Human papillomavirus-associated oropharyngeal cancer: a new clinical entity

The incidence of oropharyngeal cancers is rising worldwide in both nonsmokers and nondrinkers. Epidemiology studies suggest a strong association between human papillomavirus (HPV) 16 infection, changing sexual behavior and cancer development. Despite initial presentation with locally advanced disease and poorly differentiated histology, HPV-associated oropharyngeal carcinoma is associated with a good prognosis because its response to chemotherapy and radiation. Clinicians should be aware of the risk of oropharyngeal cancer in young people to avoid unnecessary delay in diagnosis and treatment. A history of oral sex should be elicited in young patients with enlarged neck nodes and/or tonsillar masse

The Newsvendor problem: analysis of the cost structure under normally distributed demand

We briefly review selected mathematical models that describe the dynamics of pattern formation phenomena in dip-coating and Langmuir-Blodgett transfer experiments, where solutions or suspensions are transferred onto a substrate producing patterned deposit layers with structure length from hundreds of nanometres to tens of micrometres. The models are presented with a focus on their gradient dynamics formulations that clearly shows how the dynamics is governed by particular free energy functionals and facilitates the comparison of the models. In particular, we include a discussion of models based on long-wave hydrodynamics as well as of more phenomenological models that focus on the pattern formation processes in such systems. The models and their relations are elucidated and examples of resulting patterns are discussed before we conclude with a discussion of implications of the gradient dynamics formulation and of some related open issues

Prevalence of persistent hypertension following pregnancy complicated by hypertensive disorders in low- and middle-income countries: a systematic review

Background: Hypertensive disorders of pregnancy can lead to persistent hypertension (pHTN) in the months and even years following delivery. However, its prevalence in low- and middle-income countries (LMICs) is not well characterized. Objective: To synthesize available evidence on the pHTN prevalence following a pregnancy complicated by hypertensive disorders of pregnancy in LMICs. Search strategy: PubMed, CINAHL Plus, Global Health (EBSCOhost), and Scopus from inception through a search date of July 12, 2022, and updated on January 2, 2024. Selection criteria: Cross-sectional studies and cohort studies reporting pHTN prevalence were eligible. Data collection and analysis: We conducted a narrative synthesis of data and categorized reported prevalence time points into several broader categories. We used the Newcastle-Ottawa checklist to assess the risk of bias. The protocol is registered in PROSPERO (CRD42022345739). Results: We reviewed 1,584 abstracts and identified 22 studies that reported pHTN between 2000 and 2023 from 14 LMICs. The overall prevalence of pHTN ranged between 6.9% and 62.2%, with the highest prevalence noted within African studies and the lowest in South American studies. Estimates at different follow-up periods postpartum were 6.9%–42.9% at six weeks, 34.0%–62.2% at three months, 14.8%–62.2% at six months, 12.7%–61.2% at 12 months, and 7.5%–31.8% at more than 12 months. The quality score of the selected studies ranged from 50% to 100%. Conclusions: The extant literature reports a high prevalence of pHTN in LMICs following a pregnancy complicated by hypertensive disorders. To reduce long-term complications of pHTN, programs should emphasize early screening and linkages to long-term care for at-risk women. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=345739, PROSPERO (CRD42022345739

Identifying barriers to ART initiation and adherence: An exploratory qualitative study on PMTCT in Zambia

