rare diseases have met with some success. Considering tropical diseases rare diseases seems inadequate to boost pharmaceutical R & D. However, some provisions of the European text may be relevant to tropical diseases, admitting the need for a more specific rule for evaluations of this kind of drug and recognizing the existence of 'diseases of exception'.
Ethical issues in haemophilia.

PubMed

DiMichele, D; Chuansumrit, A; London, A J; Thompson, A R; Cooper, C G; Killian, R M; Ross, L F; Lillicrap, D; Kimmelman, J

2006-07-01

Ethical issues surrounding both the lack of global access to care as well as the implementation of advancing technologies, continue to challenge the international haemophilia community. Haemophilia is not given the priority it deserves in most developing countries. Given the heavy burdens of sickness and disease and severe resource constraints, it may not be possible to provide effective treatment to all who suffer from the various 'orphan' diseases. Nevertheless, through joint efforts, some package of effective interventions can be deployed for a significant number of those who are afflicted with 'orphan' diseases. With cost-effective utilization of limited resources, a national standard of care is possible and affordable. Gene-based diagnosis carries attendant ethical concerns whether for clinical testing or for research purposes, even as the list of its potential benefits to the haemophilia community grows rapidly. As large-scale genetic sequencing becomes quicker and cheaper, moving from the research to the clinic, we will face decisions about the implementation of prenatal, neonatal and other screening programs. Such debates will require input from not just the health care professionals but from all stakeholders in the haemophilia community. Finally, long-term therapeutic success gene transfer in small and large animal models raises the question of when and in which patient population the novel therapeutic approach should first be studied in humans with haemophilia. Although gene therapy represents a worthy goal, the central question for the haemophilia community should be whether it wishes to volunteer itself as a model for a much broader set of innovations.
'Unknown' proteins and 'orphan' enzymes: the missing half of the engineering parts list--and how to find it.

PubMed

Hanson, Andrew D; Pribat, Anne; Waller, Jeffrey C; de Crécy-Lagard, Valérie

2009-12-14

Like other forms of engineering, metabolic engineering requires knowledge of the components (the 'parts list') of the target system. Lack of such knowledge impairs both rational engineering design and diagnosis of the reasons for failures; it also poses problems for the related field of metabolic reconstruction, which uses a cell's parts list to recreate its metabolic activities in silico. Despite spectacular progress in genome sequencing, the parts lists for most organisms that we seek to manipulate remain highly incomplete, due to the dual problem of 'unknown' proteins and 'orphan' enzymes. The former are all the proteins deduced from genome sequence that have no known function, and the latter are all the enzymes described in the literature (and often catalogued in the EC database) for which no corresponding gene has been reported. Unknown proteins constitute up to about half of the proteins in prokaryotic genomes, and much more than this in higher plants and animals. Orphan enzymes make up more than a third of the EC database. Attacking the 'missing parts list' problem is accordingly one of the great challenges for post-genomic biology, and a tremendous opportunity to discover new facets of life's machinery. Success will require a co-ordinated community-wide attack, sustained over years. In this attack, comparative genomics is probably the single most effective strategy, for it can reliably predict functions for unknown proteins and genes for orphan enzymes. Furthermore, it is cost-efficient and increasingly straightforward to deploy owing to a proliferation of databases and associated tools.
Some Numbers behind Canada's Decision to Adopt an Orphan Drug Policy: US Orphan Drug Approvals in Canada, 1997-2012.

PubMed

Herder, Matthew; Krahn, Timothy Mark

2016-05-01

We examined whether access to US-approved orphan drugs in Canada has changed between 1997 (when Canada chose not to adopt an orphan drug policy) and 2012 (when Canada reversed its policy decision). Specifically, we looked at two dimensions of access to US-approved orphan drugs in Canada: (1) regulatory access; and (2) temporal access. Whereas only 63% of US-approved orphan drugs were granted regulatory approval in 1997, we found that regulatory access to US-approved orphan drugs in Canada increased to 74% between 1997 and 2012. However, temporal access to orphan drugs is slower in Canada: in a head-on comparison of 40 matched drugs, only two were submitted and four were approved first in Canada; moreover, the mean review time in Canada (423 days) was longer than that in the US (mean = 341 days), a statistically significant difference (t[39] = 2.04, p = 0.048). These results raise questions about what motivated Canada's apparent shift in orphan drug policy. Copyright © 2016 Longwoods Publishing.
Orphan drugs: the regulatory environment.

PubMed

Franco, Pedro

2013-02-01

The definition of a rare disease is not universal and depends on the legislation and policies adopted by each region or country. The main objective of this article is to describe and discuss the legal framework and the regulatory environment of orphan drugs worldwide. Some reflections and discussions on the need for specific orphan drug legislation or policies are described at length. Furthermore, some aspects of the history of each region in respect of the orphan drug legislation evolution are outlined. This article describes and compares the orphan drug legislation or policies of the following countries or regions: United Sates of America (US), European Union (EU), Japan, Australia, Singapore, Taiwan and Canada. The incentives described in the orphan drug legislations or policies, the criteria for designation of orphan status and the authorisation process of an orphan drug are also described and compared. The legislations and policies are to some extent similar but not the same. It is important to understand the main differences among all available legislative systems to improve the international collaboration in the field of orphan drugs and rare diseases. Copyright © 2012 Elsevier Ltd. All rights reserved.
Care arrangements, grief and psychological problems among children orphaned by AIDS in China.

PubMed

Zhao, G; Li, X; Fang, X; Zhao, J; Yang, H; Stanton, B

2007-10-01

The China Ministry of Health has estimated that there are at least 100,000 AIDS orphans in China. The UNICEF China Office estimates that between 150,000 and 250,000 additional children will be orphaned by AIDS over the next five years. However, limited data are available regarding the sociodemographic characteristics, care arrangements, barriers to appropriate grief resolution and psychological problems among AIDS orphans in China. In this article, we review secondary data and reports from scientific literature, government, non-governmental organisations and public media regarding children orphaned by AIDS in China to address their living situation, bereavement process and psychological problems. Our review suggests that AIDS orphans in China are living in a stressful environment, with many orphans struggling with psychological problems and unmet basic needs such as food, shelter, education and medical care. Based on our review, we suggest that future studies should address the psychosocial needs of AIDS orphans in China and develop health promotion programmes to mitigate the negative impact of parental death on the physical and psychosocial well-being of these orphans.
Harry Potter Versus Muggles: Literary Criticism and Legal Challenge

ERIC Educational Resources Information Center

Carney, John; DeMitchell, Todd

2005-01-01

J. K. Rowling's series about the young, orphaned Harry Potter who escapes his often hostile, nonmagical Muggle (or human) existence for a world of ghosts, spells, and potions, magical objects, and exotic creatures to be found at the Hogwarts School of Witchcraft and Wizardry has captivated a worldwide audience. Since the publication in England of…
Democracy's Orphans: Rights, Responsibility, and the Role of the State in the Lives of Incarcerated Youth

ERIC Educational Resources Information Center

Gardner, Joby

2010-01-01

Transition to adulthood is increasingly complex, extended, and challenging. Working-class Brown and Black young men face very difficult transitions, as they are overrepresented in the justice system, poverty, foster care, special education, and among victims of violence. What effects do these developments have on young people's places in free…
Finding Sequences for over 270 Orphan Enzymes

PubMed Central

Shearer, Alexander G.; Altman, Tomer; Rhee, Christine D.

2014-01-01

Despite advances in sequencing technology, there are still significant numbers of well-characterized enzymatic activities for which there are no known associated sequences. These ‘orphan enzymes’ represent glaring holes in our biological understanding, and it is a top priority to reunite them with their coding sequences. Here we report a methodology for resolving orphan enzymes through a combination of database search and literature review. Using this method we were able to reconnect over 270 orphan enzymes with their corresponding sequence. This success points toward how we can systematically eliminate the remaining orphan enzymes and prevent the introduction of future orphan enzymes. PMID:24826896
A comparative study of European rare disease and orphan drug markets.

PubMed

Denis, Alain; Mergaert, Lut; Fostier, Christel; Cleemput, Irina; Simoens, Steven

2010-10-01

This article aims to compare regulatory aspects of rare disease and orphan drug markets in Belgium, France, Italy, the Netherlands, Sweden and the United Kingdom. Information was derived from the international literature, analysis of legal texts, and a survey completed by national experts. These countries adopted varying approaches towards regulating rare disease and orphan drug markets and, hence, the availability, pricing and reimbursement of orphan drugs vary between countries. Strategies to keep down prices include public procurement in Sweden, profit controls in the United Kingdom, and price comparisons with other countries. To gain reimbursement, the cost-effectiveness and/or budget impact of orphan drugs is considered in some countries. Other societal considerations, such as whether the drug treats a life-threatening disease, are sometimes taken into account. Extensive government intervention exists in rare disease and orphan drug markets in the countries studied. Our recommendations are to define priorities for research on rare diseases and orphan drugs at the European level, to set up disease and patient registries with a view to investigating the long-term effectiveness and cost-effectiveness of orphan drugs, to assess the profitability of orphan drugs, and to take into account societal considerations when evaluating orphan drugs. Copyright (c) 2010 Elsevier Ireland Ltd. All rights reserved.

Orphan drugs for rare diseases: is it time to revisit their special market access status?

PubMed

Simoens, Steven; Cassiman, David; Dooms, Marc; Picavet, Eline

2012-07-30

Orphan drugs are intended for diseases with a very low prevalence, and many countries have implemented legislation to support market access of orphan drugs. We argue that it is time to revisit the special market access status of orphan drugs. Indeed, evidence suggests that there is no societal preference for treating rare diseases. Although society appears to assign a greater value to severity of disease, this criterion is equally relevant to many common diseases. Furthermore, the criterion of equity in access to treatment, which underpins orphan drug legislation, puts more value on health improvement in rare diseases than in common diseases and implies that population health is not maximized. Finally, incentives for the development, pricing and reimbursement of orphan drugs have created market failures, including monopolistic prices and the artificial creation of rare diseases. We argue that, instead of awarding special market access status to orphan drugs, there is scope to optimize research and development (R&D) of orphan drugs and to control prices of orphan drugs by means of, for example, patent auctions, advance purchase commitments, pay-as-you-go schemes and dose-modification studies. Governments should consider carefully the right incentive strategy for R&D of orphan drugs in rare diseases.
Assertiveness and Attitudes of HIV/AIDS Orphaned Girls Towards Education in Kampala (Uganda).

PubMed

Kitara, David Lagoro; Amongin, Hellen Christine; Oonyu, Joseph C; Baguma, Peter K

2013-08-09

Whereas HIV/AIDS prevalence has been declining in Uganda from 30% to less than 10% in the last 2 decades, the number of HIV/AIDS orphaned girls in secondary schools is still high and girl children have tended to carry the heaviest burdens of family responsibilities thereby adversely affecting their assertiveness and attitudes towards education. Assertiveness is a critical life skill that enables a person to state an opinion, claim a right, or establish authority and it is important to improve attitude towards education. This study examined the relationship between assertiveness and attitude towards education of HIV/AIDS orphaned and non-orphaned adolescent school girls in Kampala. The California Psychological Inventory (CPI) Dominance (Do) Assertiveness Scale and the Attitude Scale were administered to 225 students consecutively selected from 6 secondary schools in Kampala. HIV/AIDS Orphaned girls had lower levels of assertiveness and most had a negative attitude towards education compared to non-orphaned girls. Girls orphaned to HIV/AIDS were less assertive compared to those orphaned by other causes. There was a positive relationship between assertiveness and attitude towards education among orphaned adolescent secondary school girls in Kampala. Girls orphaned to HIV/AIDS were less assertive compared to other school girls and have a poor attitude towards education.
Barriers and incentives to orphan care in a time of AIDS and economic crisis: a cross-sectional survey of caregivers in rural Zimbabwe.

PubMed

Howard, Brian H; Phillips, Carl V; Matinhure, Nelia; Goodman, Karen J; McCurdy, Sheryl A; Johnson, Cary A

2006-02-09

Africa is in an orphan-care crisis. In Zimbabwe, where one-fourth of adults are HIV-positive and one-fifth of children are orphans, AIDS and economic decline are straining society's ability to care for orphans within their extended families. Lack of stable care is putting thousands of children at heightened risk of malnourishment, emotional underdevelopment, illiteracy, poverty, sexual exploitation, and HIV infection, endangering the future health of the society they are expected to sustain. To explore barriers and possible incentives to orphan care, a quantitative cross-sectional survey in rural eastern Zimbabwe asked 371 adults caring for children, including 212 caring for double orphans, about their well-being, needs, resources, and perceptions and experiences of orphan care. Survey responses indicate that: 1) foster caregivers are disproportionately female, older, poor, and without a spouse; 2) 98% of non-foster caregivers are willing to foster orphans, many from outside their kinship network; 3) poverty is the primary barrier to fostering; 4) financial, physical, and emotional stress levels are high among current and potential fosterers; 5) financial need may be greatest in single-orphan AIDS-impoverished households; and 6) struggling families lack external support. Incentives for sustainable orphan care should focus on financial assistance, starting with free schooling, and development of community mechanisms to identify and support children in need, to evaluate and strengthen families' capacity to provide orphan care, and to initiate and support placement outside the family when necessary.
Optimised management of orphan wastes in the UK

DOE Office of Scientific and Technical Information (OSTI.GOV)

Doudou, Slimane; McTeer, Jennifer; Wickham, Stephen

2013-07-01

Orphan wastes have properties preventing them from being managed according to existing or currently planned management routes, or lack characterisation so that their management is uncertain. The identification of new management opportunities for orphan wastes could realise significant benefits by reducing the number of processing facilities required, reducing waste volumes, reducing hazard or leading to the development of centres of excellence for the processing of certain types of orphan wastes. Information on the characteristics of orphan waste existing at nuclear licensed sites across the UK has been collated and a database developed to act as a repository for the informationmore » gathered. The database provides a capability to analyse the data and to explore possible treatment technologies for each orphan waste type. Thirty five distinct orphan waste types have been defined and possible treatment options considered. Treatment technologies (including chemical, high temperature, immobilisation and physical technologies) that could be applied to one or more of the generic orphan waste streams have been identified. Wiring diagrams have been used to highlight the waste treatment / lifecycle management options that are available for each of the generic orphan groups as well as identifying areas for further research and development. This work has identified the potential for optimising the management of orphan wastes in a number of areas, and many potential opportunities were identified. Such opportunities could be investigated by waste managers at waste producing nuclear sites, to facilitate the development of new management routes for orphan wastes. (authors)« less
A Young Orphan Finds His "Voice" in the Theater.

ERIC Educational Resources Information Center

Morse, Richard

2001-01-01

Describes the author's experiences in Santa Cruz, Bolivia creating a theater program in an orphanage. Notes how Gueddy, a deaf boy, worked his way into the drama program and was very successful finding his "voice" in theater. Concludes that Gueddy is now the star of the orphanage, the talk of the town, and front page news in Bolivia. (SG)
Mentoring by Modem. Connect for Kids: Guidance for Grown-Ups.

ERIC Educational Resources Information Center

Newberger, Julee

This article describes the use of an eMentoring program by the Orphan Foundation of America, a nonprofit organization dedicated to helping young people move out of foster care and into adult life. The eMentoring program, which allows youth and their mentors to communicate via e-mail, helps foster youth prepare for work life by matching them with…
Profitability and Market Value of Orphan Drug Companies: A Retrospective, Propensity-Matched Case-Control Study.

PubMed

Hughes, Dyfrig A; Poletti-Hughes, Jannine

2016-01-01

Concerns about the high cost of orphan drugs has led to questions being asked about the generosity of the incentives for development, and associated company profits. We conducted a retrospective, propensity score matched study of publicly-listed orphan companies. Cases were defined as holders of orphan drug market authorisation in Europe or the USA between 2000-12. Control companies were selected based on their propensity for being orphan drug market authorisation holders. We applied system General Method of Moments to test whether companies with orphan drug market authorization are valued higher, as measured by the Tobin's Q and market to book value ratios, and are more profitable based on return on assets, than non-orphan drug companies. 86 companies with orphan drug approvals in European (4), USA (61) or both (21) markets were matched with 258 controls. Following adjustment, orphan drug market authorization holders have a 9.6% (95% confidence interval, 0.6% to 18.7%) higher return on assets than non-orphan drug companies; Tobin's Q was higher by 9.9% (1.0% to 19.7%); market to book value by 15.7% (3.1% to 30.0%) and operating profit by 516% (CI 19.8% to 1011%). For each additional orphan drug sold, return on assets increased by 11.1% (0.6% to 21.3%), Tobin's Q by 2.7% (0.2% to 5.2%), and market to book value ratio by 5.8% (0.7% to 10.9%). Publicly listed pharmaceutical companies that are orphan drug market authorization holders are associated with higher market value and greater profits than companies not producing treatments for rare diseases.
Profitability and Market Value of Orphan Drug Companies: A Retrospective, Propensity-Matched Case-Control Study

PubMed Central

Hughes, Dyfrig A.; Poletti-Hughes, Jannine

2016-01-01

Background Concerns about the high cost of orphan drugs has led to questions being asked about the generosity of the incentives for development, and associated company profits. Methods We conducted a retrospective, propensity score matched study of publicly-listed orphan companies. Cases were defined as holders of orphan drug market authorisation in Europe or the USA between 2000–12. Control companies were selected based on their propensity for being orphan drug market authorisation holders. We applied system General Method of Moments to test whether companies with orphan drug market authorization are valued higher, as measured by the Tobin’s Q and market to book value ratios, and are more profitable based on return on assets, than non-orphan drug companies. Results 86 companies with orphan drug approvals in European (4), USA (61) or both (21) markets were matched with 258 controls. Following adjustment, orphan drug market authorization holders have a 9.6% (95% confidence interval, 0.6% to 18.7%) higher return on assets than non-orphan drug companies; Tobin’s Q was higher by 9.9% (1.0% to 19.7%); market to book value by 15.7% (3.1% to 30.0%) and operating profit by 516% (CI 19.8% to 1011%). For each additional orphan drug sold, return on assets increased by 11.1% (0.6% to 21.3%), Tobin’s Q by 2.7% (0.2% to 5.2%), and market to book value ratio by 5.8% (0.7% to 10.9%). Conclusions Publicly listed pharmaceutical companies that are orphan drug market authorization holders are associated with higher market value and greater profits than companies not producing treatments for rare diseases. PMID:27768685
Emotional development and nutritional status of HIV/AIDS orphaned children aged 6-12 years old in Thailand.

PubMed

Isaranurug, Sirikul; Chompikul, Jiraporn

2009-01-01

To explore the emotional development and nutritional status of HIV/AIDS orphans by their infection status. A community-based cross-sectional survey was conducted during January and December 2005 in four provinces and Bangkok Metropolis where the prevalence of HIV/AIDS among pregnant women was high. The study population consisted of 388 HIV/AIDS orphans who were maternal or paternal or double orphans aged 6-12 years old. The orphans' main caregivers gave informed consent to the project and assessed the emotional development of their orphaned children. The children were measured for weight, height, and emotional development by standard instruments. They were divided into three groups regarding their HIV/AIDS infection status reported by their caregivers: infected, non-infected, and unknown. The chi(2) test was used to determine the association between nutritional status and infection status. Regarding HIV/AIDS infected children, 19.1% were infected, 57.5% were not infected, and 23.4% were unknown. The main caregivers of all types of orphans were grandparents. Only 13.7% of infected orphans lived with their mothers. Most caregivers were females and more than 40 years old. Infected orphans had mean scores of overall emotional development and for each domain less than other groups. The mean scores of self-control and quick recovery were significantly different between infected and non-infected groups (P-value < 0.05). Nearly 50% of infected orphans were rather short and approximately 42% were under weight and light. The findings revealed a significant association between height for age, weight for age and infection status of orphans at a P-value of <0.001. Orphanhood itself is a vulnerable status and HIV/AIDS infected orphans are most vulnerable. Acceptable and friendly services for orphans and their families are crucial. The services should continue and protect stigmatization.
Orphan Status, HIV Risk Behavior, and Mental Health Among Adolescents in Rural Kenya

PubMed Central

Drabkin, Anya S.; Stashko, Allison L.; Broverman, Sherryl A.; Ogwang-Odhiambo, Rose A.; Sikkema, Kathleen J.

2012-01-01

Objective To examine orphan status, mental health, social support, and HIV risk among adolescents in rural Kenya. Methods Randomly selected adolescents aged 10–18 years completed surveys assessing sexual activity, sex-related beliefs and self-efficacy, mental health, social support, caregiver–child communication, time since parental death, and economic resources. Analysis of covariance and regression analyses compared orphans and nonorphans; orphan status was tested as a moderator between well-being and HIV risk. Results Orphans reported poorer mental health, less social support, and fewer material resources. They did not differ from nonorphans on HIV risk indicators. Longer time since parental death was associated with poorer outcomes. In moderator analyses, emotional problems and poorer caregiver–youth communication were more strongly associated with lower sex-related self-efficacy for orphans. Conclusions Orphans are at higher risk for psychosocial problems. These problems may affect orphans’ self-efficacy for safer sex practices more than nonorphans. Decreased HIV risk could be one benefit of psychosocial interventions for orphans. PMID:22728899
The relationship between orphanhood and child fostering in sub-Saharan Africa, 1990s–2000s

PubMed Central

Grant, Monica J.; Yeatman, Sara

2012-01-01

In countries most afflicted by HIV/AIDS in sub-Saharan Africa, orphanhood has increased dramatically, but the potential consequences of the increase have been mitigated by the ability of households to absorb orphans. This paper examines what the rising levels of orphanhood mean for the common practice of non-orphan child fostering in regions of high and low HIV prevalence in sub-Saharan Africa, which has a long history of child fostering. Using Demographic and Health Survey data from 135 regions within 14 sub-Saharan countries that undertake HIV testing and have had at least two surveys, we examine changes in fostering patterns. In most regions, we find a more accommodating relationship between orphan and non-orphan fostering: communities are able to absorb the demand for both orphans and non-orphans. Where HIV prevalence exceeds ten per cent there is some evidence that the need to care for orphans is beginning to reduce opportunities for non-orphan fostering. PMID:22607126
From novice to expert: agroecological competences of children orphaned by AIDS compared to non-orphans in Benin.

PubMed

Fagbemissi, Rose C; Price, Lisa L

2011-01-10

AIDS has created new vulnerabilities for rural African households due to prime-age adult mortality and is assumed to lead to impairment of the intergenerational transfer of farming knowledge. There has been scant research to date, however, on the impacts of parental death on farming knowledge of children made orphans by AIDS. The question we investigate is if there is a difference in agricultural expertise between AIDS affected and non-affected adults and children. The research was carried out in rural Benin with 77 informants randomly selected according to their AIDS status: 13 affected and 13 non-affected adults; 13 paternal, 13 maternal and 13 double orphans; and 12 non-orphan children. Informants descriptions from pile sorting exercises of maize and cowpea pests were categorized and then aggregated into descriptions based form (morphology) and function (utility) and used to determine whether the moving from novice to expert is impaired by children orphaned by AIDS. Differences and similarities in responses were determined using the Fischer exact test and the Cochran-Mantzel-Haenszel test. No significant differences were found between AIDS affected and non-affected adults. Results of the study do reveal differences in the use of form and function descriptors among the children. There is a statistically significant difference in the use of form descriptors between one-parent orphans and non-orphans and in descriptors of specific damages to maize. One-parent paternal orphans were exactly like non-affected adults in their 50/50 balanced expertise in the use of both form and function descriptors. One-parent orphans also had the highest number of descriptors used by children overall and these descriptors are spread across the various aspects of the knowledge domain relative to non-orphans. Rather than a knowledge loss for one-parent orphans, particularly paternal orphans, we believe we are witnessing acceleration into adult knowledge frames. This expertise of one-parent orphans may be a result of a combination of factors deserving further investigation including enhanced hands-on work experience with the food crops in the field and the expertise available from the surviving parent coupled with the value of the food resource to the household.
Impact of the Kenya Cash Transfer for Orphans and Vulnerable Children on early pregnancy and marriage of adolescent girls.

PubMed

Handa, Sudhanshu; Peterman, Amber; Huang, Carolyn; Halpern, Carolyn; Pettifor, Audrey; Thirumurthy, Harsha

2015-09-01

There is promising evidence that poverty-targeted cash transfer programs can have positive impacts on adolescent transitions to adulthood in resource poor settings, however existing research is typically from small scale programs in diverse geographic and cultural settings. We provide estimates of the impact of a national unconditional cash transfer program, the Kenya Cash Transfer for Orphans and Vulnerable Children, on pregnancy and early marriage among females aged 12 to 24, four years after program initiation. The evaluation was designed as a clustered randomized controlled trial and ran from 2007 to 2011, capitalizing on the existence of a control group, which was delayed entry to the program due to budget constraints. Findings indicate that, among 1549 females included in the study, while the program reduced the likelihood of pregnancy by five percentage points, there was no significant impact on likelihood of early marriage. Program impacts on pregnancy appear to work through increasing the enrollment of young women in school, financial stability of the household and delayed age at first sex. The Kenyan program is similar in design to most other major national cash transfer programs in Eastern and Southern Africa, suggesting a degree of generalizability of the results reported here. Although the objective of the program is primarily poverty alleviation, it appears to have an important impact on facilitating the successful transition of adolescent girls into adulthood. Copyright © 2015 Elsevier Ltd. All rights reserved.
Impact of the Kenya Cash Transfer for Orphans and Vulnerable Children on early pregnancy and marriage of adolescent girls

PubMed Central

Handa, Sudhanshu; Huang, Carolyn; Halpern, Carolyn; Pettifor, Audrey; Thirumurthy, Harsha

2015-01-01

There is promising evidence that poverty-targeted cash transfer programs can have positive impacts on adolescent transitions to adulthood in resource poor settings, however existing research is typically from small scale programs in diverse geographic and cultural settings. We provide estimates of the impact of a national unconditional cash transfer program, the Kenya Cash Transfer for Orphans and Vulnerable Children, on pregnancy and early marriage among females aged 12 to 24, four years after program initiation. The evaluation was designed as a clustered randomized controlled trial and ran from 2007 to 2011, capitalizing on the existence of a control group, which was delayed entry to the program due to budget constraints. Findings indicate that, among 1,549 females included in the study, while the program reduced the likelihood of pregnancy by five percentage points, there was no significant impact on likelihood of early marriage. Program impacts on pregnancy appear to work through increasing the enrollment of young women in school, financial stability of the household and delayed age at first sex. The Kenyan program is similar in design to most other major national cash transfer programs in Eastern and Southern Africa, suggesting a degree of generalizability of the results reported here. Although the objective of the program is primarily poverty alleviation, it appears to have an important impact on facilitating the successful transition of adolescent girls into adulthood. PMID:26246032
Adverse childhood experiences, psychosocial well-being and cognitive development among orphans and abandoned children in five low income countries

PubMed Central

2014-01-01

Background Development policymakers and child-care service providers are committed to improving the educational opportunities of the 153 million orphans worldwide. Nevertheless, the relationship between orphanhood and education outcomes is not well understood. Varying factors associated with differential educational attainment leave policymakers uncertain where to intervene. This study examines the relationship between psychosocial well-being and cognitive development in a cohort of orphans and abandoned children (OAC) relative to non-OAC in five low and middle income countries (LMICs) to understand better what factors are associated with success in learning for these children. Methods Positive Outcomes for Orphans (POFO) is a longitudinal study, following a cohort of single and double OAC in institutional and community-based settings in five LMICs in Southeast Asia and sub-Saharan Africa: Cambodia, Ethiopia, India, Kenya, and Tanzania. Employing two-stage random sampling survey methodology to identify representative samples of OAC in six sites, the POFO study aimed to better understand factors associated with child well-being. Using cross-sectional and child-level fixed effects regression analyses on 1,480 community based OAC and a comparison sample of non-OAC, this manuscript examines associations between emotional difficulties, cognitive development, and a variety of possible co-factors, including potentially traumatic events. Results The most salient finding is that increases in emotional difficulties are associated with lags in cognitive development for two separate measures of learning within and across multiple study sites. Exposure to potentially traumatic events, male gender, and lower socio-economic status are associated with more reported emotional difficultiesin some sites. Being female and having an illiterate caregiver is associated with lower performance on cognitive development tests in some sites, while greater wealth is associated with higher performance. There is no significant association between orphan status per se and cognitive development, though the negative and significant association between higher emotional difficulties and lags in cognitive development hold across all orphan subgroups. Conclusions These findings suggest that interventions targeting psychosocial support for vulnerable children, especially vis a vis traumatic experiences, may ease strains inhibiting a child’s learning. Family based interventions to stabilize socioeconomic conditions may help overcome psychosocial challenges that otherwise would present as barriers to the child’s learning. PMID:24606949
[Orphan diseases and orphan medicines: a Belgian and European study].

PubMed

Denis, Alain; Mergaert, Lut; Fostier, Christel; Cleemput, Irina; Simoens, Steven

2009-12-01

The objective of this study is to analyze policies concerning orphan medicines, used to treat patients suffering from a rare disease. The decisions about orphan designation and marketing authorization of orphan medicines are taken at European level, but each Member State is responsible for decisions regarding reimbursement. The European measures to encourage the development of orphan medicines, such as market exclusivity for a period of ten years, seem to be successful. However, this market exclusivity should be revised once the profitability of such medicines has clearly been demonstrated. Our study recommends the implementation of patient registries at the European level in order to describe the natural evolution of rare diseases and the efficacy of orphan medicines, the majority of which are relatively expensive. In 2008, Belgian social security services reimbursed orphan medicines for an amount of 66 million euro, accounting for more than 5% of the hospital pharmaceutical budget. The reimbursement of an orphan medicine to an individual patient is subject to multiple conditions. Our study recommends that a unique counter within the NIHDI is created which centralizes all reimbursement requests. The reimbursement of an orphan medicine must be linked to the provision of standardized information needed for a patient register. The NIHDI administration could then, in collaboration with external experts, evaluate reimbursement requests and ensure a coherent application of reimbursement criteria.
Role of traditional healers in psychosocial support in caring for the orphans: a case of Dar-es Salaam City, Tanzania.

PubMed

Kayombo, Edmund J; Mbwambo, Zakaria H; Massila, Mariam

2005-07-29

Orphans are an increasing problem in developing countries particularly in Africa; due to the HIV/AIDS pandemic; and needs collective effort in intervention processes by including all stakeholders right from the grass roots level. This paper attempts to present the role of traditional healers in psychosocial support for orphan children in Dar-es-Salaam City with special focus on those whose parents have died because of HIV/AIDS. Six traditional healers who were involved in taking care of orphans were visited at their "vilinge" (traditional clinics). In total they had 72 orphans, 31 being boys and 41 being girls with age range from 3 years to 19. It was learned that traditional healers, besides providing remedies for illnesses/diseases of orphans, they also provided other basic needs. Further, they even provided psychosocial support allowing children to cope with orphan hood life with ease. Traditional healers are living within communities at the grass roots level; and appear unnoticed hidden forces, which are involved in taking care of orphans. This role of traditional healers in taking care of orphans needs to be recognised and even scaling it up by empowering them both in financial terms and training in basic skills of psychosocial techniques in how to handle orphans, in order to reduce discrimination and stigmatisation in the communities where they live.
Nurturing Care for China's Orphaned Children

ERIC Educational Resources Information Center

Cotton, Janice N.; Edwards, Carolyn Pope; Zhao, Wen; Gelabert, Jeronia Muntaner

2007-01-01

Half the Sky, an international NGO, works in partnership with Chinese national and provincial governments inside state-run orphanages (welfare institutions). Through their infant nurture programs infants and toddlers in institutions begin to thrive through primary relationship-based care by trained community paraprofessionals. In preschool…
Inverse association of natural mentoring relationship with distress mental health in children orphaned by AIDS.

PubMed

Onuoha, Francis N; Munakata, Tsunetsugu

2010-01-16

The magnitude of the AIDS-orphaned children crisis in sub-Saharan Africa has so overstretched the resource of most families that the collapse of fostering in the sub-region seems imminent (UNICEF, 2003), fueling the need for a complementary/alternative care. This paper examines the probability of the natural mentoring care to ameliorate distress mental health in children orphaned by AIDS. 952 children, mean age about 14 years, from local community schools and child-care centers in Kampala (Uganda) and Mafikeng/Klerksdorp (South Africa) towns participated in the study. The design has AIDS-orphaned group (n = 373) and two control groups: Other-causes orphaned (n = 287) and non-orphaned (n = 290) children. We use measures of child abuse, depression, social discrimination, anxiety, parental/foster care, self-esteem, and social support to estimate mental health. Natural mentoring care is measured with the Ragins and McFarlin (1990) Mentor Role Instrument as adapted. AIDS-orphaned children having a natural mentor showed significant decreased distress mental health factors. Similar evidence was not observed in the control groups. Also being in a natural mentoring relationship inversely related to distress mental health factors in the AIDS-orphaned group, in particular. AIDS-orphaned children who scored high mentoring relationship showed significant lowest distress mental health factors that did those who scored moderate and low mentoring relationship. Natural mentoring care seems more beneficial to ameliorate distress mental health in AIDS-orphaned children (many of whom are double-orphans, having no biological parents) than in children in the control groups.
Inverse association of natural mentoring relationship with distress mental health in children orphaned by AIDS

PubMed Central

2010-01-01

Background The magnitude of the AIDS-orphaned children crisis in sub-Saharan Africa has so overstretched the resource of most families that the collapse of fostering in the sub-region seems imminent (UNICEF, 2003), fueling the need for a complementary/alternative care. This paper examines the probability of the natural mentoring care to ameliorate distress mental health in children orphaned by AIDS. Methods 952 children, mean age about 14 years, from local community schools and child-care centers in Kampala (Uganda) and Mafikeng/Klerksdorp (South Africa) towns participated in the study. The design has AIDS-orphaned group (n = 373) and two control groups: Other-causes orphaned (n = 287) and non-orphaned (n = 290) children. We use measures of child abuse, depression, social discrimination, anxiety, parental/foster care, self-esteem, and social support to estimate mental health. Natural mentoring care is measured with the Ragins and McFarlin (1990) Mentor Role Instrument as adapted. Results AIDS-orphaned children having a natural mentor showed significant decreased distress mental health factors. Similar evidence was not observed in the control groups. Also being in a natural mentoring relationship inversely related to distress mental health factors in the AIDS-orphaned group, in particular. AIDS-orphaned children who scored high mentoring relationship showed significant lowest distress mental health factors that did those who scored moderate and low mentoring relationship. Conclusions Natural mentoring care seems more beneficial to ameliorate distress mental health in AIDS-orphaned children (many of whom are double-orphans, having no biological parents) than in children in the control groups. PMID:20078888

Children’s psychosocial wellbeing in the context of HIV/AIDS and poverty: a comparative investigation of orphaned and non-orphaned children living in South Africa

PubMed Central

2014-01-01

Background Recent studies have questioned whether orphanhood is primarily associated with key dimensions of psycho-social wellbeing in children living in circumstances of material deprivation and high prevalence of HIV and AIDS. Methods This study uses cross-sectional data from a longitudinal study conducted between 2004-2007 to examine the psychosocial well-being of orphans and non-orphans in the Amajuba District of KwaZulu-Natal, South Africa. Psychosocial wellbeing included an assessment of orphans’ and non orphans’ level of anxiety and depression, affability and resilience. Stratified cluster sampling, based on both school and age, was used to construct a cohort of recent orphans and non-orphans and their households, randomly selected from schools. Results Levels of anxiety and depression, affability and resilience did not differ significantly between orphans and non-orphans, nor did salient household, poverty and caregiver characteristics vary substantially amongst orphans and non-orphans. Multivariate analyses indicated that children’s psychosocial outcomes, when controlling for orphan status and related demographic variables were more strongly influenced by household composition/size, living above or below the poverty threshold and factors associated with the caregiver-child relationship and caregiver health. Conclusions The results muster additional evidence for moving beyond narrow definitions of vulnerability associated exclusively with orphanhood to consider the multitude of material, social and relational factors affecting the psycho-social well-being of children in general who are living in circumstances of poverty and HIV and AIDS. PMID:24938864
Predictors of Mental Health Resilience in Children who Have Been Parentally Bereaved by AIDS in Urban South Africa.

PubMed

Collishaw, Stephan; Gardner, Frances; Lawrence Aber, J; Cluver, Lucie

2016-05-01

Children parentally bereaved by AIDS experience high rates of mental health problems. However, there is considerable variability in outcomes, and some show no mental health problems even when followed over time. Primary aims were to identify predictors of resilient adaptation at child, family and community levels within a group of AIDS-orphaned children, and to consider their cumulative influence. A secondary aim was to test whether predictors were of particular influence among children orphaned by AIDS relative to non-orphaned and other-orphaned children. AIDS-orphaned (n = 290), other-orphaned (n = 163) and non-orphaned (n = 202) adolescents living in informal settlements in Cape Town, South Africa were assessed on two occasions 4 years apart (mean age 13.5 years at Time 1, range = 10-19 years). Self-report mental health screens were used to operationalise resilience in AIDS-orphaned children as the absence of clinical-range symptoms of PTSD, anxiety, depression, conduct problems, and suicidality. A quarter of AIDS-orphaned children (24 %) showed no evidence of mental health problems at either wave. Child physical health, better caregiving quality, food security, better peer relationship quality, and lower exposure to community violence, bullying or stigma at baseline predicted sustained resilience. There were cumulative influences across predictors. Associations with mental health showed little variation by child age or gender, or between orphaned and non-orphaned children. Mental health resilience is associated with multiple processes across child, family and community levels of influence. Caution is needed in making causal inferences.
Collaborative Partnerships to Increase Resilience among AIDS Orphans: Some Unforeseen Challenges and Caveats

ERIC Educational Resources Information Center

Wood, L.; Theron, L.; Mayaba, N.

2012-01-01

Previous research has attested to the power of metaphor-rich stories to enable resilience during individual therapy, but this has not been researched in a group context. We aimed to ascertain if the reading of brief stories in a group setting, with no other therapeutic intervention, would prove to be a valuable, inexpensive and accessible…
[GPCRs heterodimerization: a new way towards the discovery of function for the orphan receptors?].

PubMed

Levoye, Angélique; Jockers, Ralf

2007-01-01

G protein-coupled receptors (GPCRs), also called seven transmembrane domain (7TM) proteins, represent the largest family of cell surface receptors. GPCRs control a variety of physiological processes, are involved in multiple diseases and are major drug targets. Despite a vast effort of academic and industrial research, more than one hundred receptors remain orphans. These orphan GPCRs offer a great potential for drug discovery, as almost 60% of currently prescribed drugs target GPCRs. Deorphenization strategies have concentrated mainly on the identification of the natural ligands of these proteins. Recent advances have shown that orphan GPCRs, similar to orphan nuclear receptors, can regulate the function of non-orphan receptors by heterodimerization. These findings not only help to better understand the extraordinary diversity of GPCRs, but also open new perspectives for the identification of the function of these orphan receptors that hold great therapeutic potential.
77 FR 46764 - Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01)

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-06

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0011] Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01) AGENCY: Food... orphan products. Orphan products are drugs, biologics, medical devices, and medical foods that are...
Hunting for the function of orphan GPCRs – beyond the search for the endogenous ligand

PubMed Central

Ahmad, Raise; Wojciech, Stefanie; Jockers, Ralf

2015-01-01

Seven transmembrane-spanning proteins (7TM), also called GPCRs, are among the most versatile and evolutionary successful protein families. Out of the 400 non-odourant members identified in the human genome, approximately 100 remain orphans that have not been matched with an endogenous ligand. Apart from the classical deorphanization strategies, several alternative strategies provided recent new insights into the function of these proteins, which hold promise for high therapeutic potential. These alternative strategies consist of the phenotypical characterization of organisms silenced or overexpressing orphan 7TM proteins, the search for constitutive receptor activity and formation of protein complexes including 7TM proteins as well as the development of synthetic, surrogate ligands. Taken together, a variety of ligand-independent functions can be attributed to orphan 7TM proteins that range from constitutive activity to complex formation with other proteins and include ‘true’ orphans for which no ligand exist and ‘conditional’ orphans that behave like orphans in the absence of ligand and as non-orphans in the presence of ligand. PMID:25231237
[Authorization and reimbursement of orphan drugs in an international comparison].

PubMed

Roll, K; Stargardt, T; Schreyögg, J

2011-08-01

This paper analyses schemes to promote the authorisation of and reimbursement for orphan drugs. 8 countries - Australia, Canada, Germany, Great Britain, France, Netherlands, Switzerland, USA - were studied to compare specific regulations for orphan drugs regarding drug admission, health technology assessment (HTA), decision-making for reimbursement, and off-label and compassionate use. Information was obtained by reviewing published and grey literature. Expert interviews were also conducted. The comparison of orphan drug legislation reveals that the EU and the USA offer the greatest incentives for the development of orphan drugs, whereas there is a tendency for Australia and Switzerland to profit from incentives in other countries. Although not explicitly stated, economic evaluation of orphan drugs takes the special circumstances for orphan drugs into account. In addition to common reimbursement practices, special schemes or programmes for the reimbursement of high-priced orphan drugs exist in all countries that were analysed. Therefore access to orphan drugs seems to be warranted. However, due to co-payments of 5%, the USA may form an exception. On the one hand, the use of special criteria for drug admission, HTA, and reimbursement promotes R&D for orphan drugs. On the other hand, high opportunity costs arise, because huge efforts are made for a minority of patients. A solution for this moral dilemma may be the application of "rule of rescue" or of "no cure, no pay" programmes. © Georg Thieme Verlag KG Stuttgart · New York.
Children, AIDS and the politics of orphan care in Ethiopia: the extended family revisited.

PubMed

Abebe, Tatek; Aase, Asbjorn

2007-05-01

The astounding rise in the number of orphans due to the HIV/AIDS epidemic has left many Ethiopian families and communities with enormous childcare problems. Available studies on the capacity and sustainability of the extended family system, which culturally performs the role of care for children in need, suggest two competing theories. The first is grounded in the social rupture thesis and assumes that the traditional system of orphan care is stretched by the impact of the epidemic, and is actually collapsing. By contrast, the second theory counter-suggests that the flexibility and strength of the informal childcare practise, if supported by appropriate interventions, can still support a large number of orphans. Based on a seven-month period of child-focused, qualitative research fieldwork in Ethiopia involving observations; in-depth interviews with orphans (42), social workers (12) and heads of households (18); focus group discussions with orphans (8), elderly people and community leaders (6); and story-writing by children in school contexts, this article explores the trade-offs and social dynamics of orphan care within extended family structures in Ethiopia. It argues that there is a rural-urban divide in the capacity to cater for orphans that emanates from structural differences as well as the socio-cultural and economic values associated with children. The care of orphans within extended family households is also characterised by multiple and reciprocal relationships in care-giving and care-receiving practices. By calling for a contextual understanding of the 'orphan burden', the paper concludes that interventions for orphans may consider care as a continuum in the light of four profiles of extended families, namely rupturing, transient, adaptive, and capable families.
Effectiveness of a Motivation and Practical Skills Development Methods on the Oral Hygiene of Orphans Children in Kaunas, Lithuania.

PubMed

Markeviciute, Greta; Narbutaite, Julija

2015-01-01

The aim of this study was to evaluate the effect of a motivation and practical skills development methods on the oral hygiene of orphans. Sixty eight orphans aged between 7 and 17 years from two orphanages in Kaunas were divided into two groups: practical application group and motivation group. Children were clinically examined by determining their oral hygiene status using Silness-Löe plaque index. Questionnaire was used to estimate the oral hygiene knowledge and practices at baseline and after 3 months. Statistical analysis included: Chi-square test (χ(2)), Fisher's exact test, Student's t-test, nonparametric Mann-Whitney test, Spearman's rho correlation coefficient and Kappa coefficient. All children had a plaque on at least one tooth in both groups: motivation 1.14 (SD 0.51), practical application 1.08 (SD 0.4) (P = 0.58). Girls in both groups showed significantly better oral hygiene than boys (P < 0.001). After 3 months educational program oral hygiene status improved in both groups significantly 0.4 (SD 0.35) (P < 0.001). Significantly better oral hygiene was determined in practical application group 0.19 (SD 0.27) in comparison with motivation group 0.55 (SD 0.32) (P < 0.001). By comparing results of first and second questionnaire surveys on use of soft drinks, the statistically significant decline of their use was in both groups (P = 0.004). Educational programs are effective in improving oral hygiene, especially when they're based on practical skills training.
Survival, family conditions and nutritional status of motherless orphans in the West Bank, Palestine.

PubMed

Al-Adili, Nadim; Shaheen, Mohammad; Bergstrom, Staffan; Johansson, Annika

2008-05-01

This study describes survival, family care and growth of the orphans of women dying at reproductive age (15-49 years) in the West Bank, Palestine, in 2000 and 2001. One hundred and sixty-seven children who were below 5 years of age at the time of the mother's death were identified. Three had died soon after birth. The family situation for the remaining 164 children was recorded. A planned baseline study could not be done at that time, due to the escalating political violence in the study area. In 2004, an average of 3 years after the mother's death, all orphan families were contacted. Of the 164 orphans, six had left the country with their fathers, and six could not be reached, due to restricted mobility. Home interviews were conducted with the 148 orphans' custodians/care-takers. Family situation and orphans' health status as judged by the interviewees were investigated, and are presented in descriptive statistics. Orphan weight and height were measured, and rates of wasting and stunting were calculated and analysed by gender. The most striking finding is the high survival rate among the orphans. With the exception of the three neonatal deaths, all orphans who could be reached were alive. Almost all lived with their fathers, most of whom had remarried shortly after the death of their wives, and a stepmother had joined the family in 85% of the cases. Of the orphans under 5 years of age at the time of the interview, 8.8% and 17.6%, respectively, suffered from wasting and stunting, all of whom were girls. These rates were higher than those in the national data from 2003 for Palestinian children. Early family reconstruction is suggested to be a contributing factor to the high survival rate. Close monitoring of motherless orphans' health and nutritional status, with a special emphasis on orphan girls, should be ensured.
Does the Orphan Disadvantage “Spill Over?” An analysis of whether living in an area with a higher concentration of orphans is associated with children’s school enrollment in sub-Saharan Africa

PubMed Central

Smith-Greenaway, Emily; Heckert, Jessica

2013-01-01

BACKGROUND Despite considerable concern regarding the social consequences of sub-Saharan Africa’s high orphan prevalence, no research investigates how living in a community densely populated with orphans is more broadly associated with children’s—including nonorphans’—acquisition of human capital. OBJECTIVE We provide a new look at the implications of widespread orphanhood in sub-Saharan Africa by examining whether living in an area with a high concentration of orphans is associated with children’s likelihood of school enrollment. METHODS We use data from the Demographic and Health Survey (DHS) and the Multiple Indicators Cluster Survey (MICS) to estimate multilevel logistic regression models to assess whether living in a setting with a higher concentration of orphans is associated with school enrollment among 383,010 children in 336 provinces in 34 sub-Saharan African countries. RESULTS Orphan concentration has a curvilinear association with children’s school enrollment in western and eastern Africa: the initially positive association becomes negative at higher levels. In central and southern Africa, orphan concentration has a positive linear association with children’s school enrollment. CONCLUSION In western and eastern Africa, the negative association between living in a setting more densely populated with orphans and children’s school enrollment provides suggestive evidence that the orphan disadvantage “spills over” in the communities most heavily affected. Conversely, in central and southern Africa, the positive association between living in a setting more densely populated with orphans and children’s school enrollment highlights the resiliency of these relatively wealthier communities with high levels of orphans. Although longitudinal research is needed to confirm these findings and clarify the underlying mechanisms, this study lays the groundwork for a new body of research aimed at understanding the broader social implications of widespread orphanhood in sub-Saharan Africa. PMID:24062628
From novice to expert: agroecological competences of children orphaned by AIDS compared to non-orphans in Benin

PubMed Central

2011-01-01

Background AIDS has created new vulnerabilities for rural African households due to prime-age adult mortality and is assumed to lead to impairment of the intergenerational transfer of farming knowledge. There has been scant research to date, however, on the impacts of parental death on farming knowledge of children made orphans by AIDS. The question we investigate is if there is a difference in agricultural expertise between AIDS affected and non-affected adults and children. Methods The research was carried out in rural Benin with 77 informants randomly selected according to their AIDS status: 13 affected and 13 non-affected adults; 13 paternal, 13 maternal and 13 double orphans; and 12 non-orphan children. Informants descriptions from pile sorting exercises of maize and cowpea pests were categorized and then aggregated into descriptions based form (morphology) and function (utility) and used to determine whether the moving from novice to expert is impaired by children orphaned by AIDS. Differences and similarities in responses were determined using the Fischer exact test and the Cochran-Mantzel-Haenszel test. Results No significant differences were found between AIDS affected and non-affected adults. Results of the study do reveal differences in the use of form and function descriptors among the children. There is a statistically significant difference in the use of form descriptors between one-parent orphans and non-orphans and in descriptors of specific damages to maize. One-parent paternal orphans were exactly like non-affected adults in their 50/50 balanced expertise in the use of both form and function descriptors. One-parent orphans also had the highest number of descriptors used by children overall and these descriptors are spread across the various aspects of the knowledge domain relative to non-orphans. Conclusions Rather than a knowledge loss for one-parent orphans, particularly paternal orphans, we believe we are witnessing acceleration into adult knowledge frames. This expertise of one-parent orphans may be a result of a combination of factors deserving further investigation including enhanced hands-on work experience with the food crops in the field and the expertise available from the surviving parent coupled with the value of the food resource to the household. PMID:21219626
Identification of Thiotetronic Acid Antibiotic Biosynthetic Pathways by Target-directed Genome Mining.

