There's an App for That: Exploring the Market for Contraceptive Fertility Tracking Apps in the Philippines.

For generations, women have relied on fertility awareness methods to plan and prevent pregnancy, for over a decade, many have been aided by digital tools to do so. New contraceptive fertility tracking apps (CFTAs)-that are backed by clinical efficacy trials to support their effectiveness as contraception-have the potential to enhance method choice and offer users a unique contraceptive option, but there is little evidence to inform the decisions around expanding access, particularly in low-and middle-income countries. We conducted a mixed methods study with quantitative online surveys (n = 1600) and qualitative interviews (n = 36) to explore the potential appeal of and demand for a hypothetical CFTA in one such market, the Philippines. Interest in using a CFTA was high among our Internet-engaged, urban study population, with 83.9% "definitely" or "probably" interested in using it. Across demographic profiles, respondents perceived the appeal of the method as "natural" and "convenient." A majority were willing to pay for the method, though notably at a price (5.20 USD) below that of currently available CFTAs. We discuss various important factors to be considered before bringing a method like this to new markets, including the potential implications of equity constraints in reaching a wider market and the unexpected prevalence of other period-tracking apps not intended as contraception being used in this market that could complicate any future roll-out. These issues could be explored further with additional research.

The safety and efficacy of the Stryker OptaBlate™ Bone Tumor Ablation system for vertebral body metastases.

Background: Metastatic spinal lesions are a significant cause of morbidity and decreased quality of life in those with a high tumor burden. Despite treatment modalities such as medical therapy (e.g., chemotherapy, steroids), spinal augmentation procedures, and radiation therapy, many patients still experience refractory back pain due to neoplastic infiltration of the vertebral body and/or pathologic compression fractures. With the aim to address refractory pain in patients who have exhausted conventional treatment options, Stryker developed the OptablateTM Bone Tumor Ablation system (BTA; Stryker Corporation, Kalamazoo, MI), which delivers radiofrequency energy to pathologic vertebral body lesions. In this preliminary single-institution study, we characterize the use of the BTA system in 11 patients undergoing kyphoplasty for pathologic spinal lesions with the goal to demonstrate the impact of this novel technology on refractory pain in this challenging clinical setting. Methods: A single-center retrospective chart review was performed on all patients identified as those receiving tumor ablation/kyphoplasty for spinal neoplasms using the OptablateTM BTA system performed by a single surgeon at the University of Oklahoma Medical Center. Sex, age, primary lesion type, presenting symptomatology, spinal level, time of follow-up, and outcome were obtained from the electronic medical record (EMR). Results: Eleven patients (4 males, 7 females) with a mean age of 62 (range, 38-82) years had an average follow-up time of 6 months. Presenting symptoms attributed to spinal pathology included back pain (n = 11, 100%), pathologic fracture (n = 6, 55%), and lower extremity weakness (n = 3, 27%). A total of 20 lesions were ablated at 12 vertebral levels. Eight patients (73%) had improved pain. No complications were reported. Conclusion: This preliminary study documents the safety of the BTA system, in addition to its diverse use across many levels. The majority of patients reported improvement in their pain. Further study is required to fully characterize the use of the BTA system in those with neoplastic spinal pathology.

Tryptophan degradation as a systems phenomenon in inflammation - an analysis across 13 chronic inflammatory diseases.

