Global Trends in Tobacco Cigarette Use among Adolescents: Prevalence of Use and Evidence Based Cessation Interventions

Tobacco use remains a global problem, and as a demographic group, adolescents are at a high risk of its adverse effects. In addition, disparities exist in strategies to address tobacco control, particularly among youth from low-socioeconomic backgrounds. The health risks associated with tobacco use provide a compelling reason for all nations to prioritize addressing and regulating its use and providing sustainable funding sources for training healthcare professionals and others under Article 14 of the World Health Framework Convention on Tobacco Control (FCTC). This article has four primary goals: (1) to provide an overview of the 2005 World Health Organization’s international public health treaty - the World Health FCTC; (2) to examine the prevalence of tobacco cigarette use among adolescents globally and the impact of cultural/social influences on use; (3) to provide an overview of current evidence based smoking cessations interventions that have shown success with this group; and (4) to discuss the overarching social work implications and practice when working with adolescents who use tobacco cigarettes

Working towards consensus on methods used to elicit participant-reported safety data in uncomplicated malaria clinical drug studies: a Delphi technique study

BACKGROUND: Eliciting adverse event (AE) and non-study medication data reports from clinical research participants is integral to evaluating drug safety. However, using different methods to question participants yields inconsistent results, compromising the interpretation, comparison and pooling of data across studies. This is particularly important given the widespread use of anti-malarials in vulnerable populations, and their increasing use in healthy, but at-risk individuals, as preventive treatment or to reduce malaria transmission. METHODS: Experienced and knowledgeable anti-malarial drug clinical researchers were invited to participate in a Delphi technique study, to facilitate consensus on what are considered optimal (relevant, important and feasible) methods, tools, and approaches for detecting participant-reported AE and non-study medication data in uncomplicated malaria treatment studies. RESULTS: Of 72 invited, 25, 16 and 10 panellists responded to the first, second and third rounds of the Delphi, respectively. Overall, 68% (68/100) of all questioning items presented for rating achieved consensus. When asking general questions about health, panellists agreed on the utility of a question/concept about any change in health, taking care to ensure that such questions/concepts do not imply causality. Eighty-nine percent (39/44) of specific signs and symptoms questions were rated as optimal. For non-study medications, a general question and most structured questioning items were considered an optimal approach. The use of mobile phones, patient diaries, rating scales as well as openly engaging with participants to discuss concerns were also considered optimal complementary data-elicitation tools. CONCLUSIONS: This study succeeded in reaching consensus within a section of the anti-malarial drug clinical research community about using a general question concept, and structured questions for eliciting data about AEs and non-study medication reports. The concepts and items considered in this Delphi to be relevant, important and feasible should be further investigated for potential inclusion in a harmonized approach to collect participant-elicited anti-malarial drug safety data. This, in turn, should improve understanding of anti-malarial drug safety

Neuroauditory Toxicity of Artemisinin Combination Therapies—Have Safety Concerns Been Addressed?

Although artemisinin-based combination therapies (ACTs) are widely viewed as safe drugs with a wide therapeutic dose range, concerns about neuroauditory safety of artemisinins arose during their development. A decade ago, reviews of human data suggested a potential neuro-ototoxic effect, but the validity of these findings was questioned. With 5–10 years of programmatic use, emerging artemisinin-tolerant falciparum malaria in southeast Asia, and the first calls to consider an increased dose of artemisinins, we review neuroauditory safety data on ACTs to treat uncomplicated falciparum malaria. Fifteen studies reported a neurological or auditory assessment. The large heterogeneity of neuro-ototoxic end points and assessment methodologies and the descriptive nature of assessments hampered a formal meta-analysis and definitive conclusions, but they highlight the persistent lack of data from young children. This subgroup is potentially most vulnerable to any neuroauditory toxicity because of their development stage, increased malaria susceptibility, and repeated ACT exposure in settings lacking robust safety monitoring

Development of a pharmacovigilance safety monitoring tool for the rollout of single low-dose primaquine and artemether-lumefantrine to treat Plasmodium falciparum infections in Swaziland: a pilot study.