Background Though antiretroviral therapy (ART) is widely available, HIV positive pregnant women in Zambia are less likely to start and remain on therapy throughout pregnancy and after delivery. This study sought to understand readiness to start ART among HIV pregnant women from the perspectives of both women and men in order to suggest more holistic programs to support women to continue life-long ART after delivery. Methods We conducted a qualitative study with HIV positive pregnant women before and after ART initiation, and men with female partners, to understand readiness to start lifelong ART. We conducted 28 in-depth interviews among women and 2 focus group discussions among male partners. Data were transcribed verbatim and analyzed in NVivo 12 using thematic analysis. Emerging themes from the data were organized using the social ecological framework. Results Men thought of their female partners as young and needing their supervision to initiate and stay on ART. Women agreed that disclosure and partner support were necessary preconditions to ART initiation and adherence and, expressed fear of divorce as a prominent barrier to disclosure. Maternal love and desire to look after one’s children instilled a sense of responsibility among women which motivated them to overcome individual, interpersonal and health system level barriers to initiation and adherence. Women preferred adherence strategies that were discrete, the effectiveness of which, depended on women’s intrinsic motivation. Conclusion The results support current policies in Zambia to encourage male engagement in ART care. To appeal to male partners, messaging on ART should be centered on emphasizing the importance of male involvement to ensure women remain engaged in ART care. Programs aimed at supporting postpartum ART adherence should design messages that appeal to both men’s role in couples’ joint decision-making and women’s maternal love as motivators for adherence

Male partners’ support and influence on pregnant women’s oral PrEP use and adherence in Malawi

Introduction: Daily oral pre-exposure prophylaxis (PrEP) is a safe and effective HIV prevention method for pregnant and postpartum women, but adherence barriers exist. Understanding the role of male partners in supporting PrEP use may inform strategies to support PrEP adherence among pregnant and breastfeeding women. Methods: To understand male partners’ involvement in women's use of PrEP, we conducted in-depth interviews with pregnant women in Lilongwe, Malawi who had recently decided to use PrEP (n = 30) and their male partners (n = 20) in the context of a PrEP adherence trial. Women were purposively recruited to ensure variation in their partners’ HIV status. Interviews were conducted in Chichewa using a semistructured guide. We followed a thematic approach to analyze the interview data. Results: Most male partners were receptive to women using PrEP during pregnancy because it eased their fears of the woman and baby acquiring HIV. Men often played a key role in women's PrEP adherence by providing daily reminders and encouragement to adhere to their medication. The majority of women appreciated this support from the men as it lessened the burden of remembering to take their medications daily on their own and aided their adherence. However, several women who lacked male partner support spoke of wanting their partners to be more involved. Many men living with HIV found the mutual support beneficial for their antiretroviral therapy adherence, while men without HIV or with status unknown appreciated knowing that the family was protected. While most men were open to women continuing PrEP beyond the current study, some would only support it if women were still at risk for acquiring HIV. Conclusion: In this study, male partners were strongly motivated to support the PrEP adherence of their female partners as a way of ensuring that the pregnant women and unborn babies were protected against HIV. Promoting disclosure and tangible support that arises organically among men may be helpful, but programs to enhance this support and identify ways to support women who do not receive support from their partners or do not wish to disclose their PrEP use to partners may be needed. 2023 Young, Saidi, Phanga, Tseka, Bula, Mmodzi, Pearce, Maman, Golin, Mutale, Chi and Hill

Multiple-path Quantum Interference Effects in a Double-Aharonov-Bohm Interferometer

We investigate quantum interference effects in a double-Aharonov-Bohm (AB) interferometer consisting of five quantum dots sandwiched between two metallic electrodes in the case of symmetric dot-electrode couplings by the use of the Green’s function equation of motion method. The analytical expression for the linear conductance at zero temperature is derived to interpret numerical results. A three-peak structure in the linear conductance spectrum may evolve into a double-peak structure, and two Fano dips (zero conductance points) may appear in the quantum system when the energy levels of quantum dots in arms are not aligned with one another. The AB oscillation for the magnetic flux threading the double-AB interferometer is also investigated in this paper. Our results show the period of AB oscillation can be converted from 2π to π by controlling the difference of the magnetic fluxes threading the two quantum rings

Implementation of cervical cancer prevention services for HIV-infected women in Zambia: Measuring program effectiveness