BACKGROUND: Chronic inflammatory diseases (CIDs) are systems disorders that affect diverse organs including the intestine, joints and skin. The essential amino acid tryptophan (Trp) can be broken down to various bioactive derivatives important for immune regulation. Increased Trp catabolism has been observed in some CIDs, so we aimed to characterise the specificity and extent of Trp degradation as a systems phenomenon across CIDs. METHODS: We used high performance liquid chromatography and targeted mass spectrometry to assess the serum and stool levels of Trp and Trp derivatives. Our retrospective study incorporates both cross-sectional and longitudinal components, as we have included a healthy population as a reference and there are also multiple observations per patient over time. FINDINGS: We found reduced serum Trp levels across the majority of CIDs, and a prevailing negative relationship between Trp and systemic inflammatory marker C-reactive protein (CRP). Notably, serum Trp was low in several CIDs even in the absence of measurable systemic inflammation. Increases in the kynurenine-to-Trp ratio (Kyn:Trp) suggest that these changes result from increased degradation along the kynurenine pathway. INTERPRETATION: Increases in Kyn:Trp indicate the kynurenine pathway as a major route for CID-related Trp metabolism disruption and the specificity of the network changes indicates excessive Trp degradation relative to other proteogenic amino acids. Our results suggest that increased Trp catabolism is a common metabolic occurrence in CIDs that may directly affect systemic immunity. FUNDING: This work was supported by the DFG Cluster of Excellence 2167 "Precision medicine in chronic inflammation" (KA, SSchr, PR, BH, SWa), the BMBF (e:Med Juniorverbund "Try-IBD" 01ZX1915A and 01ZX2215, the e:Med Network iTREAT 01ZX2202A, and GUIDE-IBD 031L0188A), EKFS (2020_EKCS.11, KA), DFG RU5042 (PR, KA), and Innovative Medicines Initiative 2 Joint Undertakings ("Taxonomy, Treatments, Targets and Remission", 831434, "ImmUniverse", 853995, "BIOMAP", 821511).

Amino acid auxotrophies in human gut bacteria are linked to higher microbiome diversity and long-term stability.

Amino acid auxotrophies are prevalent among bacteria. They can govern ecological dynamics in microbial communities and indicate metabolic cross-feeding interactions among coexisting genotypes. Despite the ecological importance of auxotrophies, their distribution and impact on the diversity and function of the human gut microbiome remain poorly understood. This study performed the first systematic analysis of the distribution of amino acid auxotrophies in the human gut microbiome using a combined metabolomic, metagenomic, and metabolic modeling approach. Results showed that amino acid auxotrophies are ubiquitous in the colon microbiome, with tryptophan auxotrophy being the most common. Auxotrophy frequencies were higher for those amino acids that are also essential to the human host. Moreover, a higher overall abundance of auxotrophies was associated with greater microbiome diversity and stability, and the distribution of auxotrophs was found to be related to the human host's metabolome, including trimethylamine oxide, small aromatic acids, and secondary bile acids. Thus, our results suggest that amino acid auxotrophies are important factors contributing to microbiome ecology and host-microbiome metabolic interactions.

Equipping providers to offer novel MPTs: Developing counseling messages for the Dual Prevention Pill in clinical studies and beyond.

Introduction: The pipeline for multi-purpose prevention technologies includes products that simultaneously prevent HIV, pregnancy and/or other sexually transmitted infections. Among these, the Dual Prevention Pill (DPP) is a daily pill co-formulating oral pre-exposure prophylaxis (PrEP), and combined oral contraception (COC). Clinical cross-over acceptability studies for the DPP require training providers to counsel on a combined product. From February 2021-April 2022, a working group of eight HIV and FP experts with clinical and implementation expertise developed counseling recommendations for the DPP based on existing PrEP/COC guidance. Assessment of policy/guidelines options and implications: The working group conducted a mapping of counseling messages from COC and oral PrEP guidance and provider training materials. Six topics were prioritized: uptake, missed pills, side effects, discontinuation and switching, drug interactions and monitoring. Additional evidence and experts were consulted to answer outstanding questions and counseling recommendations for the DPP were developed. Missed pills was the topic with the most complexity, raising questions about whether women could "double up" on missed pills or skip the last week of the pack to recover protection faster. Uptake required aligning the time to reach protective levels for both DPP components and explaining the need to take DPP pills during week 4 of the pack. The potential intensity of DPP side effects, given the combination of oral PrEP with COC, was an important consideration. Discontinuation and switching looked at managing risk of HIV and unintended pregnancy when stopping or switching from the DPP. Guidance on drug interactions contended with differing contraindications for COC and PrEP. Monitoring required balancing clinical requirements with potential user burden. Actionable recommendations: The working group developed counseling recommendations for the DPP to be tested in clinical acceptability studies. Uptake: Take one pill every day for the DPP until the pack is empty. Days 1-21 contain COC and oral PrEP. Days 22-28 do not contain COC to allow for monthly bleeding, but do contain oral PrEP and pills should be taken to maintain HIV protection. Take the DPP for 7 consecutive days to reach protective levels against pregnancy and HIV. Missed pills: If you miss 1 pill multiple times in a month or 2+ consecutive pills, take the DPP as soon as you remember. Do not take more than 2 pills in a day. If 2+ consecutive pills are missed, only take the last missed pill and discard the other missed pills. Side effects: You may experience side effects when you start using the DPP, including changes to monthly bleeding. Side effects are typically mild and go away without treatment. Discontinuation/switching: If you decide to discontinue use of the DPP, but want to be protected from HIV and/or unintended pregnancy, in most cases, you can begin using PrEP or another contraceptive method right away. Drug interactions: There are no drug-drug interactions from combining oral PrEP and COC in the DPP. Certain medications are not recommended due to their contraindication with oral PrEP or COC. Monitoring: You will need to get an HIV test prior to initiating or restarting the DPP, and every 3 months during DPP use. Your provider may recommend other screening or testing. Discussion: Developing recommendations for the DPP as a novel MPT posed unique challenges, with implications for efficacy, cost, and user and provider comprehension and burden. Incorporating counseling recommendations into clinical cross-over acceptability studies allows for real-time feedback from providers and users. Supporting women with information to use the DPP correctly and confidently is critically important for eventual scale and commercialization.

