Abstract
Background
The advent of new methods of male contraception would increase contraceptive options for men and women and advance male contraceptive agency. Pharmaceutical R&D for male ...contraception has been dormant since the 1990s. The Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) has supported a contraceptive development program since 1969 and supports most ongoing hormonal male contraceptive development. Nonhormonal methods are in earlier stages of development.
Content
Several hormonal male contraceptive agents have entered clinical trials. Novel single agent products being evaluated include dimethandrolone undecanoate, 11β-methyl-nortestosterone dodecylcarbonate, and 7α-methyl-19-nortestosterone. A contraceptive efficacy trial of Nestorone®/testosterone gel is underway. Potential nonhormonal methods are at preclinical stages of development. Many nonhormonal male contraceptive targets that affect sperm production, sperm function, or sperm transport have been identified.
Summary
NICHD supports development of reversible male contraceptive agents. Other organizations such as the World Health Organization, the Population Council, and the Male Contraception Initiative are pursuing male contraceptive development, but industry involvement remains limited.
Children and adolescents with early-stage classical Hodgkin lymphoma have a 5-year event-free survival of 90% or more with vincristine, etoposide, prednisone, and doxorubicin (OEPA) plus ...radiotherapy, but late complications of treatment affect survival and quality of life. We investigated whether radiotherapy can be omitted in patients with adequate morphological and metabolic responses to OEPA.
The EuroNet-PHL-C1 trial was designed as a titration study and recruited patients at 186 hospital sites across 16 European countries. Children and adolescents with newly diagnosed stage IA, IB, and IIA classical Hodgkin lymphoma younger than 18 years of age were assigned to treatment group 1 to be treated with two cycles of OEPA (vincristine 1·5 mg/m2 intravenously, capped at 2 mg, on days 1, 8, and 15; etoposide 125 mg/m2 intravenously, on days 1–5; prednisone 60 mg/m2 orally on days 1–15; and doxorubicin 40 mg/m2 intravenously on days 1 and 15). If no adequate response (a partial morphological remission or greater and PET negativity) had been achieved after two cycles of OEPA, involved-field radiotherapy was administered at a total dose of 19·8 Gy (usually in 11 fractions of 1·8 Gy per day). The primary endpoint was event-free survival. The primary objective was maintaining a 5-year event-free survival rate of 90% in patients with an adequate response to OEPA without radiotherapy. We performed intention-to-treat and per-protocol analyses. The trial was registered at ClinicalTrials.gov (NCT00433459) and with EUDRACT, (2006–000995-33) and is completed.
Between Jan 31, 2007, and Jan 30, 2013, 2131 patients were registered and 2102 patients were enrolled onto EuroNet-PHL-C1. Of these 2102 patients, 738 with early-stage disease were allocated to treatment group 1. Median follow-up was 63·3 months (IQR 60·1–69·8). We report on 714 patients assigned to and treated on treatment group 1; the intention-to-treat population comprised 713 patients with 323 (45%) male and 390 (55%) female patients. In 440 of 713 patients in the intention-to-treat group who had an adequate response and did not receive radiotherapy, 5-year event-free survival was 86·5% (95% CI 83·3–89·8), which was less than the 90% target rate. In 273 patients with an inadequate response who received radiotherapy, 5-year event-free survival was 88·6% (95% CI 84·8–92·5), for which the 95% CI included the 90% target rate. The most common grade 3–4 adverse events were neutropenia (in 597 88% of 680 patients) and leukopenia (437 61% of 712). There were no treatment-related deaths.
On the basis of all the evidence, radiotherapy could be omitted in patients with early-stage classical Hodgkin lymphoma and an adequate response to OEPA, but patients with risk factors might need more intensive treatment.
Deutsche Krebshilfe, Elternverein für Krebs-und leukämiekranke Kinder, Gießen, Kinderkrebsstiftung Mainz of the Journal Oldtimer Markt, Tour der Hoffnung, Menschen für Kinder, Mitteldeutsche Kinderkrebsforschung, Programme Hospitalier de Recherche Clinique, and Cancer Research UK.
After working in hospitals in London, including St Mary’s Hospital where Alexander Fleming was researching antibiotic resistance during that time, he returned to Ireland, first as a locum on ...Arranmore Island in Donegal and then as a GP in Ballina, County Mayo. “Loughran firmly believed that the prohibition of effective family planning was wrong and the so called ‘natural’ method of contraception—which involved women abstaining from sex during the fertile stage of their menstrual cycle and which was permitted by the Catholic Church—was unreliable.” According to his son, John, his father remained active and in relatively good health, despite atrial fibrillation, cardiovascular disease, and a stroke and walked two kilometres every day until the last months of his life.