PubMed

Tang, Xiaoyu; Li, Jie; Millán-Aguiñaga, Natalie; Zhang, Jia Jia; O'Neill, Ellis C; Ugalde, Juan A; Jensen, Paul R; Mantovani, Simone M; Moore, Bradley S

2015-12-18

Recent genome sequencing efforts have led to the rapid accumulation of uncharacterized or "orphaned" secondary metabolic biosynthesis gene clusters (BGCs) in public databases. This increase in DNA-sequenced big data has given rise to significant challenges in the applied field of natural product genome mining, including (i) how to prioritize the characterization of orphan BGCs and (ii) how to rapidly connect genes to biosynthesized small molecules. Here, we show that by correlating putative antibiotic resistance genes that encode target-modified proteins with orphan BGCs, we predict the biological function of pathway specific small molecules before they have been revealed in a process we call target-directed genome mining. By querying the pan-genome of 86 Salinispora bacterial genomes for duplicated house-keeping genes colocalized with natural product BGCs, we prioritized an orphan polyketide synthase-nonribosomal peptide synthetase hybrid BGC (tlm) with a putative fatty acid synthase resistance gene. We employed a new synthetic double-stranded DNA-mediated cloning strategy based on transformation-associated recombination to efficiently capture tlm and the related ttm BGCs directly from genomic DNA and to heterologously express them in Streptomyces hosts. We show the production of a group of unusual thiotetronic acid natural products, including the well-known fatty acid synthase inhibitor thiolactomycin that was first described over 30 years ago, yet never at the genetic level in regards to biosynthesis and autoresistance. This finding not only validates the target-directed genome mining strategy for the discovery of antibiotic producing gene clusters without a priori knowledge of the molecule synthesized but also paves the way for the investigation of novel enzymology involved in thiotetronic acid natural product biosynthesis.
Ethical and legal constraints to children’s participation in research in Zimbabwe: experiences from the multicenter pediatric HIV ARROW trial

PubMed Central

2012-01-01

Background Clinical trials involving children previously considered unethical are now considered essential because of the inherent physiological differences between children and adults. An integral part of research ethics is the informed consent, which for children is obtained by proxy from a consenting parent or guardian. The informed consent process is governed by international ethical codes that are interpreted in accordance with local laws and procedures raising the importance of contextualizing their implementation. Findings In Zimbabwe the parental informed consent document for children participating in clinical research is modeled along western laws of ethics and requires that the parent or legally authorized representative provide consent on behalf of a minor. This article highlights the experiences and lessons learnt by Zimbabwean researchers in obtaining informed consent from guardians of orphaned children participating in a collaborative HIV clinical trial involving the Medical Research Council, United Kingdom and four centers, three of which are in Uganda. Researchers were faced with a situation where caregivers of orphaned children were not permitted to provide informed consent for trial participation. The situation contrasted with general clinical practice where consent for procedures on orphans is obtained from their caregivers who are not legal guardians. Conclusion The challenges faced in obtaining informed consent for orphans in this clinical trial underscores the need for the Zimbabwe ethics committee to develop an ethical and legal framework for pediatric research that is based on international guidelines while taking into account the cultural context. The Medical Research Council of Zimbabwe has since started the process that is expected to involve critical stakeholders namely the community including children, ethicists, the legal fraternity and researchers. PMID:22818109
Health promotion strategies for families with adolescents orphaned by HIV and AIDS.

PubMed

Peu, M D

2014-06-01

This paper aims to explore and describe health promotion strategies for adolescents orphaned by human immunodeficiency virus (HIV) and acquired immunodeficiency syndrome (AIDS), as well as the evaluation thereof. Among the Sub-Saharan countries, such as Swaziland, Botswana and Lesotho, South Africa is rated as fourth in the list of countries with the highest number of people living with HIV and AIDS. The study employed phenomenological qualitative design. The population consisted of the purposively selected health promoters working in the Hammanskraal region, directly and indirectly involved with families with adolescents orphaned by HIV and AIDS. Following the focus group interviews, data were analysed using the seven steps of Colaizzi. Four categories and eight subcategories were concluded as the strategies for adolescents orphaned by HIV and AIDS as well as the evaluation thereof. The main categories identified were: the door-to-door outcome, workshop outputs, statistical data and community projects. It is evident that the health promotion strategies informed by the four themes will be implemented. The outcomes may raise an awareness in the community, support families and provide statistics on the impact of HIV and AIDS on families. The study was limited to one subdistrict and to health promoters in a rural area, therefore the results cannot be generalized to all other subdistricts including health promoters, especially those in urban areas. The successful evaluation programme will pin out the strong points and challenges while assisting in improving the quality of work provided in the communities. Continuing professional and practice development are required to maintain the standard of health care in South Africa. Therefore the policymakers need to include relevant information regarding health promotion strategies in reducing the statistics of people living with HIV and AIDS. © 2014 International Council of Nurses.
Ethical and legal constraints to children's participation in research in Zimbabwe: experiences from the multicenter pediatric HIV ARROW trial.

PubMed

Bwakura-Dangarembizi, Mutsa; Musesengwa, Rosemary; Nathoo, Kusum J; Takaidza, Patrick; Mhute, Tawanda; Vhembo, Tichaona

2012-07-20

Clinical trials involving children previously considered unethical are now considered essential because of the inherent physiological differences between children and adults. An integral part of research ethics is the informed consent, which for children is obtained by proxy from a consenting parent or guardian. The informed consent process is governed by international ethical codes that are interpreted in accordance with local laws and procedures raising the importance of contextualizing their implementation. In Zimbabwe the parental informed consent document for children participating in clinical research is modeled after Western laws of ethics and requires that the parent or legally authorized representative provide consent on behalf of a minor. This article highlights the experiences and lessons learnt by Zimbabwean researchers in obtaining informed consent from guardians of orphaned children participating in a collaborative HIV clinical trial involving the Medical Research Council, United Kingdom and four centers, three of which are in Uganda. Researchers were faced with a situation where caregivers of orphaned children were not permitted to provide informed consent for trial participation. The situation contrasted with general clinical practice where consent for procedures on orphans is obtained from their caregivers who are not legal guardians. The challenges faced in obtaining informed consent for orphans in this clinical trial underscores the need for the Zimbabwe ethics committee to develop an ethical and legal framework for pediatric research that is based on international guidelines while taking into account the cultural context. The Medical Research Council of Zimbabwe has since started the process that is expected to involve critical stakeholders namely the community including children, ethicists, the legal fraternity and researchers.
“Orphan” γ-Ray Flares and Stationary Sheaths of Blazar Jets

NASA Astrophysics Data System (ADS)

MacDonald, Nicholas R.; Jorstad, Svetlana G.; Marscher, Alan P.

2017-11-01

Blazars exhibit flares across the entire electromagnetic spectrum. Many γ-ray flares are highly correlated with flares detected at longer wavelengths; however, a small subset appears to occur in isolation, with little or no correlated variability at longer wavelengths. These “orphan” γ-ray flares challenge current models of blazar variability, most of which are unable to reproduce this type of behavior. MacDonald et al. have developed the Ring of Fire model to explain the origin of orphan γ-ray flares from within blazar jets. In this model, electrons contained within a blob of plasma moving relativistically along the spine of the jet inverse-Compton scatter synchrotron photons emanating off of a ring of shocked sheath plasma that enshrouds the jet spine. As the blob propagates through the ring, the scattering of the ring photons by the blob electrons creates an orphan γ-ray flare. This model was successfully applied to modeling a prominent orphan γ-ray flare observed in the blazar PKS 1510-089. To further support the plausibility of this model, MacDonald et al. presented a stacked radio map of PKS 1510-089 containing the polarimetric signature of a sheath of plasma surrounding the spine of the jet. In this paper, we extend our modeling and stacking techniques to a larger sample of blazars: 3C 273, 4C 71.01, 3C 279, 1055+018, CTA 102, and 3C 345, the majority of which have exhibited orphan γ-ray flares. We find that the model can successfully reproduce these flares, while our stacked maps reveal the existence of jet sheaths within these blazars.
A bill to restore the application of the 340B drug discount program to orphan drugs with respect to children's hospitals.

THOMAS, 111th Congress

Sen. Brown, Scott P. [R-MA

2010-09-28

Senate - 09/28/2010 Read twice and referred to the Committee on Health, Education, Labor, and Pensions. (All Actions) Tracker: This bill has the status IntroducedHere are the steps for Status of Legislation:
Can genomics boost productivity of orphan crops?

USDA-ARS?s Scientific Manuscript database

Advances in genomics over the past 20 years have enhanced the precision and efficiency of breeding programs in many temperate cereal crops. One of the first applications of genomics-assisted breeding has been the introgression of loci for resistance to biotic stresses or major quantitative trait loc...
Extended family caring for children orphaned by AIDS: balancing essential work and caregiving in a high HIV prevalence nations.

PubMed

Heymann, J; Earle, A; Rajaraman, D; Miller, C; Bogen, K

2007-03-01

While over 90 per cent of the 15 million children who have been orphaned by HIV/AIDS are cared for by family members, there is little information about whether adults can meet orphans' essential caregiving needs while working to economically survive. Using a survey we conducted in Botswana of 1033 working adults, we analyse the experience of adults who are caring for orphans. Over one-third of working adults were caring for orphans and many with few financial resources: 82% were living on household incomes below US$10 purchasing power parity adjusted per person per day. Because of their caregiving responsibilities, they were less able to supplement income with overtime, weekend, evening, or night work. At the same time caregiving responsibilities meant orphan caregivers spent fewer hours caring for their own children and other family members. Nearly half of orphan caregivers had difficulties meeting their children's needs, and nearly 75% weren't able to meet with children's teachers. Pay loss at work compounded the problems: One-quarter of orphan caregivers reported having to take unpaid leave to meet sick childcare needs and nearly half reported being absent from work for children's routine health care. This paper makes clear that if families are to provide adequate care for orphans while economically surviving there needs to be increases in social supports and improvements in working conditions.

Accessing Social Grants to Meet Orphan Children School Needs: Namibia and South Africa Perspective

ERIC Educational Resources Information Center

Taukeni, Simon; Matshidiso, Taole

2013-01-01

In this comparative paper we interrogate the access of social grants to meet orphan children school needs in Namibia and South Africa. We noted that the two governments are committed to provide orphan children with social grants to enable them to meet the school needs. However, accessing social grant to benefit most vulnerable orphan children…
Longitudinal evaluation of the psychosocial wellbeing of recent orphans compared with non-orphans in a school-attending cohort in KwaZulu-Natal, South Africa

PubMed Central

Bachman DeSilva, Mary; Skalicky, Anne M.; Beard, Jennifer; Cakwe, Mandisa; Zhuwau, Tom; Simon, Jonathon L.

2013-01-01

To assess differences in psychosocial wellbeing between recent orphans and non-orphans, we followed a cohort of 157 school-going orphans and 480 non-orphans ages 9-15 in a context of high HIV/AIDS mortality in South Africa from 2004 to 2007. Several findings were contrary to published evidence to date, as we found no difference between orphans and non-orphans in anxiety/depression symptoms, oppositional behavior, self-esteem, or resilience. Female gender, self-reported poor health, and food insecurity were the most important predictors of children’s psychosocial wellbeing. Notably, girls had greater odds of reporting anxiety/depression symptoms than boys, and scored lower on self-esteem and resilience scales. Food insecurity predicted greater anxiety/depression symptoms and lower resilience. Perceived social support was a protective factor, as it was associated with lower odds of anxiety/depression symptoms, lower oppositional scores, and greater self-esteem and resilience. Our findings suggest a need to identify and strengthen psychosocial supports for girls, and for all children in contexts of AIDS-affected and economic adversity. PMID:23457424
[Hope for patients with rare diseases--"orphan" drugs].

PubMed

Kuzelová, M; Kubácková, K; Palágyi, M; Smíd, M

2006-01-01

Rare diseases are defined as those affected less than five in every 10 000 person in European Union. The purpose of this paper is to present activities, which make possible to stimulate research development and marketing of appropriate medicine for tretment of rare disease, named "Orphan" medicinal products. EU "Orphan" medicinal products legislation which entered into force in April 2000 is described. Definition of "Orphan" medicinal products as well as the procedure of designation and placing the products into the Community register is presented. Those incentives to industry are described, which are already five years very well implemented oh the European level mostly on the pre-authorisation phase of "Orphan" medicinal products development, but also in the registration process as well as the post-authorisation phase. Finaly, the first twenty "Orphan" medicinal products, which have been given positive opinion in the Community for the grant of a marketing authorisation till April 2005 are mentioned in this work. The real availability of "Orphan" medicinal products in the particular EU member states is analysed.
DOE Office of Scientific and Technical Information (OSTI.GOV)

Greenberg, Raymond; Wright, Kyle A.; McCaw, Erica E.

The Global Threat Reduction Initiative (GTRI) reduces and protects vulnerable nuclear and radiological material located at civilian sites worldwide. Internationally, over 40 countries are cooperating with GTRI to enhance the security of these materials. The GTRI program has worked successfully with foreign countries to remove and protect nuclear and radioactive materials, including orphaned and disused high-activity sources. GTRI began cooperation with the Republic of Colombia in April 2004. This cooperation has been a resounding success by securing forty high-risk sites, consolidating disused/orphan sources at an interim secure national storage facility, and developing a comprehensive approach to security, training, and sustainability.more » In 2005 the Colombian Ministry of Mines and Energy requested the Department of Energy’s support in the construction of a new Central Storage Facility (CSF). In December 2005, the Ministry selected to construct this facility at the Institute of Geology and Mining (Ingeominas) site in Bogota. This site already served as Colombia’s national repository, where disused sources were housed in various buildings around the complex. The CSF project was placed under contract in May 2006, but environmental issues and public protests, which led to a class action lawsuit against the Colombian Government, forced the Ministry to quickly suspend activities, thereby placing the project in jeopardy. Despite these challenges, however, the Ministry of Mines and Energy worked closely with public and environmental authorities to resolve these issues, and continued to be a strong advocate of the GTRI program. In June 2008, the Ministry of Mines and Energy was granted the construction and environmental licenses. As a result, construction immediately resumed and the CSF was completed by December 2008. A commissioning ceremony was held for the new facility in January 2009, which was attended by representatives from the Department of Energy, U.S. Embassy, and the Ministry of Mines and Energy, including the Minister and Vice Minister.« less
Orphan drug development: an economically viable strategy for biopharma R&D.

PubMed

Meekings, Kiran N; Williams, Cory S M; Arrowsmith, John E

2012-07-01

Orphan drug incentives have stimulated research into diseases with significant unmet medical need. Although the targeting of orphan diseases is seen by industry as an attractive strategy, there are limited economic data available to support its use. In this paper we show that the revenue-generating potential of orphan drugs is as great as for non-orphan drugs, even though patient populations for rare diseases are significantly smaller. Moreover, we suggest that orphan drugs have greater profitability when considered in the full context of developmental drivers including government financial incentives, smaller clinical trial sizes, shorter clinical trial times and higher rates of regulatory success. The data support the targeting of rare diseases as an important component of a successful biopharma R&D strategy. Copyright © 2012 Elsevier Ltd. All rights reserved.
Socio-Pedagogical Challenges Facing Orphaned and Vulnerable Children in the Aftermath of the 2007-2008 Election Violence in Nakuru County, Kenya

ERIC Educational Resources Information Center

Majanga, Eunice; Mukonyi, Phillip; Vundi, Silvia

2015-01-01

The conflict situations that have afflicted parts of Kenya every five years, in the wake of general elections, since 1992 were most prominent after the disputed presidential elections of 2007. The magnitude of the clashes, loss of life, destruction of property and internal displacement of people were hitherto unwitnessed. The situation of Orphans…
Enriching Orphans' Potentials through Interpersonal and Intrapersonal Intelligence Enrichment Activities

ERIC Educational Resources Information Center

Azid, Nurulwahida Hj; Yaacob, Aizan

2016-01-01

Orphans are considered a minority and they should be given a greater emphasis so that they do not feel left out and can build their own lives without a sense of humility. This does not mean that the orphans should be pampered instead they should be given the confidence and motivation to strive for success in later life. Humility among orphans can…
The Self-Concept and Academic Performance of Institutionalized and Non-Institutionalized HIV/AIDS Orphaned Children in Kisumu Municipality

ERIC Educational Resources Information Center

Kimani, Chege Gabriel; Cheboswony, M.; Kodero, H. M.; Misigo, Benard L.

2009-01-01

The HIV/AIDS pandemic has increasingly become a major factor in the emergence of orphans in the developing countries. These orphans are usually traumatized due to the multiple losses, isolation, stigma and grief. The study sought to investigate the effect of institutionalization of children on the self-concept of the AIDS-orphaned children and to…
The Deep Lens Survey : Real--time Optical Transient and Moving Object Detection

NASA Astrophysics Data System (ADS)

Becker, Andy; Wittman, David; Stubbs, Chris; Dell'Antonio, Ian; Loomba, Dinesh; Schommer, Robert; Tyson, J. Anthony; Margoniner, Vera; DLS Collaboration

2001-12-01

We report on the real-time optical transient program of the Deep Lens Survey (DLS). Meeting the DLS core science weak-lensing objective requires repeated visits to the same part of the sky, 20 visits for 63 sub-fields in 4 filters, on a 4-m telescope. These data are reduced in real-time, and differenced against each other on all available timescales. Our observing strategy is optimized to allow sensitivity to transients on several minute, one day, one month, and one year timescales. The depth of the survey allows us to detect and classify both moving and stationary transients down to ~ 25th magnitude, a relatively unconstrained region of astronomical variability space. All transients and moving objects, including asteroids, Kuiper belt (or trans-Neptunian) objects, variable stars, supernovae, 'unknown' bursts with no apparent host, orphan gamma-ray burst afterglows, as well as airplanes, are posted on the web in real-time for use by the community. We emphasize our sensitivity to detect and respond in real-time to orphan afterglows of gamma-ray bursts, and present one candidate orphan in the field of Abell 1836. See http://dls.bell-labs.com/transients.html.
Profiling the orphan enzymes

PubMed Central

2014-01-01

The emergence of Next Generation Sequencing generates an incredible amount of sequence and great potential for new enzyme discovery. Despite this huge amount of data and the profusion of bioinformatic methods for function prediction, a large part of known enzyme activities is still lacking an associated protein sequence. These particular activities are called “orphan enzymes”. The present review proposes an update of previous surveys on orphan enzymes by mining the current content of public databases. While the percentage of orphan enzyme activities has decreased from 38% to 22% in ten years, there are still more than 1,000 orphans among the 5,000 entries of the Enzyme Commission (EC) classification. Taking into account all the reactions present in metabolic databases, this proportion dramatically increases to reach nearly 50% of orphans and many of them are not associated to a known pathway. We extended our survey to “local orphan enzymes” that are activities which have no representative sequence in a given clade, but have at least one in organisms belonging to other clades. We observe an important bias in Archaea and find that in general more than 30% of the EC activities have incomplete sequence information in at least one superkingdom. To estimate if candidate proteins for local orphans could be retrieved by homology search, we applied a simple strategy based on the PRIAM software and noticed that candidates may be proposed for an important fraction of local orphan enzymes. Finally, by studying relation between protein domains and catalyzed activities, it appears that newly discovered enzymes are mostly associated with already known enzyme domains. Thus, the exploration of the promiscuity and the multifunctional aspect of known enzyme families may solve part of the orphan enzyme issue. We conclude this review with a presentation of recent initiatives in finding proteins for orphan enzymes and in extending the enzyme world by the discovery of new activities. Reviewers This article was reviewed by Michael Galperin, Daniel Haft and Daniel Kahn. PMID:24906382
Profiling the orphan enzymes.

PubMed

Sorokina, Maria; Stam, Mark; Médigue, Claudine; Lespinet, Olivier; Vallenet, David

2014-06-06

The emergence of Next Generation Sequencing generates an incredible amount of sequence and great potential for new enzyme discovery. Despite this huge amount of data and the profusion of bioinformatic methods for function prediction, a large part of known enzyme activities is still lacking an associated protein sequence. These particular activities are called "orphan enzymes". The present review proposes an update of previous surveys on orphan enzymes by mining the current content of public databases. While the percentage of orphan enzyme activities has decreased from 38% to 22% in ten years, there are still more than 1,000 orphans among the 5,000 entries of the Enzyme Commission (EC) classification. Taking into account all the reactions present in metabolic databases, this proportion dramatically increases to reach nearly 50% of orphans and many of them are not associated to a known pathway. We extended our survey to "local orphan enzymes" that are activities which have no representative sequence in a given clade, but have at least one in organisms belonging to other clades. We observe an important bias in Archaea and find that in general more than 30% of the EC activities have incomplete sequence information in at least one superkingdom. To estimate if candidate proteins for local orphans could be retrieved by homology search, we applied a simple strategy based on the PRIAM software and noticed that candidates may be proposed for an important fraction of local orphan enzymes. Finally, by studying relation between protein domains and catalyzed activities, it appears that newly discovered enzymes are mostly associated with already known enzyme domains. Thus, the exploration of the promiscuity and the multifunctional aspect of known enzyme families may solve part of the orphan enzyme issue. We conclude this review with a presentation of recent initiatives in finding proteins for orphan enzymes and in extending the enzyme world by the discovery of new activities.
Renewable Orphans: Adopting Legal Renewable Standards at the State Level

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ferrey, Steven

To keep making progress on renewable energy deployment, state incentives must be structured to comply with constitutional requirements. While states can experiment, and indeed have taken the lead on renewable policy initiatives, the programs must be carefully sculpted within the legal parameters of the dormant Commerce Clause. (author)
Understanding orphan and non-orphan adolescents' sexual risks in the context of poverty: a qualitative study in Nyanza Province, Kenya.

PubMed

Juma, Milka; Alaii, Jane; Bartholomew, L Kay; Askew, Ian; Van den Born, Bart

2013-07-25

Some studies show orphanhood to be associated with increased sexual risk-taking while others have not established this relationship, but have found factors other than orphanhood as predictors of sexual risk behaviours and outcomes among adolescents. This study examines community members' perceptions of how poverty influences adolescent sexual behaviour and outcomes in four districts of Nyanza Province, Kenya. Eight study sites within the four districts were randomly selected. Focus group discussions were conducted with a purposive sample of adolescents, parents and caregivers. Key informant interviews were undertaken with a purposive sample of community leaders, child welfare and healthcare workers, and adolescents. The two methods elicited information on factors perceived to predispose adolescent orphans and non-orphans to sexual risks. Data were analysed through line-by-line coding, grouped into families and retrieved as themes and sub-themes. Participants included 147 adolescents and parents/caregivers in 14 focus groups and 13 key informants. Poverty emerged as a key predisposing factor to sexual risk behaviour among orphans and non-orphans. Poverty was associated with lack of food, poor housing, school dropout, and engaging in income generating activities, all of which increase their vulnerability to transactional sex, early marriage, sexual experimentation, and the eventual consequences of increased risk of unintended pregnancies and STI/HIV. Poverty was perceived to contribute to increasing sexual risks among orphan and non-orphan adolescents through survival strategies adopted to be able to meet their basic needs. Policies for prevention and intervention that target adolescents in a generalized poverty and HIV epidemic should integrate economic empowerment for caregivers and life skills for adolescents to reduce vulnerabilities of orphan and non-orphan adolescents to sexual risk behaviour.
The Vulnerabilities of Orphaned Children Participating in Research: A Critical Review and Factors for Consideration for Participation in Biomedical and Behavioral Research

PubMed Central

Thompson, Rachel T.; Meslin, Eric M.; Braitstein, Paula K. A.; Nyandiko, Winstone M.; Ayaya, Samuel O.; Vreeman, Rachel C.

2013-01-01

Orphans are a subpopulation with a unique set of additional vulnerabilities. Increasing focus on children’s rights, pediatric global health, and pediatric research makes it imperative to recognize and address unique vulnerabilities of orphaned children. This paper describes the unique vulnerabilities of the orphaned pediatric population and offers a structured set of factors that require consideration when including orphans in biomedical research. Pediatric orphans are particularly vulnerable due to decreased economic resources, psychosocial instability, increased risk of abuse, and delayed/decreased access to healthcare. These vulnerabilities are significant. By carefully considering each issue in a population in a culturally specific and study-specific manner, researchers can make valuable contributions to the overall health and well-being of this uniquely vulnerable population. PMID:23086048
Neglect and perceived stigmatization impact psychological distress of orphans in Tanzania

PubMed Central

Hermenau, Katharin; Eggert, Ina; Landolt, Markus A.; Hecker, Tobias

2015-01-01

Background Research has shown that orphans in sub-Saharan Africa are at increased risk for mental health problems. Exposure to maltreatment and HIV/AIDS-related stigmatization are related to orphans’ psychological distress. Yet, researchers stress the need for more research in low-income countries to identify which factors of being an orphan may lead to psychological distress. Objectives The present study aims to systematically investigate orphans’ experiences of maltreatment and stigmatization to identify factors that relate to their psychological distress. Methods In total, 89 Tanzanian children who had lost at least one parent were compared to 89 matched non-orphans (mean age: 11 years; 51% boys). We measured exposure to maltreatment and perceived stigmatization as an orphan. Mental health was assessed using the Strengths and Difficulties Questionnaire, the Children's Depression Inventory, the UCLA PTSD Index for Children, and the Reactive–Proactive Questionnaire. Results Orphans reported significantly more experiences of neglect, but not of abuse. A group comparison revealed more depressive symptoms, posttraumatic stress symptoms, and aggressive behavior among orphans. Neglect, abuse, and stigmatization correlated with orphans’ internalizing and externalizing problems, yet only neglect and stigmatization were related to orphans’ depression severity. Perceived stigmatization moderated the relationship between neglect and depression. Conclusions Our findings suggest that orphans in Tanzania are at increased risk of experiencing neglect. Maltreatment and perceived stigmatization may play a role in orphans’ psychological distress. Culturally appropriate and evidence-based interventions may help to prevent maltreatment and stigmatization of orphans. PMID:26589257
Barriers and Incentives to Orphan Care in a Time of AIDS and Economic Crisis: A Cross-Sectional Survey of Caregivers in Rural Zimbabwe

ERIC Educational Resources Information Center

Howard, Brian H.; Phillips, Carl V.; Matinhure, Nelia; Goodman, Karen J.; McCurdy, Sheryl A; Johnson, Cary A.

2007-01-01

Background: Africa is in an orphan-care crisis. In Zimbabwe, where one-fourth of adults are HIV-positive and one-fifth of children are orphans, AIDS and economic decline are straining society's ability to care for orphans within their extended families. Lack of stable care is putting thousands of children at heightened risk of malnourishment,…
True Religion Cares for Orphans: Creating and Sustaining an Orphan Care Culture in the Local Churches in Rwanda a Phenomenological Study

ERIC Educational Resources Information Center

McMillan, Mary Ann

2017-01-01

This research, a phenomenological study, examined four different local churches in Rwanda to identify the key strategies and methods used to establish an orphan care culture and ministry. Saddleback Church in Lake Forest, California has partnered with the country of Rwanda to end the orphan crisis. As of today, 35 orphanages in the country of…
Large-scale computational drug repositioning to find treatments for rare diseases.

PubMed

Govindaraj, Rajiv Gandhi; Naderi, Misagh; Singha, Manali; Lemoine, Jeffrey; Brylinski, Michal

2018-01-01

Rare, or orphan, diseases are conditions afflicting a small subset of people in a population. Although these disorders collectively pose significant health care problems, drug companies require government incentives to develop drugs for rare diseases due to extremely limited individual markets. Computer-aided drug repositioning, i.e., finding new indications for existing drugs, is a cheaper and faster alternative to traditional drug discovery offering a promising venue for orphan drug research. Structure-based matching of drug-binding pockets is among the most promising computational techniques to inform drug repositioning. In order to find new targets for known drugs ultimately leading to drug repositioning, we recently developed e MatchSite, a new computer program to compare drug-binding sites. In this study, e MatchSite is combined with virtual screening to systematically explore opportunities to reposition known drugs to proteins associated with rare diseases. The effectiveness of this integrated approach is demonstrated for a kinase inhibitor, which is a confirmed candidate for repositioning to synapsin Ia. The resulting dataset comprises 31,142 putative drug-target complexes linked to 980 orphan diseases. The modeling accuracy is evaluated against the structural data recently released for tyrosine-protein kinase HCK. To illustrate how potential therapeutics for rare diseases can be identified, we discuss a possibility to repurpose a steroidal aromatase inhibitor to treat Niemann-Pick disease type C. Overall, the exhaustive exploration of the drug repositioning space exposes new opportunities to combat orphan diseases with existing drugs. DrugBank/Orphanet repositioning data are freely available to research community at https://osf.io/qdjup/.
The evolving drug development landscape: from blockbusters to niche busters in the orphan drug space.

PubMed

Kumar Kakkar, Ashish; Dahiya, Neha

2014-06-01

Strategy, Management and Health Policy Large pharmaceutical companies have traditionally focused on the development of blockbuster drugs that target disease states with large patient populations. However, with large-scale patent expirations and competition from generics and biosimilars, anemic pipelines, escalating clinical trial costs, and global health-care reform, the blockbuster model has become less viable. Orphan drug initiatives and the incentives accompanied by these have fostered renewed research efforts in the area of rare diseases and have led to the approval of more than 400 orphan products. Despite targeting much smaller patient populations, the revenue-generating potential of orphan drugs has been shown to be huge, with a greater return on investment than non-orphan drugs. The success of these "niche buster" therapeutics has led to a renewed interest from "Big Pharma" in the rare disease landscape. This article reviews the key drivers for orphan drug research and development, their profitability, and issues surrounding the emergence of large pharmaceutical firms into the orphan drug space. © 2014 Wiley Periodicals, Inc.
Effectiveness of a Motivation and Practical Skills Development Methods on the Oral Hygiene of Orphans Children in Kaunas, Lithuania

PubMed Central

Narbutaite, Julija

2015-01-01

ABSTRACT Objectives The aim of this study was to evaluate the effect of a motivation and practical skills development methods on the oral hygiene of orphans. Material and Methods Sixty eight orphans aged between 7 and 17 years from two orphanages in Kaunas were divided into two groups: practical application group and motivation group. Children were clinically examined by determining their oral hygiene status using Silness-Löe plaque index. Questionnaire was used to estimate the oral hygiene knowledge and practices at baseline and after 3 months. Statistical analysis included: Chi-square test (χ2), Fisher‘s exact test, Student‘s t-test, nonparametric Mann-Whitney test, Spearman’s rho correlation coefficient and Kappa coefficient. Results All children had a plaque on at least one tooth in both groups: motivation 1.14 (SD 0.51), practical application 1.08 (SD 0.4) (P = 0.58). Girls in both groups showed significantly better oral hygiene than boys (P < 0.001). After 3 months educational program oral hygiene status improved in both groups significantly 0.4 (SD 0.35) (P < 0.001). Significantly better oral hygiene was determined in practical application group 0.19 (SD 0.27) in comparison with motivation group 0.55 (SD 0.32) (P < 0.001). By comparing results of first and second questionnaire surveys on use of soft drinks, the statistically significant decline of their use was in both groups (P = 0.004). Conclusions Educational programs are effective in improving oral hygiene, especially when they’re based on practical skills training. PMID:26539284

The Orphan Drug Act: Restoring the Mission to Rare Diseases.

PubMed

Daniel, Michael G; Pawlik, Timothy M; Fader, Amanda N; Esnaola, Nestor F; Makary, Martin A

2016-04-01

The Orphan Drug Act has fostered drug development for patients with rare cancers and other diseases; however, current data suggest that companies are gaming the system to use the law for mainstream drugs. We identify a pattern of pharmaceutical companies submitting drugs to the Food and Drug Administration (FDA) as orphan drugs but once approved, the drugs are used broadly off-label with the lucrative orphan drug protections and exclusivity benefits. Since the law was passed, the proportion of new FDA-approved drugs that were submitted as orphan drugs has increased with a peak last year of 41% of all FDA-approved drugs approved as orphan drugs. On the basis of the current data, we suggest that patients with rare cancers and other diseases may suffer due to dilution of the incentives and benefits. We propose reform to increase submission scrutiny, decrease benefits based on off-label use, and increase price transparency.
Difference in Psychosocial Well-being Between Paternal and Maternal AIDS Orphans in Rural China

PubMed Central

Zhao, Qun; Li, Xiaoming; Fang, Xiaoyi; Zhao, Guoxiang; Zhao, Junfeng; Lin, Xiuyun; Stanton, Bonita

2009-01-01

This study compares psychosocial well-being between paternal and maternal orphans in rural China in a sample (N = 459) of children who had lost one parent to HIV and who were in family-based care. Measures included academic marks, education expectation, trusting relationships with current caregivers, self-reported health status, depression, loneliness, posttraumatic stress, and social support. No significant differences were found between maternal and paternal orphans, except that paternal orphans reported better trusting relationships with caregivers than maternal orphans. Children with a healthy surviving parent reported significantly better depression, loneliness, posttraumatic stress, and social support scores than children with a sick parent. Analyses revealed significance with regard to orphan status on academic marks and trusting relationships with caregivers while controlling for age, gender, surviving parent’s health status, and family SES. Findings underscore the importance of psychosocial support for children whose surviving parent is living with HIV or another illness. PMID:20133172
Orphan strontium-87 in abyssal peridotites: daddy was a granite.

PubMed

Snow, J E; Hart, S R; Dick, H J

1993-12-17

The (87)Sr/(86)Sr ratios in some bulk abyssal and alpine peridotites are too high to be binary mixtures of depleted mantle and seawater components. The apparent excess, or "orphan," (87)Sr appears to be separated from its radioactive parent. Such observations were widely held to be analytical artifacts. Study of several occurrences of orphan (87)Sr shows that the orphan component in abyssal peridotite is located in the alteration products of olivine and enstatite in the peridotite. The orphan (87)Sr is most likely introduced by infiltration of low-temperature (<200 degrees C) seawater bearing suspended detrital particulates. These particulates include grains of detrital clay that are partly derived from continental (that is, granitic) sources and thus are highly radiogenic. Orphan (87)Sr and other radiogenic isotopes may provide a tracer for low-temperature seawater penetrating into the oceanic crust.
Orphan Strontium-87 in Abyssal Peridotites: Daddy Was a Granite

NASA Astrophysics Data System (ADS)

Snow, Jonathan E.; Hart, Stanley R.; Dick, Henry J. B.

1993-12-01

The 87Sr/86Sr ratios in some bulk abyssal and alpine peridotites are too high to be binary mixtures of depleted mantle and seawater components. The apparent excess, or "orphan," 87Sr appears to be separated from its radioactive parent. Such observations were widely held to be analytical artifacts. Study of several occurrences of orphan 87Sr shows that the orphan component in abyssal peridotite is located in the alteration products of olivine and enstatite in the peridotite. The orphan 87Sr is most likely introduced by infiltration of low-temperature (<200^circC) seawater bearing suspended detrital particulates. These particulates include grains of detrital clay that are partly derived from continental (that is, granitic) sources and thus are highly radiogenic. Orphan 87Sr and other radiogenic isotopes may provide a tracer for low-temperature seawater penetrating into the oceanic crust.
Why orphan drug coverage reimbursement decision-making needs patient and public involvement.

PubMed

Douglas, Conor M W; Wilcox, Elizabeth; Burgess, Michael; Lynd, Larry D

2015-05-01

Recently there has been an increase in the active involvement of publics and patients in healthcare and research, which is extending their roles beyond the passive recipients of medicines. However, there has been noticeably less work engaging them into decision-making for healthcare rationing exercises, priority setting, health technology assessment, and coverage decision-making. This is particularly evident in reimbursement decision-making for 'orphan drugs' or drugs for rare diseases. Medicinal products for rare disease offer particular challenges in coverage decision-making because they often lack the 'evidence of efficacy' profiles of common drugs that have been trialed on larger populations. Furthermore, many of these drugs are priced in the high range, and with limited health care budgets the prospective opportunity costs of funding them means that those resources cannot be allocated elsewhere. Here we outline why decision-making for drugs for rare diseases could benefit from increased levels of publics and patients involvement, suggest some possible forms that involvement could take, and advocate for empirical experimentation in this area to evaluate the effects of such involvement. Focus is given to the Canadian context in which we are based; however, potentialities and challenges relating to involvement in this area are likely to be similar elsewhere. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.
Parental Bereavement in Young Children Living in South Africa and Malawi: Understanding Mental Health Resilience.

PubMed

Macedo, A; Sherr, L; Tomlinson, M; Skeen, S; Roberts, K J

2018-04-17

Parental loss is a major stressful event found to increase risk of mental health problems in childhood. Yet, some children show resilient adaptation in the face of adversity across time. This study explores predictors of mental health resilience among parentally bereaved children in South Africa and Malawi, and their cumulative effect. The study also explores whether predictors of resilience differed between orphaned and non-orphaned children. Consecutive attenders of community based organisations (children;4-13 years, and their caregivers) were interviewed at baseline and 15-18 month follow up (n=833). Interviews comprised of inventories on demographic information, family data, child mental health, bereavement experience and community characteristics. Mental health screens were used to operationalise resilience as the absence of symptoms of depression, suicidality, trauma, emotional and behavioural problems. Almost 60% of children experienced parental loss. One quarter of orphaned children showed no mental health problems at either wave and were classified as resilient. There were equal proportions of children classified as resilient within the orphaned (25%) vs. non-orphaned group (22%). Being a quick learner, aiding ill family members, positive caregiving, household employment, higher community support, and lower exposure to domestic violence, physical punishment, or stigma at baseline predicted sustained resilience. There were cumulative influences of resilience predictors among orphaned children. Predictors of resilience did not vary by child age, gender, country of residence or between orphaned and non-orphaned children. This study enhances understanding of resilience in younger children and identifies a number of potential environmental and psychosocial factors for bolstering resilience in orphaned children.
Characterizing a Hidden Group of At-Risk Drinkers: Epidemiological Profiles of Alcohol-Use Disorder Diagnostic Orphans.

PubMed

Gilbert, Paul A; Marzell, Miesha

2017-11-29

Drinkers who report some symptoms of alcohol-use disorder (AUD) but fail to meet full criteria are "diagnostic orphans." To improve risk-reduction efforts, we sought to develop better epidemiologic profiles of this underrecognized subgroup. This study estimated the population prevalence and described AUD symptoms of diagnostic orphans using the 2012-2013 National Epidemiological Survey of Alcohol and Related Conditions-III. Multivariate logistic regression was used to model odds of being a diagnostic orphan or meeting mild, moderate, and severe AUD criteria versus no AUD symptoms. Models were adjusted for the complex survey design using sampling weights and survey procedures (e.g., proc surveylogistic). Among drinkers, 14% of men and 11% of women were classified as diagnostic orphans. The most common symptoms were drinking more or for longer periods than intended, wanting or trying unsuccessfully to quit or cut back, and drinking in ways that increased risk of injury. We noted broad similarities between diagnostic orphans and mild/moderate AUD groups. There were no differences in odds of diagnostic orphans status by race/ethnicity; however, female gender was associated with lower odds of diagnostic orphan status and all levels of AUD. Individual history of AUD, family history of problem drinking, concurrent smoking, and concurrent marijuana use were associated with greater odds of problem drinking, with stronger associations as AUD severity increased. Diagnostic orphans remain a sizeable and overlooked population of problem drinkers. Clarifying the array of symptoms and cooccurring disorders can improve screening and facilitate alcohol risk-reduction intervention efforts.
Reimbursement of orphan drugs in Belgium: what (else) matters?

PubMed

Picavet, Eline; Cassiman, David; Simoens, Steven

2014-09-12

Most orphan drugs do not meet traditional standards of cost-effectiveness. Yet, most orphan drugs are reimbursed, which implies that other factors are taken into account at the time of reimbursement. To increase accountability of decision-makers, there is a need for more transparency in the factors that play a role in reimbursement decisions of orphan drugs. Therefore, the aim of this study is to use a combination of qualitative research methods to examine which official and non-official factors influence reimbursement decisions for orphan drugs in Belgium. Six semi-structured interviews with past or present members of the Drug Reimbursement Committee (DRC) were performed with a view to obtaining an overview of the potential factors influencing reimbursement. Additionally, these presence of these factors was assessed in the reimbursement dossiers of all orphan drugs (n = 64) for which an application for reimbursement was submitted to the National Institute for Health and Disability Insurance in Belgium between January 2002 and July 2013. Different official (i.e. therapeutic value, budget impact, price and impact in clinical practice) and non-official factors (i.e. pricing and reimbursement in other countries, interference by patient organisations and experts, arguments related to quality of branded drug versus compounding, media attention, innovative character, economic importance, ethical arguments and the political climate) may have influenced past reimbursement decisions for orphan drugs in Belgium. The identification of factors influencing orphan drug reimbursement is a crucial step in the development of a transparent and consistent framework which will guide future decision-making for reimbursement of orphan drugs.
Effects of cash transfers on Children's health and social protection in Sub-Saharan Africa: differences in outcomes based on orphan status and household assets.

PubMed

Crea, Thomas M; Reynolds, Andrew D; Sinha, Aakanksha; Eaton, Jeffrey W; Robertson, Laura A; Mushati, Phyllis; Dumba, Lovemore; Mavise, Gideon; Makoni, J C; Schumacher, Christina M; Nyamukapa, Constance A; Gregson, Simon

2015-05-28

Unconditional and conditional cash transfer programmes (UCT and CCT) show potential to improve the well-being of orphans and other children made vulnerable by HIV/AIDS (OVC). We address the gap in current understanding about the extent to which household-based cash transfers differentially impact individual children's outcomes, according to risk or protective factors such as orphan status and household assets. Data were obtained from a cluster-randomised controlled trial in eastern Zimbabwe, with random assignment to three study arms - UCT, CCT or control. The sample included 5,331 children ages 6-17 from 1,697 households. Generalized linear mixed models were specified to predict OVC health vulnerability (child chronic illness and disability) and social protection (birth registration and 90% school attendance). Models included child-level risk factors (age, orphan status); household risk factors (adults with chronic illnesses and disabilities, greater household size); and household protective factors (including asset-holding). Interactions were systematically tested. Orphan status was associated with decreased likelihood for birth registration, and paternal orphans and children for whom both parents' survival status was unknown were less likely to attend school. In the UCT arm, paternal orphans fared better in likelihood of birth registration compared with non-paternal orphans. Effects of study arms on outcomes were not moderated by any other risk or protective factors. High household asset-holding was associated with decreased likelihood of child's chronic illness and increased birth registration and school attendance, but household assets did not moderate the effects of cash transfers on risk or protective factors. Orphaned children are at higher risk for poor social protection outcomes even when cared for in family-based settings. UCT and CCT each produced direct effects on children's social protection which are not moderated by other child- and household-level risk factors, but orphans are less likely to attend school or obtain birth registration. The effects of UCT and CCT are not moderated by asset-holding, but greater household assets predict greater social protection outcomes. Intervention efforts need to focus on ameliorating the additional risk burden carried by orphaned children. These efforts might include caregiver education, and additional incentives based on efforts made specifically for orphaned children.
Quantitative analysis to guide orphan drug development.

PubMed

Lesko, L J

2012-08-01

The development of orphan drugs for rare diseases has made impressive strides in the past 10 years. There has been a surge in orphan drug designations, but new drug approvals have not kept up. This article presents a three-pronged hierarchical strategy for quantitative analysis of data at the descriptive, mechanistic, and systems levels of the biological system that could represent a standardized and rational approach to orphan drug development. Examples are provided to illustrate the concept.
Parental HIV/AIDS and psychological health of younger children in South Africa.

PubMed

Asanbe, Comfort; Moleko, Anne-Gloria; Visser, Maretha; Thomas, Angela; Makwakwa, Catherine; Salgado, Waleska; Tesnakis, Alexandra

2016-07-01

We examined several indicators of psychological health in a sample of orphans and vulnerable children (OVC) to determine if there were significant differences between those orphaned by AIDS and those orphaned by other causes, and if there were gender differences. Our sample consisted of 119 young children (ages 6-10 years) who participated in a non-governmental organisation (NGO)-supported social services programme in a low-resource, non-urban community in South Africa. We collected data on three groups: non-orphans (OVC1; n = 45); orphans due to AIDS (OVC2; n = 43); and other orphans (OVC3; n = 31). Parents of non-orphans and legal guardians of orphans rated their children on a 112-item, age appropriate Child Behaviour Checklist (CBCL), South Africa version. Children in the OVC2 group were significantly different from their peers on Internalising Problems and Somatic Complaints, while OVC3 group had a higher proportion of children in the at-risk range on Social Problems compared to OVC2. Females had elevated scores on the anxious/depressed, internalising problems, total problems, and sluggish cognitive tempo scales compared to males. There was an interaction between factors, such that boys in OVC2 had elevated mean scores on Somatic Complaints. These findings suggest increased vulnerability for girls on emotional issues and for boys on somatic problems.
Caregiver alcohol use and mental health among children orphaned by HIV/AIDS in South Africa.