Increased protease-activated receptor 1 autoantibodies are associated with severe COVID-19.

In patients with severe #COVID19, increased levels of autoantibodies against PAR1 were found. These might serve as allosteric agonists of PAR1 on endothelial cells and platelets, and thus might contribute to the pathogenesis of microthrombosis in COVID-19. https://bit.ly/3pqM9Vv.

Barriers and Enablers Influencing Women's Adoption and Continuation of Vaginally Inserted Contraceptive Methods: A Literature Review.

Most vaginally inserted methods have limited availability and use despite offering characteristics that align with many women's stated preferences (e.g., nonhormonal and/or on demand). The objective of this review was to identify enablers and barriers to women's adoption and continuation of vaginally inserted contraceptive methods in low- and middle-income countries (LMICs). We searched three databases (PubMed, Embase, and Web of Science) and 18 websites using keywords related to five vaginally inserted contraceptive methods (diaphragm, vaginal ring, female condom, copper intrauterine device [IUD], hormonal IUD) and terms associated with their adoption and continuation. Searches were limited to resources published between January 2010 and September 2020. Studies eligible for inclusion in our review presented results on women's use and perspectives on the enablers and barriers to adoption and continuation of the vaginally inserted contraceptive methods of interest in LMICs. Relevant studies among women's partners were also included, but not those of providers or other stakeholders. Data were coded, analyzed, and disaggregated according to a framework grounded in family planning (FP) literature and behavioral theories common to FP research and program implementation. Our initial search yielded 13,848 results, with 182 studies ultimately included in the analysis. Across methods, we found common enablers for method adoption, including quality contraceptive counseling as well as alignment between a woman's preferences and a method's duration of use and side effect profile. Common barriers included a lack of familiarity with the methods and product cost. Notably, vaginal insertion was not a major barrier to adoption in the literature reviewed. Vaginally inserted methods of contraception have the potential to fill a gap in method offerings and expand choice. Programmatic actions should address key barriers and enable voluntary use.

Gender-specific HIV and substance abuse prevention strategies for South African men: study protocol for a randomized controlled trial.

BACKGROUND: Young men in South Africa face concurrent epidemics of HIV, drug and alcohol abuse, and unemployment. Standard HIV prevention programs, located in healthcare settings and/or using counseling models, fail to engage men. Soccer and vocational training are examined as contexts to deliver male-specific, HIV prevention programs. METHODS: Young men (n = 1200) are randomly assigned by neighborhood to one of three conditions: 1) soccer league (n = 400; eight neighborhoods); 2) soccer league plus vocational training (n = 400; eight neighborhoods); or 3) a control condition (n = 400; eight neighborhoods). Soccer practices and games occur three times per week and vocational training is delivered by Silulo Ulutho Technologies and Zenzele Training and Development. At baseline, 6 months, 12 months, and 24 months, the relative efficacy of these strategies to increase the number of significant outcomes (NSO) among 15 outcomes which occur (1) or not (0) are summed and compared using binomial logistic regressions. The summary primary outcome reflects recent HIV testing, substance abuse, employment, sexual risk, violence, arrests, and mental health status. DISCUSSION: The failure of men to utilize HIV prevention programs highlights the need for gender-specific intervention strategies. However, men in groups can provoke and encourage greater risk-taking among themselves. The current protocol evaluates a male-specific strategy to influence men's risk for HIV, as well as to improve their ability to contribute to family income and daily routines. Both interventions are expected to significantly benefit men compared with the control condition. TRIAL REGISTRATION: ClinicalTrials.gov registration, NCT02358226 . Registered 24 November 2014.