A combination of levonorgestrel—known as “plan B” or the “morning after pill”—and the anti-inflammatory drug piroxicam is more effective in preventing pregnancy compared with levonorgestrel alone, ...according to a randomised controlled trial.1 The study involved 860 women who sought emergency contraception within 72 hours of unprotected intercourse at a major community sexual and reproductive health service in Hong Kong between 2018 and 2022. Alternative methods of emergency contraception are insertion of a copper IUD, which requires medical personnel to insert the device, or ulipristal, which is less widely available than levonorgestrel and more expensive. 2 Meanwhile, Janet Nooney, expect scientific assessor in the UK Medicines and Healthcare Products Regulatory Agency’s benefit risk management unit, said, “In the UK oral piroxicam tablets are no longer recommended for acute pain relief or inflammatory conditions as it is associated with serious gastrointestinal side effects and rare but possibly fatal skin reactions.
Summary A new Global Investment Framework for Women's and Children's Health demonstrates how investment in women's and children's health will secure high health, social, and economic returns. We ...costed health systems strengthening and six investment packages for: maternal and newborn health, child health, immunisation, family planning, HIV/AIDS, and malaria. Nutrition is a cross-cutting theme. We then used simulation modelling to estimate the health and socioeconomic returns of these investments. Increasing health expenditure by just $5 per person per year up to 2035 in 74 high-burden countries could yield up to nine times that value in economic and social benefits. These returns include greater gross domestic product (GDP) growth through improved productivity, and prevention of the needless deaths of 147 million children, 32 million stillbirths, and 5 million women by 2035. These gains could be achieved by an additional investment of $30 billion per year, equivalent to a 2% increase above current spending.
Background
Recently, among others due to the COVID-19 pandemic and the war in Ukraine, European countries have been experiencing rising inflation. Value-added taxes (VAT) on essential goods have ...gained public attention, and abolishing VAT for these goods has been discussed as a measure to prevent poverty and inequities. The study aims to investigate the relevance of value-added tax on medicines in European countries.
Methods
We collated information on medicines-specific and standard VAT rates in 41 countries of the WHO European Region (all 27 European Union Member States, Albania, Armenia, Iceland, Israel, Kazakhstan, Kyrgyzstan, Kosovo, Moldova, North Macedonia, Norway, Serbia, Switzerland, Turkey and United Kingdom). Data were reviewed from literature and were validated by national public authorities.
Results
In three countries (Albania, Kazakhstan and Malta), all medicines are exempt from VAT. 28 of the 38 countries with VAT on medicines impose a single VAT rate on all medicines, and in most of these countries (21 countries) the medicines-related VAT is lower than the standard VAT rate. Ten countries have differentiated VAT rates: In Ireland, Kyrgyzstan, Sweden and the UK defined medicines (e.g. oral medicines, prescription-only medicines) are exempt from VAT, whereas for the other medicines the standard VAT rate applies; six further countries have a lower VAT rate for some medicines (e.g. heparins, blood products, contraceptives or reimbursed medicines in general) compared to the remaining medicines, whose VAT rate equal the standard rate or is lower.
Conclusions
Some European countries apply specific mechanisms (exemptions, reduced rates) regarding the VAT for defined or all medicines. This may act as a protective measure for patients in case of non-reimbursed medicines and help public payers to ensure financial sustainability to funded medicines. Further medicines-specific research is needed to understand the impact of inflation.
Key messages
* Value-added tax is a relevant component of medicine prices.
* Lowering or abolishing the VAT on medicines can be an important policy espeically when patients pay out-of-pocket.
To determine cervical cancer risk associated with contemporary hormonal contraceptives, we conducted a cohort study of women aged 15 to 49 living in Denmark from 1995 to 2014, using routinely ...collected information about redeemed prescriptions, incident cancer and potential confounders. Poisson regression calculated adjusted cervical cancer risks among different contraceptive user groups by duration of use, time since last use, hormonal content and cancer histology. During >20 million person‐years, 3643 incident cervical cancers occurred. Ever users of any hormonal contraceptives compared to never users had a relative risk (RR) of 1.19 (95% confidence interval CI 1.10‐1.29). Increased risks were seen in current or recent users of any hormonal: RR 1.30 (95% CI 1.20‐1.42) and combined: RR 1.40 (95% CI 1.28‐1.53), but not progestin‐only contraception: RR 0.91 (95% CI 0.78‐1.07). Current or recent users of any hormonal contraception had an increased risk of both adenocarcinoma (RR 1.29, 95% CI 1.05‐1.60) and squamous cancer (RR 1.31, 95% CI 1.19‐1.44). The risk pattern among any hormonal and combined contraceptive users generally increased with longer duration of use and declined after stopping, possibly taking longer to disappear among prolonged users. Combined products containing different progestins had similar risks. Approximately one extra cervical cancer occurred for every 14 700 women using combined contraceptives for 1 year. Most women in our study were not vaccinated against human papillomavirus (HPV) infections. Our findings reinforce the urgent need for global interventions such as systematic screening, treatment of cervical intraepithelial neoplasia and HPV vaccination programmes to prevent cervical cancer, especially among users of combined contraceptives.
