Perfect- and typical-use effectiveness of the Dot fertility app over 13 cycles: results from a prospective contraceptive effectiveness trial

Objective: Dynamic Optimal Timing (Dot) is a smartphone application (app) that estimates the menstrual cycle fertile window based on the user’s menstrual period start dates. Dot uses machine learning to adapt to cycles over time and informs users of ‘low’ and ‘high’ fertility days. We investigated Dot’s effectiveness, calculating perfect- and typical-use failure rates.

Methods: This prospective, 13 cycle observational study (ClinicalTrials.gov NCT02833922) followed 718 women who were using Dot to prevent pregnancy. Participants contributed 6616 cycles between February 2017 and October 2018, providing data on menstrual period start dates, daily sexual activity and prospective intent to prevent pregnancy. We determined pregnancy through participant-administered urine pregnancy tests and/or written or verbal confirmation. We calculated perfect- and typical-use failure rates using multi-censoring, single-decrement life-table analysis, and conducted sensitivity, attrition and survival analyses.

Results: The perfect-use failure rate was calculated to be 1.0% (95% confidence interval [CI]: 0.9%, 2.9%) and the typical-use failure rate was 5.0% (95% CI: 3.4%, 6.6%) for women aged 18–39 (n?=?718). Survival analyses identified no significant differences among age or racial/ethnic groups or women in different types of relationships. Attrition analyses revealed no significant sociodemographic differences, except in age, between women completing 13 cycles and those exiting the study earlier.

Conclusion: Dot’s effectiveness is within the range of other user-initiated contraceptive methods.     

The Protective Effects of Up-Regulating Prostacyclin Biosynthesis on Neuron Survival in Hippocampus

Cellular arachidonic acid (AA), an unsaturated fatty acid found ubiquitously in plasma membranes, is metabolized to different prostanoids, such as prostacyclin (PGI₂) and prostaglandin E₂ (PGE₂), by the three-step reactions coupling the upstream cyclooxygenase (COX) isoforms (COX-1 and COX-2) with the corresponding individual downstream synthases. While the vascular actions of these prostanoids are well-characterized, their specific roles in the hippocampus, a major brain area for memory, are poorly understood. The major obstacle for its understanding in the brain was to mimic the biosynthesis of each prostanoid. To solve the problem, we utilized Single-Chain Hybrid Enzyme Complexes (SCHECs), which could successfully control cellular AA metabolites to the desired PGI₂ or PGE₂. Our in vitro studies suggested that neurons with higher PGI₂ content and lower PGE₂ content exhibited survival protection and resistance to Amyloid-β-induced neurotoxicity. Further extending to an in vivo model, the hybrid of PGI₂-producing transgenic mice and Alzheimer’s disease (AD) mice showed restored long-term memory. These findings suggested that the vascular prostanoids, PGI₂ and PGE₂, exerted significant regulatory influences on neuronal protection (by PGI₂), or damage (by PGE₂) in the hippocampus, and raised a concern that the wide uses of aspirin in cardiovascular diseases may exert negative impacts on neurodegenerative protection.

Our study intended to understand the crosstalk of prostanoids in the hippocampus, a major brain area impacted in AD, by using hybrid enzymes to redirect the synthesis of prostanoids to PGE₂ and PGI₂, respectively. Our data indicated that during inflammation, the vascular mediators, PGI₂ and PGE₂, exerted significant regulatory influences on neuronal protection (by PGI₂), or damage (by PGE₂) in the hippocampus. These findings also raised a concern that the widely uses of non-steroidal anti-inflammatory drugs in cardiovascular diseases may exert negative impacts on neurodegenerative protection.

     

HIV/AIDS among pastoralists and refugees in north-east Africa: a neglected problem