Replicating Evidence-Based Practices with Flexibility for Perinatal Home Visiting by Paraprofessionals.

Introduction Strategies are needed to improve the efficacy of paraprofessional home visitors for pregnant women in the United States. This study evaluates the maternal and child outcomes when evidence-based practices (EBP) are replicated with flexibility, rather than fidelity to a manualized intervention. Methods Pregnant mothers (N = 203) in five clinics were recruited in the waiting rooms and randomized to standard clinic care as the control condition (n = 104) or standard care plus home visiting (n = 99). Home visitors (n = 9) were selected, trained in foundational skills common to EBP and four problem domains (weight control, breastfeeding, daily habits, and depression). Independent interviewers assessed targeted outcomes at birth (82%) and 6 months later (83%). RESULTS: Home visitors, called Mentor Mothers [MM], made an average of 14.9 home visits or telephone contacts (SD = 9; total contacts = 1491) addressing maternal daily habits, breastfeeding, and depression. Intervention and control mothers were similar in weight, Body Mass Index (BMI), depression and social support at baseline and 6 months later. The percentage of low birth weight babies was similar; intervention infants' growth (weight/height Z score) tended to be significantly better compared to the control condition. DISCUSSION: There are many explanations for the failure to find significant benefits: insufficient statistical power; the benefits of repeated assessments by warm, supportive peers to improve outcomes; or the failure of EBP and the need to maintain replication with fidelity. All study mothers had better outcomes than documented among comparable published samples of low-income, Latina and Korean-American mothers in Los Angeles, CA. ClinicalTrials.gov registration NCT01687634.

Perceived mHealth barriers and benefits for home-based HIV testing and counseling and other care: Qualitative findings from health officials, community health workers, and persons living with HIV in South Africa.

mHealth has been proposed to address inefficiencies in the current South African healthcare system, including home-based HIV testing and counseling (HTC) programs. Yet wide-scale adoption of mHealth has not occurred. Even as infrastructure barriers decrease, a need to better understand perceived adoption barriers by stakeholders remains. We conducted focus group discussions (FGD) in South Africa in 2016 with 10 home-based HTC field staff, 12 community health workers (CHWs) and 10 persons living with HIV (PLH). Key informant (KI) interviews were conducted with five health officials. Perceptions about current home-based HTC practices, future mHealth systems and the use of biometrics for patient identification were discussed, recorded and transcribed for qualitative analysis. Themes were based on a conceptual model for perceived mHealth service quality. Stakeholders brought up a lack of communication in sharing patient health information between clinics, between clinics and CHWs, and between clinics and patients as major barriers to care that mHealth can address. CHWs need better patient information from clinics in terms of physical location and health status to plan visitation routes and address patient needs. CHWs perceive that communication barriers create distrust towards them by clinic staff. PLH want automated appointment and medication reminders. KI see mHealth as a way to improve health information transfer to government officials to better allocate healthcare resources. Stakeholders are also optimistic about the ability for biometrics to improve patient identification but disagreed as to which biometrics would be acceptable, especially in older patients. All stakeholders provided useful information towards the development of mHealth systems. Hospitals are adopting patient-centered approaches that solicit feedback from patients and incorporate them into decision-making processes. A similar approach is needed in the development of mHealth systems. Further, such systems are critical to the successful extension of the health system from health facilities into people's homes.

Adjustment of a Population of South African Children of Mothers Living With/and Without HIV Through Three Years Post-Birth.