What's new?
Globally, millions of hormonal contraception users are unvaccinated against human papillomavirus (HPV) infections, which are known to cause cervical cancer. Little is known about contemporary hormonal contraceptives and cervical cancer risk. In this cohort of mostly unvaccinated women, current or recent use of any hormonal and combined but not progestin‐only contraceptives increased cervical cancer risk. The effect strengthened with increasing duration and took longer to decline with prolonged use. The results reinforce the urgency for global interventions to prevent cervical cancer including HPV vaccination programmes, systematic cervical screening and treatment of cervical intraepithelial neoplasia, especially among users of combined contraceptives.
Improving the reproductive health of young women in developing countries requires access to safe and effective methods of fertility control, but most rely on traditional rather than modern ...contraceptives such as condoms or oral/injectable hormonal methods. We conducted a systematic review of qualitative research to examine the limits to modern contraceptive use identified by young women in developing countries. Focusing on qualitative research allows the assessment of complex processes often missed in quantitative analyses.
Literature searches of 23 databases, including Medline, Embase and POPLINE(R), were conducted. Literature from 1970-2006 concerning the 11-24 years age group was included. Studies were critically appraised and meta-ethnography was used to synthesise the data.
Of the 12 studies which met the inclusion criteria, seven met the quality criteria and are included in the synthesis (six from sub-Saharan Africa; one from South-East Asia). Sample sizes ranged from 16 to 149 young women (age range 13-19 years). Four of the studies were urban based, one was rural, one semi-rural, and one mixed (predominantly rural). Use of hormonal methods was limited by lack of knowledge, obstacles to access and concern over side effects, especially fear of infertility. Although often more accessible, and sometimes more attractive than hormonal methods, condom use was limited by association with disease and promiscuity, together with greater male control. As a result young women often relied on traditional methods or abortion. Although the review was limited to five countries and conditions are not homogenous for all young women in all developing countries, the overarching themes were common across different settings and contexts, supporting the potential transferability of interventions to improve reproductive health.
Increasing modern contraceptive method use requires community-wide, multifaceted interventions and the combined provision of information, life skills, support and access to youth-friendly services. Interventions should aim to counter negative perceptions of modern contraceptive methods and the dual role of condoms for contraception and STI prevention should be exploited, despite the challenges involved.
To explore the effect of Medicaid expansion on US infant mortality rate.
We examined data from 2010 to 2016 and 2014 to 2016 to compare infant mortality rates in states and Washington, DC, that ...accepted the Affordable Care Act Medicaid expansion (Medicaid expansion states) and states that did not (non-Medicaid expansion states), stratifying data by race/ethnicity.
Mean infant mortality rate in non-Medicaid expansion states rose (6.4 to 6.5) from 2014 to 2016 but declined in Medicaid expansion states (5.9 to 5.6). Mean difference in infant mortality rate in Medicaid expansion versus non-Medicaid expansion states increased from 0.573 (P = .08) in 2014 to 0.838 in 2016 (P = .006) because of smaller declines in non-Medicaid expansion (11.0%) than in Medicaid expansion (15.2%) states. The 14.5% infant mortality rate decline from 11.7 to 10.0 in African American infants in Medicaid expansion states was more than twice that in non-Medicaid expansion states (6.6%: 12.2 to 11.4; P = .012).
Infant mortality rate decline was greater in Medicaid expansion states, with greater declines among African American infants. Future research should explore what aspects of Medicaid expansion may improve infant survival.
Despite efforts to expand contraceptive access for young people, few studies have considered where young women (age 15–24) in low- and middle-income countries obtain modern contraceptives and how the ...capacity and content of care of sources used compares with older users.
We examined the first source of respondents' current modern contraceptive method using the most recent Demographic and Health Survey since 2000 for 33 sub-Saharan African countries. We classified providers according to sector (public/private) and capacity to provide a range of short- and long-term methods (limited/comprehensive). We also compared the content of care obtained from different providers.
Although the public and private sectors were both important sources of family planning (FP), young women (15–24) used more short-term methods obtained from limited-capacity, private providers, compared with older women. The use of long-term methods among young women was low, but among those users, more than 85% reported a public sector source. Older women (25+) were significantly more likely to utilize a comprehensive provider in either sector compared with younger women. Although FP users of all ages reported poor content of care across all providers, young women had even lower content of care.
The results suggest that method and provider choice are strongly linked, and recent efforts to increase access to long-term methods among young women may be restricted by where they seek care. Interventions to increase adolescents' access to a range of FP methods and quality counseling should target providers frequently used by young people, including limited-capacity providers in the private sector.
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