BACKGROUND Countries remain reluctant to adopt the 2012 World Health Organization recommendation for single low-dose (0.25 mg/kg) primaquine (SLD PQ) for Plasmodium falciparum transmission-blocking due to concerns over drug-related haemolysis risk, especially among glucose-6-phosphate dehydrogenase-deficient (G6PDd) people, without evidence demonstrating that it can be safely deployed in their settings. Pharmacovigilance methods provide a systematic way of collecting safety data and supporting the rollout of SLD PQ. METHODS The Primaquine Roll Out Monitoring Pharmacovigilance Tool (PROMPT), comprising: (1) a standardized form to support the surveillance of possible adverse events following SLD PQ treatment; (2) a patient information card to enhance awareness of known adverse drug reactions of SLD PQ use; and (3) a database compiling recorded information, was developed and piloted. Data on patient characteristics, malaria diagnosis and treatment are collected. Blood samples are taken to measure haemoglobin (Hb) and test for G6PD deficiency. Active follow-up includes a repeat Hb measurement and adverse event monitoring on or near day 7. A 13-month prospective pilot study in two hospital facilities in Swaziland alongside the introduction of SLD PQ generated preliminary evidence on the feasibility and acceptability of PROMPT. RESULTS PROMPT was well received by nurses as a simple, pragmatic approach to active surveillance of SLD PQ safety data. Of the 102 patients enrolled and administered SLD PQ, none were G6PDd. 93 (91.2 %) returned on or near day 7 for follow-up. Four (4.6 %) patients had falls in Hb ≥25 % from baseline, none of whom presented with signs or symptoms of anaemia. No patient's Hb fell below 7 g/dL and none required a blood transfusion. Of the 11 (11 %) patients who reported an adverse event over the study period, three were considered serious and included two deaths and one hospitalization; none were causally related to SLD PQ. Four non-serious adverse events were considered definitely, probably, or possibly related to SLD PQ. CONCLUSION Improved pharmacovigilance to monitor and promote the safety of the WHO recommendation is needed. The successful application of PROMPT demonstrates its potential as an important tool to rapidly generate locally acquired safety data and support pharmacovigilance in resource-limited settings

Menstrual cups and cash transfer to reduce sexual and reproductive harm and school dropout in adolescent schoolgirls: study protocol of a cluster-randomised controlled trial in western Kenya

Background Adolescent girls in sub-Saharan Africa are disproportionally vulnerable to sexual and reproductive health (SRH) harms. In western Kenya, where unprotected transactional sex is common, young females face higher rates of school dropout, often due to pregnancy, and sexually transmitted infections (STIs), including HIV. Staying in school has shown to protect girls against early marriage, teen pregnancy, and HIV infection. This study evaluates the impact of menstrual cups and cash transfer interventions on a composite of deleterious outcomes (HIV, HSV-2, and school dropout) when given to secondary schoolgirls in western Kenya, with the aim to inform evidence-based policy to improve girls’ health, school equity, and life-chances. Methods Single site, 4-arm, cluster randomised controlled superiority trial. Secondary schools are the unit of randomisation, with schoolgirls as the unit of measurement. Schools will be randomised into one of four intervention arms using a 1:1:1:1 ratio and block randomisation: (1) menstrual cup arm; (2) cash transfer arm, (3) cups and cash combined intervention arm, or (4) control arm. National and county agreement, and school level consent will be obtained prior to recruitment of schools, with parent consent and girls’ assent obtained for participant enrolment. Participants will be trained on safe use of interventions, with all arms receiving puberty and hygiene education. Annually, the state of latrines, water availability, water treatment, handwashing units and soap in schools will be measured. The primary endpoint is a composite of incident HIV, HSV-2, and all-cause school dropout, after 3 years follow-up. School dropout will be monitored each term via school registers and confirmed through home visits. HIV and HSV-2 incident infections and risk factors will be measured at baseline, mid-line and end-line. Intention to treat analysis will be conducted among all enrolled participants. Focus group discussions will provide contextual information on uptake of interventions. Monitoring for safety will occur throughout. Discussion If proved safe and effective, the interventions offer a potential contribution toward girls’ schooling, health, and equity in low- and middle-income countries

APOBEC3G expression is dysregulated in primary HIV-1 infection and polymorphic variants influence CD4R T-cell counts and plasma viral load.