Mothers living with HIV (MLH) and their children are typically studied to ensure that perinatal HIV transmission is blocked. Yet, HIV impacts MLH and their children lifelong. We examine child outcomes from pregnancy to 3 years post-birth among a peri-urban population of pregnant MLH and mothers without HIV (MWOH). Almost all pregnant women in 12 neighborhoods (98 %; N = 584) in Cape Town, South Africa were recruited and repeatedly assessed within 2 weeks of birth (92 %), at 6 months (88 %), 18 months (84 %), and 3 years post-birth (86 %). There were 186 MLH and 398 MWOH. Controlling for neighborhood and repeated measures, child and maternal outcomes were contrasted over time using longitudinal random effects regression analyses. For measures collected only at 3 years, outcomes were analyzed using multiple regressions. Compared to MWOH, MLH had less income, more informal housing and food insecurity, used alcohol more often during pregnancy, and were more depressed during pregnancy and over time. Only 4.8 % of MLH's children were seropositive; seropositive children were excluded from additional analyses. Children of MLH tended to have significantly lower weights (p < .10) over time (i.e., lower weight-for-age Z-scores) and were also hospitalized significantly more often than children of MWOH (p < .01). Children of MLH and MWOH died at similar rates (8.5 %) and were similar in social and behavioral adjustment, vocabulary, and executive functioning at 3 years post-birth. Despite living in households with fewer resources and having more depressed mothers, only the physical health of children of MLH is compromised, compared to children of MWOH. In township neighborhoods with extreme poverty, social, behavioral, language, and cognitive functioning appear similar over the first three years of life between children of MLH and MWOH.

Regulation of indole-3-acetic acid biosynthesis by branched-chain amino acids in Enterobacter cloacae UW5.

The soil bacterium Enterobacter cloacae UW5 produces the rhizosphere signaling molecule indole-3-acetic acid (IAA) via the indolepyruvate pathway. Expression of indolepyruvate decarboxylase, a key pathway enzyme encoded by ipdC, is upregulated by the transcription factor TyrR in response to aromatic amino acids. Some members of the TyrR regulon may also be controlled by branched-chain amino acids and here we show that expression from the ipdC promoter and production of IAA are downregulated by valine, leucine and isoleucine. Regulation of the IAA synthesis pathway by both aromatic and branched-chain amino acids suggests a broader role for this pathway in bacterial physiology, beyond plant interactions.

Is NASH underdiagnosed among African Americans?

OBJECTIVE: Obesity and type 2 diabetes mellitus are considered risk factors for nonalcoholic steatohepatitis (NASH) and cryptogenic cirrhosis. Because obesity and type 2 diabetes are prevalent among African American females by the 5th and 6th decades, one would expect an increased number of African Americans among patients with NASH and cryptogenic cirrhosis. METHODS: We determined the percentage of patients of African American and European American descent among all of the patients in our liver disease registry and those with NASH and cryptogenic cirrhosis. We also assessed the ethnicity of patients in our registry with other common liver diseases including hepatitis C, and we determined the ethnicity of patients seen at our center with type 2 diabetes and a primary diagnosis of obesity over a 4-yr period. Using census data, we compared these results to our local and regional ethnic demographics. RESULTS: Overall, 199 of 2,253 patients (9%) in the registry were of African American descent, whereas 1,906 were of European American descent (85%). This distribution is similar to the ethnic mix in central Virginia (12% African American, 86% European American) and Albemarle County (12% African American, 83% European American). The prevalence of African American patients among individuals seen at our center for either type 2 diabetes or a primary diagnosis of obesity was over two times the prevalence of African Americans in the county or regional population. In contrast, of 159 NASH patients only one (0.6%) was of African American descent and 154 (97%) were of European American descent (p < 0.001 compared to the total registry, county, or region). Among 206 cryptogenic cirrhosis patients, only two (1%) were of African American descent, whereas 195 (95%) were of European American descent (p < 0.001 compared to the total registry). With regard to other liver diseases, African American patients were slightly overrepresented among hepatitis C patients and markedly overrepresented among patients with hepatic sarcoidosis, similar to previously reported national figures. CONCLUSION: Although there is overrepresentation of African Americans among patients with major risk factors for NASH, individuals of primarily African American descent are infrequently represented among our patients with NASH or cryptogenic cirrhosis. This could result from underrecognition, underreferral, or a true lower prevalence of these disorders among African Americans.