PubMed

Jardin, Charles; Marais, Lochner; Bakhshaie, Jafar; Skinner, Donald; Neighbors, Clayton; Zvolensky, Michael; Sharp, Carla

2017-03-01

Research in the developed world suggests that parental alcohol use negatively impacts child mental health. However, little research has examined these relations among children in the developing world and no studies to date have done so in the context of AIDS-orphanhood. Therefore, the present study tested the interactive effect of AIDS-orphan status with caregiver alcohol use on child mental health. The sample included 742 children (51.2% female; M age = 9.18; age range: 7-11 years; 29.8 AIDS-orphans; 36.8% orphaned by causes other than AIDS; 33.4% non-orphaned) recruited from Mangaung in the Free State Province of South Africa. Child mental health was assessed via child self-report, caregiver, and teacher reports; and caregiver alcohol use via self-report. Path analyses, via structural equation modeling, revealed significant direct effects for AIDS-orphan status on caregiver-reported child mental health; and for caregiver alcohol-use problems on teacher-reported child mental health. However, the interaction effect of AIDS-orphan status with caregiver alcohol use did not reach significance on all three reports of child mental health problems. These results suggest that orphan status and caregiver alcohol use may independently relate to mental health problems in children and that the effects of both should be considered in the context of the mental health needs of children in AIDS-affected countries.
Lipid-sensors, enigmatic-orphan and orphan nuclear receptors as therapeutic targets in breast-cancer.

PubMed

Garattini, Enrico; Bolis, Marco; Gianni', Maurizio; Paroni, Gabriela; Fratelli, Maddalena; Terao, Mineko

2016-07-05

Breast-cancer is heterogeneous and consists of various groups with different biological characteristics. Innovative pharmacological approaches accounting for this heterogeneity are needed. The forty eight human Nuclear-Hormone-Receptors are ligand-dependent transcription-factors and are classified into Endocrine-Receptors, Adopted-Orphan-Receptors (Lipid-sensors and Enigmatic-Orphans) and Orphan-receptors. Nuclear-Receptors represent ideal targets for the design/synthesis of pharmacological ligands. We provide an overview of the literature available on the expression and potential role played by Lipid-sensors, Enigmatic-Orphans and Orphan-Receptors in breast-cancer. The data are complemented by an analysis of the expression levels of each selected Nuclear-Receptor in the PAM50 breast-cancer groups, following re-elaboration of the data publicly available. The major aim is to support the idea that some of the Nuclear-Receptors represent largely unexploited therapeutic-targets in breast-cancer treatment/chemo-prevention. On the basis of our analysis, we conclude that the Lipid-Sensors, NR1C3, NR1H2 and NR1H3 are likely to be onco-suppressors in breast-cancer. The Enigmatic-Orphans, NR1F1 NR2A1 and NR3B3 as well as the Orphan-Receptors, NR0B1, NR0B2, NR1D1, NR2F1, NR2F2 and NR4A3 exert a similar action. These Nuclear-Receptors represent candidates for the development of therapeutic strategies aimed at increasing their expression or activating them in tumor cells. The group of Nuclear-Receptors endowed with potential oncogenic properties consists of the Lipid-Sensors, NR1C2 and NR1I2, the Enigmatic-Orphans, NR1F3, NR3B1 and NR5A2, as well as the Orphan-Receptors, NR2E1, NR2E3 and NR6A1. These oncogenic Nuclear-Receptors should be targeted with selective antagonists, reverse-agonists or agents/strategies capable of reducing their expression in breast-cancer cells.
Little Orphan Annie

ERIC Educational Resources Information Center

Hyatt, Sarah

2009-01-01

The benefits of therapeutic riding and hippotherapy can be numerous and long lasting for children and adults with special needs. The connection that a child or adult with disabilities can make with a horse is evident in therapeutic riding programs all over the country. In this article, the author, who is the Equestrian Center Director at Heartland…
Nuclear receptor TLX prevents retinal dystrophy and recruits the corepressor atrophin1.

PubMed

Zhang, Chun-Li; Zou, Yuhua; Yu, Ruth T; Gage, Fred H; Evans, Ronald M

2006-05-15

During mammalian embryogenesis, precise coordination of progenitor cell proliferation and differentiation is essential for proper organ size and function. The involvement of TLX (NR2E1), an orphan nuclear receptor, has been implicated in ocular development, as Tlx-/- mice exhibit visual impairment. Using genetic and biochemical approaches, we show that TLX modulates retinal progenitor cell proliferation and cell cycle re-entry by directly regulating the expression of Pten and its target cyclin D1. Additionally, TLX finely tunes the progenitor differentiation program by modulating the phospholipase C and mitogen-activated protein kinase (MAPK) pathways and the expression of an array of cell type-specific transcriptional regulators. Consequently, Tlx-/- mice have a dramatic reduction in retina thickness and enhanced generation of S-cones, and develop severe early onset retinal dystrophy. Furthermore, TLX interacts with atrophin1 (Atn1), a corepressor that is involved in human neurodegenerative dentatorubral-pallidoluysian atrophy (DRPLA) and that is essential for development of multiple tissues. Together, these results reveal a molecular strategy by which an orphan nuclear receptor can precisely orchestrate tissue-specific proliferation and differentiation programs to prevent retinal malformation and degeneration.
The impact of the declining extended family support system on the education of orphans in Lesotho

PubMed Central

Tanga, Pius T

2013-01-01

This paper examines the impact of the weakening of the extended family on the education of double orphans in Lesotho through in-depth interviews with participants from 3 of the 10 districts in Lesotho. The findings reveal that in Lesotho the extended family has not yet disintegrated as the literature suggests. However, it shows signs of rupturing, as many orphans reported that they are being taken into extended family households, the incentive for these households being, presumably, the financial and other material assistance that they receive from the government and non-governmental organisations (NGOs) which supplements household income and material wellbeing. The findings show that financial and other assistance given by the government and NGOs have resulted in conflict between the orphans and caregivers. This has also prompted many extended families to shift responsibilities to the government and NGOs. Most of the extended households provided the orphans with poor living conditions, such as unhygienic houses, poor nutrition, and little or no provision of school materials, which has had a negative impact on the education of the orphans. The combined effects of economic crisis and HIV and AIDS have resulted in extended families not being able to care for the needs of the orphans adequately, whilst continuing to accept them into their households. It is recommended that although extended families are still accepting orphans, the government should strengthen and recognise the important role played by families and the communities in caring for these vulnerable children. The government should also introduce social grants for orphans and other vulnerable children and review the current meagre public assistance (R100) it provides for orphans and vulnerable children in Lesotho. Other stakeholders should concentrate on strengthening the capacity of families and communities through programmes and projects which could be more sustainable than the current handouts given by many NGOs. PMID:24587791
[The Euro-orphans phenomenon and the courses in therapeutic work and psychiatric treatment--a case study].

PubMed

Nowak, Marta; Gaweda, Agnieszka; Janas-Kozik, Małgorzata

2012-01-01

Today, the phenomenon of Euro-orphan is more and more frequently reported in the literature. This term refers to children with one or both parents emigrated from the country for work purposes. In connection with the social transformations of orphan-hood types described in the literature (nature, spiritual, social), the definition has been broadened by the definition ofeuro-orphan. The Ministry of Education describes the euro-orphan as the destruction of the family structure, the disorder of the socialisation process of children and reduction of the emotional exchanges among family members, as a result of migration of their parents. It provides further that not every child whose parents are not present in the country is covered as an euro-orphan. However, this group has become an increasingly larger populations. Lack of physical proximity and accessibility of important persons may have some psychological and pedagogical implications. These in turn can be shaped over time, into pathological symptoms, which are diagnostic entities in developmental psychiatry. It is not know precisely how many children in Poland are Euro-orphans. The aim of this paper is an attempt to understand the social phenomenon of Euro-orphanhood in the light of the observed psychopathologies of children and adolescents. The case study of the psychotherapy of a patient suffering from the Euro-orphanhood syndrome. Euro-orphanhood is a social phenomenon that generates Euro-orphans with a wide range of psychopathological symptoms classified in different diagnostic categories. The type and intensification of the psychopathological symptoms depend on the quality of relationships with meaningful persons prior to the Euro-orphanhood period. The course of the psychotherapeutic work with Euro-orphans should cover an individual aspect taking into consideration the maturity of defensive mechanisms as well as the work-through of negative feelings cumulated due to becoming a Euro-orphan.
Priority setting for orphan drugs: an international comparison.

PubMed

Rosenberg-Yunger, Zahava R S; Daar, Abdallah S; Thorsteinsdóttir, Halla; Martin, Douglas K

2011-04-01

To describe the process of priority setting for two orphan drugs - Cerezyme and Fabrazyme - in Canada, Australia and Israel, in order to understand and improve the process based on stakeholder perspectives. We conducted qualitative case studies of how three independent drug advisory committees made decisions relating to the funding of Cerezyme and Fabrazyme. Interviews were conducted with 22 informants, including committee members, patient groups and industry representatives. (1) DESCRIPTION: Orphan drugs reimbursement recommendations by expert panels were based on clinical evidence, cost and cost-effectiveness analysis. (2) EVALUATION: Committee members expressed an overall preference for the current drug review process used by their own committee, but were concerned with the fairness of the process particularly for orphan drugs. Other informants suggested the inclusion of other relevant values (e.g. lack of alternative treatments) in order to improve the priority setting process. Some patient groups suggested the use of an alternative funding mechanism for orphan drugs. Priority setting for drugs is not solely a technical process (involving cost-effective analysis, evidence-based medicine, etc.). Understanding the process by which reimbursement decisions are made for orphan drugs may help improve the system for future orphan drugs. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.
Orphan drugs: trends and issues in drug development.

PubMed

Rana, Proteesh; Chawla, Shalini

2018-04-12

Research in rare diseases has contributed substantially toward the current understanding in the pathophysiology of the common diseases. However, medical needs of patients with rare diseases have always been neglected by the society and pharmaceutical industries based on their small numbers and unprofitability. The Orphan Drug Act (1983) was the first serious attempt to address the unmet medical needs for patients with rare diseases and to provide impetus for the pharmaceutical industry to promote orphan drug development. The process of drug development for rare diseases is no different from common diseases but involves significant cost and infrastructure. Further, certain aspect of drug research may not be feasible for the rare diseases. The drug-approving authority must exercise their scientific judgment and ensure due flexibility while evaluating data at various stages of orphan drug development. The emergence of patent cliff combined with the government incentives led the pharmaceutical industry to realize the good commercial prospects in developing an orphan drug despite the small market size. Indeed, many drugs that were given orphan designation ended up being blockbusters. The orphan drug market is projected to reach $178 billion by 2020, and the prospects of research and development in rare diseases appears to be quite promising and rewarding.
Hereditary Angioedema: The Economics of Treatment of an Orphan Disease.

PubMed

Lumry, William Raymond

2018-01-01

This review will discuss the cost burden of hereditary angioedema on patients, healthcare systems, and society. The impact of availability of and access to novel and specific therapies on morbidity, mortality, and the overall burden of disease will be explored along with potential changes in treatment paradigms to improve effectiveness and reduce cost of treatment. The prevalence of orphan diseases, legislative incentives to encourage development of orphan disease therapies and the impact of orphan disease treatment on healthcare payment systems will be discussed.

National Plans of Action for Orphans and Vulnerable Children in Sub-Saharan Africa. Where Are the Youngest Children? Working Papers in Early Childhood Development, No. 50

ERIC Educational Resources Information Center

Engle, Patrice

2008-01-01

In 2005, an estimated 48 million children aged 0-18 years--12 percent of all children in sub-Saharan Africa--were orphans, and that number is expected to rise to 53 million by 2010. One quarter of all orphans are orphaned because of AIDS, and about 2.6 million children are currently infected with HIV. Untreated, most children born with HIV will…
Orphan drug development in the United States.

PubMed

Groft, S C

1985-05-01

Drug research and development in the U.S. tends to focus on drugs to treat common diseases because of the anticipated return on investment. To stimulate pharmaceutical manufacturers to pursue the development of drugs for rare conditions, the Orphan Drug Act was enacted by Congress on January 4, 1983. Under the provisions of this Act, the FDA can make recommendations on the investigations necessary for marketing approval; exclusive marketing privileges can be obtained; tax credits for expenses incurred are allowed; availability of orphan drugs on an investigational basis is encouraged; and the Orphan Product Board is established for the coordination of research efforts and their reimbursement. The effects of this legislation are evident in the continuing increase in orphan drug designations.
78 FR 35117 - Orphan Drug Regulations

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-12

...The Food and Drug Administration (FDA) is issuing final regulations amending the 1992 Orphan Drug Regulations issued to implement the Orphan Drug Act. These amendments are intended to clarify regulatory provisions and make minor improvements to address issues that have arisen since those regulations were issued.
The Use of Social Media in Orphan Drug Development.

PubMed

Milne, Christopher-Paul; Ni, Wendi

2017-11-01

Social media has transformed how people interact with one another through the Internet, and it has the potential to do the same for orphan drug development. Currently, social media influences the orphan drug development process in the following three ways: assisting the study of orphan diseases, increasing the awareness of orphan disease, and playing a vital role in clinical trials. However, there are some caveats to the utilization of social media, such as the need to protect patient privacy by adequately de-identifying personal health information, assuring consistent quality and representativeness of the data, and preventing the unblinding of patient group assignments. Social media has both potential for improving orphan drug development and pitfalls, but with proper oversight on the part of companies, support and participation of patients and their advocacy groups, and timely guidance from regulatory authorities, the positives outweigh the negatives for this powerful and patient-centric tool. Copyright © 2017 Elsevier HS Journals, Inc. All rights reserved.
Parental HIV/AIDS and psychosocial adjustment among rural Chinese children.

PubMed

Fang, Xiaoyi; Li, Xiaoming; Stanton, Bonita; Hong, Yan; Zhang, Liying; Zhao, Guoxiang; Zhao, Junfeng; Lin, Xiuyun; Lin, Danhua

2009-01-01

To assess the relationship between parental HIV/AIDS and psychosocial adjustment of children in rural central China. Participants included 296 double AIDS orphans (children who had lost both their parents to AIDS), 459 single orphans (children who had lost one parent to AIDS), 466 vulnerable children who lived with HIV-infected parents, and 404 comparison children who did not experience HIV/AIDS-related illness and death in their families. The measures included depressive symptoms, loneliness, self-esteem, future expectations, hopefulness about the future, and perceived control over the future. AIDS orphans and vulnerable children consistently demonstrated poorer psychosocial adjustment than comparison children in the same community. The level of psychosocial adjustment was similar between single orphans and double orphans, but differed by care arrangement among double orphans. The findings underscore the urgency and importance of culturally and developmentally appropriate intervention efforts targeting psychosocial problems among children affected by AIDS and call for more exploration of risk and resilience factors, both individual and contextual, affecting the psychosocial wellbeing of these children.
Diagnostic orphans: comparing self-report lifetime course to groups with DSM-IV alcohol abuse and dependence.

PubMed

McBride, Orla; Adamson, Gary; Bunting, Brendan; McCann, Siobhan

2009-01-01

Research has highlighted the significant alcohol symptoms and mental health problems experienced by diagnostic orphans - individuals who experience 1-2 criteria of DSM-IV alcohol dependence but do not meet the criteria for a DSM-IV alcohol use disorder. This study used a sub-sample (n=34827) from the National Epidemiologic Survey on Alcohol and Related Conditions (NESARC), and formed mutually exclusive groups to compare the self-report retrospective course of diagnostic orphans to individuals with DSM-IV abuse and dependence. Multinomial logistic regressions were conducted to examine the associations between the groups and a range of demographic and clinical variables. Collectively, the findings demonstrate that diagnostic orphans shared similar characteristics to the abuse and dependence groups, but appeared to experience specific comorbid mental health problems. Orphan status has the potential to be a persistent condition and may result in significant dysfunction. In conclusion, diagnostic orphans represent a distinct group that may benefit from cost-effective treatment or intervention, designed to prevent the escalation of alcohol symptoms.
Budget impact analysis of drugs for ultra-orphan non-oncological diseases in Europe.

PubMed

Schlander, Michael; Adarkwah, Charles Christian; Gandjour, Afschin

2015-02-01

Ultra-orphan diseases (UODs) have been defined by a prevalence of less than 1 per 50,000 persons. However, little is known about budget impact of ultra-orphan drugs. For analysis, the budget impact analysis (BIA) had a time horizon of 10 years (2012-2021) and a pan-European payer's perspective, based on prevalence data for UODs for which patented drugs are available and/or for which drugs are in clinical development. A total of 18 drugs under patent protection or orphan drug designation for non-oncological UODs were identified. Furthermore, 29 ultra-orphan drugs for non-oncological diseases under development that have the potential of reaching the market by 2021 were found. Total budget impact over 10 years was estimated to be €15,660 and €4965 million for approved and pipeline ultra-orphan drugs, respectively (total: €20,625 million). The analysis does not support concerns regarding an uncontrolled growth in expenditures for drugs for UODs.
The multiple universes of estrogen-related receptor α and γ in metabolic control and related diseases

PubMed Central

Audet-walsh, Étienne; Giguére, Vincent

2015-01-01

The identification of the estrogen-related receptors (ERRs) as the first orphan nuclear receptors ignited a new era in molecular endocrinology, which led to the discovery of new ligand-dependent response systems. Although ERR subfamily members have yet to be associated with a natural ligand, the characterization of these orphan receptors has demonstrated that they occupy a strategic node in the transcriptional control of cellular energy metabolism. In particular, ERRs are required for the response to various environmental challenges that require high energy levels by the organism. As central regulators of energy homeostasis, ERRs may also be implicated in the etiology of metabolic disorders, such as type 2 diabetes and metabolic syndrome. Here, we review the recent evidence that further highlights the role of ERRs in metabolic control, particularly in liver and skeletal muscle, and their likely involvement in metabolic diseases. Consequently, we also explore the promises and pitfalls of ERRs as potential therapeutic targets. PMID:25500872
An orphan cbb3-type cytochrome oxidase subunit supports Pseudomonas aeruginosa biofilm growth and virulence

PubMed Central

Jo, Jeanyoung; Cortez, Krista L; Cornell, William Cole; Price-Whelan, Alexa

2017-01-01

Hypoxia is a common challenge faced by bacteria during associations with hosts due in part to the formation of densely packed communities (biofilms). cbb3-type cytochrome c oxidases, which catalyze the terminal step in respiration and have a high affinity for oxygen, have been linked to bacterial pathogenesis. The pseudomonads are unusual in that they often contain multiple full and partial (i.e. ‘orphan’) operons for cbb3-type oxidases and oxidase subunits. Here, we describe a unique role for the orphan catalytic subunit CcoN4 in colony biofilm development and respiration in the opportunistic pathogen Pseudomonas aeruginosa PA14. We also show that CcoN4 contributes to the reduction of phenazines, antibiotics that support redox balancing for cells in biofilms, and to virulence in a Caenorhabditis elegans model of infection. These results highlight the relevance of the colony biofilm model to pathogenicity and underscore the potential of cbb3-type oxidases as therapeutic targets. PMID:29160206
Developing treatments for inborn errors: incentives available to the clinician.

PubMed

Haffner, Marlene E

2004-04-01

Disorders resulting from inborn errors of metabolism (IEM) affect very small numbers of individuals. The entire population, however, of patients suffering the results of inherited metabolic disorders is large, and has been of increasing concern to patient groups and health care professionals in the United States as well as other countries throughout the world. The 1983 US Orphan Drug Act (ODA) serves to facilitate the development of drugs to treat rare diseases by providing several economic incentives. The sponsor of a product designated as an orphan by the Food & Drugs Administration (FDA) Office of Orphan Products Development (OPD) qualifies for tax credits on clinical trial expenses, the award of grant funding by FDA, through the OPD, and 7 years of marketing exclusivity for a designated drug, or biological product that receives FDA market approval. Orphan drug legislation in the US has benefited victims of IEM by encouraging development of drugs for metabolic deficiencies affecting populations that otherwise would be ignored. America's solution to the orphan drug problem has had worldwide impact. The success of this legislation was a factor leading to the 1993 orphan drug law in Japan; the 1997 implementation of a process whereby most FDA-approved orphan drugs and biological products will be similarly approved in Australia; and, in 1999, regulation on orphan medicinal products in the European Union (EU). Today, international support for rare disease research is providing stimulus and motivation to overcome the financial barriers and encourage development of treatment for very rare diseases throughout the world.
Observations of recent flares of the blazar 1ES1959+650 with VERITAS

NASA Astrophysics Data System (ADS)

Zhou, Yuyang; Santander, Marcos; VERITAS Collaboration

2017-01-01

VERITAS (Very Energetic Radiation Imaging Telescope Array System) is a an array of imaging atmospheric Cherenkov telescopes that carries out an extensive observation program of the gamma-ray sky at energies above 0.1 TeV. Blazars, active galactic nuclei powered by supermassive black holes, are gamma-ray sources of major interest. The relativistic jets they emit are among the most energetic phenomena in the universe and constitute a significant amount of study in high energy astrophysics. In particular, the blazar 1ES 1959+650 (z=0.048) has garnered special attention due to its emission of an ``orphan'' flare in 2002. An orphan flare is an extremely bright emission in gamma rays that is not coupled to X-rays. This phenomenon is incompatible with our current model of gamma-ray production, the self-synchrotron Compton (SSC) process. This study aims to characterize recent TeV flares of this source by analyzing the time variability of its light curve and spectrum and comparing these findings to observations made in other wavelengths. We hope to determine if these recent flares have also been orphan in nature, put an upper limit on the size of the emission region, and understand the nature of the gamma-ray emission in the source.
Paying for the Orphan Drug System: break or bend? Is it time for a new evaluation system for payers in Europe to take account of new rare disease treatments?

PubMed Central

2012-01-01

Since its enactment in 2000, the European Orphan Medicinal Products Regulation has allowed the review and approval of approaching 70 treatments for some 55 different conditions in Europe. Success does not come without a price, however. Many of these so-called “orphan drugs” have higher price points than treatments for more common diseases. This has been raising debate as to whether the treatments are worth it, which, in turn risks blocking patient access to treatment. To date, orphan drugs have only accounted for a small percentage of the overall drug budget. It would appear that, with increasing numbers of orphan drugs, governments are concerned about the future budget impact and their cost-effectiveness in comparison with other healthcare interventions. Orphan drugs are under the spotlight, something that is likely to continue as the economic crisis in Europe takes hold and governments respond with austerity measures that include cuts to healthcare expenditures. Formally and informally, governments are looking at how they are going to handle orphan drugs in the future. Collaborative proposals between EU governments to better understand the value of orphan drugs are under consideration. In recent years there has been increasing criticism of behaviours in the orphan drug field, mainly centring on two key perceptions of the system: the high prices of orphan drugs and their inability to meet standard cost-effectiveness thresholds; and the construct of the system itself, which allows companies to gain the benefits that accrue from being badged as an orphan drug. The authors hypothesise that, by examining these criticisms individually, one might be able to turn these different “behaviours” into criteria for the creation of a system to evaluate new orphan drugs coming onto the market. It has been acknowledged that standard methodologies for Health Technology Assessments (HTA) will need to be tailored to take into account the specificities of orphan drugs given that the higher price-points claimed by orphan drugs are unlikely to meet current cost-effectiveness thresholds. The authors propose the development of a new assessment system based on several evaluation criteria, which would serve as a tool for Member State governments to evaluate each new orphan drug at the time of pricing and reimbursement. These should include rarity, disease severity, the availability of other alternatives (level of unmet medical need), the level of impact on the condition that the new treatment offers, whether the product can be used in one or more indications, the level of research undertaken by the developer, together with other factors, such as manufacturing complexity and follow-up measures required by regulatory or other authorities. This will allow governments to value an orphan drug that fulfilled all the criteria very differently from one that only met some of them. An individual country could determine the (monetary) value that it places on each of the different criteria, according to societal preferences, the national healthcare system and the resources at its disposal – each individual government deciding on the weighting attributed to each of the criteria in question, based on what each individual society values most. Such a systematic and transparent system will help frame a more structured dialogue between manufacturers and payers, with the involvement of the treating physicians and the patients; and foster a more certain environment to stimulate continued investment in the field. A new approach could also offer pricing and reimbursement decision-makers a tool to handle the different characteristics amongst new orphan drugs and to redistribute the national budgets in accordance with the outcome of a differentiated assessment. The authors believe that this could, therefore, facilitate the approach for all stakeholders. PMID:23013790
The Global Threat Reduction Initiative's Orphan Source Recovery Project in the Russian Federation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Russell, J. W.; Ahumada, A. D.; Blanchard, T. A.

After 9/11, officials at the United States Department of Energy (DOE), National Nuclear Security Administration (NNSA) grew more concerned about radiological materials that were vulnerable to theft and illicit use around the world. The concern was that terrorists could combine stolen radiological materials with explosives to build and detonate a radiological dispersal device (RDD), more commonly known as a “dirty bomb.” In response to this and other terrorist threats, the DOE/NNSA formed what is now known as the Global Threat Reduction Initiative (GTRI) to consolidate and accelerate efforts to reduce and protect vulnerable nuclear and radiological materials located at civilianmore » sites worldwide. Although a cooperative program was already underway in the Russian Federation to secure nuclear materials at a range of different facilities, thousands of sealed radioactive sources remained vulnerable at medical, research, and industrial sites. In response, GTRI began to focus efforts on addressing these materials. GTRI’s Russia Orphan Source Recovery Project, managed at the Nevada National Security Site’s North Las Vegas facility, was initiated in 2002. Throughout the life of the project, Joint Stock Company “Isotope” has served as the primary Russian subcontractor, and the organization has proven to be a successful partner. Since the first orphan source recovery of an industrial cobalt-60 irradiator with 647 curies (Ci) at an abandoned facility in Moscow in 2003, the GTRI Orphan Source Recovery Project in the Russian Federation has accomplished substantial levels of threat reduction. To date, GTRI has recovered and securely disposed of more than 5,100 sources totaling more that 628,000 Ci. This project serves as an extraordinary example of how international cooperation can be implemented by partners with mutual interests to achieve significant goals.« less
Exploiting EST databases for the development and characterisation of 3425 gene-tagged CISP markers in biofuel crop sugarcane and their transferability in cereals and orphan tropical grasses.

PubMed

Chandra, Amaresh; Jain, Radha; Solomon, Sushil; Shrivastava, Shiksha; Roy, Ajoy K

2013-02-04

Sugarcane is an important cash crop, providing 70% of the global raw sugar as well as raw material for biofuel production. Genetic analysis is hindered in sugarcane because of its large and complex polyploid genome and lack of sufficiently informative gene-tagged markers. Modern genomics has produced large amount of ESTs, which can be exploited to develop molecular markers based on comparative analysis with EST datasets of related crops and whole rice genome sequence, and accentuate their cross-technical functionality in orphan crops like tropical grasses. Utilising 246,180 Saccharum officinarum EST sequences vis-à-vis its comparative analysis with ESTs of sorghum and barley and the whole rice genome sequence, we have developed 3425 novel gene-tagged markers - namely, conserved-intron scanning primers (CISP) - using the web program GeMprospector. Rice orthologue annotation results indicated homology of 1096 sequences with expressed proteins, 491 with hypothetical proteins. The remaining 1838 were miscellaneous in nature. A total of 367 primer-pairs were tested in diverse panel of samples. The data indicate amplification of 41% polymorphic bands leading to 0.52 PIC and 3.50 MI with a set of sugarcane varieties and Saccharum species. In addition, a moderate technical functionality of a set of such markers with orphan tropical grasses (22%) and fodder cum cereal oat (33%) is observed. Developed gene-tagged CISP markers exhibited considerable technical functionality with varieties of sugarcane and unexplored species of tropical grasses. These markers would thus be particularly useful in identifying the economical traits in sugarcane and developing conservation strategies for orphan tropical grasses.
Oncology drugs for orphan indications: how are HTA processes evolving for this specific drug category?

PubMed

Adkins, Elizabeth M; Nicholson, Lindsay; Floyd, David; Ratcliffe, Mark; Chevrou-Severac, Helene

2017-01-01

Orphan drugs (ODs) are intended for the diagnosis, prevention, or treatment of rare diseases. Many cancer subtypes, including all childhood cancers, are defined as rare diseases, and over one-third of ODs are now intended to treat oncology indications. However, market access for oncology ODs is becoming increasingly challenging; ODs are prone to significant uncertainty around their cost-effectiveness, while payers must balance the need for these vital innovations with growing sensitivity to rising costs. The objective of this review was to evaluate different mechanisms that have been introduced to facilitate patient access to oncology ODs in five different countries (Australia, Canada, England, France, and Sweden), using eight oncology ODs and non-orphan oncology drugs as examples of their application. A targeted literature review of health technology assessment (HTA) agency websites was undertaken to identify country-specific guidance and HTA documentation for recently evaluated oncology ODs and non-orphan oncology drugs. None of these countries were found to have explicit HTA criteria for the assessment of ODs, and therefore, oncology ODs are assessed through the usual HTA process. However, distinct and additional processes are adopted to facilitate access to oncology ODs. Review of eight case-study drugs showed that these additional assessment processes were rarely used, and decisions were largely driven by proving cost-effectiveness using standard incremental cost-effectiveness ratio (ICER) thresholds. The predominant implication arising from this study is that application of standard HTA criteria to oncology ODs in many countries fails to take into account any uncertainties around their clinical- and cost-effectiveness, resulting in disparities in HTA reimbursement decisions based on differences in addressing or accepting uncertainty. In order to address this issue, HTA agencies should adopt a more flexible approach to cost-effectiveness, as typified by the Tandvårds-och Läkemedelsförmånsverket in Sweden, which takes into account the small patient numbers involved, limited budget impact, and high unmet medical needs.
Oncology drugs for orphan indications: how are HTA processes evolving for this specific drug category?

PubMed Central

Adkins, Elizabeth M; Nicholson, Lindsay; Floyd, David; Ratcliffe, Mark; Chevrou-Severac, Helene

2017-01-01

Orphan drugs (ODs) are intended for the diagnosis, prevention, or treatment of rare diseases. Many cancer subtypes, including all childhood cancers, are defined as rare diseases, and over one-third of ODs are now intended to treat oncology indications. However, market access for oncology ODs is becoming increasingly challenging; ODs are prone to significant uncertainty around their cost-effectiveness, while payers must balance the need for these vital innovations with growing sensitivity to rising costs. The objective of this review was to evaluate different mechanisms that have been introduced to facilitate patient access to oncology ODs in five different countries (Australia, Canada, England, France, and Sweden), using eight oncology ODs and non-orphan oncology drugs as examples of their application. A targeted literature review of health technology assessment (HTA) agency websites was undertaken to identify country-specific guidance and HTA documentation for recently evaluated oncology ODs and non-orphan oncology drugs. None of these countries were found to have explicit HTA criteria for the assessment of ODs, and therefore, oncology ODs are assessed through the usual HTA process. However, distinct and additional processes are adopted to facilitate access to oncology ODs. Review of eight case-study drugs showed that these additional assessment processes were rarely used, and decisions were largely driven by proving cost-effectiveness using standard incremental cost-effectiveness ratio (ICER) thresholds. The predominant implication arising from this study is that application of standard HTA criteria to oncology ODs in many countries fails to take into account any uncertainties around their clinical- and cost-effectiveness, resulting in disparities in HTA reimbursement decisions based on differences in addressing or accepting uncertainty. In order to address this issue, HTA agencies should adopt a more flexible approach to cost-effectiveness, as typified by the Tandvårds-och Läkemedelsförmånsverket in Sweden, which takes into account the small patient numbers involved, limited budget impact, and high unmet medical needs. PMID:28652787
Using phase II data for the analysis of phase III studies: An application in rare diseases.

PubMed

Wandel, Simon; Neuenschwander, Beat; Röver, Christian; Friede, Tim

2017-06-01

Clinical research and drug development in orphan diseases are challenging, since large-scale randomized studies are difficult to conduct. Formally synthesizing the evidence is therefore of great value, yet this is rarely done in the drug-approval process. Phase III designs that make better use of phase II data can facilitate drug development in orphan diseases. A Bayesian meta-analytic approach is used to inform the phase III study with phase II data. It is particularly attractive, since uncertainty of between-trial heterogeneity can be dealt with probabilistically, which is critical if the number of studies is small. Furthermore, it allows quantifying and discounting the phase II data through the predictive distribution relevant for phase III. A phase III design is proposed which uses the phase II data and considers approval based on a phase III interim analysis. The design is illustrated with a non-inferiority case study from a Food and Drug Administration approval in herpetic keratitis (an orphan disease). Design operating characteristics are compared to those of a traditional design, which ignores the phase II data. An analysis of the phase II data reveals good but insufficient evidence for non-inferiority, highlighting the need for a phase III study. For the phase III study supported by phase II data, the interim analysis is based on half of the patients. For this design, the meta-analytic interim results are conclusive and would justify approval. In contrast, based on the phase III data only, interim results are inconclusive and require further evidence. To accelerate drug development for orphan diseases, innovative study designs and appropriate methodology are needed. Taking advantage of randomized phase II data when analyzing phase III studies looks promising because the evidence from phase II supports informed decision-making. The implementation of the Bayesian design is straightforward with public software such as R.
Gogo care and protection of vulnerable children in rural Malawi: changing responsibilities, capacity to provide, and implications for well-being in the era of HIV and AIDS.

PubMed

Littrell, Megan; Murphy, Laura; Kumwenda, Moses; Macintyre, Kate

2012-12-01

The role of older women in the care and protection of vulnerable children in sub-Saharan Africa may be changing given increasing rates of orphanhood due to AIDS. Concern regarding their capacity to provide for children and implications for their health and well-being dominate the literature. However, studies have not yet examined the situation of older caregivers in comparison to their younger counterparts over time. In this study, panel data on 1,219 caregivers in rural Malawi between 2007 and 2009 is complemented by in-depth interview (N=62) and group discussion (N=4) data. Caregiver responsibilities, capacity to care for children, and implications for well-being are examined. Chi-square tests examine differences in these measures between older foster caregivers and younger foster caregivers, parents of orphans, and parents of non-orphans. Older women, in comparison with younger counterparts, are more stable as primary caregivers for orphans. Care by older women is particularly valued when younger family stability is threatened by burdens of orphan care. Qualitative data reveal many challenges that older caregivers face, most notably provision of food. However, survey data suggest that the capacity to provide food, schooling and other basic needs is similar among older and younger caregivers. Self-reported health status is generally poorer among older caregivers, however levels of emotional distress and social capital are similar among older and younger caregivers. Providing care for children in old age appears to entail a number of benefits. Older women committed to providing care and protection for children are important assets, particularly in the context of threats to child well-being due to HIV and AIDS. Bolstering older caregivers with material and social support to help sustain their key roles in fostering is a promising avenue for maintaining extended family responses to HIV and AIDS.
8 CFR 204.3 - Orphan cases under section 101(b)(1)(F) of the Act (non-Convention cases).

Code of Federal Regulations, 2013 CFR

2013-01-01

... advanced processing application (or the advanced processing application concurrently with the orphan... home study preparer and/or fingerprint check. Advanced processing application means Form I-600A (Application for Advanced Processing of Orphan Petition) completed in accordance with the form's instructions...
8 CFR 204.3 - Orphan cases under section 101(b)(1)(F) of the Act (non-Convention cases).

Code of Federal Regulations, 2010 CFR

2010-01-01

... advanced processing application (or the advanced processing application concurrently with the orphan... home study preparer and/or fingerprint check. Advanced processing application means Form I-600A (Application for Advanced Processing of Orphan Petition) completed in accordance with the form's instructions...

8 CFR 204.3 - Orphan cases under section 101(b)(1)(F) of the Act (non-Convention cases).

Code of Federal Regulations, 2014 CFR

2014-01-01

... advanced processing application (or the advanced processing application concurrently with the orphan... home study preparer and/or fingerprint check. Advanced processing application means Form I-600A (Application for Advanced Processing of Orphan Petition) completed in accordance with the form's instructions...
8 CFR 204.3 - Orphan cases under section 101(b)(1)(F) of the Act (non-Convention cases).

Code of Federal Regulations, 2011 CFR

2011-01-01

... advanced processing application (or the advanced processing application concurrently with the orphan... home study preparer and/or fingerprint check. Advanced processing application means Form I-600A (Application for Advanced Processing of Orphan Petition) completed in accordance with the form's instructions...
8 CFR 204.3 - Orphan cases under section 101(b)(1)(F) of the Act (non-Convention cases).

Code of Federal Regulations, 2012 CFR

2012-01-01

... advanced processing application (or the advanced processing application concurrently with the orphan... home study preparer and/or fingerprint check. Advanced processing application means Form I-600A (Application for Advanced Processing of Orphan Petition) completed in accordance with the form's instructions...
Educational Inequalities and Ukrainian Orphans' Future Pathways: Social Reproduction or Transformation through the Hidden Curriculum?

ERIC Educational Resources Information Center

Korzh, Alla

2013-01-01

This qualitative multi-site case study, situated in the context of Ukraine's post-Soviet political economy, examined how orphanage educators' expectations and beliefs about orphans' academic abilities and potential, curriculum, peer relationships, and education policy shaped orphans' post-secondary education decisions and trajectories. Examination…
Using multi-criteria decision analysis to appraise orphan drugs: a systematic review.

PubMed

Friedmann, Carlotta; Levy, Pierre; Hensel, Paul; Hiligsmann, Mickaël

2018-04-01

Multi-criteria decision analysis (MCDA) could potentially solve current methodological difficulties in the appraisal of orphan drugs. Areas covered: We provide an overview of the existing evidence regarding the use of MCDA in the appraisal of orphan drugs worldwide. Three databases (Pubmed, Embase, Web of Science) were searched for English, French and German literature published between January 2000 and April 2017. Full-text articles were supplemented with conference abstracts. A total of seven articles and six abstracts were identified. Expert commentary: The literature suggests that MCDA is increasingly being used in the context of appraising orphan drugs. It has shown itself to be a flexible approach with the potential to assist in decision-making regarding reimbursement for orphan drugs. However, further research regarding its application must be conducted.
eRepo-ORP: Exploring the Opportunity Space to Combat Orphan Diseases with Existing Drugs.

PubMed

Brylinski, Michal; Naderi, Misagh; Govindaraj, Rajiv Gandhi; Lemoine, Jeffrey

2017-12-10

About 7000 rare, or orphan, diseases affect more than 350 million people worldwide. Although these conditions collectively pose significant health care problems, drug companies seldom develop drugs for orphan diseases due to extremely limited individual markets. Consequently, developing new treatments for often life-threatening orphan diseases is primarily contingent on financial incentives from governments, special research grants, and private philanthropy. Computer-aided drug repositioning is a cheaper and faster alternative to traditional drug discovery offering a promising venue for orphan drug research. Here, we present eRepo-ORP, a comprehensive resource constructed by a large-scale repositioning of existing drugs to orphan diseases with a collection of structural bioinformatics tools, including eThread, eFindSite, and eMatchSite. Specifically, a systematic exploration of 320,856 possible links between known drugs in DrugBank and orphan proteins obtained from Orphanet reveals as many as 18,145 candidates for repurposing. In order to illustrate how potential therapeutics for rare diseases can be identified with eRepo-ORP, we discuss the repositioning of a kinase inhibitor for Ras-associated autoimmune leukoproliferative disease. The eRepo-ORP data set is available through the Open Science Framework at https://osf.io/qdjup/. Copyright © 2017. Published by Elsevier Ltd.
Novel Treatments for Rare Cancers: The U.S. Orphan Drug Act Is Delivering-A Cross-Sectional Analysis.

PubMed

Stockklausner, Clemens; Lampert, Anette; Hoffmann, Georg F; Ries, Markus

2016-04-01

Rare cancers are a heterogeneous group of conditions with highly unmet medical needs. Although infrequent in individuals, rare cancers affect millions of people who deserve effective treatments. Therefore, we systematically analyzed the impact of the U.S. Orphan Drug Act of 1983 on delivery of novel treatments for rare cancers. Quantitative cross-sectional analysis was conducted on the U.S. Food and Drug Administration Orphan Drug Product database according to Strengthening the Reporting of Observational Studies in Epidemiology Statement criteria between 1983 and 2015. Since 1983, a total of 177 approvals have originated from 1,391 orphan drug designations to treat rare cancers, which represents 36% of all approvals within the U.S. orphan drug act (n = 492). Two compounds (1%) to treat rare cancer were withdrawn after approval. Median time from designation to approval was 2.49 years (interquartile range 1.13-4.64) and decreased significantly over time (p < .001, linear regression). Over the last decade, rare cancer treatments have been transformed from nonspecific cytotoxic agents toward targeted therapies, such as protein kinase inhibitors and monoclonal antibodies, representing the largest groups of innovative rare cancer treatments today. Most compounds were approved to treat solid tumors and hematological malignancies. The U.S. Orphan Drug Act and associated incentives, such as 7 years of marketing exclusivity, have fostered delivery of novel treatments for rare cancers. More than one-third of all orphan drug approvals address needs of patients suffering from rare cancers. Over the last decade, the understanding of tumorigenesis and genetic driver mutations in different tumor entities has produced innovative treatments, of which many were first approved within the U.S. Orphan Drug Act. Over the last 30 years, the U.S. Orphan Drug Act successfully delivered numerous novel treatments for rare cancers, of which some were subsequently used in other, nonorphan indications. The understanding of molecular mechanisms of diseases is directly connected to the search for novel therapies. The constant pursuit to translate basic research findings into clinical practice is a crucial prerequisite to address unmet medical needs in rare cancers, as in other rare diseases. Oncological drug development proves to be a major player in overall orphan drug research, displayed by more than one-third of all U.S. Food and Drug Administration-approved orphan drugs with oncological indications. ©AlphaMed Press.
Orphaned and abused youth are vulnerable to pregnancy and suicide risk.

PubMed

Zapata, Lauren B; Kissin, Dmitry M; Bogoliubova, Olga; Yorick, Roman V; Kraft, Joan Marie; Jamieson, Denise J; Marchbanks, Polly A; Hillis, Susan D

2013-05-01

Little is known about the magnitude and consequences of violence against children for those living outside family care. We sought to estimate the frequency of childhood abuse and examine its association with lifetime pregnancy involvement (LPI) and past year suicide ideation among orphaned youth. We analyzed data collected via cross-sectional interviewer-administered surveys completed by 293 orphaned youth aged 16-23 years living outside of family care in St. Petersburg, Russia. We used multivariable logistic regression to estimate adjusted odds ratios (AORs) of LPI and past year suicide ideation associated with childhood physical and sexual abuse. Other risk factors were also examined (e.g., social vulnerability, sexual and substance use behaviors), and characteristics of orphaned youth with LPI and past year suicide ideation were described. The prevalence of childhood abuse was higher among females than among males (23.3% versus 15.6% for physical abuse, and 20.3% versus 5.6% for sexual abuse), as was the prevalence of LPI and past year suicide ideation among those with histories of abuse. Experiences of childhood abuse were strong risk factors for both LPI and past year suicide ideation, with significant variation by gender. While both types of abuse were significantly associated with LPI and past year suicide ideation among females, physical abuse was significantly associated with LPI and sexual abuse was associated with suicide ideation for males. Of the other characteristics examined, strong modifiable risk factors included having no one to turn to for help and no involvement in activities outside of class. Among those with LPI (n=36), nearly 20% had been pregnant or gotten someone pregnant ≥2 times, most (61.8%) reported at least one induced abortion, and current use of effective contraception was nearly non-existent. Among those with past year suicide ideation (n=30), nearly half (44.8%) reported attempting suicide. There is an urgent need for interventions to prevent and mitigate the negative influence of childhood abuse experiences. Programs providing services to orphaned youth should increase access to sexual education, effective contraceptives, and mental health counseling. Published by Elsevier Ltd.
Orphaned and abused youth are vulnerable to pregnancy and suicide risk☆, ☆☆

PubMed Central

Kissin, Dmitry M.; Bogoliubova, Olga; Yorick, Roman V.; Kraft, Joan Marie; Jamieson, Denise J.; Marchbanks, Polly A.; Hillis, Susan D.

2015-01-01

Objective Little is known about the magnitude and consequences of violence against children for those living outside family care. We sought to estimate the frequency of childhood abuse and examine its association with lifetime pregnancy involvement (LPI) and past year suicide ideation among orphaned youth. Methods We analyzed data collected via cross-sectional interviewer-administered surveys completed by 293 orphaned youth aged 16–23 years living outside of family care in St. Petersburg, Russia. We used multivariable logistic regression to estimate adjusted odds ratios (AORs) of LPI and past year suicide ideation associated with childhood physical and sexual abuse. Other risk factors were also examined (e.g., social vulnerability, sexual and substance use behaviors), and characteristics of orphaned youth with LPI and past year suicide ideation were described. Results The prevalence of childhood abuse was higher among females than among males (23.3% versus 15.6% for physical abuse, and 20.3% versus 5.6% for sexual abuse), as was the prevalence of LPI and past year suicide ideation among those with histories of abuse. Experiences of childhood abuse were strong risk factors for both LPI and past year suicide ideation, with significant variation by gender. While both types of abuse were significantly associated with LPI and past year suicide ideation among females, physical abuse was significantly associated with LPI and sexual abuse was associated with suicide ideation for males. Of the other characteristics examined, strong modifiable risk factors included having no one to turn to for help and no involvement in activities outside of class. Among those with LPI (n = 36), nearly 20% had been pregnant or gotten someone pregnant ≥2 times, most (61.8%) reported at least one induced abortion, and current use of effective contraception was nearly non-existent. Among those with past year suicide ideation (n = 30), nearly half (44.8%) reported attempting suicide. Conclusions There is an urgent need for interventions to prevent and mitigate the negative influence of childhood abuse experiences. Programs providing services to orphaned youth should increase access to sexual education, effective contraceptives, and mental health counseling. PMID:23290621
Are We Doing Everything We Should for the Health of Our Children? An Interview with Nikolai Nikolaevich Baganov.

ERIC Educational Resources Information Center

Russian Education and Society, 1998

1998-01-01

Presents an interview with Nikolai Nikolaevich Baganov addressing the presidential program "Russia's Children" that is made up of nine subprograms: Children of Chernobyl, Children of the North, Family Planning, The Baby-food Industry, Orphaned Children, Handicapped Children, Gifted Children, Children of Refugee Families, and Children's…
78 FR 44016 - Exclusion of Orphan Drugs for Certain Covered Entities Under 340B Program

Federal Register 2010, 2011, 2012, 2013, 2014

2013-07-23

... request or upon a government-approved manufacturer audit request that directly pertains to the covered entity's compliance with section 340B(e) of the PHSA. Any HRSA audit of an affected covered entity will... approval, a manufacturer has the right to audit an affected covered entity's compliance with this section...
42 CFR 414.906 - Competitive acquisition program as the basis for payment.

Code of Federal Regulations, 2010 CFR

2010-10-01

... section, payment for CAP drugs is based on bids submitted as a result of the bidding process as described... established. (d) Adjustments. There is an established process for adjustments to payments to account for drugs... of— (A) One or more newly issued HCPCS codes; or (B) One of the following single indication orphan...
Utilizing the Antarctic Master Directory to find orphan datasets

NASA Astrophysics Data System (ADS)

Bonczkowski, J.; Carbotte, S. M.; Arko, R. A.; Grebas, S. K.