Objectives: In the absence of HIV-1 virion infectivity factor (Vif), cellular cytosine deaminases such as apolipoprotein B mRNA-editing enzyme catalytic polypeptide-like 3G (APOBEC3G) inhibit the virus by inducing hypermutations on viral DNA, among other mechanisms of action. We investigated the association of APOBEC3G mRNA levels and genetic variants on HIV-1 susceptibility, and early disease pathogenesis using viral load and CD4+ T-cell counts as outcomes. Methods: Study participants were 250 South African women at high risk for HIV-1 subtype C infection.We used real-time PCR to measure the expression of APOBEC3G in HIV-negative and HIV-positive primary infection samples. APOBEC3G variants were identified by DNA re-sequencing and TaqMan genotyping. Results: We found no correlation between APOBEC3G expression levels and plasma viral loads (r=0.053, P=0.596) or CD4+ T-cell counts (r=0.030, P=0.762) in 32 seroconverters. APOBEC3G expression levels were higher in HIV-negative individuals as compared with HIV-positive individuals (P<0.0001), including matched pre and postinfection samples from the same individuals (n=13, P<0.0001). Twenty-four single nucleotide polymorphisms, including eight novel, were identified within APOBEC3G by re-sequencing and genotyping. The H186R mutation, a codon-changing variant in exon 4, and a 3' extragenic mutation (rs35228531) were associated with high viral loads (P=0.0097 and P<0.0001) and decreased CD4+ T-cell levels (P=0.0081 and P<0.0001), respectively. Conclusion: These data suggest that APOBEC3G transcription is rapidly downregulated upon HIV-1 infection. During primary infection, APOBEC3G expression levels in peripheral blood mononuclear cells do not correlate with viral loads or CD4+ T-cell counts. Genetic variation of APOBEC3G may significantly affect early HIV-1 pathogenesis, although the mechanism remains unclear and warrants further investigation

Perceptions and utilization of the anti-malarials artemether-lumefantrine and dihydroartemisinin-piperaquine in young children in the Chikhwawa District of Malawi: a mixed methods study

Background Adherence to anti-malarial dosing schedules is essential to ensure effective treatment. Measuring adherence is challenging due to recall issues and the participants’ awareness of the desired behaviour influencing their actions or responses. This study used qualitative methods, which allow for rapport building, to explore issues around anti-malarial utilization in young children, and used the results to guide the development of a context specific questionnaire on perceptions and adherence to artemether-lumefantrine (AL) and dihydroartemisinin-piperaquine (DHA-PPQ). Methods Qualitative data collection included 12 focus group discussions which explored community perceptions of anti-malarials and experiences of administering medications to children. Critical incidence interviews were conducted with 22 caregivers to explore experiences of administering the dispersible or original formulation of AL to young children during recent febrile episodes. A structured questionnaire was used to gather data on experience of recent treatment and adherence to anti-malarials during follow-up visits with 218 caregivers whose child was recently treated with either dispersible AL or DHA-PPQ. Discussion/Conclusion Caregivers experience great difficulty in administering medication to children. While the sweet taste of dispersible AL may have reduced conflict between the child and caregiver, sub-optimal dosing due to medication loss remained a problem and overall adherence was greater among those receiving DHA-PPQ, which requires fewer doses. Some caregivers were found to deliberately alter the dosing schedule according to whether they perceived the medication to be too weak or strong. They also developed theories for poor treatment outcomes, such as attributing this to lack of compatibility between the medication and the child. Health education messages should be strengthened to ensure a combination of clear pictorial and verbal instructions are used during dispensing, and consequences of under and over-dosing are explained alongside appropriate responses to possible adverse events. Further optimizing of anti-malarial adherence among children requires the development of anti-malarials with pharmacological properties that allow user-friendly administration and simplified dosing schedules

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead

Search for gravitational-lensing signatures in the full third observing run of the LIGO-Virgo network

Gravitational lensing by massive objects along the line of sight to the source causes distortions of gravitational wave-signals; such distortions may reveal information about fundamental physics, cosmology and astrophysics. In this work, we have extended the search for lensing signatures to all binary black hole events from the third observing run of the LIGO--Virgo network. We search for repeated signals from strong lensing by 1) performing targeted searches for subthreshold signals, 2) calculating the degree of overlap amongst the intrinsic parameters and sky location of pairs of signals, 3) comparing the similarities of the spectrograms amongst pairs of signals, and 4) performing dual-signal Bayesian analysis that takes into account selection effects and astrophysical knowledge. We also search for distortions to the gravitational waveform caused by 1) frequency-independent phase shifts in strongly lensed images, and 2) frequency-dependent modulation of the amplitude and phase due to point masses. None of these searches yields significant evidence for lensing. Finally, we use the non-detection of gravitational-wave lensing to constrain the lensing rate based on the latest merger-rate estimates and the fraction of dark matter composed of compact objects