Background: Cervical cancer kills more women in low-income nations than any other malignancy. A variety of research and demonstration efforts have proven the efficacy and effectiveness of low-cost cervical cancer prevention methods but none in routine program implementation settings of the developing world, particularly in HIV-infected women. Methods: In our public sector cervical cancer prevention program in Zambia, nurses conduct screening using visual inspection with acetic acid aided by digital cervicography. Women with visible lesions are offered same-visit cryotherapy or referred for histologic evaluation and clinical management. We analyzed clinical outcomes and modeled program effectiveness among HIV-infected women by estimating the total number of cervical cancer deaths prevented through screening and treatment. Results: Between 2006 and 2008, 6572 HIV-infected women were screened, 53.6% (3523) had visible lesions, 58.5% (2062) were eligible for cryotherapy and 41.5% (1461) were referred for histologic evaluation. A total of 75% (1095 out of 1462) of patients who were referred for evaluation complied. Pathology results from 65% (715 out of 1095) of women revealed benign abnormalities in 21% (151), cervical intraepithelial neoplasia (CIN) I in 30% (214), CIN 2/3 in 33% (235) and invasive cervical cancer in 16.1% (115, of which 69% were early stage). Using a conditional probability model, we estimated that our program prevented 142 cervical cancer deaths (high/low range: 238-96) among the 6572 HIV-infected women screened, or one cervical cancer death prevented per 46 (corresponding range: 28-68) HIV-infected women screened. Conclusion: Our prevention efforts using setting-appropriate human resources and technology have reduced morbidity and mortality from cervical cancer among HIV-infected women in Zambia. Financial support for implementing cervical cancer prevention programs integrated within HIV/AIDS care programs is warranted. Our prevention model can serve as the implementation platform for future low-cost HPV-based screening methods, and our results mayprovide the basis for comparison of programmatic effectiveness of future prevention efforts

Apalutamide plus Androgen Deprivation Therapy for Metastatic Castration-Sensitive Prostate Cancer: Analysis of Pain and Fatigue in the Phase 3 TITAN Study

PURPOSE: We performed an exploratory analysis of prostate cancer-related pain and fatigue on health-related quality of life in patients with metastatic castration-sensitive prostate cancer receiving apalutamide (240 mg/day) or placebo, with continuous androgen deprivation therapy (ADT), in the phase 3, randomized, double-blind, placebo controlled TITAN trial (NCT02489318). MATERIALS AND METHODS: Patient-reported outcomes for pain and fatigue were evaluated using the Brief Pain Inventory-Short Form and Brief Fatigue Inventory. Time to deterioration (TTD) was estimated by Kaplan-Meier method; hazard ratios and 95% confidence intervals were calculated using Cox proportional hazards model. General estimating equations for logistic regression estimated treatment-related differences in the likelihood of worsening pain or fatigue. RESULTS: Compliance for completing the Brief Pain Inventory-Short Form and Brief Fatigue Inventory was high (96% to 97%) in the first year. Median followup times were similar between treatments (19 to 22 months). Median pain TTD was longer with apalutamide than placebo for "pain at its least in the last 24 hours" (28.7 vs 21.8 months, respectively; p=0.0146), "pain interfered with mood" (not estimable vs 22.4 months; p=0.0017), "pain interfered with walking ability" (28.7 vs 20.2 months; p=0.0027), "pain interfered with relations" (not estimable vs 23.0 months; p=0.0139) and "pain interfered with sleep" (28.7 vs 20.9 months; p=0.0167). Likelihood for fatigue and worsening fatigue were similar between groups. CONCLUSIONS: Patients with metastatic castration-sensitive prostate cancer receiving apalutamide plus ADT vs placebo plus ADT reported consistently favorable TTD of pain. No difference for change in fatigue was observed with apalutamide vs placebo

Health-related quality of life after apalutamide treatment in patients with metastatic castration-sensitive prostate cancer (TITAN): a randomised, placebo-controlled, phase 3 study