2011-12-01

While most Antarctic data are housed at an established disciplinary-specific data repository, there are data types for which no suitable repository exists. In some cases, these "orphan" data, without an appropriate national archive, are served from local servers by the principal investigators who produced the data. There are many pitfalls with data served privately, including the frequent lack of adequate documentation to ensure the data can be understood by others for re-use and the impermanence of personal web sites. For example, if an investigator leaves an institution and the data moves, the link published is no longer accessible. To ensure continued availability of data, submission to long-term national data repositories is needed. As stated in the National Science Foundation Office of Polar Programs (NSF/OPP) Guidelines and Award Conditions for Scientific Data, investigators are obligated to submit their data for curation and long-term preservation; this includes the registration of a dataset description into the Antarctic Master Directory (AMD), http://gcmd.nasa.gov/Data/portals/amd/. The AMD is a Web-based, searchable directory of thousands of dataset descriptions, known as DIF records, submitted by scientists from over 20 countries. It serves as a node of the International Directory Network/Global Change Master Directory (IDN/GCMD). The US Antarctic Program Data Coordination Center (USAP-DCC), http://www.usap-data.org/, funded through NSF/OPP, was established in 2007 to help streamline the process of data submission and DIF record creation. When data does not quite fit within any existing disciplinary repository, it can be registered within the USAP-DCC as the fallback data repository. Within the scope of the USAP-DCC we undertook the challenge of discovering and "rescuing" orphan datasets currently registered within the AMD. In order to find which DIF records led to data served privately, all records relating to US data within the AMD were parsed. After identifying the records containing a URL leading to a national data center or other disciplinary data repository, the remaining records were individually inspected for data type, format, and quality of metadata and then assessed to determine how best to preserve. Of the records reviewed, those for which appropriate repositories could be identified were submitted. An additional 35 were deemed acceptable in quality of metadata to register in the USAP-DCC. The content of these datasets were varied in nature, ranging from penguin counts to paleo-geologic maps to results of meteorological models all of which are discoverable through our search interface, http://www.usap-data.org/search.php. The remaining 40 records linked to either no data or had inadequate documentation for preservation highlighting the danger of serving datasets on local servers where minimal metadata standards can not be enforced and long-term access can not be ensured.
A comparative assessment of generalized anxiety, conduct and peer relationship problems among AIDS and other orphaned children in India.

PubMed

Sg, Prem Kumar; G, Anil Kumar; Sp, Ramgopal; V, Venkata Srinivas; Dandona, Rakhi

2016-09-21

Data on mental health among orphaned children in India are scanty. We compared the generalized anxiety, conduct and peer relationship problems and their associated risk factors among children orphaned by HIV/AIDS and those due to other reasons in the Indian city of Hyderabad. Four hundred orphaned children aged 12 to 16 years residing in orphanages in Hyderabad were sampled, half being AIDS orphans (COA) and the rest orphaned due to other reasons (COO). Interviews were done using standardized scales to assess generalized anxiety, conduct and peer relationship problems. A score >8, >4, and >5 was considered as indicator of generalized anxiety, conduct problem and peer relationship problem, respectively. Variations in the intensity of these three conditions due to possible factors including co-existing depression were assessed using multiple classification analysis (MCA). A total of 396 (99.3 %) orphans participated of whom 199 (50.3 %) were COA. The mean generalized anxiety, conduct and peer relationship problem scores were 11.1 (SD 5.2), 3.8 (SD 2.5) and 3.8 (SD 2.5) for COA; and 7.6 (SD 4), 2.6 (SD 2) and 2.3 (SD 1.8) for COO, respectively. Among COA, the prevalence of generalized anxiety score of >8 was 74.4 % (95 % CI 67.8-80.0 %), of conduct problem score of >4 was 33.2 % (95 % CI 26.9-40.1 %), and of peer relationship problem score of >5 was 27.6 %, (95 % CI 21.8-34.3 %), with these being significantly lower in COO. In MCA, a higher mean depression score had the highest effect on the intensity of generalized anxiety, conduct and peer relationship problem (Beta 0.477; 0.379 and 0.453 respectively); being COA and a girl had the most impact on generalized anxiety (0.100 and 0.115, respectively). A significantly high proportion of AIDS orphans deal with generalized anxiety, conduct and peer relationship problem as compared with other orphans highlighting the need to address the poor mental health of orphans in India.
Multi-informant perspective on psychological distress among Ghanaian orphans and vulnerable children within the context of HIV/AIDS.

PubMed

Doku, P N; Minnis, H

2016-08-01

There is little knowledge about the psychosocial distress of children affected by human immunodeficiency virus infection and acquired immune deficiency syndrome (HIV/AIDS) in Ghana, to aid the planning of services. This study investigated mental health problems among children affected by HIV/AIDS, compared with control groups of children orphaned by other causes, and non-orphans. The study employed a cross-sectional survey that interviewed 291 children and their caregivers. Both children and caregivers completed the Strengths and Difficulties Questionnaire that measured children's psychosocial wellbeing. Verbal autopsy was used to identify whether children lost one or both parents from AIDS. The results indicated that controlling for relevant sociodemographic factors, both children's self-reports and caregivers' reports indicate that both children living with HIV/AIDS-infected caregivers and children orphaned by AIDS were at heightened risk for mental health problems than both children orphaned by other causes and non-orphans. The findings further indicated that a significant proportion of orphaned and vulnerable children exhibited symptoms for depression and other psychiatric disorders (approximately 63%) compared with 7% among the non-orphaned group. Caregivers gave higher ratings for children on externalizing problems and lower on internalizing problems, and vice versa when the children's self-reports were analysed. The findings suggest that both children and their informants have diverse yet complementary perspectives on psychological outcomes. The study discusses the theoretical and practical implications of these findings and urgently calls for necessary intervention programmes that target all children affected by HIV/AIDS to effectively alleviate psychological distress and enhance the mental health of these children.
Orphan drugs, orphan diseases. The first decade of orphan drug legislation in the EU.

PubMed

Joppi, Roberta; Bertele', Vittorio; Garattini, Silvio

2013-04-01

To assess the methodological quality of Orphan Medicinal Product (OMP) dossiers and discuss possible reasons for the small number of products licensed. Information about orphan drug designation, approval, refusal or withdrawal was obtained from the website of the European Medicines Agency and from the European Public Assessment Reports. From 2000 up to 2010, 80.9 % of the 845 candidate orphan drug designations received a positive opinion from the European Medicines Agency (EMA)'s Committee on Orphan Medicinal Products. Of the 108 OMP marketing authorizations applied for, 63 were granted. Randomised clinical trials were done for 38 OMPs and placebo was used as comparator for nearly half the licensed drugs. One third of the OMPs were tested in trials involving fewer than 100 patients and more than half in trials with 100-200 cases. The clinical trials lasted less than one year for 42.9 % of the approved OMPs. Although there may have been some small improvements over time in the methods for developing OMPs, in our opinion, the number of patients studied, the use of placebo as control, the type of outcome measure and the follow-up have often been inadequate. The present system should be changed to find better ways of fostering the development of effective and sustainable treatments for patients with orphan diseases. Public funds supporting independent clinical research on OMPs could bridge the gap between designation and approval. More stringent criteria to assess OMPs' efficacy and cost/effectiveness would improve the clinical value and the affordability of products allowed onto the market.
77 FR 65709 - Agency Information Collection Activities: Petition To Classify Orphan as an Immediate Relative...

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-30

...-0028] Agency Information Collection Activities: Petition To Classify Orphan as an Immediate Relative, Form I-600; Application for Advance Processing of Orphan Petition, Form I-600A; Listing of Adult Member... currently approved collection of information or new collection of information. In accordance with the...
78 FR 5828 - Agency Information Collection Activities: Petition To Classify Orphan as an Immediate Relative...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-01-28

...-0028] Agency Information Collection Activities: Petition To Classify Orphan as an Immediate Relative, Form I-600; Application for Advance Processing of Orphan Petition, Form I-600A; Listing of Adult Member... be submitting the following information collection request to the Office of Management and Budget...
Anxiety and Autonomy in Adolescence among Father-Orphaned Kibbutz Children.

ERIC Educational Resources Information Center

Kurtz, Chaya; And Others

1993-01-01

Measured anxiety and autonomy in kibbutz father-orphaned (n=28) and nonorphaned (n=42) adolescents. Found no significant differences on levels of manifest anxiety and autonomy. When groups were broken down according to gender and age, found that older father-orphan girls manifested significantly greater anxiety than any group and significantly…
Psychological Characteristics of Adolescents Orphans with Different Experience of Living in a Family

ERIC Educational Resources Information Center

Shulga, Tatyana I.; Savchenko, Daria D.; Filinkova, Evgeniya B.

2016-01-01

The complexity of settling adolescents-orphans in foster families and significant number of break-downs in these families are the problems which determine the relevance of current research. Many adolescent orphans get in social institutions repeatedly, because their psychological features lead to difficulties that their foster parents are unable…

Persisting Mental Health Problems among AIDS-Orphaned Children in South Africa

ERIC Educational Resources Information Center

Cluver, Lucie D.; Orkin, Mark; Gardner, Frances; Boyes, Mark E.

2012-01-01

Background: By 2008, 12 million children in sub-Saharan Africa were orphaned by AIDS. Cross-sectional studies show psychological problems for AIDS-orphaned children, but until now no longitudinal study has explored enduring psychological effects of AIDS-orphanhood in the developing world. Methods: A 4-year longitudinal follow-up of AIDS-orphaned…
21 CFR 316.26 - Amendment to orphan-drug designation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Amendment to orphan-drug designation. 316.26 Section 316.26 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... designation. (a) At any time prior to approval of a marketing application for a designated orphan drug, the...
Parental HIV/AIDS and Psychosocial Adjustment among Rural Chinese Children

PubMed Central

Fang, Xiaoyi; Stanton, Bonita; Hong, Yan; Zhang, Liying; Zhao, Guoxiang; Zhao, Junfeng; Lin, Xiuyun; Lin, Danhua

2009-01-01

Objective To assess the relationship between parental HIV/AIDS and psychosocial adjustment of children in rural central China. Methods Participants included 296 double AIDS orphans (children who had lost both their parents to AIDS), 459 single orphans (children who had lost one parent to AIDS), 466 vulnerable children who lived with HIV-infected parents, and 404 comparison children who did not experience HIV/AIDS-related illness and death in their families. The measures included depressive symptoms, loneliness, self-esteem, future expectations, hopefulness about the future, and perceived control over the future. Results AIDS orphans and vulnerable children consistently demonstrated poorer psychosocial adjustment than comparison children in the same community. The level of psychosocial adjustment was similar between single orphans and double orphans, but differed by care arrangement among double orphans. Conclusion The findings underscore the urgency and importance of culturally and developmentally appropriate intervention efforts targeting psychosocial problems among children affected by AIDS and call for more exploration of risk and resilience factors, both individual and contextual, affecting the psychosocial wellbeing of these children. PMID:19208701
What is wrong with orphan drug policies?

PubMed

Côté, André; Keating, Bernard

2012-12-01

The effects of orphan drug policies raise serious concerns among payer organizations and lead to often-tragic disappointment for patients who are denied much anticipated drug reimbursements. We evaluate the effects of orphan drug policies on the basis of this concern for real accessibility to drugs. We highlight two unforeseen effects of orphan drug policies: 1) they provide unique business opportunities for manufacturers and 2) drugs approved through these policies are often inaccessible because of their high price. We identify six causes of this emergence of effects. The first four are the direct result of incentives included in orphan drug policies. The fifth cause is the "off-label" use of orphan drugs. These emergent effects have several implications: 1) they raise doubts about the equity of access to drugs, 2) they highlight the limitations of the cohort paradigm in medicine, and c) they force third-party payers to make drugs accessible even when the prices of drugs are believed to be disproportionate to the clinical effects obtained. Copyright © 2012 International Society for Pharmacoeconomics and Outcomes Research (ISPOR). Published by Elsevier Inc. All rights reserved.
Nutrition of orphan marsupials.

PubMed

Stephens, T

1975-10-01

Marsupial milk has been found to be high in fats, protein and ash compared to eutherian milk. The generally low lactose content of marsupial milk and the corresponding low intestinal lactase activity of pouch young marsupials, when considered with the incidence of diarrhoea and the occasional formation of cataracts in orphan kangaroos fed on cow's milk (which has a high lactose content), suggests that a lactose-free milk be fed to orphan marsupials. Of the lactose-free milk substitutes for children now available, it is recommended that Pregestimil, Glucose Nutramigen and particularly CFI be used for very young orphan marsupial herbivores (especially kangaroos), as these are both lactose- and sucrose-free. Isomil, Prosobee and Triglyde, containing sucrose, may be suitable for older kangaroos which are also ingesting solids and brush-tailed possums of all ages. The appropriate natural diet of the orphan marsupial should be available at the time when initial solid food ingestion would occur in the natural state. It is suggested that milk substitute continue to be given until the orphan animal reaches the age where, in the natural state, it would be full independent.
Timing of Orphanhood, Early Sexual Debut, and Early Marriage in Four Sub-Saharan African Countries

PubMed Central

Chae, Sophia

2014-01-01

According to a growing body of literature, some orphans are at heightened risk of early sexual debut and early marriage. This study examines a rarely explored aspect of orphanhood: the timing and type of parental death and their relationship to these outcomes. The study also explores whether education mediates orphans’ risk of early sexual initiation and early marriage. The data are drawn from the 2004 National Survey of Adolescents, which includes interviews with 12–19-year-old adolescents in Burkina Faso, Ghana, Malawi, and Uganda. Results from discrete-time event history analysis indicate that female double orphans, regardless of timing of orphanhood, have greater odds of early sexual debut than do nonorphans. Education explains little of their increased risk. In contrast, male orphans of any type reveal no increased vulnerability to early sexual debut. Uganda is the only country where female orphans, specifically double orphans and those who are paternal orphans before age 10, have greater odds of early marriage, with education accounting for a small portion of the risk. PMID:23719999
Unintended Effects of Orphan Product Designation for Rare Neurological Diseases

PubMed Central

Murphy, Sinéad M; Puwanant, Araya; Griggs, Robert C.

2012-01-01

Since the introduction of the Orphan Drug Act in 1983, designed to promote development of treatments for rare diseases, at least 378 orphan drugs have been approved. Incentives include financial support, tax credits and, perhaps most importantly, extended market exclusivity. These incentives have encouraged industry interest and accelerated research on rare diseases, allowing patients with orphan diseases access to treatments. However, extended market exclusivity has been associated with unacceptably high drug costs; both for newly developed drugs and even for drugs which were previously widely available. We suggest that a paradoxical effect of orphan product exclusivity can be reduced patient access to existing drugs. In addition, the costs of each new drug are arguably unsustainable for patients and for the American health care system. Of all the specialties, neurology has the third highest number of orphan product designations, and neurological diseases account for at least one fifth of rare diseases. Citing the use of tetrabenazine for chorea in Huntington’s disease, adrenocorticotropic hormone for infantile spasms and enzyme replacement therapy with alglucosidase alpha for Pompe’s disease we highlight these paradoxical effects. PMID:23109143
Extended families and perceived caregiver support to AIDS orphans in Rakai district of Uganda

PubMed Central

Karimli, Leyla; Ssewamala, Fred M.; Ismayilova, Leyla

2012-01-01

Purpose To understand the role of extended family in responding to problems of AID-orphaned children and adolescents in Uganda, the study examines who are the primary caregivers of AIDS-orphaned children and adolescents, what are the types of caregiving provided to orphans and whether the quality of caregiving varies by the primary caregiver’s gender and type. Methods The study uses bivariate analyses and mixed effects models utilizing baseline data from a cluster randomized experimental design including 283 orphaned adolescents in Uganda. Results The analysis revealed a generally dominating role of female caregivers for both single and double orphans. In the absence of biological parents – as in the case of double orphans – grandparents’ role as caregivers prevail. On average, the study participants indicated receiving the high level of perceived caregiver support: the average score of 3.56 out of 4 (95% CI=3.5, 3.65). Results of mixed effect models (adjusting for school effects) revealed significant differences in perceived caregiver support by caregiver’s gender. Compared to their male counterparts, female participants with whom the child/adolescent lives (B=0.22, 95% CI=0.11, 0.34) and women who are currently taking care of a child/adolescent (B=0.15, 95% CI=0.05, 0.26) provide greater caregiver support as perceived and reported by a child/adolescent. Similarly, female financiers – compared to male source of financial support - provide greater caregiver support as perceived and reported by a child/adolescent (B=0.16, 95% CI=0.04, 0.3). Conclusions Our findings demonstrate that extended families are still holding up as an important source of care and support for AIDS orphaned children and adolescents in Uganda. The findings support the argument about importance of matrilineal and grandparental care for AIDS orphans. PMID:23188930
Flexible kinship: caring for AIDS orphans in rural Lesotho

PubMed Central

Block, Ellen

2015-01-01

HIV/AIDS has devastated families in rural Lesotho, leaving many children orphaned. Families have adapted to the increase in the number of orphans and HIV-positive children in ways that provide children with the best possible care. Though local ideas about kinship and care are firmly rooted in patrilineal social organization, in practice, maternal caregivers, often grandmothers, are increasingly caring for orphaned children. Negotiations between affinal kin capitalize on flexible kinship practices in order to legitimate new patterns of care, which have shifted towards a model that often favours matrilocal practices of care in the context of idealized patrilineality. PMID:25866467
Multiple transitions and HIV risk among orphaned Kenyan schoolgirls.

PubMed

Mojola, Sanyu A

2011-03-01

Why are orphaned girls at particular risk of acquiring HIV infection? Using a transition-to-adulthood framework, this study employs qualitative data from Nyanza Province, Kenya, to explore pathways to HIV risk among orphaned and nonorphaned high-school girls. It shows how simultaneous processes such as leaving their parental home, negotiating financial access, and relationship transitions interact to produce disproportionate risk for orphaned girls. The role of financial provision and parental love in modifying girls' trajectories to risk are also explored. A testable theoretical model is proposed based on the qualitative findings, and policy implications are suggested.
MULTIPLE TRANSITIONS AND HIV RISK AMONG AFRICAN SCHOOL GIRLS

PubMed Central

Mojola, Sanyu A

2012-01-01

Why are orphaned girls at particular risk of contracting HIV? Using a transition to adulthood framework, this paper uses qualitative data from Nyanza province, Kenya to explore pathways to HIV risk among orphaned and non-orphaned high school girls. I show how co-occurring processes such as residential transition out of the parental home, negotiating financial access and relationship transitions interact to produce disproportionate risk for orphan girls. I also explore the role of financial provision and parental love in modifying girls’ trajectories to risk. I propose a testable theoretical model based on the qualitative findings and suggest policy implications. PMID:21500699
The current status of orphan drug development in Europe and the US.

PubMed

Hall, Anthony K; Carlson, Marilyn R

2014-02-01

Orphan drug legislation has been introduced in a number of countries in order to stimulate the development of treatments for rare diseases by introducing commercial incentives for companies wishing to undertake that development. In order to navigate the maze of regulatory regulations and procedures so that companies can make proper use of the orphan drug incentives, specialist knowledge is required. This article will review the current status of orphan drug development in the EU and the US, explain the incentives and procedures, and touch on the role of patient organisations in the process.
Policies and availability of orphan medicines in outpatient care in 24 European countries.

PubMed

Sarnola, Kati; Ahonen, Riitta; Martikainen, Jaana E; Timonen, Johanna

2018-04-09

To assess pricing and reimbursement policies specific to orphan medicines and the availability and distribution settings of ten recently authorised medicinal products suitable for outpatient care with orphan status and centralised marketing authorisation in Europe, and whether patients receive these products free of charge or have to pay some or all of the costs themselves. Web survey to authorities and representatives of third party payers in the Pharmaceutical Pricing and Reimbursement Information (PPRI) network in April 2016. In most of the 24 countries, special policies were not implemented in the assessment of reimbursement status (22 countries) or in the pricing (20 countries) of orphan medicines. An average of five of the ten recently authorised products per country were available for outpatient care. Products were dispensed from community pharmacies in eight countries and from health care units in five countries. In four countries, both distribution settings were used. When products were dispensed from community pharmacies, patients typically paid some of the price themselves. Products dispensed from health care units were often free of charge for patients. Most European countries had not implemented pricing and reimbursement policies specific to orphan medicines. The availability of orphan products varied between countries. It is important to discuss whether orphan medicines should be considered as a separate group in the reimbursement regulations in order to secure patient access to these medicines.
[Orphan drugs: some legal, ethical and economics aspects].

PubMed

Pabst, J Y

2001-09-01

Besides well-known diseases, about 5,000 identified are classed as "orphan" because of the lack of any response in terms of diagnosis, prevention and treatment. The development of drugs for these diseases, intended for a limited number of patients, often requires considerable research, and subsequently, cost. The aim of the present article is to discuss the ethical, political and economic problems relevant to the development and disposal of drugs specifically designed for these diseases, now commonly called "orphan" drugs. These questions have been raised at discussions and dialogues at the European Parliament where European regulations on orphan drugs were adopted on December 15, 1999. These regulations (141/2000/EEC) came into effect in the European Union on January 22, 2000, and are widely inspired from the American model. The regulations stipulate that the criterion for designation of the drug is based on a disease prevalence of 5/10000). Advantages commonly recognized for the orphan drug status concern: community registration (centralized marketing approval), eligibility for grants and national or community fiscal support, lower or canceled registration fees, technical contribution via the European drug agency (EMEA), and exclusive rights for a 10-year period. On May 12, 2000, the European Commission completed the status by adopting rules establishing the criteria used for designating a drug as an orphan drug. This document implements the dispositions available to pharmaceutical firms inciting them to invest in the development of orphan drugs.
Growth status of Korean orphans raised in the affluent West: anthropometric trend, multivariate determinants, and descriptive comparison with their North and South Korean peers.

PubMed

Schwekendiek, Daniel J

2017-04-01

This paper investigates the trend in height among adult Korean orphans who were adopted in early life into affluent Western nations. Final heights of 148 females were analyzed based on a Korean government survey conducted in 2008. Height of the orphans was descriptively compared against final heights of South and North Koreans. Furthermore, statistical determinants of orphan height were investigated in multivariate regressions. Mean height of Korean orphans was 160.44 cm (SD 5.89), which was higher than that of South Koreans at 158.83 cm (SD 5.01). Both Korean orphans and South Koreans were taller than North Koreans at 155.30 cm (SD 4.94). However, height of Korean orphans stagnated at around 160-161 cm while those of North and South Koreans improved over time. In the regression analysis, the socioeconomic status of the adoptive family was statistically significant in all models, while dummies for the adoptive nations and age at adoption were insignificant. This study shows that the mean final height of women experiencing extreme environmental improvements in early-life is capped at 160-161 cm, tentatively suggesting that social stress factors in the host nation or early-life factors in the birth nation might have offset some of the environmental enrichment effects achieved through intercountry adoption.
21 CFR 316.3 - Definitions.

Code of Federal Regulations, 2014 CFR

2014-04-01

... Health Service Act (42 U.S.C. 262). (10) Orphan drug means a drug intended for use in a rare disease or... already been approved for the same use or indication. (13) Orphan subset of a non-rare disease or condition (“orphan subset”) means that use of the drug in a subset of persons with a non-rare disease or...
Orphan Children: Adjusting to Life after the Boarding Institution

ERIC Educational Resources Information Center

Prisiazhnaia, N. V.

2008-01-01

According to official statistics, in Russia there are over 800,000 orphans and children who are deprived of parental care; 260,000 are living and being taught in more than 4,000 state boarding institutions. The category "orphan child" consists of children up to the age of eighteen, one or both of whose parents have died. The term…
77 FR 52744 - Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant Workshop

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-30

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2012-N-0001] Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of meeting. The Food and Drug Administration's (FDA) Office of Orphan Products Development...
FDA grants orphan drug status to selumetinib for neurofibromatosis type 1 (NF1) treatment | Center for Cancer Research

Cancer.gov

The U.S. Food and Drug Administration granted orphan drug status in February to selumetinib for use in patients with the genetic disorder neurofibromatosis type 1 (NF1), who often develop tumors of the peripheral nervous system. Receiving orphan drug designation is a helpful step for selumetinib.
Risk and Resilience in Orphaned Adolescents Living in a Community Affected by AIDS

ERIC Educational Resources Information Center

Wild, Lauren G.; Flisher, Alan J.; Robertson, Brian A.

2013-01-01

The AIDS pandemic has resulted in a dramatic rise in the number of orphans in South Africa. This study was designed to investigate the associations between family, peer, and community factors and resilience in orphaned adolescents. Self-report questionnaires were administered verbally to 159 parentally bereaved adolescents (aged 10-19) in an…

Social Support Disparities for Caregivers of AIDS-Orphaned Children in South Africa

ERIC Educational Resources Information Center

Kuo, Caroline; Fitzgerald, Jane; Operario, Don; Casale, Marisa

2012-01-01

Drawing upon a sample of 1,599 adults caring for children in HIV-endemic Umlazi Township in South Africa, this cross-sectional survey investigated whether perceived social support varied among caregivers of AIDS-orphaned children (n = 359) as compared with caregivers of children orphaned by other causes (n = 171) and caregivers of nonorphaned…
The Varying Vulnerability of African Orphans: The Case of the Langi, Northern Uganda

ERIC Educational Resources Information Center

Oleke, Christopher; Blystad, Astrid; Moland, Karen Marie; Rekdal, Ole Bjorn; Heggenhougen, Kristian

2006-01-01

This article is based on a qualitative study carried out in Lira District, northern Uganda, to assess the situation of orphans cared for in extended families. The objective of the article is to bring attention to the varying vulnerability of different categories of orphans. The methods employed in data collection included ethnographic fieldwork,…
75 FR 65499 - Agency Information Collection Activities: Form I-600/I-600A, Extension of a Currently Approved...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-10-25

... Classify Orphan as an Immediate Relative and Application for Advance Processing of Orphan Petition; OMB... encouraged and will be accepted until November 24, 2010. This process is conducted in accordance with 5 CFR...) Title of the Form/Collection: Petition to Classify Orphan as an Immediate Relative and Application for...
Achieving the "triple aim" for inborn errors of metabolism: a review of challenges to outcomes research and presentation of a new practice-based evidence framework.

PubMed

Potter, Beth K; Chakraborty, Pranesh; Kronick, Jonathan B; Wilson, Kumanan; Coyle, Doug; Feigenbaum, Annette; Geraghty, Michael T; Karaceper, Maria D; Little, Julian; Mhanni, Aizeddin; Mitchell, John J; Siriwardena, Komudi; Wilson, Brenda J; Syrowatka, Ania

2013-06-01

Across all areas of health care, decision makers are in pursuit of what Berwick and colleagues have called the "triple aim": improving patient experiences with care, improving health outcomes, and managing health system impacts. This is challenging in a rare disease context, as exemplified by inborn errors of metabolism. There is a need for evaluative outcomes research to support effective and appropriate care for inborn errors of metabolism. We suggest that such research should consider interventions at both the level of the health system (e.g., early detection through newborn screening, programs to provide access to treatments) and the level of individual patient care (e.g., orphan drugs, medical foods). We have developed a practice-based evidence framework to guide outcomes research for inborn errors of metabolism. Focusing on outcomes across the triple aim, this framework integrates three priority themes: tailoring care in the context of clinical heterogeneity; a shift from "urgent care" to "opportunity for improvement"; and the need to evaluate the comparative effectiveness of emerging and established therapies. Guided by the framework, a new Canadian research network has been established to generate knowledge that will inform the design and delivery of health services for patients with inborn errors of metabolism and other rare diseases.
Knowing Kids Dying of HIV: A Traumatic Event for AIDS Orphans

PubMed Central

Zhao, Qun; Li, Xiaoming; Lin, Xiuyun; Fang, Xiaoyi; Zhao, Guoxiang; Zhao, Junfeng

2009-01-01

Data from 755 AIDS orphans living in a rural area of China with high rates of HIV infection were used to examine the association between a child’s trauma symptoms and knowing a peer with HIV infection or one who had died of HIV. Trauma symptoms were measured by the Traumatic Symptoms Checklist for Children-Chinese Version (TSCC-CV). About 47% of participants reported they knew a child with HIV or one who had died of HIV. More orphans living in family-based care reported such knowledge, and trauma symptoms were significantly higher in children who reported such knowledge. Multivariate analysis revealed that such knowledge was significantly associated with traumatic symptoms, controlling for gender, age, family socioeconomic status, orphan status (double vs. single), and care arrangement (family-based vs. institutional care). The findings underscored the importance of psychosocial support and counseling to orphans in communities with high levels of HIV-related mortality. PMID:19576544
Nuclear receptor TLX prevents retinal dystrophy and recruits the corepressor atrophin1

PubMed Central

Zhang, Chun-Li; Zou, Yuhua; Yu, Ruth T.; Gage, Fred H.; Evans, Ronald M.

2006-01-01

During mammalian embryogenesis, precise coordination of progenitor cell proliferation and differentiation is essential for proper organ size and function. The involvement of TLX (NR2E1), an orphan nuclear receptor, has been implicated in ocular development, as Tlx−/− mice exhibit visual impairment. Using genetic and biochemical approaches, we show that TLX modulates retinal progenitor cell proliferation and cell cycle re-entry by directly regulating the expression of Pten and its target cyclin D1. Additionally, TLX finely tunes the progenitor differentiation program by modulating the phospholipase C and mitogen-activated protein kinase (MAPK) pathways and the expression of an array of cell type-specific transcriptional regulators. Consequently, Tlx−/− mice have a dramatic reduction in retina thickness and enhanced generation of S-cones, and develop severe early onset retinal dystrophy. Furthermore, TLX interacts with atrophin1 (Atn1), a corepressor that is involved in human neurodegenerative dentatorubral-pallidoluysian atrophy (DRPLA) and that is essential for development of multiple tissues. Together, these results reveal a molecular strategy by which an orphan nuclear receptor can precisely orchestrate tissue-specific proliferation and differentiation programs to prevent retinal malformation and degeneration. PMID:16702404
21 CFR 316.20 - Content and format of a request for orphan-drug designation.

Code of Federal Regulations, 2013 CFR

2013-04-01

... designation of a drug for a specified rare disease or condition shall submit each request in the form and... and obtain orphan-drug designation for the subsequent drug for the same rare disease or condition if.... More than one sponsor may receive orphan-drug designation of the same drug for the same rare disease or...
21 CFR 316.20 - Content and format of a request for orphan-drug designation.

Code of Federal Regulations, 2011 CFR

2011-04-01

... designation of a drug for a specified rare disease or condition shall submit each request in the form and... and obtain orphan-drug designation for the subsequent drug for the same rare disease or condition if.... More than one sponsor may receive orphan-drug designation of the same drug for the same rare disease or...
21 CFR 316.20 - Content and format of a request for orphan-drug designation.

Code of Federal Regulations, 2012 CFR

2012-04-01

... designation of a drug for a specified rare disease or condition shall submit each request in the form and... and obtain orphan-drug designation for the subsequent drug for the same rare disease or condition if.... More than one sponsor may receive orphan-drug designation of the same drug for the same rare disease or...
21 CFR 316.20 - Content and format of a request for orphan-drug designation.

Code of Federal Regulations, 2010 CFR

2010-04-01

... designation of a drug for a specified rare disease or condition shall submit each request in the form and... and obtain orphan-drug designation for the subsequent drug for the same rare disease or condition if.... More than one sponsor may receive orphan-drug designation of the same drug for the same rare disease or...
Provision of Vocational Skills Education to Orphans: Lessons from Orphanage Centres in Dar es Salaam City, Tanzania

ERIC Educational Resources Information Center

Meli, Benjamin Mbeba

2015-01-01

This paper utilises data from a study that investigated the efficacy of vocational skills training provided to orphans from three orphanages in Temeke District, Dar es Salaam. The three orphanage centres that were studied are Kurasini National Children Home, Saudia and Don Bosco Vocational Centre. The sample comprised of 45 orphans, an official…
Assessing the feasibility of a web-based registry for multiple orphan lung diseases: the Australasian Registry Network for Orphan Lung Disease (ARNOLD) experience.

PubMed

Casamento, K; Laverty, A; Wilsher, M; Twiss, J; Gabbay, E; Glaspole, I; Jaffe, A

2016-04-18

We investigated the feasibility of using an online registry to provide prevalence data for multiple orphan lung diseases in Australia and New Zealand. A web-based registry, The Australasian Registry Network of Orphan Lung Diseases (ARNOLD) was developed based on the existing British Paediatric Orphan Lung Disease Registry. All adult and paediatric respiratory physicians who were members of the Thoracic Society of Australia and New Zealand in Australia and New Zealand were sent regular emails between July 2009 and June 2014 requesting information on patients they had seen with any of 30 rare lung diseases. Prevalence rates were calculated using population statistics. Emails were sent to 649 Australian respiratory physicians and 65 in New Zealand. 231 (32.4%) physicians responded to emails a total of 1554 times (average 7.6 responses per physician). Prevalence rates of 30 rare lung diseases are reported. A multi-disease rare lung disease registry was implemented in the Australian and New Zealand health care settings that provided prevalence data on orphan lung diseases in this region but was limited by under reporting.
Perceived social support disparities among children affected by HIV/AIDS in Ghana: a cross-sectional survey.

PubMed

Doku, Paul Narh; Dotse, John Enoch; Mensah, Kofi Akohene

2015-06-06

The study investigated whether perceived social support varied among children who have lost their parents to AIDS, those who have lost their parents to other causes, those who are living with HIV/AIDS-infected caregivers and children from intact families (comparison group). This study employed cross-sectional, quantitative survey that involved 291 children aged 10-18 years in the Lower Manya Krobo District of Ghana and examined their social support disparities. Multivariate linear regressions indicate that children living with HIV/AIDS-infected caregivers reported significantly lower levels of social support compared with AIDS-orphaned children, other-orphaned children and non-orphaned children independent of socio-demographic covariates. Children who have lost their parents to other causes and other-orphaned children reported similar levels of social support. In terms of sources of support, all children orphans and vulnerable children were more likely to draw support from friends and significant others rather than from the family. The findings indicate a need to develop interventions that can increase levels of social support for orphaned and vulnerable children within the context of HIV/AIDS in Ghana, particularly networks that include the family.
[Shift of focus in the financing of Hungarian drugs. Reimbursement for orphan drugs for treating rare diseases: financing of enzyme replacement therapy in Hungary].

PubMed

Szegedi, Márta; Molnár, Mária Judit; Boncz, Imre; Kosztolányi, György

2014-11-02

Focusing on the benefits of patients with rare disease the authors analysed the aspects of orphan medicines financed in the frame of the Hungarian social insurance system in 2012 in order to make the consumption more rational, transparent and predictable. Most of the orphan drugs were financed in the frame of compassionate use by the reimbursement system. Consequently, a great deal of crucial problems occurred in relation to the unconventional subsidized method, especially in the case of the highest cost enzyme replacement therapies. On the base of the findings, proposals of the authors are presented for access to orphan drugs, fitting to the specific professional, economical and ethical aspects of this unique field of the health care system. The primary goal is to provide a suitable subsidized method for the treatment of rare disease patients with unmet medical needs. The financial modification of orphans became indispensible in Hungary. Professionals from numerous fields dealing with rare disease patients' care expressed agreement on the issue. Transforming the orphan medicines' financial structure has been initiated according to internationally shared principles.
Characterizing Milky Way Tidal Streams and Dark Matter with MilkyWay@home

NASA Astrophysics Data System (ADS)

Newberg, Heidi Jo; Shelton, Siddhartha; Weiss, Jake

2018-01-01

MilkyWay@home is a 0.5 PetaFLOPS volunteer computing platform that is mapping out the density substructure of the Sagittarius Dwarf Tidal Stream, the so-called bifurcated portion of the Sagittarius Stream, and the Virgo Overdensity, using turnoff stars from the Sloan Digital Sky Survey. It is also using the density of stars along tidal streams such as the Orphan Stream to constrain properties of the dwarf galaxy progenitor of this stream, including the dark matter portion. Both of these programs are enabled by a specially-built optimization package that uses differential evolution or particle swarm methods to find the optimal model parameters to fit a set of data. To fit the density of tidal streams, 20 parameters are simultaneously fit to each 2.5-degree-wide stripe of SDSS data. Five parameters describing the stellar and dark matter profile of the Orphan Stream progenitor and the time that the dwarf galaxy has been evolved through the Galactic potential are used in an n-body simulation that is then fit to observations of the Orphan Stream. New results from MilkyWay@home will be presented. This project was supported by NSF grant AST 16-15688, the NASA/NY Space Grant fellowship, and contributions made by The Marvin Clan, Babette Josephs, Manit Limlamai, and the 2015 Crowd Funding Campaign to Support Milky Way Research.
ORPHANED PROTOSTARS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Reipurth, Bo; Connelley, Michael; Mikkola, Seppo

2010-12-10

We explore the origin of a population of distant companions ({approx}1000-5000 AU) to Class I protostellar sources recently found by Connelley and coworkers, who noted that the companion fraction diminished as the sources evolved. Here, we present N-body simulations of unstable triple systems embedded in dense cloud cores. Many companions are ejected into unbound orbits and quickly escape, but others are ejected with insufficient momentum to climb out of the potential well of the cloud core and associated binary. These loosely bound companions reach distances of many thousands of AU before falling back and eventually being ejected into escapes asmore » the cloud cores gradually disappear. We use the term orphans to denote protostellar objects that are dynamically ejected from their placental cloud cores, either escaping or for a time being tenuously bound at large separations. Half of all triple systems are found to disintegrate during the protostellar stage, so if multiple systems are a frequent outcome of the collapse of a cloud core, then orphans should be common. Bound orphans are associated with embedded close protostellar binaries, but escaping orphans can travel as far as {approx}0.2 pc during the protostellar phase. The steep climb out of a potential well ensures that orphans are not kinematically distinct from young stars born with a less violent pre-history. The identification of orphans outside their heavily extincted cloud cores will allow the detailed study of protostars high up on their Hayashi tracks at near-infrared and in some cases even at optical wavelengths.« less
Experiences of grandmothers caring for orphan grandchildren in Botswana.

PubMed

Shaibu, Sheila

2013-12-01

The purpose of the study was to identify the experiences of the grandparents who were taking care of orphan grandchildren in Botswana. A descriptive qualitative design was used to interview 12 grandmothers 60 years and older in a semi-urban village in Botswana. Content analysis was used to analyze the data. The ages of the grandmothers interviewed ranged from 60 to 80 years, while the number of orphans under their care ranged from 1 to 9 years. The themes that emerged included context of caregiving, acceptance of the caregiver role, consequences of caregiving, social support, and coping strategies. Although they accepted the caregiving role and appreciated the government assistance, it was fraught with difficulties. They reported very limited or no support from the extended family, and their health concerns compromised their financial circumstances. Although the grandmothers accepted this role, it was described as difficult, and had profound consequences for them. Recommendations include comprehensive support for grandmothers and orphans that include psychological support and health promotion. Grandparents are an important support system of orphans in Botswana since there are very few orphanages. In order to support grandparents in this role, community health nurses need to provide comprehensive health promotion for grandmothers caring for orphans that includes support groups and multidisciplinary care teams to ensure that the grandmothers' health is not neglected. Nurse educators should also include care of grandmothers caring for orphans in their curricula. © 2013 Sigma Theta Tau International.
The emerging roles of orphan nuclear receptors in prostate cancer.

PubMed

Wu, Dinglan; Cheung, Alyson; Wang, Yuliang; Yu, Shan; Chan, Franky L

2016-08-01

Orphan nuclear receptors are members of the nuclear receptor (NR) superfamily and are so named because their endogenous physiological ligands are either unknown or may not exist. Because of their important regulatory roles in many key physiological processes, dysregulation of signalings controlled by these receptors is associated with many diseases including cancer. Over years, studies of orphan NRs have become an area of great interest because their specific physiological and pathological roles have not been well-defined, and some of them are promising drug targets for diseases. The recently identified synthetic small molecule ligands, acting as agonists or antagonists, to these orphan NRs not only help to understand better their functional roles but also highlight that the signalings mediated by these ligand-independent NRs in diseases could be therapeutically intervened. This review is a summary of the recent advances in elucidating the emerging functional roles of orphan NRs in cancers, especially prostate cancer. In particular, some orphan NRs, RORγ, TR2, TR4, COUP-IFII, ERRα, DAX1 and SHP, exhibit crosstalk or interference with androgen receptor (AR) signaling in either normal or malignant prostatic cells, highlighting their involvement in prostate cancer progression as androgen and AR signaling pathway play critical roles in this process. We also propose that a better understanding of the mechanism of actions of these orphan NRs in prostate gland or prostate cancer could help to evaluate their potential value as therapeutic targets for prostate cancer. Copyright © 2016 Elsevier B.V. All rights reserved.
Effectiveness of the Group Play Therapy on the Insecure Attachment and Social Skills of Orphans in Ahvaz City

ERIC Educational Resources Information Center

Mousavi, Bahareh; Safarzadeh, Sahar

2016-01-01

This study aimed to determine the effectiveness of the group play therapy on the insecure attachment and social skills of orphans in Ahvaz city. Statistical population included all orphans in Ahvaz city, of whom 30 students were selected whose scores in insecure attachment and in social skills were one standard deviation higher and one standard…
Between Charity and Education: Orphans and Orphanages in Early Modern Times

ERIC Educational Resources Information Center

Jacobi, Juliane

2009-01-01

In early modern times orphans have been children who could not expect sufficient support from their family because of lack of at least one parent, in most cases the father. This article will clarify of whom we are talking if we talk about orphans and what have been the conditions of living in a society which was organised by a high variety of…

Determinants of orphan drugs prices in France: a regression analysis.

PubMed

Korchagina, Daria; Millier, Aurelie; Vataire, Anne-Lise; Aballea, Samuel; Falissard, Bruno; Toumi, Mondher

2017-04-21

The introduction of the orphan drug legislation led to the increase in the number of available orphan drugs, but the access to them is often limited due to the high price. Social preferences regarding funding orphan drugs as well as the criteria taken into consideration while setting the price remain unclear. The study aimed at identifying the determinant of orphan drug prices in France using a regression analysis. All drugs with a valid orphan designation at the moment of launch for which the price was available in France were included in the analysis. The selection of covariates was based on a literature review and included drug characteristics (Anatomical Therapeutic Chemical (ATC) class, treatment line, age of target population), diseases characteristics (severity, prevalence, availability of alternative therapeutic options), health technology assessment (HTA) details (actual benefit (AB) and improvement in actual benefit (IAB) scores, delay between the HTA and commercialisation), and study characteristics (type of study, comparator, type of endpoint). The main data sources were European public assessment reports, HTA reports, summaries of opinion on orphan designation of the European Medicines Agency, and the French insurance database of drugs and tariffs. A generalized regression model was developed to test the association between the annual treatment cost and selected covariates. A total of 68 drugs were included. The mean annual treatment cost was €96,518. In the univariate analysis, the ATC class (p = 0.01), availability of alternative treatment options (p = 0.02) and the prevalence (p = 0.02) showed a significant correlation with the annual cost. The multivariate analysis demonstrated significant association between the annual cost and availability of alternative treatment options, ATC class, IAB score, type of comparator in the pivotal clinical trial, as well as commercialisation date and delay between the HTA and commercialisation. The orphan drug pricing is a multivariate phenomenon. The complex association between drug prices and the studied attributes and shows that payers integrate multiple variables in decision making when setting orphan drug prices. The interpretation of the study results is limited by the small sample size and the complex data structure.
Systematic review on the evaluation criteria of orphan medicines in Central and Eastern European countries.

PubMed

Zelei, Tamás; Molnár, Mária J; Szegedi, Márta; Kaló, Zoltán

2016-06-04

In case of orphan drugs applicability of the standard health technology assessment (HTA) process is limited due to scarcity of good clinical and health economic evidence. Financing these premium priced drugs is more controversial in the Central and Eastern European (CEE) region where the public funding resources are more restricted, and health economic justification should be an even more important aspect of policy decisions than in higher income European countries. To explore and summarize the recent scientific evidence on value drivers related to the health technology assessment of ODs with a special focus on the perspective of third party payers in CEE countries. The review aims to list all potentially relevant value drivers in the reimbursement process of orphan drugs. A systematic literature review was performed; PubMed and Scopus databases were systematically searched for relevant publications until April 2015. Extracted data were summarized along key HTA elements. From the 2664 identified publications, 87 contained relevant information on the evaluation criteria of orphan drugs, but only 5 had direct information from the CEE region. The presentation of good clinical evidence seems to play a key role especially since this should be the basis of cost-effectiveness analyses, which have more importance in resource-constrained economies. Due to external price referencing of pharmaceuticals, the relative budget impact of orphan drugs is expected to be higher in CEE than in Western European (WE) countries unless accessibility of patients remains more limited in poorer European regions. Equity principles based on disease prevalence and non-availability of alternative treatment options may increase the price premium, however, societies must have some control on prices and a rationale based on multiple criteria in reimbursement decisions. The evaluation of orphan medicines should include multiple criteria to appropriately measure the clinical added value of orphan drugs. The search found only a small number of studies coming from CEE, therefore European policies on orphan drugs may be based largely on experiences in WE countries. More research should be done in the future in CEE because financing high-priced orphan drugs involves a greater burden for these countries.
Reimbursed Price of Orphan Drugs: Current Strategies and Potential Improvements.

PubMed

Mincarone, Pierpaolo; Leo, Carlo Giacomo; Sabina, Saverio; Sarriá-Santamera, Antonio; Taruscio, Domenica; Serrano-Aguilar, Pedro Guillermo; Kanavos, Panos

2017-01-01

The pricing and reimbursement policies for pharmaceuticals are relevant to balance timely and equitable access for all patients, financial sustainability, and reward for valuable innovation. The proliferation of high-cost specialty medicines is particularly true in rare diseases (RDs) where the pricing mechanism is characterised by a lack of transparency. This work provides an overall picture of current strategies for the definition of the reimbursed prices of orphan drugs (ODs) and highlights some potential improvements. Current strategies and suggestions are presented along 4 dimensions: (1) comprehensive value assessment, (2) early dialogs among relevant stakeholders, (3) innovative reimbursement approaches, and (4) societal participation in producing ODs. Comprehensive value assessment could be achieved by clarifying the approach of distributive justice to adopt, ensuring a representative participation of stakeholders, and with a broad consideration of value-bearing factors. With respect to early dialogs, cross-border cooperation can be determinant to companies and agencies. The cost-benefit ratio of early dialogs needs to be demonstrated and the "regulatory capture" effect should be monitored. Innovative reimbursement approaches were developed to balance the need for evidence-based decisions with the timely access to innovative drugs. The societal participation in producing ODs needs to be recognised in a collaborating framework where adaptive agreements can be developed with mutual satisfaction. Such agreements could also impact on coverage and reimbursement decisions as additional elements for the determination of a comprehensive societal value of ODs. Further research is needed to investigate the highlighted open challenges so that RDs will not remain, in practical terms, orphan diseases. © 2017 S. Karger AG, Basel.
Differential effects of single and double parental death on child emotional functioning and daily life in South Africa.