The eight member states (Djibouti, Eritrea, Ethiopia, Kenya, Somalia, South Sudan, Sudan and Uganda) of the Intergovernmental Authority for Development (IGAD) have the largest proportions of cross-border mobile pastoralists and refugees in Africa. Although all IGAD countries have had national HIV/AIDS prevention, care and treatment programmes since the late 1980s, the IGAD Regional HIV & AIDS Partnership Program was (IRAPP) established in 2007 to mitigate the challenges of HIV among neglected pastoral and refugee communities. This article assesses vulnerability of pastoralists and refugee communities to HIV and interventions targeting these groups in the IGAD countries. Outcomes from this study may serve as a baseline for further research and to improve interventions. Published articles were accessed through web searches using PubMed and Google Scholar engines and unpublished documents were collected manually. The search terms were HIV risk behaviour, vulnerability, HIV prevalence and interventions, under the headings pastoralists, refugees, IGAD and north-east Africa for the period 2001–2014. Of the 214 documents reviewed, 78 met the inclusion criteria and were included. Most HIV/AIDS related studies focusing of pastoral communities in IGAD countries were found to be limited in scope and coverage but reveal precarious situations. Sero-prevalence among various pastoral populations ranged from 1% to 21% in Ethiopia, Kenya, Somalia and Uganda and from 1% to 5% among refugees in Sudan, Kenya and Uganda. Socioeconomic, cultural, logistic, infrastructure and programmatic factors were found to contribute to continuing vulnerability to HIV. Interventions need to be further contextualised to the needs of those impoverished populations and integrated into national HIV/AIDS programmes. HIV/AIDS remains a major public health concern among the pastoral and refugee communities of IGAD countries. This calls for IGAD to collaborate with national and international partners in designing and implementing more effective prevention and control programmes. Furthermore, interventions must extend beyond the health sector and improve the livelihood of these populations.     

Methanol poisoning: a review and case study of four patients from Central Australia

Methanol intoxication, a rare and potentially lethal form of poisoning, usually results from ingestion and occasionally inhalation of methanol. Initial symptoms of blurred vision, elongated anion gap and metabolic acidosis are typically delayed and may not at first be recognised as methanol-related complaints. Once diagnosed, treatment must be prompt and definitive. As well as general supportive care, ethanol infusion, dialysis and alkalinization form the mainstays of treatment.

The cases described in this paper are compared to previous reports from other countries worldwide and contrast the variance in outcome often seen in methanol poisoning. The paper describes two tragic deaths and two lucky survivors, all of whom had consumed a cocktail of methanol and other alcoholic beverages at the same party.

The ICU nurse's role in managing the methanol-intoxicated patient relies on that person's sound knowledge of the unusual biochemical reactions occurring in the body and the need to institute definitive and supportive measures to help both patient and family recover.     

Trichinella infection and clinical disease

Trichinellosis is caused by ingestion of insufficiently cooked meat contaminated with infective larvae of <it>Trichinella</it> species. The clinical course is highly variable, ranging from no apparent infection to severe and even fatal disease. We report two illustrative cases of trichinellosis. Returning to Denmark a few days after having eaten roasted pork in the Republic of Serbia, a female patient suffered from severe vomiting, epigastric pain, diarrhoea, and later myalgia, generalized oedema, and prostration. A biopsy showed heavy infestation with <it>Trichinella spiralis</it>, 2000 larvae/g of muscle. Life-threatening cardiopulmonary, renal and central nervous system complications developed. The patient recovered after several months. Her husband, who also ate the pork, did not have clinical symptoms, but an increased eosinophil count and a single larva in a muscle biopsy confirmed infection. The epidemiology, clinical manifestations, diagnosis, treatment and prevention of trichinellosis are reviewed.      

Quality assessment and correlation of microsatellite instability and immunohistochemical markers among population- and clinic-based colorectal tumors results from the Colon Cancer Family Registry

The detection of defective mismatch repair (MMR), as assessed by the presence of tumor microsatellite instability (MSI) and/or loss of MMR protein expression by IHC, has been useful for risk assessment, prognosis, and prediction of treatment in patients with colorectal cancer. We analyzed tumors for the presence of defective MMR from 5927 Colorectal Cancer Family Registry patients recruited at six international consortium sites. We evaluated the appropriate percentage instability cutoff used to distinguish the three MSI phenotypes [ie, stable (MSS), low instability (MSI-L), and high instability (MSI-H)]; the sensitivity, specificity, and performance characteristics of individual markers; and the concordance between MSI and IHC phenotypes. Guided by the results of the IHC testing, our findings indicate that the distinction between an MSI-H phenotype from a low-instability or MSS phenotype can best be accomplished by using a cutoff of 30% or greater of the markers showing instability. The sensitivity and specificity of the mononucleotide markers were higher than those of the dinucleotide markers. Specifically, BAT26 and BAT25 had the highest sensitivity (94%) and specificity (98%), and the use of mononucleotide markers alone identified 97% of the MSI-H cases correctly. As expected, the presence of MSI-H correlated with an older age of diagnosis, the presence of tumor in the proximal colon, and female sex.