Background: In the phase 3 TITAN study, the addition of apalutamide to androgen deprivation therapy (ADT) significantly improved the primary endpoints of overall survival and radiographic progression-free survival in patients with metastatic castration-sensitive prostate cancer. We aimed to assess health-related quality of life (HRQOL) in TITAN, including pain and fatigue. Methods: In this randomised, placebo-controlled, double-blind, phase 3 study, patients with metastatic castration-sensitive prostate cancer (defined as not receiving ADT at the time of metastatic disease progression) aged 18 years and older, receiving continuous ADT (selected at the investigator's discretion), and with an Eastern Cooperative Oncology Group performance status score of 0 or 1 were randomly assigned (1:1), using an interactive web response system, to receive oral apalutamide (four 60 mg tablets, once daily) or matching placebo. Previous localised disease treatment or previous docetaxel for metastatic castration-sensitive prostate cancer were allowed. Randomisation was stratified by Gleason score at diagnosis, region, and previous docetaxel treatment. Randomisation was done using randomly permuted blocks (block size of four). Investigators, research staff, sponsor study team, and patients were masked to the identities of test and control treatments. Patient-reported outcomes were prespecified exploratory endpoints and were the Brief Pain Inventory-Short Form (BPI-SF), Brief Fatigue Inventory (BFI), Functional Assessment of Cancer Therapy-Prostate (FACT-P), and EuroQoL 5D questionnaire 5 level (EQ-5D-5L). BPI and BFI were completed for 7 consecutive days (days −6 to 1 inclusive of each cycle visit), then at months 4, 8, and 12 in follow-up. FACT-P and EQ-5D-5L were completed during cycles 1–7, then every other cycle until the end of treatment, and at months 4, 8, and 12 in follow-up. Analyses were based on the intention-to-treat population. Missing patient-reported outcome assessments were calculated as the expected number of assessments for a visit minus the actual number of assessments received for that visit. For time-to-event endpoints, when median values could not be calculated because less than 50% of patients had degradation, 25th percentiles were compared. This study is registered with ClinicalTrials.gov, number NCT02489318, and is ongoing. Findings: Between Dec 9, 2015, and July 25, 2017, 1052 eligible patients were enrolled randomly assigned to apalutamide (n=525) or placebo (n=527). Data cutoff for this analysis of patient-reported outcomes was Nov 23, 2018. Median follow-up for time to pain-related endpoints ranged from 19·4 to 22·1 months. Patients were mostly asymptomatic at baseline: on the BPI-SF pain severity scale of 0–10, median pain scores (indicating worst pain in the past 24 h) were 1·14 (IQR 0–3·17) in the apalutamide group and 1·00 (0–2·86) in the placebo group, and median worst fatigue scores on the BFI were 1·29 (IQR 0–3·29) in the apalutamide group and 1·43 (0·14–3·14) in the placebo group. Patient experience of pain and fatigue (intensity and interference) did not differ between the groups for the duration of treatment. Median time to worst pain intensity progression was 19·09 months (95% CI 11·04–not reached) in the apalutamide group versus 11·99 months (8·28–18·46) in the placebo group (HR 0·89 [95% CI 0·75–1·06]; p=0·20). Median time to pain interference progression was not reached in either group (95% CI 28·58–not reached in the apalutamide group; not reached–not reached in the placebo group). 25th percentiles for time to pain interference progression were 9·17 months (5·55–11·96) in the apalutamide group and 6·24 months (4·63–7·43) in the placebo group (HR 0·90 [95% CI 0·73–1·10]; p=0·29). FACT-P total scores and EQ-5D-5L data showed preservation of HRQOL in both groups. The median time to deterioration as determined by FACT-P total score was 8·87 months (95% CI 4·70–11·10) in the apalutamide group and 9·23 months (7·39–12·91) in the placebo group (HR 1·02 [95% CI 0·85–1·22]; p=0·85). Interpretation: Apalutamide with ADT is a well-tolerated and effective option for men with metastatic castration-sensitive prostate cancer. The combination significantly improves survival outcomes compared with ADT alone while maintaining HRQOL despite additive androgen blockade. Funding: Janssen Research & Development