PubMed

Sherr, Lorraine; Croome, Natasha; Clucas, Claudine; Brown, Elizabeth

2014-01-01

There is a high level of orphaning in Africa due to war, violence, and more recently HIV and AIDS. This study examines parental death in South African children and examines the differential impact on child functioning of double, single and non-orphanhoods. Bereavement, depression, behavior problems, and violence were examined in a consecutive sample of 381 children/adolescents (51.2% girls) between 8 and 19 years of age (M = 12.8). Parental death experience was high; 70 (17.5%) reported the death of one parent, and a further 24 (6%) reported the death of both. Group comparisons showed double orphans had elevated depression, worse psychosocial functioning, were more likely to be kept home from school for household chores, and were more likely to be slapped. Single orphans were more similar to the non-orphans than the double orphans on most scores. Our study reveals that parental loss should be studied with more fine-grained definitions and that emotional sequelae should be addressed.
The Socioeconomic Impact of HIV/AIDS on Education Outcomes in Uganda: School Enrolment and the Schooling Gap in 2002/2003

ERIC Educational Resources Information Center

Kasirye, Ibrahim; Hisali, Eria

2010-01-01

Due to high prime-age mortality--a result of the HIV/AIDS scourge, the number of orphans in Uganda continues to rise. Using the 2002/2003 Uganda National Household Survey, this paper investigates how HIV/AIDS orphan status affects schooling enrolment and grade progression. Our results show that HIV/AIDS orphans are not significantly less likely to…
Rare essentials: drugs for rare diseases as essential medicines.

PubMed

Stolk, Pieter; Willemen, Marjolein J C; Leufkens, Hubert G M

2006-09-01

Since 1977, the WHO Model List of Essential Medicines (EML), published by WHO, has provided advice for Member States that struggle to decide which pharmaceutical technologies should be provided to patients within their public health systems. Originating from outside WHO, an incentive system has been put in place by various governments for the development of medicines for rare diseases ("orphan drugs"). With progress in pharmaceutical research (e.g. drugs targeted for narrower indications), these medicines will feature more often on future public health agendas. However, when current definitions for selecting essential medicines are applied strictly, orphan drugs cannot be part of the WHO Essential Medicines Programme, creating the risk that WHO may lose touch with this field. In our opinion WHO should explicitly include orphan drugs in its policy sphere by composing a complementary Orphan Medicines Model List as an addition to the EML. This complementary list of "rare essentials" could aid policy-makers and patients in, for example, emerging countries to improve access to these drugs and stimulate relevant policies. Furthermore, inconsistencies in the current EML with regard to medicines for rare diseases can be resolved. In this paper we propose selection criteria for an Orphan Medicines Model List that could form a departure point for future work towards an extensive WHO Orphan Medicines Programme.
Rare essentials: drugs for rare diseases as essential medicines.

PubMed Central

Stolk, Pieter; Willemen, Marjolein J. C.; Leufkens, Hubert G. M.

2006-01-01

Since 1977, the WHO Model List of Essential Medicines (EML), published by WHO, has provided advice for Member States that struggle to decide which pharmaceutical technologies should be provided to patients within their public health systems. Originating from outside WHO, an incentive system has been put in place by various governments for the development of medicines for rare diseases ("orphan drugs"). With progress in pharmaceutical research (e.g. drugs targeted for narrower indications), these medicines will feature more often on future public health agendas. However, when current definitions for selecting essential medicines are applied strictly, orphan drugs cannot be part of the WHO Essential Medicines Programme, creating the risk that WHO may lose touch with this field. In our opinion WHO should explicitly include orphan drugs in its policy sphere by composing a complementary Orphan Medicines Model List as an addition to the EML. This complementary list of "rare essentials" could aid policy-makers and patients in, for example, emerging countries to improve access to these drugs and stimulate relevant policies. Furthermore, inconsistencies in the current EML with regard to medicines for rare diseases can be resolved. In this paper we propose selection criteria for an Orphan Medicines Model List that could form a departure point for future work towards an extensive WHO Orphan Medicines Programme. PMID:17128345
Accounting for orphaned aftershocks in the earthquake background rate

USGS Publications Warehouse

Van Der Elst, Nicholas

2017-01-01

Aftershocks often occur within cascades of triggered seismicity in which each generation of aftershocks triggers an additional generation, and so on. The rate of earthquakes in any particular generation follows Omori's law, going approximately as 1/t. This function decays rapidly, but is heavy-tailed, and aftershock sequences may persist for long times at a rate that is difficult to discriminate from background. It is likely that some apparently spontaneous earthquakes in the observational catalogue are orphaned aftershocks of long-past main shocks. To assess the relative proportion of orphaned aftershocks in the apparent background rate, I develop an extension of the ETAS model that explicitly includes the expected contribution of orphaned aftershocks to the apparent background rate. Applying this model to California, I find that the apparent background rate can be almost entirely attributed to orphaned aftershocks, depending on the assumed duration of an aftershock sequence. This implies an earthquake cascade with a branching ratio (the average number of directly triggered aftershocks per main shock) of nearly unity. In physical terms, this implies that very few earthquakes are completely isolated from the perturbing effects of other earthquakes within the fault system. Accounting for orphaned aftershocks in the ETAS model gives more accurate estimates of the true background rate, and more realistic expectations for long-term seismicity patterns.
Accounting for orphaned aftershocks in the earthquake background rate

NASA Astrophysics Data System (ADS)

van der Elst, Nicholas J.

2017-11-01

Aftershocks often occur within cascades of triggered seismicity in which each generation of aftershocks triggers an additional generation, and so on. The rate of earthquakes in any particular generation follows Omori's law, going approximately as 1/t. This function decays rapidly, but is heavy-tailed, and aftershock sequences may persist for long times at a rate that is difficult to discriminate from background. It is likely that some apparently spontaneous earthquakes in the observational catalogue are orphaned aftershocks of long-past main shocks. To assess the relative proportion of orphaned aftershocks in the apparent background rate, I develop an extension of the ETAS model that explicitly includes the expected contribution of orphaned aftershocks to the apparent background rate. Applying this model to California, I find that the apparent background rate can be almost entirely attributed to orphaned aftershocks, depending on the assumed duration of an aftershock sequence. This implies an earthquake cascade with a branching ratio (the average number of directly triggered aftershocks per main shock) of nearly unity. In physical terms, this implies that very few earthquakes are completely isolated from the perturbing effects of other earthquakes within the fault system. Accounting for orphaned aftershocks in the ETAS model gives more accurate estimates of the true background rate, and more realistic expectations for long-term seismicity patterns.
A comparative study of orphan drug prices in Europe

PubMed Central

Young, Katherine Eve; Soussi, Imen; Hemels, Michiel; Toumi, Mondher

2017-01-01

ABSTRACT Background and Objective: This study assessed price differences by comparing annual treatment costs of similarly available orphan drugs in France, Germany, Italy, Norway, Spain, Sweden, and UK. Methods: Annual treatment costs per drug were calculated using ex-factory prices from IHS POLI and country price databases. The treatment cost in the comparator country was compared to the UK and ratios were analysed. Subanalyses were done on disease areas and UK cost quartiles. Results: 120 orphan drugs were included. Compared to the UK, the average costs were more expensive in France (1.13), Germany (1.11), Italy (1.08), Spain (1.07), and were cheaper in Sweden (0.99) and Norway (0.88). The average ratios offered a restrictive view as ratios were greatly heterogeneous (0.26 to 1.92) which was also seen in the different disease areas. The averaged ratios varied minimally among the cost quartiles which shows that cost differences were similar for the most expensive and least expensive orphan drugs in the UK. Conclusions: Individual orphan drug prices can vary widely across European countries, although on average these differences are relatively minor. This study suggests that in Europe, we may not be able predict which country may have higher or lower prices for orphan drugs. PMID:28473887
Early developmental milestones and age of independent walking in orphans compared with typical home-raised infants.

PubMed

Chaibal, Supattra; Bennett, Surussawadi; Rattanathanthong, Korrawan; Siritaratiwat, Wantana

2016-10-01

Early gross motor development is a major indicator of global milestones in the first year of life, affecting the walking ability of a child. There has been limited research reporting on early motor development and the age of independent walking of orphaned infants compared to typical home-raised infants. The purpose of this study was to compare the mean scores of early gross motor movement at 4, 6 and 8months of age and at the age of walking attainment of typically raised infants and orphaned infants. In addition, we looked to compare the walking age between these same infants. This cross-sectional study recruited 59 typical home-raised infants and 62 orphans. Their gross motor development was assessed using the Alberta Infant Motor Scale (AIMS). The age of walking attainment was also prospectively monitored and ascertained. The Student's independent t-test was used to analyse the differences of the AIMS scores at 4, 6 and 8months of age and at the age of independent walking between the two groups. The orphans showed significantly lower AIMS scores at 4, 6 and 8months of age and the age of independent walking (P-value<0.05). The orphan group had a 5-month older mean age of walking attainment (15.0±4.2months) compared with typical home-raised infants (9.9±1.4months). Orphans have delays in early gross motor development and walk independently at an older age, compared with home-raised infants. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.
Orphan Crops Browser: a bridge between model and orphan crops.

PubMed

Kamei, Claire Lessa Alvim; Severing, Edouard I; Dechesne, Annemarie; Furrer, Heleen; Dolstra, Oene; Trindade, Luisa M

2016-01-01

Many important crops have received little attention by the scientific community, either because they are not considered economically important or due to their large and complex genomes. De novo transcriptome assembly, using next-generation sequencing data, is an attractive option for the study of these orphan crops. In spite of the large amount of sequencing data that can be generated, there is currently a lack of tools which can effectively help molecular breeders and biologists to mine this type of information. Our goal was to develop a tool that enables molecular breeders, without extensive bioinformatics knowledge, to efficiently study de novo transcriptome data from any orphan crop (http://www.bioinformatics.nl/denovobrowser/db/species/index). The Orphan Crops Browser has been designed to facilitate the following tasks (1) search and identification of candidate transcripts based on phylogenetic relationships between orthologous sequence data from a set of related species and (2) design specific and degenerate primers for expression studies in the orphan crop of interest. To demonstrate the usability and reliability of the browser, it was used to identify the putative orthologues of 17 known lignin biosynthetic genes from maize and sugarcane in the orphan crop Miscanthus sinensis . Expression studies in miscanthus stem internode tissue differing in maturation were subsequently carried out, to follow the expression of these genes during lignification. Our results showed a negative correlation between lignin content and gene expression. The present data are in agreement with recent findings in maize and other crops, and it is further discussed in this paper.
The Orphan Disease Networks

PubMed Central

Zhang, Minlu; Zhu, Cheng; Jacomy, Alexis; Lu, Long J.; Jegga, Anil G.

2011-01-01

The low prevalence rate of orphan diseases (OD) requires special combined efforts to improve diagnosis, prevention, and discovery of novel therapeutic strategies. To identify and investigate relationships based on shared genes or shared functional features, we have conducted a bioinformatic-based global analysis of all orphan diseases with known disease-causing mutant genes. Starting with a bipartite network of known OD and OD-causing mutant genes and using the human protein interactome, we first construct and topologically analyze three networks: the orphan disease network, the orphan disease-causing mutant gene network, and the orphan disease-causing mutant gene interactome. Our results demonstrate that in contrast to the common disease-causing mutant genes that are predominantly nonessential, a majority of orphan disease-causing mutant genes are essential. In confirmation of this finding, we found that OD-causing mutant genes are topologically important in the protein interactome and are ubiquitously expressed. Additionally, functional enrichment analysis of those genes in which mutations cause ODs shows that a majority result in premature death or are lethal in the orthologous mouse gene knockout models. To address the limitations of traditional gene-based disease networks, we also construct and analyze OD networks on the basis of shared enriched features (biological processes, cellular components, pathways, phenotypes, and literature citations). Analyzing these functionally-linked OD networks, we identified several additional OD-OD relations that are both phenotypically similar and phenotypically diverse. Surprisingly, we observed that the wiring of the gene-based and other feature-based OD networks are largely different; this suggests that the relationship between ODs cannot be fully captured by the gene-based network alone. PMID:21664998
Therapies for inborn errors of metabolism: what has the orphan drug act delivered?

PubMed

Talele, Sonali S; Xu, Kui; Pariser, Anne R; Braun, M Miles; Farag-El-Massah, Sheiren; Phillips, M Ian; Thompson, Barry H; Coté, Timothy R

2010-07-01

The 1983 US Orphan Drug Act established a process through which promising therapies are designated as orphan products and, later, with satisfactory safety and efficacy data, receive marketing approval and fiscal incentives. We examined accomplishments in drug development for inborn errors of metabolism (IEMs). Food and Drug Administration data were used to identify orphan product designations and approvals for IEMs, and the trends for the past 26 years were summarized. Individual clinical development times (CDTs) from filing investigational new drug application to marketing approval were determined. We examined 1956 orphan product designations from 1983 through 2008 and found 93 (4.8%) for IEMs. Of those, 24 (25.8%) received marketing approval. This proportion of approval was significantly (P = .036) higher than that for non-IEM orphan products (17%). Among the IEM products, disorders of complex molecules received the most designations and approvals (61 and 11, respectively). Among the subgroups, lysosomal storage diseases received the most designations and approvals (43 and 9, respectively), whereas mitochondrial diseases (other than fatty acid oxidation disorders) received 7 designations with no approvals. We then examined the CDTs for the approved IEM products and found a median of 6.4 years (range: 2.6-25.1 years). Biological products had significantly shorter CDTs than drugs (mean: 4.6 vs 11.0 years; P = .003). For 26 years, the Orphan Drug Act has generated new therapies for IEMs. Why some IEMs have motivated successful drug development and others have not remains enigmatic; yet the needs of IEM patients without treatment are a certainty.
What is known about the cost-effectiveness of orphan drugs? Evidence from cost-utility analyses.

PubMed

Picavet, E; Cassiman, D; Simoens, S

2015-06-01

In times of financial and economic hardship, governments are looking to contain pharmaceutical expenditure by focusing on cost-effective drugs. Because of their high prices and difficulties in demonstrating effectiveness in small patient populations, orphan drugs are often perceived as not able to meet traditional reimbursement threshold value for money. The aim of this study was to provide an overview of the available evidence on the cost-effectiveness of orphan drugs. All orphan drugs listed as authorized on the website of the European Medicines Agency on 21 November 2013 were included in the analysis. Cost-utility analyses (CUAs) were identified by searching the Tufts Medical Center Cost-Effectiveness Analysis Registry and Embase. For each CUA, a number of variables were collected. The search identified 23 articles on the Tufts registry and 167 articles on Embase. The final analysis included 45 CUAs and 61 incremental cost-utility ratios (ICURs) for 19 orphan drugs. Of all ICURS, 16·3% were related to dominant drugs (i.e. more effective and less expensive than the comparator), 70·5% were related to drugs that are more effective, but at a higher cost, and 13·1% were related to dominated drugs (i.e. less effective and more expensive than the comparator). The median overall ICUR was €40 242 per quality-adjusted life year (QALY) with a minimum ICUR of €6311/QALY and a maximum ICUR of €974,917/QALY. This study demonstrates that orphan drugs can meet traditional reimbursement thresholds. Considering a threshold of £30,000/QALY, in this study, ten (52·6%) of a total of 19 orphan drugs for which data were available meet the threshold. As much as fifteen orphan drugs (78·9%) are eligible for reimbursement if a threshold of €80,000/QALY is considered. © 2015 John Wiley & Sons Ltd.
TRACING THE ORPHAN STREAM TO 55 kpc WITH RR LYRAE STARS

DOE Office of Scientific and Technical Information (OSTI.GOV)

Sesar, Branimir; Cohen, Judith G.; Bellm, Eric C.

2013-10-10

We report positions, velocities, and metallicities of 50 ab-type RR Lyrae (RRab) stars observed in the vicinity of the Orphan stellar stream. Using about 30 RRab stars classified as being likely members of the Orphan stream, we study the metallicity and the spatial extent of the stream. We find that RRab stars in the Orphan stream have a wide range of metallicities, from –1.5 dex to –2.7 dex. The average metallicity of the stream is –2.1 dex, identical to the value obtained by Newberg et al. using blue horizontal branch stars. We find that the most distant parts of themore » stream (40-50 kpc from the Sun) are about 0.3 dex more metal-poor than the closer parts (within ∼30 kpc), suggesting a possible metallicity gradient along the stream's length. We have extended the previous studies and have mapped the stream up to 55 kpc from the Sun. Even after a careful search, we did not identify any more distant RRab stars that could plausibly be members of the Orphan stream. If confirmed with other tracers, this result would indicate a detection of the end of the leading arm of the stream. We have compared the distances of Orphan stream RRab stars with the best-fit orbits obtained by Newberg et al. We find that model 6 of Newberg et al. cannot explain the distances of the most remote Orphan stream RRab stars, and conclude that the best fit to distances of Orphan stream RRab stars and to the local circular velocity is provided by potentials where the total mass of the Galaxy within 60 kpc is M{sub 60} ∼ 2.7 × 10{sup 11} M{sub ☉}, or about 60% of the mass found by previous studies. More extensive modeling that would consider non-spherical potentials and the possibility of misalignment between the stream and the orbit is highly encouraged.« less
ORENZA: a web resource for studying ORphan ENZyme activities

PubMed Central

Lespinet, Olivier; Labedan, Bernard

2006-01-01

Background Despite the current availability of several hundreds of thousands of amino acid sequences, more than 36% of the enzyme activities (EC numbers) defined by the Nomenclature Committee of the International Union of Biochemistry and Molecular Biology (NC-IUBMB) are not associated with any amino acid sequence in major public databases. This wide gap separating knowledge of biochemical function and sequence information is found for nearly all classes of enzymes. Thus, there is an urgent need to explore these sequence-less EC numbers, in order to progressively close this gap. Description We designed ORENZA, a PostgreSQL database of ORphan ENZyme Activities, to collate information about the EC numbers defined by the NC-IUBMB with specific emphasis on orphan enzyme activities. Complete lists of all EC numbers and of orphan EC numbers are available and will be periodically updated. ORENZA allows one to browse the complete list of EC numbers or the subset associated with orphan enzymes or to query a specific EC number, an enzyme name or a species name for those interested in particular organisms. It is possible to search ORENZA for the different biochemical properties of the defined enzymes, the metabolic pathways in which they participate, the taxonomic data of the organisms whose genomes encode them, and many other features. The association of an enzyme activity with an amino acid sequence is clearly underlined, making it easy to identify at once the orphan enzyme activities. Interactive publishing of suggestions by the community would provide expert evidence for re-annotation of orphan EC numbers in public databases. Conclusion ORENZA is a Web resource designed to progressively bridge the unwanted gap between function (enzyme activities) and sequence (dataset present in public databases). ORENZA should increase interactions between communities of biochemists and of genomicists. This is expected to reduce the number of orphan enzyme activities by allocating gene sequences to the relevant enzymes. PMID:17026747
Recent trends in specialty pharma business model.

PubMed

Ku, Mannching Sherry

2015-12-01

The recent rise of specialty pharma is attributed to its flexible, versatile, and open business model while the traditional big pharma is facing a challenging time with patent cliff, generic threat, and low research and development (R&D) productivity. These multinational pharmaceutical companies, facing a difficult time, have been systematically externalizing R&D and some even establish their own corporate venture capital so as to diversify with more shots on goal, with the hope of achieving a higher success rate in their compound pipeline. Biologics and clinical Phase II proof-of-concept (POC) compounds are the preferred licensing and collaboration targets. Biologics enjoys a high success rate with a low generic biosimilar threat, while the need is high for clinical Phase II POC compounds, due to its high attrition/low success rate. Repurposing of big pharma leftover compounds is a popular strategy but with limitations. Most old compounds come with baggage either in lackluster clinical performance or short in patent life. Orphan drugs is another area which has gained popularity in recent years. The shorter and less costly regulatory pathway provides incentives, especially for smaller specialty pharma. However, clinical studies on orphan drugs require a large network of clinical operations in many countries in order to recruit enough patients. Big pharma is also working on orphan drugs starting with a small indication, with the hope of expanding the indication into a blockbuster status. Specialty medicine, including orphan drugs, has become the growth engine in the pharmaceutical industry worldwide. Big pharma is also keen on in-licensing technology or projects from specialty pharma to extend product life cycles, in order to protect their blockbuster drug franchises. Ample opportunities exist for smaller players, even in the emerging countries, to collaborate with multinational pharmaceutical companies provided that the technology platforms or specialty medicinal products are what the big pharma wants. The understanding of intellectual properties and international drug regulations are the key for specialty pharma to have a workable strategy for product registration worldwide. Copyright © 2015. Published by Elsevier B.V.
Legal Briefing: Adult Orphans and the Unbefriended: Making Medical Decisions for Unrepresented Patients without Surrogates.

PubMed

Pope, Thaddeus Mason

2015-01-01

This issue's "Legal Briefing" column covers recent legal developments involving medical decision making for incapacitated patients who have no available legally authorized surrogate decision maker. These individuals are frequently referred to either as "adult orphans" or as "unbefriended," "isolated," or "unrepresented" patients. The challenges involved in obtaining consent for medical treatment on behalf of these individuals have been the subject of major policy reports. Indeed, caring for the unbefriended has even been described as the "single greatest category of problems" encountered in bioethics consultation. In 2012, JCE published a comprehensive review of the available mechanisms by which to make medical decisions for the unbefriended. The purpose of this "Legal Briefing" is to update the 2012 study. Accordingly, this "Legal Briefing" collects and describes significant legal developments from only the past three years. My basic assessment has not changed. "Existing mechanisms to address the issue of decision making for the unbefriended are scant and not uniform." Most facilities are "muddling through on an ad hoc basis." But the situation is not wholly negative. There have been a number of promising new initiatives. I group these developments into the following seven categories: 1. Increased Attention and Discussion 2. Prevention through Better Advance Care Planning 3. Prevention through Expanded Default Surrogate Lists 4. Statutorily Authorized Intramural Mechanisms 5. California Litigation Challenging the Team Approach 6. Public Guardianship 7. Improving Existing Guardianship Processes. Copyright 2015 The Journal of Clinical Ethics. All rights reserved.
Intergenerational impacts of maternal mortality: Qualitative findings from rural Malawi

PubMed Central

2015-01-01

Background Maternal mortality, although largely preventable, remains unacceptably high in developing countries such as Malawi and creates a number of intergenerational impacts. Few studies have investigated the far-reaching impacts of maternal death beyond infant survival. This study demonstrates the short- and long-term impacts of maternal death on children, families, and the community in order to raise awareness of the true costs of maternal mortality and poor maternal health care in Neno, a rural and remote district in Malawi. Methods Qualitative in-depth interviews were conducted to assess the impact of maternal mortality on child, family, and community well-being. We conducted 20 key informant interviews, 20 stakeholder interviews, and six sex-stratified focus group discussions in the seven health centers that cover the district. Transcripts were translated, coded, and analyzed in NVivo 10. Results Participants noted a number of far-reaching impacts on orphaned children, their new caretakers, and extended families following a maternal death. Female relatives typically took on caregiving responsibilities for orphaned children, regardless of the accompanying financial hardship and frequent lack of familial or governmental support. Maternal death exacerbated children’s vulnerabilities to long-term health and social impacts related to nutrition, education, employment, early partnership, pregnancy, and caretaking. Impacts were particularly salient for female children who were often forced to take on the majority of the household responsibilities. Participants cited a number of barriers to accessing quality child health care or support services, and many were unaware of programming available to assist them in raising orphaned children or how to access these services. Conclusions In order to both reduce preventable maternal mortality and diminish the impacts on children, extended families, and communities, our findings highlight the importance of financing and implementing universal access to emergency obstetric and neonatal care, and contraception, as well as social protection programs, including among remote populations. PMID:26000733

Instruments of Science and Citizenship: Science Education for Dutch Orphans During the Late Eighteenth Century

NASA Astrophysics Data System (ADS)

Roberts, Lissa L.

2012-01-01

One of the two most extensive instrument collections in the Netherlands during the second half of the eighteenth century—rivaling the much better known collection at the University of Leiden—belonged to an orphanage in The Hague that was specially established to mold hand-picked orphans into productive citizens. (The other was housed at the Mennonite Seminary in Amsterdam, for use in the education of its students.) The educational program at this orphanage, one of three established by the Fundatie van Renswoude, grew out of a marriage between the socially-oriented generosity of the wealthy Baroness van Renswoude and the pedagogical vision of the institute's director and head teacher—a vision that fit with the larger movement of oeconomic patriotism. Oeconomic patriotism, similar to `improvement' and oeconomic movements in other European countries and their colonies, sought to tie the investigation of nature to an improvement of society's material and moral well-being. Indeed, it was argued that these two facets of society should be viewed as inseparable from each other, distinguishing the movement from more modern conceptions of economics. While a number of the key figures in this Dutch movement also became prominent Patriots during the revolutionary period at the end of the century, fighting against the House of Orange, they did not have a monopoly on oeconomic ideas of societal improvement. This is demonstrated by the fact that an explicitly pro-Orangist society, Mathesis Scientiarum Genitrix, was organized in 1785 to teach science and mathematics to poor boys and orphans for very similar reasons: to turn them into productive and useful citizens. As was the case with the Fundatie van Renswoude, a collection of instruments was assembled to help make this possible. This story is of interest because it discusses a hitherto under-examined use to which science education was put during this period, by revealing the link between such programs and the highly charged question of citizenry.
Models of care for orphaned and separated children and upholding children’s rights: cross-sectional evidence from western Kenya

PubMed Central

2014-01-01

Background Sub-Saharan Africa is home to approximately 55 million orphaned children. The growing orphan crisis has overwhelmed many communities and has weakened the ability of extended families to meet traditional care-taking expectations. Other models of care and support have emerged in sub-Saharan Africa to address the growing orphan crisis, yet there is a lack of information on these models available in the literature. We applied a human rights framework using the United Nations Convention on the Rights of the Child to understand what extent children’s basic human rights were being upheld in institutional vs. community- or family-based care settings in Uasin Gishu County, Kenya. Methods The Orphaned and Separated Children’s Assessments Related to their Health and Well-Being Project is a 5-year cohort of orphaned children and adolescents aged ≤18 year. This descriptive analysis was restricted to baseline data. Chi-Square test was used to test for associations between categorical /dichotomous variables. Fisher’s exact test was also used if some cells had expected value of less than 5. Results Included in this analysis are data from 300 households, 19 Charitable Children’s Institutions (CCIs) and 7 community-based organizations. In total, 2871 children were enrolled and had baseline assessments done: 1390 in CCI’s and 1481 living in households in the community. We identified and described four broad models of care for orphaned and separated children, including: institutional care (sub-classified as ‘Pure CCI’ for those only providing residential care, ‘CCI-Plus’ for those providing both residential care and community-based supports to orphaned children , and ‘CCI-Shelter’ which are rescue, detention, or other short-term residential support), family-based care, community-based care and self-care. Children in institutional care (95%) were significantly (p < 0.0001) more likely to have their basic material needs met in comparison to those in family-based care (17%) and institutions were better able to provide an adequate standard of living. Conclusions Each model of care we identified has strengths and weaknesses. The orphan crisis in sub-Saharan Africa requires a diversity of care environments in order to meet the needs of children and uphold their rights. Family-based care plays an essential role; however, households require increased support to adequately care for children. PMID:24685118
Models of care for orphaned and separated children and upholding children's rights: cross-sectional evidence from western Kenya.

PubMed

Embleton, Lonnie; Ayuku, David; Kamanda, Allan; Atwoli, Lukoye; Ayaya, Samuel; Vreeman, Rachel; Nyandiko, Winstone; Gisore, Peter; Koech, Julius; Braitstein, Paula

2014-04-01

Sub-Saharan Africa is home to approximately 55 million orphaned children. The growing orphan crisis has overwhelmed many communities and has weakened the ability of extended families to meet traditional care-taking expectations. Other models of care and support have emerged in sub-Saharan Africa to address the growing orphan crisis, yet there is a lack of information on these models available in the literature. We applied a human rights framework using the United Nations Convention on the Rights of the Child to understand what extent children's basic human rights were being upheld in institutional vs. community- or family-based care settings in Uasin Gishu County, Kenya. The Orphaned and Separated Children's Assessments Related to their Health and Well-Being Project is a 5-year cohort of orphaned children and adolescents aged ≤18 year. This descriptive analysis was restricted to baseline data. Chi-Square test was used to test for associations between categorical /dichotomous variables. Fisher's exact test was also used if some cells had expected value of less than 5. Included in this analysis are data from 300 households, 19 Charitable Children's Institutions (CCIs) and 7 community-based organizations. In total, 2871 children were enrolled and had baseline assessments done: 1390 in CCI's and 1481 living in households in the community. We identified and described four broad models of care for orphaned and separated children, including: institutional care (sub-classified as 'Pure CCI' for those only providing residential care, 'CCI-Plus' for those providing both residential care and community-based supports to orphaned children , and 'CCI-Shelter' which are rescue, detention, or other short-term residential support), family-based care, community-based care and self-care. Children in institutional care (95%) were significantly (p < 0.0001) more likely to have their basic material needs met in comparison to those in family-based care (17%) and institutions were better able to provide an adequate standard of living. Each model of care we identified has strengths and weaknesses. The orphan crisis in sub-Saharan Africa requires a diversity of care environments in order to meet the needs of children and uphold their rights. Family-based care plays an essential role; however, households require increased support to adequately care for children.
[Orphan drugs].

PubMed

Golocorbin Kon, Svetlana; Vojinović, Aleksandra; Lalić-Popović, Mladena; Pavlović, Nebojsa; Mikov, Momir

2013-01-01

Drugs used for treatment of rare diseases are known worldwide under the term of orphan drugs because pharmaceutical companies have not been interested in "adopting" them, that is in investing in research, developing and producing these drugs. This kind of policy has been justified by the fact that these drugs are targeted for small markets, that only a small number of patients is available for clinical trials, and that large investments are required for the development of drugs meant to treat diseases whose pathogenesis has not yet been clarified in majority of cases. The aim of this paper is to present previous and present status of orphan drugs in Serbia and other countries. THE BEGINNING OF ORPHAN DRUGS DEVELOPMENT: This problem was first recognized by Congress of the United States of America in January 1983, and when the "Orphan Drug Act" was passed, it was a turning point in the development of orphan drugs. This law provides pharmaceutical companies with a series of reliefs, both financial ones that allow them to regain funds invested into the research and development and regulatory ones. Seven years of marketing exclusivity, as a type of patent monopoly, is the most important relief that enables companies to make large profits. There are no sufficient funds and institutions to give financial support to the patients. It is therefore necessary to make health professionals much more aware of rare diseases in order to avoid time loss in making the right diagnosis and thus to gain more time to treat rare diseases. The importance of discovery, development and production of orphan drugs lies in the number of patients whose life quality can be improved significantly by administration of these drugs as well as in the number of potential survivals resulting from the treatment with these drugs.
Psychosocial support and parents' social life determine the self-esteem of orphan children.

PubMed

Erango, Markos Abiso; Ayka, Zikie Ataro

2015-01-01

Parental death affects the life of children in many ways, one of which is self-esteem problems. Providing psychosocial support and equipping orphans play a vital role in their lifes. A cross-sectional study was conducted on 7-18-year-old orphans at 17 local districts of Gamo Gofa Zone, Southern Regional State of Ethiopia. From a total of 48,270 orphans in these areas, 4,368 were selected using stratified simple random sampling technique. Data were collected with a designed questionnaire based on the Rosenberg's rating scale to measure their self-esteem levels. Self-esteem with a score less than or equal to an average score was considered to be low self-esteem in the analysis. Binary logistic regression model was used to analyze the data using the SPSS software. The results of the study revealed that the probability of orphans suffering from low self-esteem was 0.59. Several risk factors were found to be significant at the level of 5%. Psychosocial support (good guidance, counseling and treatment, physical protection and amount of love shared, financial and material support, and fellowship with other children), parents living together before death, strong relationship between parents before death, high average monthly income, voluntary support, and consideration from the society are some of the factors that decrease the risk of being low in self-esteem. There are many orphans with low self-esteem in the study areas. The factors negatively affecting the self-esteem of orphans include the lack of psychosocial support, poor social life of parents, and death of parents due to AIDS. Society and parents should be aware of the consequences of these factors which can influence their children's future self-esteem.
Evolution and dynamics of orphan penumbrae in the solar photosphere: Analysis from multi-instrument observations

DOE Office of Scientific and Technical Information (OSTI.GOV)

Zuccarello, Francesca; Guglielmino, Salvo L.; Romano, Paolo, E-mail: fzu@oact.inaf.it

2014-05-20

We investigate the dynamics and magnetic properties of orphan penumbrae observed in the solar photosphere to understand the formation process of such structures. We observed two orphan penumbrae in active region NOAA 11089 during a coordinated observing campaign carried out in 2010 July, involving the Hinode/Solar Optical Telescope (SOT) and Dutch Open Telescope (DOT), benefiting also from continuous observations acquired by the SDO satellite. We follow their evolution during about three days. The two structures form in different ways: one seems to break off the penumbra of a nearby sunspot, the other is formed through the emergence of new flux.more » Then they fragment while evolving. The SDO Helioseismic and Magnetic Imager measurements indicate the presence of strong line-of-sight motions in the regions occupied by these orphan penumbrae, lasting for several hours and decreasing with time. This is confirmed by SOT spectro-polarimetric measurements of the Fe I 630.2 nm pair. The latter also show that Stokes parameters exhibit significant asymmetries in the orphan penumbral regions, typical of an uncombed filamentary structure. The orphan penumbrae lie above polarity inversion lines, where peculiar plasma motions take place with velocities larger than ±3 km s{sup –1}. The vector magnetic field in these regions is highly inclined, with the average magnetic field strength decreasing with time. The DOT observations in the Hα line and SDO Atmospheric Imaging Assembly measurements in the He II 30.4 nm line indicate that there is no counterpart for the orphan penumbrae at midchromospheric heights or above. Our findings suggest that in at least one of the features investigated the emerging flux may be trapped in the low atmospheric layers by the overlying pre-existing fields, forming these filamentary structures.« less
Tectono-stratigraphic evolution and crustal architecture of the Orphan Basin during North Atlantic rifting

NASA Astrophysics Data System (ADS)

Gouiza, Mohamed; Hall, Jeremy; Welford, J. Kim

2017-04-01

The Orphan Basin is located in the deep offshore of the Newfoundland margin, and it is bounded by the continental shelf to the west, the Grand Banks to the south, and the continental blocks of Orphan Knoll and Flemish Cap to the east. The Orphan Basin formed in Mesozoic time during the opening of the North Atlantic Ocean between eastern Canada and western Iberia-Europe. This work, based on well data and regional seismic reflection profiles across the basin, indicates that the continental crust was affected by several extensional episodes between the Jurassic and the Early Cretaceous, separated by events of uplift and erosion. The preserved tectono-stratigraphic sequences in the basin reveal that deformation initiated in the eastern part of the Orphan Basin in the Jurassic and spread towards the west in the Early Cretaceous, resulting in numerous rift structures filled with a Jurassic-Lower Cretaceous syn-rift succession and overlain by thick Upper Cretaceous to Cenozoic post-rift sediments. The seismic data show an extremely thinned crust (4-16 km thick) underneath the eastern and western parts of the Orphan Basin, forming two sub-basins separated by a wide structural high with a relatively thick crust (17 km thick). Quantifying the crustal architecture in the basin highlights the large discrepancy between brittle extension localized in the upper crust and the overall crustal thinning. This suggests that continental deformation in the Orphan Basin involved, in addition to the documented Jurassic and Early Cretaceous rifting, an earlier brittle rift phase which is unidentifiable in seismic data and a depth-dependent thinning of the crust driven by localized lower crust ductile flow.
Cost Effectiveness of Monoclonal Antibody Therapy for Rare Diseases: A Systematic Review.

PubMed

Park, Taehwan; Griggs, Scott K; Suh, Dong-Churl

2015-08-01

Monoclonal antibody (mAb)-based orphan drugs have led to advances in the treatment of diseases by selectively targeting molecule functions. However, their high treatment costs impose a substantial cost burden on patients and society. The study aimed to systematically review cost-effectiveness evidence of mAb orphan drugs. Ovid MEDLINE(®), EMBASE(®), and PsycINFO(®) were searched in June 2014 and articles were selected if they conducted economic evaluations of the mAb orphan drugs that had received marketing approval in the USA. The quality of the selected studies was assessed using the Quality of Health Economic Studies (QHES) instrument. We reviewed 16 articles that included 24 economic evaluations of nine mAb orphan drugs. Six of these nine drugs were included in cost-utility analysis studies, whereas three drugs were included in cost-effectiveness analysis studies. Previous cost-utility analysis studies revealed that four mAb orphan drugs (cetuximab, ipilimumab, rituximab, and trastuzumab) were found to be cost effective; one drug (bevacizumab) was not cost effective; and one drug (infliximab) was not consistent across the studies. Prior cost-effectiveness analysis studies which included three mAb orphan drugs (adalimumab, alemtuzumab, and basiliximab) showed that the incremental cost per effectiveness gained for these drugs ranged from $US4669 to $Can52,536 Canadian dollars. The quality of the included studies was good or fair with the exception of one study. Some mAb orphan drugs were reported as cost effective under the current decision-making processes. Use of these expensive drugs, however, can raise an equity issue which concerns fairness in access to treatment. The issue of equal access to drugs needs to be considered alongside other societal values in making the final health policy decisions.
Perceived social support and the psychological well-being of AIDS orphans in urban Kenya.

PubMed

Okawa, Sumiyo; Yasuoka, Junko; Ishikawa, Naoko; Poudel, Krishna C; Ragi, Allan; Jimba, Masamine

2011-09-01

Parental deaths due to AIDS seriously affect the psychological well-being of children. Social support may provide an effective resource in the care of vulnerable children in resource-limited settings. However, few studies have examined the relationships between social support and psychological well-being among AIDS orphans. This cross-sectional study was conducted to explore associations between perceived social support (PSS) and the psychological well-being of AIDS orphans, and to identify socio-demographic factors that are associated with PSS. Data were collected from 398 pairs of AIDS orphans (aged 10-18 years) and their caregivers in Nairobi, Kenya. The participants provided information on their socio-demographic characteristics, the children's PSS, and the children's psychological status (based on measures of depressive symptoms and self-esteem). Of the 398 pairs, 327 were included in the analysis. PSS scores of AIDS orphans showed significant correlations with depressive symptoms (ρ =-0.31, p<0.001) and self-esteem (ρ=0.32, p<0.001). Socio-demographic factors, such as HIV-positive status of children (β=3.714, p=0.014) and cohabitation with siblings (β=3.044, p=0.016), were also associated with higher PSS scores. In particular, HIV-infected children (n=37) had higher scores of PSS from a special person (β=2.208, p=0.004), and children living with biological siblings (n=269) also had higher scores of PSS from both a special person (β=1.411, p=0.029) and friends (β=1.276, p=0.039). In conclusion, this study showed that PSS is positively associated with the psychological well-being of AIDS orphans. Siblings and special persons can be effective sources of social support for AIDS orphans, which help to promote their psychological well-being.
They are not always a burden: Older people and child fostering in Uganda during the HIV epidemic

PubMed Central

Kasedde, Susan; Doyle, Aoife M.; Seeley, Janet A.; Ross, David A.

2014-01-01

This qualitative study examines the role of older people (60 years and above) in fostering decisions for orphans and non-orphans within extended families in a rural Ugandan community heavily affected by HIV. Fieldwork conducted in 2006 provided information on the influence of HIV on fostering decisions through 48 individual in-depth interviews and two group interviews with foster-children and family members to develop detailed case studies related to 13 fostered adolescents. The adolescents included five non-orphans and eight orphans (five were double orphans because they had lost both parents). Older people play a very important role in fostering decisions as potential foster-parents, advisers, mediators and gatekeepers. They have a high level of authority over the foster-children, who are regarded as important resources within the extended family. With fewer potential caregivers available because of HIV-related deaths, the responsibility for fostering orphans has often fallen to surviving older people. Fostering is used by older people and the child's extended family as a strategy to ensure the welfare of the foster-child. When the foster-parent is an older person, it is also used to ensure physical and emotional support for the older person themselves. Support from the extended family towards foster households is widely reported to have been reduced by HIV by diminishing resources that would otherwise have been made available to support foster care. New initiatives and investment are required to complement community and family resources within well-managed social protection and welfare programmes. To be effective, such programmes will require adequate investment in administrative capacity and monitoring. They must aim to strengthen families and, recognizing that resources are limited, should prioritize the community's poorest households, rather than specifically targeting households with orphans or other foster-children. PMID:24880658
Causes and consequences of psychological distress among orphans in eastern Zimbabwe

PubMed Central

Nyamukapa, C.A.; Gregson, S.; Wambe, M.; Mushore, P.; Lopman, B.; Mupambireyi, Z.; Nhongo, K.; Jukes, M.C.H.

2010-01-01

Substantial resources are invested in psychological support for children orphaned or otherwise made vulnerable in the context of HIV/AIDS (OVC). However, there is still only limited scientific evidence for greater psychological distress amongst orphans and even less evidence for the effectiveness of current support strategies. Furthermore, programmes that address established mechanisms through which orphanhood can lead to greater psychological distress should be more effective. We use quantitative and qualitative data from Eastern Zimbabwe to measure the effects of orphanhood on psychological distress and to test mechanisms for greater distress amongst orphans suggested in a recently published theoretical framework. Orphans were found to suffer greater psychological distress than non-orphans (sex- and age-adjusted co-efficient: 0.15; 95% CI 0.03–0.26; P = 0.013). Effects of orphanhood contributing to their increased levels of distress included trauma, being out-of-school, being cared for by a non-parent, inadequate care, child labour, physical abuse, and stigma and discrimination. Increased mobility and separation from siblings did not contribute to greater psychological distress in this study. Over 40% of orphaned children in the sample lived in households receiving external assistance. However, receipt of assistance was not associated with reduced psychological distress. These findings and the ideas put forward by children and caregivers in the focus group discussions suggest that community-based programmes that aim to improve caregiver selection, increase support for caregivers, and provide training in parenting responsibilities and skills might help to reduce psychological distress. These programmes should be under-pinned by further efforts to reduce poverty, increase school attendance and support out-of-school youth. PMID:20552465
Evolution and Dynamics of Orphan Penumbrae in the Solar Photosphere: Analysis from Multi-instrument Observations

NASA Astrophysics Data System (ADS)

Zuccarello, Francesca; Guglielmino, Salvo L.; Romano, Paolo

2014-05-01

We investigate the dynamics and magnetic properties of orphan penumbrae observed in the solar photosphere to understand the formation process of such structures. We observed two orphan penumbrae in active region NOAA 11089 during a coordinated observing campaign carried out in 2010 July, involving the Hinode/Solar Optical Telescope (SOT) and Dutch Open Telescope (DOT), benefiting also from continuous observations acquired by the SDO satellite. We follow their evolution during about three days. The two structures form in different ways: one seems to break off the penumbra of a nearby sunspot, the other is formed through the emergence of new flux. Then they fragment while evolving. The SDO Helioseismic and Magnetic Imager measurements indicate the presence of strong line-of-sight motions in the regions occupied by these orphan penumbrae, lasting for several hours and decreasing with time. This is confirmed by SOT spectro-polarimetric measurements of the Fe I 630.2 nm pair. The latter also show that Stokes parameters exhibit significant asymmetries in the orphan penumbral regions, typical of an uncombed filamentary structure. The orphan penumbrae lie above polarity inversion lines, where peculiar plasma motions take place with velocities larger than ±3 km s-1. The vector magnetic field in these regions is highly inclined, with the average magnetic field strength decreasing with time. The DOT observations in the Hα line and SDO Atmospheric Imaging Assembly measurements in the He II 30.4 nm line indicate that there is no counterpart for the orphan penumbrae at midchromospheric heights or above. Our findings suggest that in at least one of the features investigated the emerging flux may be trapped in the low atmospheric layers by the overlying pre-existing fields, forming these filamentary structures.
The CanOE strategy: integrating genomic and metabolic contexts across multiple prokaryote genomes to find candidate genes for orphan enzymes.

PubMed

Smith, Adam Alexander Thil; Belda, Eugeni; Viari, Alain; Medigue, Claudine; Vallenet, David

2012-05-01

Of all biochemically characterized metabolic reactions formalized by the IUBMB, over one out of four have yet to be associated with a nucleic or protein sequence, i.e. are sequence-orphan enzymatic activities. Few bioinformatics annotation tools are able to propose candidate genes for such activities by exploiting context-dependent rather than sequence-dependent data, and none are readily accessible and propose result integration across multiple genomes. Here, we present CanOE (Candidate genes for Orphan Enzymes), a four-step bioinformatics strategy that proposes ranked candidate genes for sequence-orphan enzymatic activities (or orphan enzymes for short). The first step locates "genomic metabolons", i.e. groups of co-localized genes coding proteins catalyzing reactions linked by shared metabolites, in one genome at a time. These metabolons can be particularly helpful for aiding bioanalysts to visualize relevant metabolic data. In the second step, they are used to generate candidate associations between un-annotated genes and gene-less reactions. The third step integrates these gene-reaction associations over several genomes using gene families, and summarizes the strength of family-reaction associations by several scores. In the final step, these scores are used to rank members of gene families which are proposed for metabolic reactions. These associations are of particular interest when the metabolic reaction is a sequence-orphan enzymatic activity. Our strategy found over 60,000 genomic metabolons in more than 1,000 prokaryote organisms from the MicroScope platform, generating candidate genes for many metabolic reactions, of which more than 70 distinct orphan reactions. A computational validation of the approach is discussed. Finally, we present a case study on the anaerobic allantoin degradation pathway in Escherichia coli K-12.
The relationship between parental presence and child sexual violence: Evidence from thirteen countries in sub-Saharan Africa

PubMed Central

Kidman, Rachel; Palermo, Tia

2015-01-01

There are compelling reasons to believe that orphans – many millions due to the AIDS epidemic – are more likely to be sexually victimized during childhood. Few studies have empirically investigated sexual violence disparities, and those that do suffer from methodological limitations and limited geographic scope. We used nationally-representative data on female adolescents (15-17 years) from 13 countries in sub-Saharan Africa. We built multilevel logistic models to test for an association between the dependent variables (orphanhood and parental absence) and sexual violence, both within countries and pooled across all countries. Approximately 10% of adolescent girls reported past experiences of sexual violence; a third of those victimized were 14 years or younger at the time of their first forced encounter. Paternal orphaning (OR 1.36, p ≤ .01), double orphaning (OR 1.47, p ≤ .05), and paternal absence (OR 1.28; p ≤.05) were significantly associated with experiencing sexual violence in pooled analyses. Fewer findings reached significance within individual countries. Our findings suggest that the lack of a father in the home (due to death or absence) places girls at heightened risk for childhood sexual abuse; further research identifying pathways of vulnerability and resilience specific to this population is needed. Our findings also indicate that abuse often starts at an early age; thus promising programs should be adapted for younger age groups and rigorously tested. PMID:26631421
Sibling separation and psychological problems of double AIDS orphans in rural China - a comparison analysis.

PubMed

Gong, J; Li, X; Fang, X; Zhao, G; Lv, Y; Zhao, J; Lin, X; Zhang, L; Chen, X; Stanton, B

2009-07-01

We investigated the psychological impact of sibling separation among children who lost both of their parents to AIDS and were placed in group care or kinship care settings in rural China. Comparative analysis of cross-sectional survey data among 155 children among whom 96 experienced sibling separation. Trauma symptoms (Anxiety, Depression, Anger, Post-traumatic stress, Dissociation, Sexual concerns) were compared between the AIDS orphans who experienced sibling separation and those who did not using analysis of variance and multivariate analysis of covariance. Among the participants (47.7% girls) with an average age of 12.4 years, univariate and multivariate analyses showed that separation from siblings was associated with significantly higher scores in anxiety, depression, anger and dissociation before or after controlling for gender, age, care arrangement, number of household replacement, trusting relationship with the current caregivers and perceived quality of current living condition. Sibling separation among orphans was not associated with level of post-traumatic stress and sexual concerns. AIDS orphans separated from their siblings suffered from increased psychological distress compared with those who remained with their siblings. The data in the current study suggest that care arrangement for AIDS orphan should include accommodating the siblings together or providing them with opportunities for frequent contact and/or communication with each other. Appropriate psychological counselling should be given to those orphans experiencing sibling separation.
Caregiver issues and AIDS orphans: perspectives from a social worker focus group.

PubMed

Paige, C Y; Johnson, M S

1997-10-01

This study examines social workers' perceptions of the needs of families coping with acquired immunodeficiency syndrome (AIDS). This research investigates the problems of family caregivers of children orphaned by human immunodeficiency virus (HIV)-related death of their parents. A qualitative semistructured interview format was used in a focus group of 18 social workers. Four questions were designed to assess family needs and resources, as well as to evaluate the social workers' perspectives of governmental policies affecting these families. A list of four problems and two recommendations for change evolved from the focus group. Inadequate finances to house and care for the children was the primary cause for distress in these families. The major governmental policy that hindered the social workers' ability to assist families pertained to the low financial entitlement for caregivers who are related to the orphaned child. It was noted that unrelated caregivers receive substantially more money for the care of these children than family caregivers receive. Recommendations were made to change this policy and to develop guardianship laws that facilitate families' abilities to provide care to AIDS orphans. Family caregivers of AIDS orphans are bombarded with great demands and limited resources. This analysis of their situation from the social workers' perspective is a positive step toward the improvement of support services for these families. Further research should include individual qualitative interviews assessing the needs of the caregivers and AIDS orphans.
Prenatal loss of father during World War One is predictive of a reduced lifespan in adulthood.

PubMed

Todd, Nicolas; Valleron, Alain-Jacques; Bougnères, Pierre

2017-04-18

Although early-life stress is known to alter health, its long-term consequences on mortality remain largely unknown. Thanks to unique French legislation established in 1917 for war orphans and children of disabled soldiers, we were able to study the adult mortality of individuals born in 1914-1916 whose fathers were killed during World War 1. Vital information and socio-demographic characteristics were extracted manually from historical civil registers for 5,671 children born between 1 August 1914 and 31 December 1916 who were granted the status of " pupille de la Nation " (orphan of the Nation). We used a database comprising 1.4 million deceased soldiers to identify war orphans and collect information on their fathers and then paired each orphan with a nonorphan from the same birth register matched for date of birth, sex, and mother's age at the infant's birth. Mortality between ages 31 and 99 y was analyzed for 2,365 orphan/nonorphan pairs. The mean loss of adult lifespan of orphans who had lost their father before birth was 2.4 y (95% CI: 0.7, 3.9 y) and was the result of increased mortality before age 65 y. Adult lifespan was not reduced when the father's death occurred after the infant's birth. These results support the notion that intrauterine exposure to a major psychological maternal stress can affect human longevity.
Effects of stigma on the mental health of adolescents orphaned by AIDS.

PubMed

Cluver, Lucie D; Gardner, Frances; Operario, Don

2008-04-01

By 2010, an estimated 18.4 million children in Sub-Saharan Africa will be orphaned by AIDS. Research in South Africa shows that AIDS orphanhood is independently associated with heightened levels of psychological problems. This study is the first to explore the mediating effects of stigma and other factors operating on a community level, on associations between AIDS orphanhood and mental health. We assessed the associations of four risk factors that can potentially be addressed at a community level (bullying, stigma, community violence, and lack of positive activities) with psychological problems and orphanhood status. One thousand twenty-five participants aged 10-19 were recruited from deprived urban settlements in South Africa. The sample included adolescents orphaned by AIDS (n = 425), adolescents orphaned by non-AIDS causes (n = 241), and nonorphaned adolescents (n = 278). Participants were interviewed using standardized psychological measures of depression, anxiety, posttraumatic stress, peer problems, delinquency, and conduct problems. Information on risk factors and demographic characteristics were also assessed. AIDS-orphaned adolescents reported higher levels of stigma and fewer positive activities than other groups. There were no reported differences on bullying or community violence. All community-level risk factors were associated with poorer psychological outcomes. Multivariate analyses controlling for age and gender showed that experience of stigma significantly mediated associations between AIDS orphanhood and poor psychological outcomes. Reduction of AIDS-related stigma could potentially reduce adverse psychological outcomes among AIDS-orphaned adolescents.
Caregiver issues and AIDS orphans: perspectives from a social worker focus group.

PubMed Central

Paige, C. Y.; Johnson, M. S.

1997-01-01

This study examines social workers' perceptions of the needs of families coping with acquired immunodeficiency syndrome (AIDS). This research investigates the problems of family caregivers of children orphaned by human immunodeficiency virus (HIV)-related death of their parents. A qualitative semistructured interview format was used in a focus group of 18 social workers. Four questions were designed to assess family needs and resources, as well as to evaluate the social workers' perspectives of governmental policies affecting these families. A list of four problems and two recommendations for change evolved from the focus group. Inadequate finances to house and care for the children was the primary cause for distress in these families. The major governmental policy that hindered the social workers' ability to assist families pertained to the low financial entitlement for caregivers who are related to the orphaned child. It was noted that unrelated caregivers receive substantially more money for the care of these children than family caregivers receive. Recommendations were made to change this policy and to develop guardianship laws that facilitate families' abilities to provide care to AIDS orphans. Family caregivers of AIDS orphans are bombarded with great demands and limited resources. This analysis of their situation from the social workers' perspective is a positive step toward the improvement of support services for these families. Further research should include individual qualitative interviews assessing the needs of the caregivers and AIDS orphans. PMID:9347683
Grieving experiences amongst adolescents orphaned by AIDS: Analysis from event history calendars.

PubMed

Thupayagale-Tshweneagae, Gloria

2012-09-07

Mental health is an essential component of adolescent health and wellbeing. Mental health practitioners assess adolescents' mental health status to identify possible issues that may lead to mental health problems. However, very few of the tools used to assess the mental health status of adolescents include assessment for grieving and coping patterns. The current tools used for assessing an individual's mental health are lengthy and not comprehensive. The purpose of this study was to assess grieving patterns of adolescents orphaned by AIDS and to appraise the usefulness of an event history calendar as an assessment tool for identifying grieving experiences, in order to guide and support these adolescents through the grieving process. One hundred and two adolescents aged 14-18 years, who had been orphaned by AIDS, completed an event history calendar, reviewed it with the researcher and reported their perceptions of it. Thematic analysis of the event history calendar content revealed that it is an effective, time-efficient, adolescent-friendly tool that facilitated identification and discussion of the orphaned adolescents' grieving patterns. Crying, isolation, silence and violent outbursts were the main grieving patterns reported by adolescents orphaned by AIDS. The researcher recommends use of the event history calendar for identification of orphaned adolescents' grieving experiences. Early identification would enable mental health practitioners to support them in order to prevent the occurrence of mental illness due to maladaptive grieving.

A review of international coverage and pricing strategies for personalized medicine and orphan drugs.

PubMed

Degtiar, Irina

2017-12-01

Personalized medicine and orphan drugs share many characteristics-both target small patient populations, have uncertainties regarding efficacy and safety at payer submission, and frequently have high prices. Given personalized medicine's rising importance, this review summarizes international coverage and pricing strategies for personalized medicine and orphan drugs as well as their impact on therapy development incentives, payer budgets, and therapy access and utilization. PubMed, Health Policy Reference Center, EconLit, Google Scholar, and references were searched through February 2017 for articles presenting primary data. Sixty-nine articles summarizing 42 countries' strategies were included. Therapy evaluation criteria varied between countries, as did patient cost-share. Payers primarily valued clinical effectiveness; cost was only considered by some. These differences result in inequities in orphan drug access, particularly in smaller and lower-income countries. The uncertain reimbursement process hinders diagnostic testing. Payer surveys identified lack of comparative effectiveness evidence as a chief complaint, while manufacturers sought more clarity on payer evidence requirements. Despite lack of strong evidence, orphan drugs largely receive positive coverage decisions, while personalized medicine diagnostics do not. As more personalized medicine and orphan drugs enter the market, registries can provide better quality evidence on their efficacy and safety. Payers need systematic assessment strategies that are communicated with more transparency. Further studies are necessary to compare the implications of different payer approaches. Copyright © 2017 Elsevier B.V. All rights reserved.
Prediction and identification of sequences coding for orphan enzymes using genomic and metagenomic neighbours

PubMed Central

Yamada, Takuji; Waller, Alison S; Raes, Jeroen; Zelezniak, Aleksej; Perchat, Nadia; Perret, Alain; Salanoubat, Marcel; Patil, Kiran R; Weissenbach, Jean; Bork, Peer

2012-01-01

Despite the current wealth of sequencing data, one-third of all biochemically characterized metabolic enzymes lack a corresponding gene or protein sequence, and as such can be considered orphan enzymes. They represent a major gap between our molecular and biochemical knowledge, and consequently are not amenable to modern systemic analyses. As 555 of these orphan enzymes have metabolic pathway neighbours, we developed a global framework that utilizes the pathway and (meta)genomic neighbour information to assign candidate sequences to orphan enzymes. For 131 orphan enzymes (37% of those for which (meta)genomic neighbours are available), we associate sequences to them using scoring parameters with an estimated accuracy of 70%, implying functional annotation of 16 345 gene sequences in numerous (meta)genomes. As a case in point, two of these candidate sequences were experimentally validated to encode the predicted activity. In addition, we augmented the currently available genome-scale metabolic models with these new sequence–function associations and were able to expand the models by on average 8%, with a considerable change in the flux connectivity patterns and improved essentiality prediction. PMID:22569339
Global functional atlas of Escherichia coli encompassing previously uncharacterized proteins.

PubMed

Hu, Pingzhao; Janga, Sarath Chandra; Babu, Mohan; Díaz-Mejía, J Javier; Butland, Gareth; Yang, Wenhong; Pogoutse, Oxana; Guo, Xinghua; Phanse, Sadhna; Wong, Peter; Chandran, Shamanta; Christopoulos, Constantine; Nazarians-Armavil, Anaies; Nasseri, Negin Karimi; Musso, Gabriel; Ali, Mehrab; Nazemof, Nazila; Eroukova, Veronika; Golshani, Ashkan; Paccanaro, Alberto; Greenblatt, Jack F; Moreno-Hagelsieb, Gabriel; Emili, Andrew

2009-04-28

One-third of the 4,225 protein-coding genes of Escherichia coli K-12 remain functionally unannotated (orphans). Many map to distant clades such as Archaea, suggesting involvement in basic prokaryotic traits, whereas others appear restricted to E. coli, including pathogenic strains. To elucidate the orphans' biological roles, we performed an extensive proteomic survey using affinity-tagged E. coli strains and generated comprehensive genomic context inferences to derive a high-confidence compendium for virtually the entire proteome consisting of 5,993 putative physical interactions and 74,776 putative functional associations, most of which are novel. Clustering of the respective probabilistic networks revealed putative orphan membership in discrete multiprotein complexes and functional modules together with annotated gene products, whereas a machine-learning strategy based on network integration implicated the orphans in specific biological processes. We provide additional experimental evidence supporting orphan participation in protein synthesis, amino acid metabolism, biofilm formation, motility, and assembly of the bacterial cell envelope. This resource provides a "systems-wide" functional blueprint of a model microbe, with insights into the biological and evolutionary significance of previously uncharacterized proteins.
A roadmap for breeding orphan leafy vegetable species: a case study of Gynandropsis gynandra (Cleomaceae).

PubMed

Sogbohossou, E O Deedi; Achigan-Dako, Enoch G; Maundu, Patrick; Solberg, Svein; Deguenon, Edgar M S; Mumm, Rita H; Hale, Iago; Van Deynze, Allen; Schranz, M Eric

2018-01-01

Despite an increasing awareness of the potential of "orphan" or unimproved crops to contribute to food security and enhanced livelihoods for farmers, coordinated research agendas to facilitate production and use of orphan crops by local communities are generally lacking. We provide an overview of the current knowledge on leafy vegetables with a focus on Gynandropsis gynandra , a highly nutritious species used in Africa and Asia, and highlight general and species-specific guidelines for participatory, genomics-assisted breeding of orphan crops. Key steps in genome-enabled orphan leafy vegetables improvement are identified and discussed in the context of Gynandropsis gynandra breeding, including: (1) germplasm collection and management; (2) product target definition and refinement; (3) characterization of the genetic control of key traits; (4) design of the 'process' for cultivar development; (5) integration of genomic data to optimize that 'process'; (6) multi-environmental participatory testing and end-user evaluation; and (7) crop value chain development. The review discusses each step in detail, with emphasis on improving leaf yield, phytonutrient content, organoleptic quality, resistance to biotic and abiotic stresses and post-harvest management.
The psychological well-being of children orphaned by AIDS in Cape Town, South Africa.

PubMed

Cluver, Lucie; Gardner, Frances

2006-07-19

An estimated 2 million children are parentally bereaved by AIDS in South Africa. Little is known about mental health outcomes for this group. This study aimed to investigate mental health outcomes for urban children living in deprived settlements in Cape Town. 30 orphaned children and 30 matched controls were compared using standardised questionnaires (SDQ) on emotional and behavioural problems, peer and attention difficulties, and prosocial behaviour. The orphan group completed a modified version of a standardised questionnaire (IES-8), measuring Post-Traumatic Stress symptoms. Group differences were tested using t-tests and Pearson's chi-square. Both groups scored highly for peer problems, emotional problems and total scores. However, orphans were more likely to view themselves as having no good friends (p = .002), to have marked concentration difficulties (p = .03), and to report frequent somatic symptoms (p = .05), but were less likely to display anger through loss of temper (p = .03). Orphans were more likely to have constant nightmares (p = .01), and 73% scored above the cut-off for Post-Traumatic Stress Disorder. Findings suggest important areas for larger-scale research for parentally-bereaved children.
Fahr's Syndrome

MedlinePlus

... 55 Kenosia Avenue Danbury CT Danbury, CT 06810 orphan@rarediseases.org http://rarediseases.org Tel: 203-744- ... 55 Kenosia Avenue Danbury CT Danbury, CT 06810 orphan@rarediseases.org http://rarediseases.org Tel: 203-744- ...
Orphans and at-risk children in Haiti: vulnerabilities and human rights issues postearthquake.

PubMed

Nicholas, Patrice K; George, Erin K; Raymond, Nadia; Lewis-OʼConnor, Annie; Victoria, Stephanie; Lucien, Sergeline; Peters-Lewis, Angelleen; Hickey, Nancy; Corless, Inge B; Tyer-Viola, Lynda; Davis, Sheila M; Barry, Donna; Marcelin, Naomie; Valcourt, Roodeline

2012-01-01

The vulnerability of children in Haiti has increased dramatically since the earthquake in January 2010. Prior to the earthquake, the prevalence of orphans and at-risk children was high but since the earthquake, more than 1 million people-with more than 380,000 children remaining displaced and living in over 1200 displacement sites. These existing conditions leave orphans and at-risk children vulnerable to exploitation, abuse, and increased risk of HIV/AIDS. This article will focus on the complex issues affecting orphans and at-risk children and the intersection with HIV/AIDS and human rights. Specific recommendations by United Nations Children's Fund are discussed. Nursing in Haiti must address the policy-related and population-specific approaches for the care of children living with or affected by HIV/AIDS.
Financing drug discovery for orphan diseases.

PubMed

Fagnan, David E; Gromatzky, Austin A; Stein, Roger M; Fernandez, Jose-Maria; Lo, Andrew W

2014-05-01

Recently proposed 'megafund' financing methods for funding translational medicine and drug development require billions of dollars in capital per megafund to de-risk the drug discovery process enough to issue long-term bonds. Here, we demonstrate that the same financing methods can be applied to orphan drug development but, because of the unique nature of orphan diseases and therapeutics (lower development costs, faster FDA approval times, lower failure rates and lower correlation of failures among disease targets) the amount of capital needed to de-risk such portfolios is much lower in this field. Numerical simulations suggest that an orphan disease megafund of only US$575 million can yield double-digit expected rates of return with only 10-20 projects in the portfolio. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.
A situational analysis of child-headed households in South Africa.

PubMed

Mogotlane, S M; Chauke, M E; van Rensburg, G H; Human, S P; Kganakga, C M

2010-09-01

The aftermath of the HIV and AIDS pandemic has resulted in great suffering in terms of loss of income, poor quality of life, morbidity and mortality, with children being destitute and orphaned at an alarming rapid rate. Families and communities are currently unable to cope with the effects of HIV and AIDS with special emphasis on the care and support of the affected orphans and vulnerable children, who as a result have been compelled to look after themselves giving rise to a new type of family, the child-headed household. The emergence of this type of family requires government's response in terms of care and support. The purpose of this study was to provide a broad picture of the location, prevalence, composition, functions, needs and challenges of child-headed households in South Africa, and explore available and required services, resources and safety nets for children in child-headed households. An exploratory and descriptive design was used for the purpose. The sample consisted of children heading households and those living in the households that are headed by children; government departments responsible for child welfare, such as, the Departments of Social Development, Health, Education and Agriculture; non-profit organisations and communities where these households are predominant. From the data collected, it was found that the rights of the affected children were compromised. Those heading the households were often not at school and were responsible for domestic chores. The households needed food, clothes, money, shelter, and education. Government in attempting to address these needs required clear policies which will provide a distinction between orphaned and vulnerable children and child-headed households. The study recommended a collaborative approach as it was shown that there was no single model of best practice to appropriately and effectively address the needs of child-headed households.
Towards a framework for personalized healthcare: lessons learned from the field of rare diseases.

PubMed

Tambuyzer, Erik

2010-09-01

A large percentage of medicines do not work for the patient populations they are intended to treat. Increased knowledge regarding genomics and the underlying biological mechanism of diseases should help us be able to stratify patients into groups of likely responders and nonresponders, and to identify those patients for whom a treatment might do more harm than good. This article sets out different policy perspectives for the healthcare systems, and draws in on 25 years of particular experience from the rare disease and orphan drug field, to illuminate the pathway forward in relation to key implementation aspects of personalized healthcare. In principle, we submit that targeting medicines to preidentified groups for whom we can predict a beneficial outcome is a good thing for everyone - first of all for the patients, but also for all the other stakeholders, including payers, treating physicians and industry - because it has the potential to create sustainable and functioning healthcare systems directed to better health and prevention of disease. Personalized healthcare over time could also lead to shorter drug-development times because of lower rates of failure in late-stage drug development. Using orphan medicines to treat well-diagnosed patients suffering from a life-threatening or seriously debilitating rare disease, is an attempt to work according to these principles. As there is much that needs to be done to turn the promise into reality, we need to identify the barriers and challenges to transform the potential opportunities into real-life benefits, and what needs to be done in order to overcome them. Learning from the field of rare diseases and orphan drugs may provide, perhaps unexpectedly, some of the answers to public policy questions related to future (personalized) healthcare, but of course not all aspects, are common between the two fields.
Orphan therapies: making best use of postmarket data.

PubMed

Maro, Judith C; Brown, Jeffrey S; Dal Pan, Gerald J; Li, Lingling

2014-08-01

Postmarket surveillance of the comparative safety and efficacy of orphan therapeutics is challenging, particularly when multiple therapeutics are licensed for the same orphan indication. To make best use of product-specific registry data collected to fulfill regulatory requirements, we propose the creation of a distributed electronic health data network among registries. Such a network could support sequential statistical analyses designed to detect early warnings of excess risks. We use a simulated example to explore the circumstances under which a distributed network may prove advantageous. We perform sample size calculations for sequential and non-sequential statistical studies aimed at comparing the incidence of hepatotoxicity following initiation of two newly licensed therapies for homozygous familial hypercholesterolemia. We calculate the sample size savings ratio, or the proportion of sample size saved if one conducted a sequential study as compared to a non-sequential study. Then, using models to describe the adoption and utilization of these therapies, we simulate when these sample sizes are attainable in calendar years. We then calculate the analytic calendar time savings ratio, analogous to the sample size savings ratio. We repeat these analyses for numerous scenarios. Sequential analyses detect effect sizes earlier or at the same time as non-sequential analyses. The most substantial potential savings occur when the market share is more imbalanced (i.e., 90% for therapy A) and the effect size is closest to the null hypothesis. However, due to low exposure prevalence, these savings are difficult to realize within the 30-year time frame of this simulation for scenarios in which the outcome of interest occurs at or more frequently than one event/100 person-years. We illustrate a process to assess whether sequential statistical analyses of registry data performed via distributed networks may prove a worthwhile infrastructure investment for pharmacovigilance.
Neuroleptic Malignant Syndrome

MedlinePlus

... 55 Kenosia Avenue Danbury CT Danbury, CT 06810 orphan@rarediseases.org http://rarediseases.org Tel: 203-744- ... 55 Kenosia Avenue Danbury CT Danbury, CT 06810 orphan@rarediseases.org http://rarediseases.org Tel: 203-744- ...
Why Assembling Plant Genome Sequences Is So Challenging

PubMed Central

Claros, Manuel Gonzalo; Bautista, Rocío; Guerrero-Fernández, Darío; Benzerki, Hicham; Seoane, Pedro; Fernández-Pozo, Noé

2012-01-01

In spite of the biological and economic importance of plants, relatively few plant species have been sequenced. Only the genome sequence of plants with relatively small genomes, most of them angiosperms, in particular eudicots, has been determined. The arrival of next-generation sequencing technologies has allowed the rapid and efficient development of new genomic resources for non-model or orphan plant species. But the sequencing pace of plants is far from that of animals and microorganisms. This review focuses on the typical challenges of plant genomes that can explain why plant genomics is less developed than animal genomics. Explanations about the impact of some confounding factors emerging from the nature of plant genomes are given. As a result of these challenges and confounding factors, the correct assembly and annotation of plant genomes is hindered, genome drafts are produced, and advances in plant genomics are delayed. PMID:24832233
Evolution of the nuclear receptor superfamily: early diversification from an ancestral orphan receptor.

PubMed

Laudet, V

1997-12-01

From a database containing the published nuclear hormone receptor (NR) sequences I constructed an alignment of the C, D and E domains of these molecules. Using this alignment, I have performed tree reconstruction using both distance matrix and parsimony analysis. The robustness of each branch was estimated using bootstrap resampling methods. The trees constructed by these two methods gave congruent topologies. From these analyses I defined six NR subfamilies: (i) a large one clustering thyroid hormone receptors (TRs), retinoic acid receptors (RARs), peroxisome proliferator-activated receptors (PPARs), vitamin D receptors (VDRs) and ecdysone receptors (EcRs) as well as numerous orphan receptors such as RORs or Rev-erbs; (ii) one containing retinoid X receptors (RXRs) together with COUP, HNF4, tailless, TR2 and TR4 orphan receptors; (iii) one containing steroid receptors; (iv) one containing the NGFIB orphan receptors; (v) one containing FTZ-F1 orphan receptors; and finally (vi) one containing to date only one gene, the GCNF1 orphan receptor. The relationships between the six subfamilies are not known except for subfamilies I and IV which appear to be related. Interestingly, most of the liganded receptors appear to be derived when compared with orphan receptors. This suggests that the ligand-binding ability of NRs has been gained by orphan receptors during the course of evolution to give rise to the presently known receptors. The distribution into six subfamilies correlates with the known abilities of the various NRs to bind to DNA as homo- or heterodimers. For example, receptors heterodimerizing efficiently with RXR belong to the first or the fourth subfamilies. I suggest that the ability to heterodimerize evolved once, just before the separation of subfamilies I and IV and that the first NR was able to bind to DNA as a homodimer. From the study of NR sequences existing in vertebrates, arthropods and nematodes, I define two major steps of NR diversification: one that took place very early, probably during the multicellularization event leading to all the metazoan phyla, and a second occurring later on, corresponding to the advent of vertebrates. Finally, I show that in vertebrate species the various groups of NRs accumulated mutations at very different rates.
21 CFR 316.50 - Guidance documents.

Code of Federal Regulations, 2010 CFR

2010-04-01

... USE ORPHAN DRUGS Availability of Information § 316.50 Guidance documents. FDA's Office of Orphan... the regulations in this part. The list is maintained on the Internet and is published annually in the...
Three Tracks on the Orphan Train.

ERIC Educational Resources Information Center

Tyson, Edith S.

1992-01-01

Discusses the "Orphan Train" (homeless children in the midnineteenth-century United States sent to new homes in the west by the Children's Aid Society of New York) through three different literary perspectives. (RS)
What Can Big Data Offer the Pharmacovigilance of Orphan Drugs?

PubMed

Price, John

2016-12-01

The pharmacovigilance of drugs for orphan diseases presents problems related to the small patient population. Obtaining high-quality information on individual reports of suspected adverse reactions is of particular importance for the pharmacovigilance of orphan drugs. The possibility of mining "big data" to detect suspected adverse reactions is being explored in pharmacovigilance generally but may have limited application to orphan drugs. Sources of big data such as social media may be infrequently used as communication channels by patients with rare disease or their caregivers or by health care providers; any adverse reactions identified are likely to reflect what is already known about the safety of the drug from the network of support that grows up around these patients. Opportunities related to potential future big data sources are discussed. Copyright © 2016 Elsevier HS Journals, Inc. All rights reserved.
Rapid Identification of Sequences for Orphan Enzymes to Power Accurate Protein Annotation

PubMed Central

Ojha, Sunil; Watson, Douglas S.; Bomar, Martha G.; Galande, Amit K.; Shearer, Alexander G.

2013-01-01

The power of genome sequencing depends on the ability to understand what those genes and their proteins products actually do. The automated methods used to assign functions to putative proteins in newly sequenced organisms are limited by the size of our library of proteins with both known function and sequence. Unfortunately this library grows slowly, lagging well behind the rapid increase in novel protein sequences produced by modern genome sequencing methods. One potential source for rapidly expanding this functional library is the “back catalog” of enzymology – “orphan enzymes,” those enzymes that have been characterized and yet lack any associated sequence. There are hundreds of orphan enzymes in the Enzyme Commission (EC) database alone. In this study, we demonstrate how this orphan enzyme “back catalog” is a fertile source for rapidly advancing the state of protein annotation. Starting from three orphan enzyme samples, we applied mass-spectrometry based analysis and computational methods (including sequence similarity networks, sequence and structural alignments, and operon context analysis) to rapidly identify the specific sequence for each orphan while avoiding the most time- and labor-intensive aspects of typical sequence identifications. We then used these three new sequences to more accurately predict the catalytic function of 385 previously uncharacterized or misannotated proteins. We expect that this kind of rapid sequence identification could be efficiently applied on a larger scale to make enzymology’s “back catalog” another powerful tool to drive accurate genome annotation. PMID:24386392
Hunting the parent of the Orphan stream. II. The first high-resolution spectroscopic study

DOE Office of Scientific and Technical Information (OSTI.GOV)

Casey, Andrew R.; Keller, Stefan C.; Da Costa, Gary

2014-03-20

We present the first high-resolution spectroscopic study on the Orphan stream for five stream candidates, observed with the Magellan Inamori Kyocera Echelle spectrograph on the Magellan Clay telescope. The targets were selected from the low-resolution catalog of Casey et al.: three high-probability members, one medium, and one low-probability stream candidate were observed. Our analysis indicates that the low- and medium-probability targets are metal-rich field stars. The remaining three high-probability targets range over ∼1 dex in metallicity, and are chemically distinct compared to the other two targets and all standard stars: low [α/Fe] abundance ratios are observed, and lower limits aremore » ascertained for [Ba/Y], which sit well above the Milky Way trend. These chemical signatures demonstrate that the undiscovered parent system is unequivocally a dwarf spheroidal galaxy, consistent with dynamical constraints inferred from the stream width and arc. As such, we firmly exclude the proposed association between NGC 2419 and the Orphan stream. A wide range in metallicities adds to the similarities between the Orphan stream and Segue 1, although the low [α/Fe] abundance ratios in the Orphan stream are in tension with the high [α/Fe] values observed in Segue 1. Open questions remain before Segue 1 could possibly be claimed as the 'parent' of the Orphan stream. The parent system could well remain undiscovered in the southern sky.« less
Orphan immunotherapies for allergic diseases.

PubMed

Ridolo, Erminia; Montagni, Marcello; Incorvaia, Cristoforo; Senna, Gianenrico; Passalacqua, Giovanni

2016-03-01

As confirmed by systematic reviews and meta-analyses, allergen immunotherapy is clinically effective in the treatment of allergic diseases. In particular, subcutaneous immunotherapy is a pivotal treatment in patients with severe reactions to Hymenoptera venom, whereas subcutaneous immunotherapy and sublingual immunotherapy are indicated in the treatment of allergic rhinitis and asthma by inhalant allergens. Other allergies related to animal dander (other than cat, which is the most studied), such as dog, molds, occupational allergens, and insects, have also been recognized. For these allergens, immunotherapy is poorly studied and often unavailable. Thus, use of the term orphan immunotherapies is appropriate. We used MEDLINE to search the medical literature for English-language articles. Randomized, controlled, masked studies for orphan immunotherapies were selected. In the remaining cases, the available reports were described. The literature on food desensitization is abundant, but for other orphan allergens, such as mosquito, Argas reflexus, dog, or occupational allergens, there are only a few studies, and most are small studies or case reports. Orphan immunotherapy is associated with insufficient evidence of efficacy from controlled trials, an erroneous belief of the limited importance of some allergen sources, and the unlikelihood for producers to have a profit in making commercially available extracts (with an expensive process for registration) to be used in few patients. It should be taken into consideration that adequate preparations should be available also for orphan allergens. Copyright © 2016 American College of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.

Legal assessment of current situation on orphan patients in Lithuania.

PubMed

Spokiene, Indre

2008-01-01

After Lithuania joined the European Union, the Regulation (EC) No. 141/2000 on orphan medicinal products and Commission Regulation (EC) No. 847/2000 came into force as part of national legislation. Member States must adopt specific measures to increase knowledge on rare diseases and to improve their detection, diagnosis, and treatment. The aim of this article was to present and to assess the current legal situation on orphan patients and their treatment in Lithuania, to identify legislation gaps, and to propose some ideas how to facilitate the solution of the existing problems in this field. For this purpose, European Union and Lithuanian legal documents on rare medicinal products are examined using a comparative method. With reference to inventory of Member States' incentives for rare diseases in national level, the most important issues, which orphan patients face to in Lithuania, are singled out. In Lithuania, the situation of orphan patients in terms of protection of patient rights is insufficiently determined. The access to effective health care services or approved therapies in some cases is restricted. Working relationships between genetic services and various clinical specialists as well as with those in primary care are not legally determined; the number of clinical trials aimed at orphan medicinal products is low. These results suggest a need for awareness raising among Lithuanian Government, health care specialists, patient organizations about the importance to improve practical implementation of European Union legislation and progressive experience of some European countries in this field.
Rapid identification of sequences for orphan enzymes to power accurate protein annotation.

PubMed

Ramkissoon, Kevin R; Miller, Jennifer K; Ojha, Sunil; Watson, Douglas S; Bomar, Martha G; Galande, Amit K; Shearer, Alexander G

2013-01-01

The power of genome sequencing depends on the ability to understand what those genes and their proteins products actually do. The automated methods used to assign functions to putative proteins in newly sequenced organisms are limited by the size of our library of proteins with both known function and sequence. Unfortunately this library grows slowly, lagging well behind the rapid increase in novel protein sequences produced by modern genome sequencing methods. One potential source for rapidly expanding this functional library is the "back catalog" of enzymology--"orphan enzymes," those enzymes that have been characterized and yet lack any associated sequence. There are hundreds of orphan enzymes in the Enzyme Commission (EC) database alone. In this study, we demonstrate how this orphan enzyme "back catalog" is a fertile source for rapidly advancing the state of protein annotation. Starting from three orphan enzyme samples, we applied mass-spectrometry based analysis and computational methods (including sequence similarity networks, sequence and structural alignments, and operon context analysis) to rapidly identify the specific sequence for each orphan while avoiding the most time- and labor-intensive aspects of typical sequence identifications. We then used these three new sequences to more accurately predict the catalytic function of 385 previously uncharacterized or misannotated proteins. We expect that this kind of rapid sequence identification could be efficiently applied on a larger scale to make enzymology's "back catalog" another powerful tool to drive accurate genome annotation.
Reconsidering the orphan problem: the emergence of male caregivers in Lesotho.

PubMed

Block, Ellen

2016-01-01

Care for AIDS orphans in southern Africa is frequently characterized as a "crisis", where kin-based networks of care are thought to be on the edge of collapse. Yet these care networks, though strained by AIDS, are still the primary mechanisms for orphan care, in large part because of the essential role grandmothers play in responding to the needs of orphans. Ongoing demographic shifts as a result of HIV/AIDS and an increasingly feminized labor market continue to disrupt and alter networks of care for orphans and vulnerable children. This paper examines the emergence of a small but growing number of male caregivers who are responding to the needs of the extended family. While these men are still few in number, the strength of gendered ideologies of female care means that this group of men is socially, if not statistically significant. Men continue to be considered caregivers of last resort, but their care will close a small but growing gap that threatens to undermine kin-based networks of care in Lesotho and across the region. The adaptation of gender roles reinforces the strength and resilience of kinship networks even when working against deeply entrenched ideas about gendered division of domestic labor.
Delayed access to treatments for rare diseases: who's to blame?

PubMed

Feltmate, Karen; Janiszewski, Peter M; Gingerich, Sheena; Cloutier, Michael

2015-04-01

The development and commercialization of drugs for rare diseases, termed 'orphan drugs', has historically been economically unattractive. However, because of the introduction of legislation that provides financial and regulatory incentives for the development of orphan drugs, new developments are making their way through the regulatory approval processes. Unfortunately, delays in availability of new drugs for treating rare disease continue to persist. This paper reviews the approach of several regulatory jurisdictions to orphan drugs in an effort to determine their relative effectiveness in providing patient access. Generally speaking, regulatory authorities across jurisdictions have recognized the need to enhance timely access to safe, effective treatment for patients with rare diseases and have been able to shift the approval timelines for access to new care. The greater impediment to orphan drug access appears to be funding, particularly in publicly sponsored health-care systems. Redundancies in federal and provincial reviews of orphan drugs can result in significant delays in access to new drugs. Clearly, more must be done to accelerate access to the treatments so desperately needed by patients. Public payers must be held accountable for their process and decisions--especially for rare disease therapies. © 2015 Asian Pacific Society of Respirology.
Variation in levels of anxiety to dental treatment among nonorphan and orphan children living under different systems.

PubMed

Chikkala, Jayanth; Chandrabhatla, Srinivas Kumar; Vanga, Narasimha Rao V

2015-08-01

It is essential to understand the factors influencing the level of anxiety to dental treatment among different children as it can influence seeking dental care. Here, we assessed the impact of parental loss on dental anxiety among 6-13-year-old children. A total of 444 children within the age group 6-13 years were selected. Group 1 consisted of orphan children living in government-run orphanages, Group 2 consisted of orphan children taken care by a person with a motherly relationship, Group 3 consisted of abandoned children living in private organization and Group 4 consisted of children living with their parents. Dental anxiety was measured using children's fear survey schedule-dental subscale and modified faces version of modified child dental anxiety scale. The highest number of anxious children were observed in Group 4 and the difference in the anxiety levels among the four groups was found to be highly statistically significant. Children living in government-run orphanages had least dental anxiety. All the orphans may not have the same anxiety levels and the environment of upbringing the orphans plays a significant role in the development of the anxiety.
The psychological well-being of children orphaned by AIDS in Cape Town, South Africa

PubMed Central

Cluver, Lucie; Gardner, Frances

2006-01-01

Background An estimated 2 million children are parentally bereaved by AIDS in South Africa. Little is known about mental health outcomes for this group. Methods This study aimed to investigate mental health outcomes for urban children living in deprived settlements in Cape Town. 30 orphaned children and 30 matched controls were compared using standardised questionnaires (SDQ) on emotional and behavioural problems, peer and attention difficulties, and prosocial behaviour. The orphan group completed a modified version of a standardised questionnaire (IES-8), measuring Post-Traumatic Stress symptoms. Group differences were tested using t-tests and Pearson's chi-square. Results Both groups scored highly for peer problems, emotional problems and total scores. However, orphans were more likely to view themselves as having no good friends (p = .002), to have marked concentration difficulties (p = .03), and to report frequent somatic symptoms (p = .05), but were less likely to display anger through loss of temper (p = .03). Orphans were more likely to have constant nightmares (p = .01), and 73% scored above the cut-off for Post-Traumatic Stress Disorder. Conclusion Findings suggest important areas for larger-scale research for parentally-bereaved children. PMID:16848910
Effect of Economic Assets on Sexual Risk-Taking Intentions Among Orphaned Adolescents in Uganda

PubMed Central

Han, Chang-Keun; Neilands, Torsten B.; Ismayilova, Leyla; Sperber, Elizabeth

2010-01-01

Objectives. We examined the effect of economic assets on sexual risk-taking intentions among school-going AIDS-orphaned adolescents in rural Uganda. Methods. AIDS-orphaned adolescents from 15 comparable schools were randomly assigned to control (n = 133) or treatment (n = 127) conditions. Treatment participants received child savings accounts, workshops, and mentorship. This economic intervention was in addition to the traditional care and support services for school-going orphaned adolescents (counseling and school supplies) provided to both treatment and control groups. Adolescents in the treatment condition were compared with adolescents in the control condition at baseline and at 10 months after the intervention. Results. After control for sociodemographic factors, child-caregiver/parental communication, and peer pressure, adolescents in the economic intervention group reported a significant reduction in sexual risk-taking intentions compared with adolescents in the control condition. Conclusions. The findings indicate that in Uganda, a country devastated by poverty and disease (including HIV/AIDS), having access to economic assets plays an important role in influencing adolescents' sexual risk-taking intentions. These findings have implications for the care and support of orphaned adolescents, especially in poor African countries devastated by poverty and sexually transmitted diseases. PMID:20075323
U.S. Government and Partners: Working Together on a Comprehensive, Coordinated and Effective Response to Highly Vulnerable Children. Third Annual Report to Congress on Public Law 109-95, the Assistance for Orphans and Other Vulnerable Children in Developing Countries Act of 2005

ERIC Educational Resources Information Center

US Agency for International Development, 2009

2009-01-01

Public Law 109-95, the Assistance for Orphans and Other Vulnerable Children in Developing Countries Act of 2005 (hereinafter, referred to as PL 109-95), was signed into law four years ago to respond to the global orphans and vulnerable children crisis. It calls for the U.S. Government (USG) response to the crisis to be comprehensive, coordinated…
Challenges in linking health research to policy: a commentary on developing a multi-stakeholder response to orphans and vulnerable children in Ghana.

PubMed

Gyapong, John Owusu; Selby, Richmond Ato; Anakwah, Kwadwo Antwi

2011-06-16

The Research and Development Division (RDD) of the Ghana Health Service (GHS) has a remit to build research capacity and conduct policy relevant research. By being situated within the GHS, RDD has good access to directors and programme managers, within and beyond the Ministry of Health. This structure has been facilitating collaboration through research cycles for 20 years, from agenda setting to discussions on policy relevance.This approach has been applied to research activities within the Addressing the Balance of Burden in AIDS (ABBA) Research Programme Consortium to tackle the challenges facing HIV affected orphans and vulnerable children (OVCs). The government strategy on OVCs recommends they should be encouraged to live in their home communities rather than in institutions. We present lessons here on efforts to use research to build a response across different agencies to address the problems that communities and families face in caring for these children in their communities.This approach to building consensus on research priorities points to the value of collaboration and dialogue with multiple stakeholders as a means of fostering ownership of a research process and supporting the relevance of research to different groups. Our experience has shown that if the context within which researchers, policy makers and stakeholders work were better understood, the links between them were improved and research were communicated more effectively, then better policy making which links across different sectors may follow. At the same time, collaboration among these different stakeholders to ensure that research meets social needs, must also satisfy the requirements of scientific rigour.
Multi-Criteria Decision Analysis for Assessment and Appraisal of Orphan Drugs.

PubMed

Iskrov, Georgi; Miteva-Katrandzhieva, Tsonka; Stefanov, Rumen

2016-01-01

Limited resources and expanding expectations push all countries and types of health systems to adopt new approaches in priority setting and resources allocation. Despite best efforts, it is difficult to reconcile all competing interests, and trade-offs are inevitable. This is why multi-criteria decision analysis (MCDA) has played a major role in recent uptake of value-based reimbursement. MCDA framework enables exploration of stakeholders' preferences, as well as explicit organization of broad range of criteria on which real-world decisions are made. Assessment and appraisal of orphan drugs tend to be one of the most complicated health technology assessment (HTA) tasks. Access to market approved orphan therapies remains an issue. Early constructive dialog among rare disease stakeholders and elaboration of orphan drug-tailored decision support tools could set the scene for ongoing accumulation of evidence, as well as for proper reimbursement decision-making. The objective of this study was to create an MCDA value measurement model to assess and appraise orphan drugs. This was achieved by exploring the preferences on decision criteria's weights and performance scores through a stakeholder-representative survey and a focus group discussion that were both organized in Bulgaria. Decision criteria that describe the health technology's characteristics were unanimously agreed as the most important group of reimbursement considerations. This outcome, combined with the high individual weight of disease severity and disease burden criteria, underlined some of the fundamental principles of health care - equity and fairness. Our study proved that strength of evidence may be a key criterion in orphan drug assessment and appraisal. Evidence is used not only to shape reimbursement decision-making but also to lend legitimacy to policies pursued. The need for real-world data on orphan drugs was largely stressed. Improved knowledge on MCDA feasibility and integration to HTA is of paramount importance, as progress in medicine and innovative health technologies should correspond to patient, health-care system, and societal values.
[Genetic mutation databases: stakes and perspectives for orphan genetic diseases].

PubMed

Humbertclaude, V; Tuffery-Giraud, S; Bareil, C; Thèze, C; Paulet, D; Desmet, F-O; Hamroun, D; Baux, D; Girardet, A; Collod-Béroud, G; Khau Van Kien, P; Roux, A-F; des Georges, M; Béroud, C; Claustres, M

2010-10-01

New technologies, which constantly become available for mutation detection and gene analysis, have contributed to an exponential rate of discovery of disease genes and variation in the human genome. The task of collecting and documenting this enormous amount of data in genetic databases represents a major challenge for the future of biological and medical science. The Locus Specific Databases (LSDBs) are so far the most efficient mutation databases. This review presents the main types of databases available for the analysis of mutations responsible for genetic disorders, as well as open perspectives for new therapeutic research or challenges for future medicine. Accurate and exhaustive collection of variations in human genomes will be crucial for research and personalized delivery of healthcare. Copyright © 2009 Elsevier Masson SAS. All rights reserved.
Lifetime incidences of traumatic events and mental health among children affected by HIV/AIDS in rural China.

PubMed

Li, Xiaoming; Barnett, Douglas; Fang, Xiaoyi; Lin, Xiuyun; Zhao, Guoxiang; Zhao, Junfeng; Hong, Yan; Zhang, Liying; Naar-King, Sylvie; Stanton, Bonita

2009-09-01

Cross-sectional data were gathered from 1,625 children (M age = 12.85, SD = 2.21) which included 755 AIDS orphans, 466 vulnerable children, and 404 comparison children. Participants completed self-report measures of exposure to traumatic events, and psychosocial adjustment including behavior problems, depression, self-esteem, and future orientation. AIDS orphans and vulnerable children reported experiencing a higher total occurrence, density, duration, initial impact and lasting impact of traumatic events compared to comparison children. Scores reflecting adjustment were lower among orphans and vulnerable children than among comparison children. Both orphan status and traumatic events contributed unique variance in the expected direction to the prediction of psychosocial adjustment. The data in the current study suggested that children affected by HIV/AIDS in China are exposed to more trauma and suffer more adjustment problems than children who do not experience HIV/AIDS in their families.
The new adult orphan: issues and considerations for health care professionals.

PubMed

McDaniel, J Goodlett; Clark, Paul G

2009-12-01

The death of the last parent has a profound effect on survivors. Health care workers are often the first source of anticipatory guidance for newly orphaned adults as they cope with grief, loss, and awareness that their lives are forever changed. It is estimated that more than 80 million Americans were born between 1946 and 1964. As this Baby Boomer generation, often defined as seeing themselves as culturally special, becomes "orphaned," they may be less aware, less prepared, and less supported than any previous group of Americans regarding this life event. For a number of adults, the loss creates many unexpected results that can destabilize life in profound ways. This article describes the unique new realities of helping adult orphans as they relate to health care providers and discusses the problems associated with prolonged and complicated grief. Implications for geriatric caregivers, mental health providers, health educators, and others are proposed. Copyright 2009, SLACK Incorporated.
Cellular and molecular biology of orphan G protein-coupled receptors.

PubMed

Oh, Da Young; Kim, Kyungjin; Kwon, Hyuk Bang; Seong, Jae Young

2006-01-01

The superfamily of G protein-coupled receptors (GPCRs) is the largest and most diverse group of membrane-spanning proteins. It plays a variety of roles in pathophysiological processes by transmitting extracellular signals to cells via heterotrimeric G proteins. Completion of the human genome project revealed the presence of approximately 168 genes encoding established nonsensory GPCRs, as well as 207 genes predicted to encode novel GPCRs for which the natural ligands remained to be identified, the so-called orphan GPCRs. Eighty-six of these orphans have now been paired to novel or previously known molecules, and 121 remain to be deorphaned. A better understanding of the GPCR structures and classification; knowledge of the receptor activation mechanism, either dependent on or independent of an agonist; increased understanding of the control of GPCR-mediated signal transduction; and development of appropriate ligand screening systems may improve the probability of discovering novel ligands for the remaining orphan GPCRs.
Increasing human Th17 differentiation through activation of orphan nuclear receptor retinoid acid-related orphan receptor γ (RORγ) by a class of aryl amide compounds.

PubMed

Zhang, Wei; Zhang, Jing; Fang, Leiping; Zhou, Ling; Wang, Shuai; Xiang, Zhijun; Li, Yuan; Wisely, Bruce; Zhang, Guifeng; An, Gang; Wang, Yonghui; Leung, Stewart; Zhong, Zhong

2012-10-01

In a screen for small-molecule inhibitors of retinoid acid-related orphan receptor γ (RORγ), we fortuitously discovered that a class of aryl amide compounds behaved as functional activators of the interleukin 17 (IL-17) reporter in Jurkat cells. Three of these compounds were selected for further analysis and found to activate the IL-17 reporter with potencies of ∼0.1 μM measured by EC₅₀. These compounds were shown to directly bind to RORγ by circular dichroism-based thermal stability experiments. Furthermore, they can enhance an in vitro Th17 differentiation process in human primary T cells. As RORγ remains an orphan nuclear receptor, discovery of these aryl amide compounds as functional agonists will now provide pharmacological tools for us to dissect functions of RORγ and facilitate drug discovery efforts for immune-modulating therapies.
Inclusiveness: a mental health strategy for preventing future mental health problems among adolescents orphaned by AIDS.

PubMed

Thupayagale-Tshweneagae, G; Mokomane, Z

2012-10-01

The purpose of this paper is to raise an argument that inclusiveness will lessen the pain of losing a parent among adolescents orphaned by AIDS and as a result, prevent future mental health problems that may occur because of inappropriate grieving and maladaptive coping strategies. Participation of adolescents orphaned by AIDS in decisions pertaining to their parents' illnesses and funeral arrangements, for example, may shorten the grieving process and allow for closure. The paper draws data from focus group discussions that were held with 15 adolescents orphaned by AIDS in urban South Africa. The focus group discussions that were structured around four themes: grieving patterns; coping strategies; experience with loss; and expectations. The results of the study demonstrate inclusiveness as an overarching factor in the healing process. The concept is thus a strong recommendation for mental health practice and further study. © 2011 Blackwell Publishing.
"Retirement lost"-the new role of the elderly as caretakers for orphans in Western Kenya.

PubMed

Nyambedha, Erick O; Wandibba, Simiyu; Aagaard-Hansen, Jens

2003-03-01

A study on the new role of the elderly as caretakers of orphans was conducted in a rural part of Kenya applying a combination of qualitative and quantitative methods. One out of three children had lost at least one biological parent and one of nine had lost both. These figures are increasing exponentially. Most orphans were cared for by relatives, and about one out of five caretakers was 55 years of age or above. These elderly caretakers faced major difficulties in caring for the orphans in terms of schooling, food and medical care. There is a major difference between the present hardships of these caretakers and the traditional position of the elderly in the past. This dramatic deterioration in the situation of the elderly should be seen in the context of the rampant HIV/AIDS epidemic, population growth, changing socio-cultural values, and unfavourable macroeconomic trends.
Determinants of Primary School Non-Enrollment and Absenteeism: Results from a Retrospective, Convergent Mixed Methods, Cohort Study in Rural Western Kenya

PubMed Central

King, Nia; Dewey, Cate; Borish, David

2015-01-01

Background Education is a key element in the socioeconomic development required to improve quality of life in Kenya. Despite the introduction of free primary education, primary school enrollment and attendance levels remain low. Drawing on qualitative and quantitative data, this study explores the determinants of non-enrollment and absenteeism in rural western Kenya and potential mitigation strategies to address these issues. Methods The study was conducted in Bwaliro village in rural western Kenya. A random sample of 64 students was obtained by blocking the village primary school’s student population according to grade level, gender, and orphan status. Qualitative and quantitative data were collected through interviews with parents, guardians, and key informants, and focus group discussions with students. Quantitative data were compared using chi-square tests, Student’s T-test, and Poisson regressions. Qualitative data were analyzed using thematic content analysis. Results Malaria, menstruation, and lack of money were among the most notable determinants of primary school dropout and absenteeism, and these factors disproportionately impacted orphans and female students. Potential mitigation strategies suggested by the community included provision of malaria treatment or prevention, reduction in education costs, expansion of the established school-feeding program, and provision of sanitary pads. Conclusion Despite free primary education, numerous factors continue to prevent children in rural western Kenya from attending primary school. The findings suggest that interventions should primarily target orphaned and female students. Prior to implementation, suggested mitigation strategies should be assessed for cost-effectiveness. PMID:26371885
Evidence of alterations in the expression of orphan receptors GPR26 and GPR39 due to the etiology of the metabolic syndrome.

PubMed

Romero-Nava, Rodrigo; Zhou, De-Shan; García, Noemí; Ruiz-Hernández, Armando; Si, Yin-Chu; Sánchez-Muñoz, Fausto; Huang, Fengyang; Hong, Enrique; Villafaña, Santiago

2017-08-01

Metabolic syndrome (MS) is composed of several metabolic abnormalities that increase the risk of cardiovascular diseases and diabetes. Although there are treatments for the components of MS, this pathology maintains a high mortality, suggesting that there are other mechanisms in which orphan receptors such as GPR26 and GPR39 may be involved. For this reason, the aim of this work was to evaluate the expression of GPR26 and GPR39 orphan receptors in two models of MS (diet and genetics). We used male Wistar rats, which received 70% fructose in drinking water for 9 weeks, and obese Zucker rats. We measured weight, blood pressure, glucose, triglycerides, total cholesterol, HDL cholesterol, LDL cholesterol to determine the MS and the expression of the orphan receptors GPR26 and GPR39 in brain, heart, aorta, liver, and kidney by RT-PCR. The analysis of the expression of the orphan receptors GPR26 and GPR39 showed that the receptors are expressed in some tissues, but the expression of the GPR26 tends to decrease in the heart and aorta, whereas in the brain, no changes were observed, this receptor is not expressed in the liver and kidney of both strains. The expression of GPR39 isoforms depends on the tissue and MS model. We conclude that the orphan receptors GPR26, GPR39v1, and GPR39v2 are expressed in different tissues and their profile expression is dependent on the etiology of the MS.
Tlx, an orphan nuclear receptor, regulates cell numbers and astrocyte development in the developing retina.

PubMed

Miyawaki, Takaya; Uemura, Akiyoshi; Dezawa, Mari; Yu, Ruth T; Ide, Chizuka; Nishikawa, Shinichi; Honda, Yoshihito; Tanabe, Yasuto; Tanabe, Teruyo

2004-09-15

Tlx belongs to a class of orphan nuclear receptors that underlies many aspects of neural development in the CNS. However, the fundamental roles played by Tlx in the control of eye developmental programs remain elusive. By using Tlx knock-out (KO) mice, we show here that Tlx is expressed by retinal progenitor cells in the neuroblastic layer during the period of retinal layer formation, and it is critical for controlling the generation of appropriate numbers of retinal progenies through the activities of cell cycle-related molecules, cyclin D1 and p27Kip1. Tlx expression is restricted to Müller cells in the mature retina and appears to control their proper development. Furthermore, we show that Tlx is expressed by immature astrocytes that migrate from the optic nerve onto the inner surface of the retina and is required for their generation and maturation, as assessed by honeycomb network formation and expression of R-cadherin, a critical component for vasculogenesis. The impaired astrocyte network formation on the inner retinal surface is accompanied by the loss of vasculogenesis in Tlx KO retinas. Our studies thus indicate that Tlx underlies a fundamental developmental program of retinal organization and controls the generation of the proper numbers of retinal progenies and development of glial cells during the protracted period of retinogenesis.

Gender and the Effects of an Economic Empowerment Program on Attitudes Toward Sexual Risk-Taking Among AIDS-Orphaned Adolescent Youth in Uganda

PubMed Central

Ssewamala, Fred; Ismayilova, Leyla; McKay, Mary; Sperber, Elizabeth; Bannon, William; Alicea, Stacey

2009-01-01

Purpose This paper examines gender differences in attitudes towards sexual risk-taking behaviors of AIDS-orphaned youth participating in a randomized control trial testing an economic empowerment intervention in rural Uganda. Methods Adolescents (average age 13.7 years) who had lost one or both parents to AIDS from fifteen comparable schools were randomly assigned to either an experimental (n=135) or control condition (n=142). Adolescents in the experimental condition, in addition to usual care, also received support and incentives to save money toward secondary education. Results Findings indicate that although adolescent boys and girls within the experimental condition saved comparable amounts, the intervention appears to have benefited girls, in regards to the attitudes towards sexual risk-taking behavior, in a different way and to a lesser extent than boys. Conclusions Future research should investigate the possibility that adolescent girls might be able to develop equally large improvements in protective attitudes towards sexual risk-taking through additional components that address gendered social norms. PMID:20307827
The perverse impact of external reference pricing (ERP): a comparison of orphan drugs affordability in 12 European countries. A call for policy change

PubMed Central

Young, K. E.; Soussi, I.; Toumi, M.

2017-01-01

ABSTRACT Objective: The study compared the relative cost differences of similar orphan drugs among high and low GDP countries in Europe: Bulgaria, France, Germany, Greece, Hungary, Italy, Norway, Poland, Romania, Spain, Sweden, UK. Methods: Annual treatment costs per patient were calculated. Relative costs were computed by dividing the costs by each economic parameter: nominal GDP per capita, GDP in PPP per capita, % GDP contributed by the government, government budget per inhabitant, % GDP spent on healthcare, % GDP spent on pharmaceuticals, and average annual salary. An international comparison of the relative costs was done using UK as the reference country and results were analysed descriptively. Results: 120 orphan drugs were included. The median annual costs of orphan drugs in all countries varied minimally (cost ratios: 0.87 to 1.08). When the costs were adjusted using GDP per capita, the EU-5 and Nordic countries maintained minimal difference in median cost. However, the lower GDP countries showed three to six times higher relative costs. The same pattern was evident when costs were adjusted using the other economic parameters. Conclusion: When the country’s ability to pay is taken into consideration, lower GDP countries pay relatively higher costs for similarly available orphan drugs in Europe. PMID:29081920
The five-year diagnostic utility of "diagnostic orphans" for alcohol use disorders in a national sample of young adults.

PubMed

Harford, Thomas C; Yi, Hsiao-Ye; Grant, Bridget F

2010-05-01

This study was conducted to assess the association of "diagnostic orphans" at baseline and subsequent development of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) alcohol use disorders (AUDs) 5 years later. A sample of 8,534 respondents was drawn from the National Longitudinal Survey of Youth for the years 1989 and 1994. Diagnostic orphans were defined as respondents who met one or two alcohol dependence symptom criteria but did not meet the criteria for a diagnosis of alcohol abuse or dependence. Using multinomial logistic regression analysis, 1994 assessments of DSM-IV AUD were regressed on 1989 baseline assessments of diagnostic orphan status and DSM-IV AUD. In addition to demographic characteristics, other background variables included heavy episodic drinking at baseline and early problem behaviors (antisocial behaviors, illicit substance use, and age at onset of alcohol use). Findings from this 5-year prospective study indicate that diagnostic orphan status at baseline was predictive of DSM-IV AUD at follow-up. These associations remained significant when other early behavioral problems were included in the models. The present findings have important diagnostic implications for the proposed DSM-V, particularly for a dimensional diagnosis incorporating less severe forms of alcohol dependence.
Unlocking the potential of orphan legumes.

PubMed

Cullis, Christopher; Kunert, Karl J

2017-04-01

Orphan, or underutilized, legumes are domesticated legumes with useful properties, but with less importance than major world crops due to use and supply constraints. However, they play a significant role in many developing countries, providing food security and nutrition to consumers, as well as income to resource-poor farmers. They have been largely neglected by both researchers and industry due to their limited economic importance in the global market. Orphan legumes are better adapted than the major legume crops to extreme soil and climatic conditions, with high tolerance to abiotic environmental stresses such as drought. As a stress response they can also produce compounds with pharmaceutical value. Orphan legumes are therefore a likely source of important traits for introduction into major crops to aid in combating the stresses associated with global climate change. Modern large-scale genomics techniques are now being applied to many of these previously understudied crops, with the first successes reported in the genomics area. However, greater investment of resources and manpower are necessary if the potential of orphan legumes is to be unlocked and applied in the future. © The Author 2016. Published by Oxford University Press on behalf of the Society for Experimental Biology. All rights reserved. For permissions, please email: journals.permissions@oup.com.
HIV-Associated Orphanhood and Children’s Psychosocial Distress: Theoretical Framework Tested With Data From Zimbabwe

PubMed Central

Nyamukapa, Constance A.; Gregson, Simon; Lopman, Ben; Saito, Suzue; Watts, Helen J.; Monasch, Roeland; Jukes, Matthew C.H.

2008-01-01

Objectives. We measured the psychosocial effect of orphanhood in a sub-Saharan African population and evaluated a new framework for understanding the causes and consequences of psychosocial distress among orphans and other vulnerable children. Methods. The framework was evaluated using data from 5321 children aged 12 to 17 years who were interviewed in a 2004 national survey in Zimbabwe. We constructed a measure of psychosocial distress using principle components analysis. We used regression analyses to obtain standardized parameter estimates of psychosocial distress and odds ratios of early sexual activity. Results. Orphans had more psychosocial distress than did nonorphans. For both genders, paternal, maternal, and double orphans exhibited more-severe distress than did nonorphaned, nonvulnerable children. Orphanhood remained associated with psychosocial distress after we controlled for differences in more-proximate determinants. Maternal and paternal orphans were significantly more likely than were nonorphaned, nonvulnerable children to have engaged in sexual activity. These differences were reduced after we controlled for psychosocial distress. Conclusions. Orphaned adolescents in Zimbabwe suffer greater psychosocial distress than do nonorphaned, nonvulnerable children, which may lead to increased likelihood of early onset of sexual intercourse and HIV infection. The effect of strategies to provide psychosocial support should be evaluated scientifically. PMID:18048777
A review and update on orphan drugs for the treatment of noninfectious uveitis

PubMed Central

You, Caiyun; Sahawneh, Haitham F; Ma, Lina; Kubaisi, Buraa; Schmidt, Alexander; Foster, C Stephen

2017-01-01

Introduction Uveitis, a leading cause of preventable blindness around the world, is a critically underserved disease in regard to the medications approved for use. Multiple immunomodulatory therapy (IMT) drugs are appropriate for uveitis therapy but are still off-label. These IMT agents, including antimetabolites, calcineurin inhibitors, alkylating agents, and biologic agents, have been designated as “orphan drugs” and are widely used for systemic autoimmune diseases or organ transplantation. Area covered The purpose of this paper is to comprehensively review and summarize the approved orphan drugs and biologics that are being used to treat systemic diseases and to discuss drugs that have not yet received approval as an “orphan drug for treating uveitis” by the US Food and Drug Administration (FDA). Our perspective IMT, as a steroid-sparing agent for uveitis patients, has shown promising clinical results. Refractory and recurrent uveitis requires combination IMT agents. IMT is continued for a period of 2 years while the patient is in remission before considering tapering medication. Our current goals include developing further assessments regarding the efficacy, optimal dose, and safety in efforts to achieve FDA approval for “on-label” use of current IMT agents and biologics more quickly and to facilitate insurance coverage and expand access to the products for this orphan disease. PMID:28203051
A Tale of Tidal Tales in the Milky Way

NASA Astrophysics Data System (ADS)

Casey, Andrew R.

2014-05-01

Hundreds of globular clusters and dwarf galaxies encircle the Milky Way. Many of these systems have undergone partial disruption due to tidal forces, littering the halo with stellar streams. These tidal tails are sensitive to the Galactic potential, facilitating an excellent laboratory to investigate galaxy formation and evolution. To better understand the emergence of the Milky Way, this thesis examines the dynamics and chemistry of a number of known stellar streams. In particular the Sagittarius, Orphan and Aquarius streams are investigated. Low-resolution spectra for hundreds of stars in the direction of the Virgo Over-Density and the Sagittarius northern leading arms have been obtained. Multiple significant kinematic groups are recovered in this accretion-dominated region, confirming detections by previous studies. A metal-poor population ([Fe/H] = -1.7) in the Sagittarius stream is discovered due to a photometric selection that was inadvertently biased towards more metal-poor stars. Positions and kinematics of Sagittarius stream members are compared with existing best-fitting dark matter models, and a triaxial dark matter halo distribution is favoured. The Orphan stream is appropriately named, as no parent system has yet been identified. The stream has an extremely low surface brightness, which makes distinguishing stream members from field stars particularly challenging. From low-resolution spectra obtained for hundreds of stars, we identify likely Orphan stream red giant branch stars on the basis of velocity, metallicity, surface gravity, and proper motions. A negligible intrinsic velocity dispersion is found, and a wide spread in metallicities is observed, which suggests the undiscovered parent is similar to the present-day dwarf galaxies in the Milky Way. High-resolution spectra were obtained for five Orphan stream candidates, and the intrinsic chemical dispersion found from low-resolution spectra is confirmed from these data. Detailed chemical abundances for high-probability Orphan stream candidates further indicates a dwarf galaxy host. Low [α/Fe] abundance ratios are observed, and lower limits for [Ba/Y] are found, which sit well above the observed chemical evolution in the Milky Way. This thesis provides the first detailed chemical evidence for a dwarf galaxy origin, allowing us to rule out any association between the Orphan stream and the globular cluster NGC 2419. High-resolution, high S/N spectra for one third of the Aquarius stream have also been obtained. Contrary to previous work, there is no evidence that the Aquarius stream has resulted from a disrupted globular cluster. Detailed chemistry suggests that the Aquarius stars are galactic in origin, and not disrupted members from either a globular cluster or a dwarf galaxy. In the absence of compelling dynamic and/or chemical evidence to suggest otherwise, we advocate the 'Aquarius Group' as a more appropriate description, and hypothesise that the moving group has resulted from a disk-satellite interaction. The high-resolution spectra presented in this thesis has been analysed using custom written software, ironically named 'Spectroscopy Made Hard'. A detailed description of the software, capabilities and algorithms are presented. Spectroscopy Made Hard includes an intuitive graphical user interface, allowing the spectroscopist to interactively modify any aspect of their analysis. The software is designed to facilitate the transition between small and massive sample sizes, while ensuring data provenance, tangibility, and reproducibility. Future applications for this software are outlined, with a particular focus on the large scale high-resolution spectroscopic surveys being planned or currently undertaken.
Sexual Behavior Among Orphaned Adolescents in Western Kenya: A Comparison of Institutional- and Family-Based Care Settings.

PubMed

Embleton, Lonnie; Nyandat, Joram; Ayuku, David; Sang, Edwin; Kamanda, Allan; Ayaya, Samuel; Nyandiko, Winstone; Gisore, Peter; Vreeman, Rachel; Atwoli, Lukoye; Galarraga, Omar; Ott, Mary A; Braitstein, Paula

2017-04-01

This study sought to assess whether risky sexual behaviors and sexual exploitation of orphaned adolescents differed between family-based and institutional care environments in Uasin Gishu County, Kenya. We analyzed baseline data from a cohort of orphaned adolescents aged 10-18 years living in 300 randomly selected households and 19 charitable children's institutions. The primary outcomes were having ever had consensual sex, number of sex partners, transactional sex, and forced sex. Multivariate logistic regression compared these between participants in institutional care and family-based care while adjusting for age, sex, orphan status, importance of religion, caregiver support and supervision, school attendance, and alcohol and drug use. This analysis included 1,365 participants aged ≥10 years: 712 (52%) living in institutional environments and 653 (48%) in family-based care. Participants in institutional care were significantly less likely to report engaging in transactional sex (adjusted odds ratio, .46; 95% confidence interval, .3-.72) or to have experienced forced sex (adjusted odds ratio, .57; 95% confidence interval, .38-.88) when controlling for age, sex, and orphan status. These associations remained when adjusting for additional variables. Orphaned adolescents living in family-based care in Uasin Gishu, Kenya, may be at increased risk of transactional sex and sexual violence compared to those in institutional care. Institutional care may reduce vulnerabilities through the provision of basic material needs and adequate standards of living that influence adolescents' sexual risk-taking behaviors. The use of single items to assess outcomes and nonexplicit definition of sex suggest the findings should be interpreted with caution. Copyright © 2016 Society for Adolescent Health and Medicine. Published by Elsevier Inc. All rights reserved.
Orphans and vulnerable children in Kenya: results from a nationally representative population-based survey.

PubMed

Lee, Veronica C; Muriithi, Patrick; Gilbert-Nandra, Ulrike; Kim, Andrea A; Schmitz, Mary E; Odek, James; Mokaya, Rose; Galbraith, Jennifer S

2014-05-01

In Kenya, it is estimated that there are approximately 3.6 million children aged <18 years who have been orphaned or who are vulnerable. We examined the data from the second Kenya AIDS Indicator Survey (KAIS 2012) to determine the number and profile of orphans and vulnerable children (OVC) in Kenya who were aged <18 years. KAIS 2012 was a nationally representative, population-based household survey. We analyzed the data for all the children from birth to age 17 years who resided in an eligible household so as to determine whether their parents were alive or had been very ill to define their OVC status. We estimated that there were 2.6 million OVC in Kenya in 2012, of whom 1.8 million were orphans and 750,000 were vulnerable. Among orphans, 15% were double orphans. Over one-third of all the OVC were aged between 10 and 14 years. Households with ≥1 OVC (12% of all households) were usually in the lowest 2 wealth quintiles, and 22% of OVC households had experienced moderate or severe hunger. Receipt of OVC support services was low for medical (3.7%), psychological (4.1%), social (1.3%), and material support (6.2%); educational support was slightly more common (11.5%). Orphanhood among children aged <15 years increased from 1993 to 2003 (P < 0.01) but declined from 2003 to 2012 (P < 0.01). The 2.6 million OVC constitute a significant proportion of Kenya's population aged <18 years. Special attention should be paid to OVC to prevent further vulnerability and ensure their well-being and development as they transition into adulthood.
Orphan Drug Regulation: A missed opportunity for children and adolescents with cancer.

PubMed

Vassal, Gilles; Kearns, Pam; Blanc, Patricia; Scobie, Nicole; Heenen, Delphine; Pearson, Andy

2017-10-01

Oncology represents a major sector in the field of orphan drug development in Europe. The objective was to evaluate whether children and adolescents with cancer benefited from the Orphan Drug Regulation. Data on orphan drug designations (ODDs) and registered orphan drugs from 8th August 2000 to 10th September 2016 were collected from the Community Register of medicinal products for human use. Assessment history, product information and existence of paediatric investigation plans were searched and retrieved from the European Medicine Agency website. Over 16 years, 272 of 657 oncology ODDs (41%) concerned a malignant condition occurring both in adults and children. The five most common were acute myeloid leukaemia, high-grade glioma, acute lymphoblastic leukaemia, graft-versus-host disease and soft-tissue sarcomas. 74% of 31 marketing authorisations (MAs) for an indication both in adults and children (26 medicines) had no information for paediatric use in their Summary of Product Characteristics (SmPC) at the time of the first MA. Furthermore, 68% still have no paediatric information in their most recently updated SmPC, at a median of 7 years after. Only 15 ODDs (2%) pertained to a malignancy occurring specifically in children and only two drugs received an MA: Unituxin for high-risk neuroblastoma and Votubia for sub-ependymal giant-cell astrocytoma. The Orphan Drug Regulation failed to promote the development of innovative therapies for malignancies occurring in children. Major delays and waivers occurred through the application of the Paediatric Medicines Regulation. The European regulatory environment needs to be improved to accelerate innovation for children and adolescents dying of cancer. Copyright © 2017 Elsevier Ltd. All rights reserved.
Drinking correlates of DSM-IV alcohol use disorder diagnostic orphans in college students.

PubMed

Hagman, Brett T; Cohn, Amy M

2012-01-01

One major limitation of the DSM-IV criteria for alcohol abuse and dependence is that a cluster of individuals who endorse a subthreshold number of dependence criteria and no abuse criteria do not receive a formal diagnosis; despite elevated risk for alcohol-related problems relative to those with an abuse diagnosis. These individuals have been referred to as diagnostic orphans. The primary aim of this study was to examine alcohol use correlates of a group of diagnostic orphans in a sample of 396 nontreatment seeking college students who reported drinking on at least one occasion in the last 90 days. DSM-IV criteria were assessed using a modified version of the Composite International Diagnostic Interview-Substance Abuse Module (CIDI-SAM). Diagnostic orphans represented 34.1% (n = 135) of the original sample who did not receive a formal diagnosis; with the most frequently endorsed dependence criteria being tolerance and drinking larger/longer amounts than intended. Diagnostic orphans reported a range of alcohol-related negative consequences and reported greater frequencies of social and enhancement drinking motives in comparison to coping motives. They were similar to alcohol abusers and dissimilar to those with dependence or those without a diagnosis on alcohol consumption, alcohol problem severity, drinking motives and restraint variables. The present findings indicate that diagnostic orphans in college students represent a distinct group of drinkers who may be at risk for the development of alcohol use disorders and may be in need of intervention, given their similarity to those with an abuse diagnosis. Prevention and intervention efforts across college campuses should target this group to prevent escalation of alcohol problem severity. Copyright © American Academy of Addiction Psychiatry.
Orphans and Vulnerable Children in Kenya: Results From a Nationally Representative Population-Based Survey

PubMed Central

Lee, Veronica C.; Muriithi, Patrick; Gilbert-Nandra, Ulrike; Kim, Andrea A.; Schmitz, Mary E.; Odek, James; Mokaya, Rose; Galbraith, Jennifer S.

2016-01-01

Background In Kenya, it is estimated that there are approximately 3.6 million children aged <18 years who have been orphaned or who are vulnerable. We examined the data from the second Kenya AIDS Indicator Survey (KAIS 2012) to determine the number and profile of orphans and vulnerable children (OVC) in Kenya who were aged <18 years. Methods KAIS 2012 was a nationally representative, population-based household survey. We analyzed the data for all the children from birth to age 17 years who resided in an eligible household so as to determine whether their parents were alive or had been very ill to define their OVC status. Results We estimated that there were 2.6 million OVC in Kenya in 2012, of whom 1.8 million were orphans and 750,000 were vulnerable. Among orphans, 15% were double orphans. Over one-third of all the OVC were aged between 10 and 14 years. Households with ≥1 OVC (12% of all households) were usually in the lowest 2 wealth quintiles, and 22% of OVC households had experienced moderate or severe hunger. Receipt of OVC support services was low for medical (3.7%), psychological (4.1%), social (1.3%), and material support (6.2%); educational support was slightly more common (11.5%). Orphanhood among children aged <15 years increased from 1993 to 2003 (P < 0.01) but declined from 2003 to 2012 (P < 0.01). Conclusions The 2.6 million OVC constitute a significant proportion of Kenya’s population aged <18 years. Special attention should be paid to OVC to prevent further vulnerability and ensure their well-being and development as they transition into adulthood. PMID:24732824
Sexual behaviour among orphaned adolescents in western Kenya: a comparison of institutional- and family-based care settings

PubMed Central

Embleton, Lonnie; Nyandat, Joram; Ayuku, David; Sang, Edwin; Kamanda, Allan; Ayaya, Samuel; Nyandiko, Winstone; Gisore, Peter; Vreeman, Rachel; Atwoli, Lukoye; Galarraga, Omar; Ott, Mary A.; Braitstein, Paula

2016-01-01

Purpose This study sought to assess whether risky sexual behaviours and sexual exploitation of orphaned adolescents differed between family-based and institutional care environments in Uasin Gishu County, Kenya. Methods We analyzed baseline data from a cohort of orphaned adolescents aged 10–18 years living in 300 randomly-selected households and 19 Charitable Children’s Institutions. The primary outcomes were having ever had consensual sex, number of sex partners, transactional sex, and forced sex. Multivariable logistic regression compared these between participants in institutional care and family-based care, while adjusting for age, sex, orphan status, importance of religion, caregiver support and supervision, school attendance, and alcohol and drug use. Results This analysis included 1,365 participants aged ≥10 years; 712 (52%) living in institutional environments and 653 (48%) in family-based care. Participants in institutional care were significantly less likely to report engaging in transactional sex (AOR 0.46 95% CI: 0.3–0.72) or to have experienced forced sex (AOR=0.57 95% CI: 0.38–0.88) when controlling for age, sex, and orphan status. These associations remained when adjusting for additional variables. Conclusion Orphaned adolescents living in family-based care in Uasin Gishu, Kenya, may be at increased risk of transactional sex and sexual violence compared to those in institutional care. Institutional care may reduce vulnerabilities through the provision of basic material needs and adequate standards of living that influence adolescents’ sexual risk-taking behaviours. The use of single items to assess outcomes and non-explicit definition of sex suggest the findings should be interpreted with caution. PMID:28110864
Parental Loss, Trusting Relationship with Current Caregivers and Psychosocial Adjustment among Children Affected by AIDS in China

PubMed Central

Zhao, Junfeng; Li, Xiaoming; Barnett, Douglas; Lin, Xiuyun; Fang, Xiaoyi; Zhao, Guoxiang; Naar-King, Sylvie; Stanton, Bonita

2011-01-01

Objective to examine the relationship between parental loss, trusting relationship with current caregivers, and psychosocial adjustment among children affected by AIDS in China. Methods Cross-sectional data were collected from 755 AIDS orphans (296 double orphans and 459 single orphans), 466 vulnerable children living with HIV-infected parents, and 404 comparison children in China. The trusting relationship with current caregivers was measured with a 15-item scale (Cronbach alpha=.84) modified from the Trusting Relationship Questionnaire (TRQ) developed by Mustillo and colleagues (2005). The psychosocial measures include rule compliance/acting out, anxiety/withdrawal, peer social skills, school interest, depressive symptoms, loneliness, self-esteem, future expectation, hopefulness about future, and perceived control over the future. Results Group mean comparisons using ANOVA suggested a significant association (p<.0001) between the trusting relationship with current caregivers and all the psychosocial measures except anxiety and depression. These associations remained significant in General Linear Model analysis, controlling for children's gender, age, family SES, orphan status (orphans, vulnerable children, and comparison children), and appropriate interaction terms among factor variables. Discussion The findings in the current study support the global literature on the importance of attachment relationship with caregivers in promoting children's psychosocial development. Future prevention intervention efforts to improve AIDS orphans' psychosocial well-being will need to take into consideration the quality of the child's attachment relationships with current caregivers and help their current caregivers to improve the quality of care for these children. Future study is needed to explore the possible reasons for the lack of association between a trusting relationship and some internalizing symptoms such as anxiety and depression among children affected by HIV/AIDS. PMID:21749241
Drug discovery and development for rare genetic disorders.

PubMed

Sun, Wei; Zheng, Wei; Simeonov, Anton

2017-09-01

Approximately 7,000 rare diseases affect millions of individuals in the United States. Although rare diseases taken together have an enormous impact, there is a significant gap between basic research and clinical interventions. Opportunities now exist to accelerate drug development for the treatment of rare diseases. Disease foundations and research centers worldwide focus on better understanding rare disorders. Here, the state-of-the-art drug discovery strategies for small molecules and biological approaches for orphan diseases are reviewed. Rare diseases are usually genetic diseases; hence, employing pharmacogenetics to develop treatments and using whole genome sequencing to identify the etiologies for such diseases are appropriate strategies to exploit. Beginning with high throughput screening of small molecules, the benefits and challenges of target-based and phenotypic screens are discussed. Explanations and examples of drug repurposing are given; drug repurposing as an approach to quickly move programs to clinical trials is evaluated. Consideration is given to the category of biologics which include gene therapy, recombinant proteins, and autologous transplants. Disease models, including animal models and induced pluripotent stem cells (iPSCs) derived from patients, are surveyed. Finally, the role of biomarkers in drug discovery and development, as well as clinical trials, is elucidated. © 2017 Wiley Periodicals, Inc.
From orphan virus to pathogen: the path to the clinical lab.

PubMed

Li, Linlin; Delwart, Eric

2011-10-01

Viral metagenomics has recently yielded numerous previously uncharacterized viral genomes from human and animal samples. We review some of the metagenomics tools and strategies to determine which orphan viruses are likely pathogens. Disease association studies compare viral prevalence in patients with unexplained symptoms versus healthy individuals but require these case and control groups to be closely matched epidemiologically. The development of an antibody response in convalescent serum can temporarily link symptoms with a recent infection. Neutralizing antibody detection require often difficult cell culture virus amplification. Antibody binding assays require proper antigen synthesis and positive control sera to set assay thresholds. High levels of viral genetic diversity within orphan viral groups, frequent co-infections, low or rare pathogenicity, and chronic virus shedding, can all complicate disease association studies. The limited availability of matched cases and controls sample sets from different age groups and geographic origins is a major block for estimating the pathogenic potential of recently characterized orphan viruses. Current limitations on the practical use of deep sequencing for viral diagnostics are listed.
A fair share for the orphans: ethical guidelines for a fair distribution of resources within the bounds of the 10-year-old European Orphan Drug Regulation.

PubMed

Pinxten, Wim; Denier, Yvonne; Dooms, Marc; Cassiman, Jean-Jacques; Dierickx, Kris

2012-03-01

For a significant number of patients, there exists no, or only little, interest in developing a treatment for their disease or condition. Especially with regard to rare diseases, the lack of commercial interest in drug development is a burning issue. Several interventions have been made in the regulatory field in order to address the commercial disinterest in these conditions. However, existing regulations mainly focus on the provision of incentives to the sponsors of clinical trials of orphan drugs, and leave unanswered the overarching question about the rightful place of orphan drugs in resource allocation systems. In this article, we analyse the ethical aspects of funding research and development in the field of rare diseases. We then propose an ethical framework that can help health policy makers move forward in the difficult matter of fairly allocating resources for the prevention, diagnosis and treatment of rare diseases.
Are female orphans at risk for early marriage, early sexual debut, and teen pregnancy? Evidence from sub-Saharan Africa.

PubMed

Palermo, Tia; Peterman, Amber

2009-06-01

Female orphans are widely cited as being at risk for early marriage, early childbearing, and risky sexual behavior; however, to date no studies have examined these linkages using population-level data across multiple countries. This study draws from recent Demographic and Health Surveys from ten sub-Saharan African countries to examine the relationship between orphanhood status and measures of early marriage, early sexual debut, and teen pregnancy among adolescent girls aged 15 to 17. Results indicate that, overall, little association is found between orphanhood and early marriage or teen pregnancy, whereas evidence from seven countries supports associations between orphanhood and early sexual debut. Findings are sensitive to the use of multivariate models, type of orphan, and country setting. Orphanhood status alone may not be a sufficient targeting mechanism for addressing these outcomes in many countries; a broader, multidimensional targeting scheme including orphan type, schooling, and poverty measures would be more robust in identifying and aiding young women at risk.
Development and implementation of a peer-based mental health support programme for adolescents orphaned by HIV/AIDS in South Africa.

PubMed

Thupayagale-Tshweneagae, Gloria

2011-12-01

The article describes a framework and the process for the development of the peer-based mental health support programme and its implementation. The development of a peer-based mental health support programme is based on Erikson's theory on the adolescent phase of development, the psycho-educational processes; the peer approach and the orphaned adolescents lived experiences as conceptual framework. A triangulation of five qualitative methods of photography, reflective diaries, focus groups, event history calendar and field notes were used to capture the lived experiences of adolescents orphaned to HIV and AIDS. Analysis of data followed Colaizzi's method of data analysis. The combination of psycho-education, Erikson's stages of development and peer support assisted the participants to gain knowledge and skills to overcome adversity and to assist them to become to more resilient. The peer based mental health support programme if used would enhance the mental health of adolescent orphans.
HIV/AIDS, childhood and governance: sundering the bonds of human society.

PubMed

Barnett, Tony

2005-12-01

There is a disharmonious resonance between the length of HIV infection in the individual human host and the length of a human generation. In brief, an infected person may have children, these may be orphaned and grow up to become infected, and afterwards they themselves may have children, who can be orphaned in turn. Hence, a basic unit of social structure in most human societies, the three-generation bond between grandparents, parents and the current generation - and on into the future - is repeatedly torn apart in the absence of treatment, a vaccine or behaviour change. This situation should be read against the threat of growing viral resistance. Certain implications of these processes for the future are outlined and discussed. The paper notes the uncertain future confronting societies that already have a relatively high number of orphans, and considers some otherwise unexpected possibilities, as well as the dangers of assuming that large-scale orphaning necessarily leads to social unrest and disorder.

Life Improvement, Life Satisfaction and Care Arrangement Among AIDS Orphans in Rural Henan, China

PubMed Central

Zhao, Qun; Li, Xiaoming; Fang, Xiaoyi; Stanton, Bonita; Zhao, Guoxiang; Zhao, Junfeng; Zhang, Liying

2009-01-01

The Chinese government’s response to the increasing number of children orphaned in the HIV epidemic included setting up AIDS orphanages and supporting community-based group homes for double orphans (children who lost both parents to HIV). The impact of these strategies, compared to traditional kinship care, on children’s outcomes has not been studied in China. The purpose of this study was to compare perceived life improvement and life satisfaction among double orphans in 3 main care arrangements (group home, AIDS orphanage, kinship care) in 2 rural Chinese counties. Participants included 176 children from 4 orphanages, 30 from 8 group homes, and 90 from kinship households. Findings indicated that children living in government-supported group homes were more likely to report greater life improvement and positive attitudes toward their current lives than children in orphanages and kinship care. Results suggested that perceived life improvements may have resulted from access to basic needs in extremely poor communities. PMID:19286124
World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients

PubMed Central

Kontoghiorghe, Christina N; Andreou, Nicholas; Constantinou, Katerina; Kontoghiorghes, George J

2014-01-01

According to global annual estimates hunger/malnutrition is the major cause of death (36 of 62 million). Cardiovascular diseases and cancer (5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis (10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countries was 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone (L1) for thalassaemia up to the stage of multicentre clinical trials. The criteria for drug development, price levels and use needs to be readdressed to improve drug safety and minimise costs. New global health policies based on cheaper drugs can help the treatment of many categories of orphan and rare diseases and millions of orphan patients in developing and developed countries. PMID:25332915
World health dilemmas: Orphan and rare diseases, orphan drugs and orphan patients.

PubMed

Kontoghiorghe, Christina N; Andreou, Nicholas; Constantinou, Katerina; Kontoghiorghes, George J

2014-09-26

According to global annual estimates hunger/malnutrition is the major cause of death (36 of 62 million). Cardiovascular diseases and cancer (5.44 of 13.43 million) are the major causes of death in developed countries, while lower respiratory tract infections, human immunodeficiency virus infection/acquired immunodeficiency syndrome, diarrhoeal disease, malaria and tuberculosis (10.88 of 27.12 million) are the major causes of death in developing countries with more than 70% of deaths occurring in children. The majority of approximately 800 million people with other rare diseases, including 100000 children born with thalassaemia annually receive no treatment. There are major ethical dilemmas in dealing with global health issues such as poverty and the treatment of orphan and rare diseases. Of approximately 50000 drugs about 10% are orphan drugs, with annual sales of the latter approaching 100 billion USD. In comparison, the annual revenue in 2009 from the top 12 pharmaceutical companies in Western countries was 445 billion USD and the top drug, atorvastatin, reached 100 billion USD. In the same year, the total government expenditure for health in the developing countries was 410 billion USD with only 6%-7% having been received as aid from developed countries. Drugs cost the National Health Service in the United Kingdom more than 20 billion USD or 10% of the annual health budget. Uncontrollable drug prices and marketing policies affect global health budgets, clinical practice, patient safety and survival. Fines of 5.3 billion USD were imposed on two pharmaceutical companies in the United States, the regulatory authority in France was replaced and clinicians were charged with bribery in order to overcome recent illegal practises affecting patient care. High expenditure for drug development is mainly related to marketing costs. However, only 2 million USD was spent developing the drug deferiprone (L1) for thalassaemia up to the stage of multicentre clinical trials. The criteria for drug development, price levels and use needs to be readdressed to improve drug safety and minimise costs. New global health policies based on cheaper drugs can help the treatment of many categories of orphan and rare diseases and millions of orphan patients in developing and developed countries.
Time Discounting and Credit Market Access in a Large-Scale Cash Transfer Programme.

PubMed

Handa, Sudhanshu; Martorano, Bruno; Halpern, Carolyn; Pettifor, Audrey; Thirumurthy, Harsha

2016-06-01

Time discounting is thought to influence decision-making in almost every sphere of life, including personal finances, diet, exercise and sexual behavior. In this article we provide evidence on whether a national poverty alleviation program in Kenya can affect inter-temporal decisions. We administered a preferences module as part of a large-scale impact evaluation of the Kenyan Government's Cash Transfer for Orphans and Vulnerable Children. Four years into the program we find that individuals in the treatment group are only marginally more likely to wait for future money, due in part to the erosion of the value of the transfer by inflation. However among the poorest households for whom the value of transfer is still relatively large we find significant program effects on the propensity to wait. We also find strong program effects among those who have access to credit markets though the program itself does not improve access to credit.
Evaluation of a Memory Book intervention with orphaned children in South Africa.

PubMed

Braband, Barbara J; Faris, Tamara; Wilson-Anderson, Kaye

2014-01-01

The purpose of this collaborative research study was to evaluate the use of the Memory Book intervention for orphaned children's grief and loss recovery. A qualitative phenomenological approach was implemented to evaluate the Memory Book intervention with orphaned children at two children's homes in South Africa. Study findings support the ability of children to work through loss and grief when they are assisted in preserving and telling their story. The Memory Book intervention assists children to chronicle their lives and demonstrates the potential to guide future interventions by care providers and nurses in this context. Copyright © 2014 Elsevier Inc. All rights reserved.
21 CFR 316.12 - Providing written recommendations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Providing written recommendations. 316.12 Section...) DRUGS FOR HUMAN USE ORPHAN DRUGS Written Recommendations for Investigations of Orphan Drugs § 316.12 Providing written recommendations. (a) FDA will provide the sponsor with written recommendations concerning...
21 CFR 316.12 - Providing written recommendations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Providing written recommendations. 316.12 Section...) DRUGS FOR HUMAN USE ORPHAN DRUGS Written Recommendations for Investigations of Orphan Drugs § 316.12 Providing written recommendations. (a) FDA will provide the sponsor with written recommendations concerning...
Accurate prediction of protein–protein interactions from sequence alignments using a Bayesian method

PubMed Central

Burger, Lukas; van Nimwegen, Erik

2008-01-01

Accurate and large-scale prediction of protein–protein interactions directly from amino-acid sequences is one of the great challenges in computational biology. Here we present a new Bayesian network method that predicts interaction partners using only multiple alignments of amino-acid sequences of interacting protein domains, without tunable parameters, and without the need for any training examples. We first apply the method to bacterial two-component systems and comprehensively reconstruct two-component signaling networks across all sequenced bacteria. Comparisons of our predictions with known interactions show that our method infers interaction partners genome-wide with high accuracy. To demonstrate the general applicability of our method we show that it also accurately predicts interaction partners in a recent dataset of polyketide synthases. Analysis of the predicted genome-wide two-component signaling networks shows that cognates (interacting kinase/regulator pairs, which lie adjacent on the genome) and orphans (which lie isolated) form two relatively independent components of the signaling network in each genome. In addition, while most genes are predicted to have only a small number of interaction partners, we find that 10% of orphans form a separate class of ‘hub' nodes that distribute and integrate signals to and from up to tens of different interaction partners. PMID:18277381
A qualitative exploration of resilience in pre-adolescent AIDS orphans living in a residential care facility.

PubMed

Pienaar, Anja; Swanepoel, Zendré; van Rensburg, Hendrik; Heunis, Christo

2011-01-01

This article presents the findings of a study among a small group of South African AIDS orphans living in a residential care facility, Lebone Land. The research was conducted between June and September 2006. A qualitative, exploratory study consisting of in-depth, semistructured interviews with eight children and seven key informants aimed to identify and investigate developmental assets operating in the children's lives to help them cope amid exposure to adversities. The findings indicate that the developmental assets that facilitate coping and foster resilience in these children relate to four main components: external stressors and challenges, external supports, inner strengths and interpersonal and problem-solving skills. Emerging key themes relate to the experience of illness, death, poverty and violence, as well as the important roles of morality, social values, resistance skills, religion and faith in assisting these children in defining their purpose in life. To this end, constructive use of time, commitment to learning, goal-setting, problem-solving ability and self-efficacy are fundamental in the children's attainment of their future projections. Therefore, qualities such as optimism, perseverance and hope seem to permeate the children's process of recovery. Strong networks of support, particularly friendships with other children, also seem to contribute to developing and sustaining resilience.
Navigating through orphan medicinal product regulations in EU and US--similarities and differences.

PubMed

Tiwari, Jyoti

2015-02-01

Rare diseases as the name suggests are the diseases which occur in a very small population due to which the development of medicinal products for these diseases is sidelined as it is anticipated that the cost of development will never be recovered from the sales. It has been estimated by National Institute of Health (NIH) that globally around 7000 rare diseases are there, many of which are of genetic origin. This paper aims to analyze the basic similarities and differences between the rules and regulations put forth by regulatory agencies of US and EU for development of medicinal products for rare diseases, also called orphan medicinal products. The basic purpose was to carve out the loopholes as well as positive aspects of each of these acts and regulations so as to have a clear understanding on the subject. It was to understand that how these legal instruments have stimulated the growth of the drug products for rare diseases and what other things can be done in order to achieve a better impact. This article also provides an overview of the various incentives offered as well as challenges and hurdles faced by each of these regulatory agencies while implementing these regulations. Copyright © 2014 Elsevier Inc. All rights reserved.
Progesterone for Prevention of Preterm Birth: Shortcomings and Unintended Consequences of the Orphan Drug Act.

PubMed

Gee, Rebekah E; Kuy, SreyRam; Karas, Laura O

2017-12-01

Preterm birth is a problem of major public health significance that continues to plague our country despite the existence of a therapy, 17α-hydroxyprogesterone caproate, with known efficacy in reducing the risk of spontaneous preterm birth among high-risk women. Over the past several years, the Louisiana Department of Health has undertaken a robust, multifaceted initiative to improve access to 17α-hydroxyprogesterone caproate, which resulted in a 3.5-fold increase in the percentage of eligible high-risk pregnant women in the Medicaid program who received the therapy between 2013 and 2016. Yet despite Louisiana's progress, the vast majority of the eligible population still fails to receive 17α-hydroxyprogesterone caproate. In this Current Commentary, we argue that the high price of progesterone since U.S. Food and Drug Administration approval has unnecessarily complicated access, and our nation has potentially suffered nearly 60,000 avoidable premature births as a consequence. We present the history of the orphan drug approval and manufacturer-imposed price increase for injectable progesterone, the interplay between the drug's high price and the persistence of racial and ethnic disparities in preterm birth, which are particularly germane in Louisiana, and Louisiana's broad-reaching efforts to improve progesterone coverage. The story of 17α-hydroxyprogesterone caproate highlights the durable barriers that high prices place in the way of access and helps illuminate the shortcomings and unintended consequences of the Orphan Drug Act. This case, however, is not an outlier; it is the far-too-common product of monopoly pricing in the U.S. pharmaceutical market, inadvertently bolstered by existing law, at the expense of affordability and patient access.
How to calculate the annual costs of NGO-implemented programmes to support orphans and vulnerable children: a six-step approach

PubMed Central

2011-01-01

Background Information on the costs of implementing programmes designed to provide support of orphans and vulnerable children (OVC) in sub-Saharan Africa and elsewhere is increasingly being requested by donors for programme evaluation purposes. To date, little information exists to document the costs and structure of costs of OVC programmes as actually implemented "on the ground" by local non-governmental organizations (NGOs). This analysis provides a practical, six-step approach that NGOs can incorporate into routine operations to evaluate their costs of implementing their OVC programmes annually. This approach is applied to the Community-Based Care for Orphans and Vulnerable Children (CBCO) Program implemented by BIDII (a Kenyan NGO) in Eastern Province of Kenya. Methods and results The costing methodology involves the following six steps: accessing and organizing the NGO's annual financial report into logical sub-categories; reorganizing the sub-categories into input cost categories to create a financial cost profile; estimating the annual equivalent payment for programme equipment; documenting donations to the NGO for programme implementation; including a portion of NGO organizational costs not attributed to specific programmes; and including the results of Steps 3-5 into an expanded cost profile. Detailed results are provided for the CBCO programme. Conclusions This paper shows through a concrete example how NGOs implementing OVC programmes (and other public health programmes) can organize themselves for data collection and documentation prospectively during the implementation of their OVC programmes so that costing analyses become routine practice to inform programme implementation rather than a painful and flawed retrospective activity. Such information is required if the costs and outcomes achieved by OVC programmes will ever be clearly documented and compared across OVC programmes and other types of programmes (prevention, treatment, etc.). PMID:22182588
How to calculate the annual costs of NGO-implemented programmes to support orphans and vulnerable children: a six-step approach.

PubMed

Larson, Bruce A; Wambua, Nancy

2011-12-19

Information on the costs of implementing programmes designed to provide support of orphans and vulnerable children (OVC) in sub-Saharan Africa and elsewhere is increasingly being requested by donors for programme evaluation purposes. To date, little information exists to document the costs and structure of costs of OVC programmes as actually implemented "on the ground" by local non-governmental organizations (NGOs). This analysis provides a practical, six-step approach that NGOs can incorporate into routine operations to evaluate their costs of implementing their OVC programmes annually. This approach is applied to the Community-Based Care for Orphans and Vulnerable Children (CBCO) Program implemented by BIDII (a Kenyan NGO) in Eastern Province of Kenya. The costing methodology involves the following six steps: accessing and organizing the NGO's annual financial report into logical sub-categories; reorganizing the sub-categories into input cost categories to create a financial cost profile; estimating the annual equivalent payment for programme equipment; documenting donations to the NGO for programme implementation; including a portion of NGO organizational costs not attributed to specific programmes; and including the results of Steps 3-5 into an expanded cost profile. Detailed results are provided for the CBCO programme. This paper shows through a concrete example how NGOs implementing OVC programmes (and other public health programmes) can organize themselves for data collection and documentation prospectively during the implementation of their OVC programmes so that costing analyses become routine practice to inform programme implementation rather than a painful and flawed retrospective activity. Such information is required if the costs and outcomes achieved by OVC programmes will ever be clearly documented and compared across OVC programmes and other types of programmes (prevention, treatment, etc.).
Candidate members of the Pal 5, GD-1, Cetus Polar and Orphan tidal stellar halo streams from SDSS DR9, LAMOST DR3 and APOGEE catalogs

DOE Office of Scientific and Technical Information (OSTI.GOV)

Li, Guang -Wei; Yanny, Brian; Zhang, Hao -Tong

We present candidate members of the Pal 5, GD-1, Cetus Polar, and Orphan tidal stellar streams found in LAMOST DR3, SDSS DR9 and APOGEE catalogs. In LAMOST DR3, we find 20, 4, 24 high confidence candidates of tidal streams GD-1, Cetus Polar and Orphan respectively. We also list from the SDSS DR9 spectroscopic catalog 59, 118, 10 high confidence candidates of tidal streams Cetus Polar, Orphan and Pal 5, respectively. Furthermore, we find 7 high confidence candidates of the Pal 5 tidal stream in APOGEE data. Compared with SDSS, the new candidates from LAMOST DR3 are brighter, so that together, more of the color-magnitude diagram, including the giant branch can be explored. Analysis of SDSS data shows that there are 3 metallicity peaks of the Orphan stream and also shows some spatial separation. LAMOST data confirms multiple metallicities in this stream. The metallicity, given by the higher resolution APOGEE instrument, of the Pal 5 tidal stream is [Fe/H]more » $$\\sim -1.2$$, higher than that given earlier by SDSS spectra. Here, many previously unidentified stream members are tabulated here for the first time, along with existing members, allowing future researchers to further constrain the orbits of these objects as they move within the Galaxy's dark matter potential.« less
Candidate members of the Pal 5, GD-1, Cetus Polar and Orphan tidal stellar halo streams from SDSS DR9, LAMOST DR3 and APOGEE catalogs

DOE PAGES

Li, Guang -Wei; Yanny, Brian; Zhang, Hao -Tong; ...

2017-05-01

We present candidate members of the Pal 5, GD-1, Cetus Polar, and Orphan tidal stellar streams found in LAMOST DR3, SDSS DR9 and APOGEE catalogs. In LAMOST DR3, we find 20, 4, 24 high confidence candidates of tidal streams GD-1, Cetus Polar and Orphan respectively. We also list from the SDSS DR9 spectroscopic catalog 59, 118, 10 high confidence candidates of tidal streams Cetus Polar, Orphan and Pal 5, respectively. Furthermore, we find 7 high confidence candidates of the Pal 5 tidal stream in APOGEE data. Compared with SDSS, the new candidates from LAMOST DR3 are brighter, so that together, more of the color-magnitude diagram, including the giant branch can be explored. Analysis of SDSS data shows that there are 3 metallicity peaks of the Orphan stream and also shows some spatial separation. LAMOST data confirms multiple metallicities in this stream. The metallicity, given by the higher resolution APOGEE instrument, of the Pal 5 tidal stream is [Fe/H]more » $$\\sim -1.2$$, higher than that given earlier by SDSS spectra. Here, many previously unidentified stream members are tabulated here for the first time, along with existing members, allowing future researchers to further constrain the orbits of these objects as they move within the Galaxy's dark matter potential.« less
Psychological Health of Orphan Bonobos and Chimpanzees in African Sanctuaries

PubMed Central

Wobber, Victoria; Hare, Brian

2011-01-01

Background Facilities across Africa care for apes orphaned by the trade for “bushmeat.” These facilities, called sanctuaries, provide housing for apes such as bonobos (Pan paniscus) and chimpanzees (Pan troglodytes) who have been illegally taken from the wild and sold as pets. Although these circumstances are undoubtedly stressful for the apes, most individuals arrive at the sanctuaries as infants and are subsequently provided with rich physical and social environments that can facilitate the expression of species-typical behaviors. Methods and Findings We tested whether bonobo and chimpanzee orphans living in sanctuaries show any behavioral, physiological, or cognitive abnormalities relative to other individuals in captivity as a result of the early-life stress they experience. Orphans showed lower levels of aberrant behaviors, similar levels of average cortisol, and highly similar performances on a broad battery of cognitive tests in comparisons with individuals of the same species who were either living at a zoo or were reared by their mothers at the sanctuaries. Conclusion Taken together, these results support the rehabilitation strategy used by sanctuaries in the Pan-African Sanctuary Alliance (PASA) and suggest that the orphans we examined did not show long-term signs of stress as a result of their capture. Our findings also show that sanctuary apes are as psychologically healthy as apes in other captive settings and thus represent a valuable resource for non-invasive research. PMID:21666743
Psychological health of orphan bonobos and chimpanzees in African sanctuaries.

PubMed

Wobber, Victoria; Hare, Brian

2011-01-01

Facilities across Africa care for apes orphaned by the trade for "bushmeat." These facilities, called sanctuaries, provide housing for apes such as bonobos (Pan paniscus) and chimpanzees (Pan troglodytes) who have been illegally taken from the wild and sold as pets. Although these circumstances are undoubtedly stressful for the apes, most individuals arrive at the sanctuaries as infants and are subsequently provided with rich physical and social environments that can facilitate the expression of species-typical behaviors. We tested whether bonobo and chimpanzee orphans living in sanctuaries show any behavioral, physiological, or cognitive abnormalities relative to other individuals in captivity as a result of the early-life stress they experience. Orphans showed lower levels of aberrant behaviors, similar levels of average cortisol, and highly similar performances on a broad battery of cognitive tests in comparisons with individuals of the same species who were either living at a zoo or were reared by their mothers at the sanctuaries. Taken together, these results support the rehabilitation strategy used by sanctuaries in the Pan-African Sanctuary Alliance (PASA) and suggest that the orphans we examined did not show long-term signs of stress as a result of their capture. Our findings also show that sanctuary apes are as psychologically healthy as apes in other captive settings and thus represent a valuable resource for non-invasive research.
Transient survey rates for orphan afterglows from compact merger jets

NASA Astrophysics Data System (ADS)

Lamb, Gavin P.; Tanaka, Masaomi; Kobayashi, Shiho

2018-06-01

Orphan afterglows from short γ-ray bursts (GRBs) are potential candidates for electromagnetic (EM) counterpart searches to gravitational wave (GW) detected neutron star or neutron star black hole mergers. Various jet dynamical and structure models have been proposed that can be tested by the detection of a large sample of GW-EM counterparts. We make predictions for the expected rate of optical transients from these jet models for future survey telescopes, without a GW or GRB trigger. A sample of merger jets is generated in the redshift limits 0 ≤ z ≤ 3.0, and the expected peak r-band flux and time-scale above the Large Synoptic Survey Telescope (LSST) or Zwicky Transient Factory (ZTF) detection threshold, mr = 24.5 and 20.4, respectively, is calculated. General all-sky rates are shown for mr ≤ 26.0 and mr ≤ 21.0. The detected orphan and GRB afterglow rate depends on jet model, typically 16≲ R≲ 76 yr-1 for the LSST, and 2≲ R ≲ 8 yr-1 for ZTF. An excess in the rate of orphan afterglows for a survey to a depth of mr ≤ 26 would indicate that merger jets have a dominant low-Lorentz factor population, or the jets exhibit intrinsic jet structure. Careful filtering of transients is required to successfully identify orphan afterglows from either short- or long-GRB progenitors.
21 CFR 316.14 - Refusal to provide written recommendations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false Refusal to provide written recommendations. 316.14... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Written Recommendations for Investigations of Orphan Drugs § 316.14 Refusal to provide written recommendations. (a) FDA may refuse to provide written recommendations...
77 FR 10804 - Submission for OMB Review; Comment Request

Federal Register 2010, 2011, 2012, 2013, 2014

2012-02-23

.... Title: Electronic Federal Tax Payment System (EFTPS). Forms: 9779, 9779(SP), 9783, 9783(SP), 9787, 9787... a currently approved collection. Title: Orphan Drug Credit. Form: 8820. Abstract: Filers use this form to elect to claim the orphan drug credit, which is 50% of the qualified clinical testing expenses...

21 CFR 316.10 - Content and format of a request for written recommendations.

Code of Federal Regulations, 2011 CFR

2011-04-01

... its recommendations for nonclinical laboratory studies and clinical investigations. [57 FR 62085, Dec... recommendations. 316.10 Section 316.10 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Written Recommendations for Investigations of Orphan...
21 CFR 316.22 - Permanent-resident agent for foreign sponsor.

Code of Federal Regulations, 2010 CFR

2010-04-01

....22 Section 316.22 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Designation of an Orphan Drug § 316.22 Permanent..., orders, decisions, requirements, and other communications may be made on behalf of the sponsor...
Children Living with HIV-Infected Adults: Estimates for 23 Countries in sub-Saharan Africa

PubMed Central

Short, Susan E.; Goldberg, Rachel E.

2015-01-01

Background In sub-Saharan Africa many children live in extreme poverty and experience a burden of illness and disease that is disproportionately high. The emergence of HIV and AIDS has only exacerbated long-standing challenges to improving children’s health in the region, with recent cohorts experiencing pediatric AIDS and high levels of orphan status, situations which are monitored globally and receive much policy and research attention. Children’s health, however, can be affected also by living with HIV-infected adults, through associated exposure to infectious diseases and the diversion of household resources away from them. While long recognized, far less research has focused on characterizing this distinct and vulnerable population of HIV-affected children. Methods Using Demographic and Health Survey data from 23 countries collected between 2003 and 2011, we estimate the percentage of children living in a household with at least one HIV-infected adult. We assess overlaps with orphan status and investigate the relationship between children and the adults who are infected in their households. Results The population of children living in a household with at least one HIV-infected adult is substantial where HIV prevalence is high; in Southern Africa, the percentage exceeded 10% in all countries and reached as high as 36%. This population is largely distinct from the orphan population. Among children living in households with tested, HIV-infected adults, most live with parents, often mothers, who are infected; nonetheless, in most countries over 20% live in households with at least one infected adult who is not a parent. Conclusion Until new infections contract significantly, improvements in HIV/AIDS treatment suggest that the population of children living with HIV-infected adults will remain substantial. It is vital to on-going efforts to reduce childhood morbidity and mortality to consider whether current care and outreach sufficiently address the distinct vulnerabilities of these children. PMID:26575484
Community interventions providing care and support to orphans and vulnerable children: a review of evaluation evidence.

PubMed

Schenk, Katie D

2009-07-01

Children affected by HIV in their families and communities face multiple risks to their health, education and psychosocial wellbeing. Community interventions for children who have been orphaned or rendered vulnerable take many forms, including educational assistance, home-based care, legal protection and psychosocial support. Despite a recent influx of funding for programme implementation, there exists little evidence to inform policymakers about whether their investments are improving the lives of vulnerable children and meeting key benchmarks including the Millennium Development Goals. This paper reviews the current evidence base on evaluations of community interventions for orphans and vulnerable children (OVC) in high HIV-prevalence African settings, focusing on studies' methodologies. Sources reviewed include published research studies and evidence from the unpublished programmatic "grey literature" located through database and internet searches. A total of 21 studies, varying in scope and generalisability, were identified. Interventions reviewed address children's wellbeing through various strategies within their communities. Evaluation methodologies reflect quantitative and qualitative approaches, including surveys (with and without baseline or comparison data), costing studies, focus groups, interviews, case studies, and participatory review techniques. Varied study methodologies reflect diverse research questions, various intervention types, and the challenges associated with evaluating complex interventions; highlighting the need to broaden the research paradigm in order to build the evidence base by including quasi-experimental and process evaluation approaches, and seeking further insights through participatory qualitative methodologies and costing studies. Although findings overall indicate the value of community interventions in effecting measurable improvements in child and family wellbeing, the quality and rigour of evidence is varied. A strategic research agenda is urgently needed to inform resource allocation and programme management decisions. Immediate imperatives include building local technical capacity to conduct quantitative and qualitative evaluation research, and strengthening monitoring and evaluation systems to collect process and outcome data (including costing) on key support models. Donors and implementers must support the collection of sound empirical evidence to inform the development and scale-up of OVC programmes.
Family and Nation: Cherokee Orphan Care, 1835-1903

ERIC Educational Resources Information Center

Reed, Julie L.

2010-01-01

On November 17, 1903, fifteen miles from the nearest railway station and fifty miles northwest of the capital of the Cherokee Nation in Tahlequah, a fire engulfed the Cherokee Orphan Asylum. After the fire the Cherokee Nation relocated the homeless children to the nation's Insane Asylum in Tahlequah, where Sequoyah School stands today. The…
Art Therapy with Orphaned Children: Dynamics of Early Relational Trauma and Repetition Compulsion

ERIC Educational Resources Information Center

Meshcheryakova, Ksenia

2012-01-01

This article explores the dynamics of orphaned children's engagement with art therapy in a group of preadolescent children living in a Russian orphanage. The phenomenon of repetition compulsion (i.e., origins in past traumatic experiences, destructive consequences, and protective psychic function) is discussed with respect to the children's…
Orphan Trains in Iowa History.

ERIC Educational Resources Information Center

Frese, Millie K., Ed.

2000-01-01

The "Goldfinch" is a magazine that introduces children to different aspects of Iowa history. Each issue contains articles that provide in-depth knowledge of a topic about Iowa. The focus of this issue is orphan trains in Iowa it introduces readers to some of the people heroes of modern history who rode the trains west between 1854 and…
Pprofessional and Labor Socialization of Orphans in China

ERIC Educational Resources Information Center

Kalashnyk, Lyubov

2014-01-01

It has been defined that the problem of labor socialization of young specialists is a problem of great interest and practical importance for modern pedagogical science. Current issues of professional socialization of young people have been considered. Special attention has been paid to orphans--inmates of institutions of social care in China. It…
21 CFR 316.28 - Publication of orphan-drug designations.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false Publication of orphan-drug designations. 316.28 Section 316.28 Food and Drugs FOOD AND DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES... placed on file at the FDA Division of Dockets Management, and will contain the following information: (a...
75 FR 53701 - Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-09-01

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2010-N-0394] Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01); Correction AGENCY: Food and Drug Administration, HHS. ACTION: Notice; correction. SUMMARY: The Food and Drug...
78 FR 51732 - The Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-08-21

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Food and Drug Administration [Docket No. FDA-2013-N-0001] The Food and Drug Administration/European Medicines Agency Orphan Product Designation and Grant Public Workshop AGENCY: Food and Drug Administration, HHS. ACTION: Notice of public workshop. The Food and Drug...
Psychological Distress amongst AIDS-Orphaned Children in Urban South Africa

ERIC Educational Resources Information Center

Cluver, Lucie; Gardner, Frances; Operario, Don

2007-01-01

Background: South Africa is predicted to have 2.3 million children orphaned by Acquired Immune Deficiency Syndrome (AIDS) by 2020 (Actuarial Society of South Africa, 2005). There is little knowledge about impacts of AIDS-related bereavement on children, to aid planning of services. This study aimed to investigate psychological consequences of AIDS…
76 FR 53912 - FDA's Public Database of Products With Orphan-Drug Designation: Replacing Non-Informative Code...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-08-30

...] FDA's Public Database of Products With Orphan-Drug Designation: Replacing Non-Informative Code Names... replaced non- informative code names with descriptive identifiers on its public database of products that... on our public database with non-informative code names. After careful consideration of this matter...
Orphaned and Abused Youth Are Vulnerable to Pregnancy and Suicide Risk

ERIC Educational Resources Information Center

Zapata, Lauren B.; Kissin, Dmitry M.; Bogoliubova, Olga; Yorick, Roman V.; Kraft, Joan Marie; Jamieson, Denise J.; Marchbanks, Polly A.; Hillis, Susan D.

2013-01-01

Objective: Little is known about the magnitude and consequences of violence against children for those living outside family care. We sought to estimate the frequency of childhood abuse and examine its association with lifetime pregnancy involvement (LPI) and past year suicide ideation among orphaned youth. Methods: We analyzed data collected via…
An Initial Exploration of the Therapeutic Impact of Music on Genocide Orphans in Rwanda

ERIC Educational Resources Information Center

d'Ardenne, Patricia; Kiyendeye, Moses

2015-01-01

The 1994 Rwandan Genocide murdered over a million and brought on incalculable distress to survivors. An non-governmental organisation, "Network for Africa," has a music programme to rehabilitate orphans in Kigali, now entering adulthood. This naturalistic study investigated whether music had transformational meaning for participants.…
The Conceptual Impact of Linguistic Input. A Comparison of German Family-Children's and Orphans' Acquisition of Kinship Terms.

ERIC Educational Resources Information Center

Deutsch, Werner

1979-01-01

The purpose of this study was to determine what effect exposure to linguistic input pertinent to kinship terms and kinship relations has on the acquisition of the meaning of such terms. The subjects were 84 German children living in families, and 84 orphans. (Author/CFM)
77 FR 71452 - Extension of Comment Period: Orphan Works and Mass Digitization

Federal Register 2010, 2011, 2012, 2013, 2014

2012-11-30

... Office hereby extends the time for filing comments to 5:00 p.m. EST on February 4, 2013. The due date for... LIBRARY OF CONGRESS Copyright Office [Docket No. 2012-10] Extension of Comment Period: Orphan Works and Mass Digitization AGENCY: Copyright Office, Library of Congress. ACTION: Extension of comment...
Doctoral "Orphans": Nurturing and Supporting the Success of Postgraduates Who Have Lost Their Supervisors

ERIC Educational Resources Information Center

Wisker, Gina; Robinson, Gillian

2013-01-01

Much research into doctoral student-supervisor relations focuses on developing positive interactions. For many students, however, the research experience can be troubled by breakdowns in communication and even the loss of the supervisor(s), turning the student into a doctoral "orphan" and impacting on their academic identity and ability…
21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 5 2011-04-01 2011-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...
21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 5 2012-04-01 2012-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...

21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 5 2013-04-01 2013-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...
21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 5 2014-04-01 2014-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...
21 CFR 316.34 - FDA recognition of exclusive approval.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 5 2010-04-01 2010-04-01 false FDA recognition of exclusive approval. 316.34... (CONTINUED) DRUGS FOR HUMAN USE ORPHAN DRUGS Orphan-drug Exclusive Approval § 316.34 FDA recognition of exclusive approval. (a) FDA will send the sponsor (or, the permanent-resident agent, if applicable) timely...
Cruel to be kind but not cruel for cash: Harm aversion in the dictator game.

PubMed

Perera, Pri; Canic, Emina; Ludvig, Elliot A

2016-06-01

People regularly take prosocial actions, making individual sacrifices for the greater good. Similarly, people generally avoid causing harm to others. These twin desires to do good and avoid harm often align, but sometimes they can diverge, creating situations of moral conflict. Here, we examined this moral conflict using a modified dictator game. Participants chose how much money to allocate away from a recipient who was designated as an orphan, creating a sense of harm. This money was then reallocated to either the participant or a charity. People were strongly prosocial: they allocated more money away from the orphan for charity than for themselves. Furthermore, people left more money with the orphan when the harm was framed as a means (taking) than as a side effect (splitting). As is predicted by dual-process theories of moral decision making, response times were longer with the take action and were positively correlated with the amount taken from the orphan. We concluded that just as people take positive actions for the greater good, they are similarly more willing to cause harm when it benefits others rather than themselves.
Hotspots and Coldspots: Household and village-level variation in orphanhood prevalence in rural Malawi

PubMed Central

Weinreb, Alexander; Gerland, Patrick; Fleming, Peter

2009-01-01

We explore the characteristics of households and villages in which orphans are resident in two areas of Malawi. We first review pertinent themes in qualitative data collected in our research sites. Then, using spatial analysis, we show how positive and negative clusters of orphans – which we term orphanhood "hotspots" and "coldspots" – can be found at the village and sub-village levels. In the third and longest section of the paper, and using multilevel analyses with both simple and complex variance structures, we evaluate the relationship between the presence of orphans and a range of individual, household and village-level characteristics, including households' spatial relationship to each other and to other local sites of significance. This series of analyses shows that the most important covariates of orphan presence are household size, wealth, and religious characteristics, with all measured simultaneously at both household and village-level. In addition, most of these have heterogenous effects across villages. We conclude by reviewing some difficulties in explaining causal mechanisms underlying these observed relationships, and discuss conceptual, theoretical and programmatic implications. PMID:20148129
Cumulative effects of HIV illness and caring for children orphaned by AIDS on anxiety symptoms among adults caring for children in HIV-endemic South Africa.

PubMed

Kuo, Caroline; Cluver, Lucie; Casale, Marisa; Lane, Tyler

2014-06-01

Adults caring for children in HIV-endemic communities are at risk for poor psychological outcomes. However, we still have a limited understanding of how various HIV impacts--including caregiver's own HIV illness, responsibilities of caring for a child orphaned by AIDS, or both--affect psychological outcomes among caregivers. Furthermore, few studies have explored the relationship between stigma, HIV, and psychological outcomes among caregivers of children in HIV-endemic communities. A cross-sectional survey conducted from 2009 to 2010 assessed anxiety among 2477 caregivers of children in HIV-endemic South Africa. Chi-square tested differences in anxiety among caregivers living with HIV, caregivers of a child orphaned by AIDS, and caregivers affected with both conditions. Multivariate logistic regressions identified whether the relationship between HIV impacts and anxiety remained after controlling for socio-demographic co-factors. Mediation analysis tested the relationship between stigma, HIV, and anxiety. The odds of meeting threshold criteria for clinically relevant anxiety symptoms were two and a half times greater among caregivers living with HIV compared to nonaffected caregivers. The odds of meeting threshold criteria for clinically relevant anxiety symptoms were greatest among caregivers living with HIV and caring for a child orphaned by AIDS. Exposure to AIDS-related stigma partially mediated the relationship between HIV and anxiety. Interventions are needed to address caregiver psychological health, particularly among caregivers affected with both conditions of living with HIV and caring for a child orphaned by AIDS.
Parental HIV/AIDS status and death, and children's psychological wellbeing.

PubMed

Doku, Paul Narh

2009-11-24

Ghana has an estimated one million orphans, 250,000 are due to AIDS parental deaths. This is the first study that examined the impact of parental HIV/AIDS status and death on the mental health of children in Ghana. In a cross-sectional survey, 4 groups of 200 children (children whose parents died of AIDS, children whose parents died of causes other than AIDS, children living with parents infected with HIV/AIDS, and non-orphaned children whose parents are not known to be infected with HIV/AIDS) aged between 10 and 19 were interviewed on their hyperactivity, emotional, conduct, and peer problems using the Strengths and Difficulties Questionnaire. Children whose parents died of AIDS showed very high levels of peer problems [F (3,196) = 7.34, p < .001] whilst both orphaned groups scored similarly high on conduct problems [F (3, 196) = 14.85, p < .001]. Hyperactivity showed no difference and was very low in the entire sample. Emotional problems were very high in all the groups except among the non-orphaned children [F (3, 196) = 5.10, p < .001]. Orphans and children living with parents infected with HIV/AIDS are at heightened risks for emotional and behavioural disorders and that efforts to address problems in children affected by HIV/AIDS must focus on both groups of children. Parallel to this, researchers should see these findings as generated hypotheses (rather than conclusions) calling for further exploration of specific causal linkages between HIV/AIDS and children's mental health, using more rigorous research tools and designs.
Weaving networks of responsibility: community work in development programs in rural Malawi.

PubMed

Rosenthal, Anat

2012-01-01

The need to cope with the impact of the AIDS epidemic on communities in Africa has resulted in the emergence of numerous community health and development programs. Initiated by governments, international nongovernmental organizations (NGOs), and local organizations, such programs target local communities with the goal of building care and support mechanisms in the local level. Based on ethnographic field research in rural Malawi, and drawing from the cross-disciplinary debate on development work, the article explores the work of an NGO offering health and care programs to orphans and vulnerable children. Through analyzing the organization's scope of work, the article demonstrates how the NGO acts to structure local social networks as instruments of care and offers a new reading of the role of NGOs in which the limitations of development work and the work of NGOs are understood within their local context and not only in the context of broad cultural critique.
Evaluation of the Relevance of Piaget’s Cognitive Principles among Parented and Orphan Children in Belagavi City, Karnataka, India: A Comparative Study

PubMed Central

M Badakar, Chandrashekhar; M Hugar, Shivayogi; Kukreja, Pratibha; G Assudani, Harsha; Gokhale, Niraj

2017-01-01

Aim To determine and compare the relevance of Piaget’s cognitive principles among 4- to 7-year-old parented and orphan children in Belagavi City, Karnataka, India. Materials and methods This study was conducted on 240 children between the ages of 4 to 7 years who were equally divided into two groups of 120 parented and 120 orphan children. These were subdivided into four groups of 30 children each. Various characteristics like egocentrism, concept of cardinal numbers based on centration, lack of conservation, and reversibility were assessed, using experiments and comparison of their prevalence between two groups was carried out. Results There is a statistically significant difference in the cognitive development among parented and orphan children age 4 to 7 years. Conclusion There is a significantly better cognitive development among parented children as compared with orphan children in Belagavi city. Clinical significance A child is not a miniature adult but rather can think and perceive the world differently from an adult. Understanding a child’s intellectual level can enable a pedodontist to deliver improved quality care to children. According to Jean Piaget, in the preoperational period, children think symbolically and their reasoning is based more on appearance rather than logic. It is often rightly said that a child’s behavior is a reflection of his parents. However, Piaget did not consider the effect of social setting and culture on the cognitive development. This study was carried out as there is not much literature available to describe the cognitive development of children in the Indian scenario and the influence of parental presence on the same. How to cite this article: Badakar CM, Thakkar PJ, Hugar SM, Kukreja P, Assudani HG, Gokhale N. Evaluation of the Relevance of Piaget’s Cognitive Principles among Parented and Orphan Children in Belagavi City, Karnataka, India: A Comparative Study. Int J Clin Pediatr Dent 2017;10(4):346-350. PMID:29403227
Parental loss, trusting relationship with current caregivers, and psychosocial adjustment among children affected by AIDS in China.

PubMed

Zhao, Junfeng; Li, Xiaoming; Barnett, Douglas; Lin, Xiuyun; Fang, Xiaoyi; Zhao, Guoxiang; Naar-King, Sylvie; Stanton, Bonita

2011-08-01

The objective of this study was to examine the relationship between parental loss, trusting relationship with current caregivers, and psychosocial adjustment among children affected by AIDS in China. In this study, cross-sectional data were collected from 755 AIDS orphans (296 double orphans and 459 single orphans), 466 vulnerable children living with HIV-infected parents, and 404 comparison children in China. The trusting relationship with current caregivers was measured with a 15-item scale (Cronbach's α = 0.84) modified from the Trusting Relationship Questionnaire developed by Mustillo et al. in 2005 (Quality of relationships between youth and community service providers: Reliability and validity of the trusting relationship questionnaire. Journal of Child and Family Studies, 14, 577-590). The psychosocial measures include rule compliance/acting out, anxiety/withdrawal, peer social skills, school interest, depressive symptoms, loneliness, self-esteem, future expectation, hopefulness about future, and perceived control over the future. Group mean comparisons using analysis of variance suggested a significant association (p < 0.0001) between the trusting relationship with current caregivers and all the psychosocial measures, except anxiety and depression. These associations remained significant in General Linear Model analysis, controlling for children's gender, age, family socioeconomic status, orphan status (orphans, vulnerable children, and comparison children), and appropriate interaction terms among factor variables. The findings in the current study support the global literature on the importance of attachment relationship with caregivers in promoting children's psychosocial development. Future prevention intervention efforts to improve AIDS orphans' psychosocial well-being will need to take into consideration the quality of the child's attachment relationships with current caregivers and help their current caregivers to improve the quality of care for these children. Future study is needed to explore the possible reasons for the lack of association between a trusting relationship and some internalizing symptoms such as anxiety and depression among children affected by HIV/AIDS.
Evolving prevalence of haematological malignancies in orphan designation procedures in the European Union.

PubMed

Polsinelli, Benedetta; Tsigkos, Stelios; Naumann-Winter, Frauke; Mariz, Segundo; Sepodes, Bruno

2017-01-21

The Committee for Orphan Medicinal Products (COMP) evaluates prevalence of rare conditions as one of the criteria for granting an orphan designation with a prevalence threshold of 5 in 10.000. At the time of Marketing Authorisation (MA) these criteria are reassessed to ensure they are still met. The COMP has noted discordance between the prevalence of certain haematological malignancies at the time of Orphan Designation and at the time of Marketing Authorisation. Consequently, we conducted a retrospective assessment of Chronic Lymphocytic Lymphoma and Multiple Myeloma/Plasma cell Myeloma as well as several other haematological rare aetiologies frequently subject of orphan designation. These were: Diffuse large B-Cell Lymphoma (DLBCL), Follicular Lymphoma (FL), Cutaneous T-Cell Lymphoma (CTCL), Mantle Cell Lymphoma (MCL) and Chronic Myeloid Leukaemia (CML). The review used submissions as well as recent publications and results from external and EMA databases. As a first step in the analysis, an increase over time in the number of people affected was evident for four conditions in the COMP designation documents, whereas for DLBCL, FL, CTCL and MCL there had been no significant change, since the introduction of the Regulation in 2000. Specifically, the prevalence estimates increased from 1.2 to 3.6 per 10,000 for multiple myeloma, from 0.4 to 1.7 in acute lymphoblastic leukaemia, and from 2.7 to 4.85 for chronic lymphocytic leukaemia/small lymphocytic leukaemia and 1 to 2 in 10,000 for chronic myeloid leukaemia. The reasons for the changes in the prevalence of these four haematological conditions over the last 15 years were not assessed but recent publications have alluded to better outcomes due to new treatments being made available. In addition, many orphan diseases have a median age of onset over 60 years so that also the aging of the population may be a relevant contributing factor.
Evaluation of the Relevance of Piaget's Cognitive Principles among Parented and Orphan Children in Belagavi City, Karnataka, India: A Comparative Study.

PubMed

M Badakar, Chandrashekhar; J Thakkar, Prachi; M Hugar, Shivayogi; Kukreja, Pratibha; G Assudani, Harsha; Gokhale, Niraj

2017-01-01

To determine and compare the relevance of Piaget's cognitive principles among 4- to 7-year-old parented and orphan children in Belagavi City, Karnataka, India. This study was conducted on 240 children between the ages of 4 to 7 years who were equally divided into two groups of 120 parented and 120 orphan children. These were subdivided into four groups of 30 children each. Various characteristics like egocentrism, concept of cardinal numbers based on centration, lack of conservation, and reversibility were assessed, using experiments and comparison of their prevalence between two groups was carried out. There is a statistically significant difference in the cognitive development among parented and orphan children age 4 to 7 years. There is a significantly better cognitive development among parented children as compared with orphan children in Belagavi city. A child is not a miniature adult but rather can think and perceive the world differently from an adult. Understanding a child's intellectual level can enable a pedodontist to deliver improved quality care to children. According to Jean Piaget, in the preoperational period, children think symbolically and their reasoning is based more on appearance rather than logic. It is often rightly said that a child's behavior is a reflection of his parents. However, Piaget did not consider the effect of social setting and culture on the cognitive development. This study was carried out as there is not much literature available to describe the cognitive development of children in the Indian scenario and the influence of parental presence on the same. How to cite this article: Badakar CM, Thakkar PJ, Hugar SM, Kukreja P, Assudani HG, Gokhale N. Evaluation of the Relevance of Piaget's Cognitive Principles among Parented and Orphan Children in Belagavi City, Karnataka, India: A Comparative Study. Int J Clin Pediatr Dent 2017;10(4):346-350.
International Union of Basic and Clinical Pharmacology. LXXXVIII. G Protein-Coupled Receptor List: Recommendations for New Pairings with Cognate Ligands

PubMed Central

Alexander, Stephen P. H.; Sharman, Joanna L.; Pawson, Adam J.; Benson, Helen E.; Monaghan, Amy E.; Liew, Wen Chiy; Mpamhanga, Chidochangu P.; Bonner, Tom I.; Neubig, Richard R.; Pin, Jean Philippe; Spedding, Michael; Harmar, Anthony J.

2013-01-01

In 2005, the International Union of Basic and Clinical Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR) published a catalog of all of the human gene sequences known or predicted to encode G protein-coupled receptors (GPCRs), excluding sensory receptors. This review updates the list of orphan GPCRs and describes the criteria used by NC-IUPHAR to recommend the pairing of an orphan receptor with its cognate ligand(s). The following recommendations are made for new receptor names based on 11 pairings for class A GPCRs: hydroxycarboxylic acid receptors [HCA1 (GPR81) with lactate, HCA2 (GPR109A) with 3-hydroxybutyric acid, HCA3 (GPR109B) with 3-hydroxyoctanoic acid]; lysophosphatidic acid receptors [LPA4 (GPR23), LPA5 (GPR92), LPA6 (P2Y5)]; free fatty acid receptors [FFA4 (GPR120) with omega-3 fatty acids]; chemerin receptor (CMKLR1; ChemR23) with chemerin; CXCR7 (CMKOR1) with chemokines CXCL12 (SDF-1) and CXCL11 (ITAC); succinate receptor (SUCNR1) with succinate; and oxoglutarate receptor [OXGR1 with 2-oxoglutarate]. Pairings are highlighted for an additional 30 receptors in class A where further input is needed from the scientific community to validate these findings. Fifty-seven human class A receptors (excluding pseudogenes) are still considered orphans; information has been provided where there is a significant phenotype in genetically modified animals. In class B, six pairings have been reported by a single publication, with 28 (excluding pseudogenes) still classified as orphans. Seven orphan receptors remain in class C, with one pairing described by a single paper. The objective is to stimulate research into confirming pairings of orphan receptors where there is currently limited information and to identify cognate ligands for the remaining GPCRs. Further information can be found on the IUPHAR Database website (http://www.iuphar-db.org). PMID:23686350
Constitutive Activity among Orphan Class-A G Protein Coupled Receptors.

PubMed

Martin, Adam L; Steurer, Michael A; Aronstam, Robert S

2015-01-01

The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1) 200% elevation over baseline reporter gene expression; 2) 40% inhibition of baseline expression; and 3) 40% inhibition of expression stimulated by 3 μM forskolin. Five patterns of activity were noted: 1) inhibition under both baseline and forskolin stimulated expression (GPR15, GPR17, GPR18, GPR20, GPR25, GPR27, GPR31, GPR32, GPR45, GPR57, GPR68, GPR83, GPR84, GPR132, GPR150, GPR176); 2) no effect on baseline expression, but inhibition of forskolin stimulated expression (GPR4, GPR26, GPR61, GPR62, GPR78, GPR101, GPR119); 3) elevation of baseline signaling coupled with inhibition of forskolin stimulated expression (GPR6, GPR12); 4) elevation of baseline signaling without inhibition of forskolin stimulated expression (GPR3, GPR21, GPR52, GPR65); and 5) no effect on expression (GPR1, GPR19, GPR22, GPR34, GPR35, GPR39, GPR63, GPR82, GPR85, GPR87). Constitutive activity was observed in 75% of the orphan class-A receptors examined (30 of 40). This constitutive signaling cannot be explained by simple overexpression of the receptor. Inhibition of cAMP mediated expression was far more common (65%) than stimulation of expression (15%). Orphan receptors that were closely related based on amino acid homology tended to have similar effects on gene expression. These results suggest that identification of inverse agonists may be a fruitful approach for categorizing these orphan receptors and targeting them for pharmacological intervention.
Constitutive Activity among Orphan Class-A G Protein Coupled Receptors

PubMed Central

Martin, Adam L.; Steurer, Michael A.; Aronstam, Robert S.

2015-01-01

The purpose of this study was to evaluate the extent of constitutive activity among orphan class-A G protein coupled receptors within the cAMP signaling pathway. Constitutive signaling was revealed by changes in gene expression under control of the cAMP response element. Gene expression was measured in Chinese hamster ovary cells transiently co-transfected with plasmids containing a luciferase reporter and orphan receptor. Criteria adopted for defining constitutive activation were: 1) 200% elevation over baseline reporter gene expression; 2) 40% inhibition of baseline expression; and 3) 40% inhibition of expression stimulated by 3 μM forskolin. Five patterns of activity were noted: 1) inhibition under both baseline and forskolin stimulated expression (GPR15, GPR17, GPR18, GPR20, GPR25, GPR27, GPR31, GPR32, GPR45, GPR57, GPR68, GPR83, GPR84, GPR132, GPR150, GPR176); 2) no effect on baseline expression, but inhibition of forskolin stimulated expression (GPR4, GPR26, GPR61, GPR62, GPR78, GPR101, GPR119); 3) elevation of baseline signaling coupled with inhibition of forskolin stimulated expression (GPR6, GPR12); 4) elevation of baseline signaling without inhibition of forskolin stimulated expression (GPR3, GPR21, GPR52, GPR65); and 5) no effect on expression (GPR1, GPR19, GPR22, GPR34, GPR35, GPR39, GPR63, GPR82, GPR85, GPR87). Constitutive activity was observed in 75% of the orphan class-A receptors examined (30 of 40). This constitutive signaling cannot be explained by simple overexpression of the receptor. Inhibition of cAMP mediated expression was far more common (65%) than stimulation of expression (15%). Orphan receptors that were closely related based on amino acid homology tended to have similar effects on gene expression. These results suggest that identification of inverse agonists may be a fruitful approach for categorizing these orphan receptors and targeting them for pharmacological intervention. PMID:26384023
Caregiver burden among adults caring for orphaned children in rural South Africa

PubMed Central

Kidman, Rachel; Thurman, Tonya R.

2014-01-01

The AIDS epidemic has created an unprecedented number of orphans. While largely absorbed by extended family, this additional responsibility can weigh heavily on their caregivers. The concept of caregiver burden captures multiple dimensions of well-being (e.g., physical, social and psychological). Measuring the extent and determinants of caregiving burden can inform the design of programmes to ease the negative consequences of caregiving. This study uses the baseline data from a study assessing interventions for orphans and vulnerable adolescents in the Eastern Cape, South Africa. Orphan caregivers (n = 726) completed an adapted version of the 12-item Zarit Burden Interview. In addition to basic caregiver and household demographics, the survey also collected information on AIDS-related illness and recent deaths. Descriptive data are presented, followed by multivariate Poisson regression models to explore factors associated with caregiver burden. Approximately 40% of caregivers reported high levels of orphan caregiving burden. Feelings of stress and inadequacy concerning their care responsibilities as well as anger towards the child were common. Household food insecurity was the most important predictor of orphan caregiving burden (marginal effect = 7.82; p < 0.001 for those reporting severe hunger); income was also a significant determinant. When other AIDS impacts were added to the model, only the AIDS-related illness of the caregiver was significantly associated with burden (marginal effect = 3.77; p < 0.001). This study suggests that caregivers with economic vulnerability and those struggling with their own AIDS-related illness feel most overburdened. These findings are particularly relevant to service providers who must identify caregivers in need of immediate assistance and allocate limited resources effectively. To alleviate caregiver burden, programmes must foster greater economic security (e.g., by facilitating access to social grants or directly providing cash transfers) and coordinate services with home-based care programmes serving the chronically ill. PMID:24999368
Sex education is key to combatting AIDS in Brazil.

PubMed

Csillag, C

1999-06-26

About 60,000 children in Brazil were born from an AIDS-affected mother, and 16,000 were orphaned by AIDS. These stark figures were released by the Global Orphan Project and the Instituto Promundo at the EducAids conference. About 90% of childhood AIDS cases were a result of perinatal exposure, and the other 10% from unknown exposure. In response to these prevalences, the EducAids initiative, which aims to promote AIDS education in schools, was considering sex education for preschool children. The coordinator of the government's AIDS prevention program, Pedro Chequer, believes sex education for children as young as 4 years old would reduce AIDS among teenagers and help avoid unwanted pregnancies. The Minister of Health supported this concept. Jose Serra, the Minister of Health declared that it was not the aim of the ministry to avoid teenage pregnancy but to prevent early sexual intercourse. In 1997 the number of deliveries by girls aged 15-19 years had risen to 25.27%, from 21.41% in 1993. However, the number of deliveries for women over age 20 are falling. Pedro Chequer, EducAids coordinator, stated that despite these facts, campaigns for sex education would be opposed by the Roman Catholic Church.
The Orbit of the Orphan Stream

DOE Office of Scientific and Technical Information (OSTI.GOV)

Newberg, Heidi Jo; Willett, Benjamin A.; Yanny, Brian

2010-01-01

We use recent SEGUE spectroscopy and SDSS and SEGUE imaging data to measure the sky position, distance, and radial velocities of stars in the tidal debris stream that is commonly referred to as the 'Orphan Stream.' We fit orbital parameters to the data, and find a prograde orbit with an apogalacticon, perigalacticon, and eccentricity of 90 kpc, 16.4 kpc and e = 0.7, respectively. Neither the dwarf galaxy UMa II nor the Complex A gas cloud have velocities consistent with a kinematic association with the Orphan Stream. It is possible that Segue-1 is associated with the Orphan Stream, but nomore » other known Galactic clusters or dwarf galaxies in the Milky Way lie along its orbit. The detected portion of the stream ranges from 19 to 47 kpc from the Sun and is an indicator of the mass interior to these distances. There is a marked increase in the density of Orphan Stream stars near (l, b) = (253{sup o}; 49{sup o}), which could indicate the presence of the progenitor at the edge of the SDSS data. If this is the progenitor, then the detected portion of the Orphan Stream is a leading tidal tail. We find blue horizontal branch (BHB) stars and F turnoff stars associated with the Orphan Stream. The turnoff color is (g-r){sub 0} = 0.22. The BHB stars have a low metallicity of [Fe/H]{sub WBG} = -2.1. The orbit is best fit to a halo potential with a halo plus disk mass of about 2.6 x 10{sup 11} M{sub {circle_dot}}, integrated to 60 kpc from the Galactic center. Our fits are done to orbits rather than full N-body simulations; we show that if N-body simulations are used, the inferred mass of the galaxy would be slightly smaller. Our best fit is found with a logarithmic halo speed of v{sub halo} = 73 {+-} 24 km s{sup -1}, a disk+bulge mass of M(R < 60 kpc) = 1.3 x 10{sup 11} M{sub {circle_dot}}, and a halo mass of M(R < 60 kpc) = 1.4 x 10{sup 11} M{sub {circle_dot}}. However, we can find similar fits to the data that use an NFW halo profile, or that have smaller disk masses and correspondingly larger halo masses. Distinguishing between different classes of models requires data over a larger range of distances. The Orphan Stream is projected to extend to 90 kpc from the Galactic center, and measurements of these distant parts of the stream would be a powerful probe of the mass of the Milky Way.« less
Availability of and access to orphan drugs: an international comparison of pharmaceutical treatments for pulmonary arterial hypertension, Fabry disease, hereditary angioedema and chronic myeloid leukaemia.

PubMed

Blankart, Carl Rudolf; Stargardt, Tom; Schreyögg, Jonas

2011-01-01

Market authorization does not guarantee patient access to any given drug. This is particularly true for costly orphan drugs because access depends primarily on co-payments, reimbursement policies and prices. The objective of this article is to identify differences in the availability of orphan drugs and in patient access to them in 11 pharmaceutical markets: Australia, Canada, England, France, Germany, Hungary, the Netherlands, Poland, Slovakia, Switzerland and the US. Four rare diseases were selected for analysis: pulmonary arterial hypertension (PAH), Fabry disease (FD), hereditary angioedema (HAE) and chronic myeloid leukaemia (CML). Indicators for availability were defined as (i) the indications for which orphan drugs had been authorized in the treatment of these diseases; (ii) the application date; and (iii) the date upon which these drugs received market authorization in each country. Indicators of patient access were defined as (i) the outcomes of technology appraisals; (ii) the extent of coverage provided by healthcare payers; and (iii) the price of the drugs in each country. For PAH we analysed bosentan, iloprost, sildenafil, treprostinil (intravenous and inhaled) as well as sitaxentan and ambrisentan; for FD we analysed agalsidase alfa and agalsidase beta; for HAE we analysed icatibant, ecallantide and two complement C1s inhibitors; for CML we analysed imatinib, dasatinib and nilotinib. Most drugs included in this study had received market authorization in all countries, but the range of indications for which they had been authorized differed by country. The broadest range of indications was found in Australia, and the largest variations in indications were found for PAH drugs. Authorization process speed (the time between application and market authorization) was fastest in the US, with an average of 362 days, followed by the EU (394 days). The highest prices for the included drugs were found in Germany and the US, and the lowest in Canada, Australia and England. Although the prices of all of the included drugs were high compared with those of most non-orphan drugs, most of the insurance plans in our country sample provided coverage for authorized drugs after a certain threshold. Availability of and access to orphan drugs play a key role in determining whether patients will receive adequate and efficient treatment. Although the present study showed some variations between countries in selected indicators of availability and access to orphan drugs, virtually all of the drugs in question were available and accessible in our sample. However, substantial co-payments in the US and Canada represent important barriers to patient access, especially in the case of expensive treatments such as those analysed in this study. Market exclusivity is a strong instrument for fostering orphan drug development and drug availability. However, despite the positive effect of this instrument, the conditions under which market exclusivity is granted should be reconsidered in cases where the costs of developing an orphan drug have already been amortized through the use of the drug's active ingredient for the treatment of a common indication.
75 FR 47602 - Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01)

Federal Register 2010, 2011, 2012, 2013, 2014

2010-08-06

...] Clinical Studies of Safety and Effectiveness of Orphan Products Research Project Grant (R01) AGENCY: Food... product will be superior to the existing therapy. FDA provides grants for clinical studies on safety and... vaccine annually) and an explanation of how the proposed study will either help support product approval...

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