Essential barriers and considerations for the implementation of electronic patient-reported outcome (ePRO) measures in oncological practice: contextualizing the results of a feasibility study with existing literature.

Aim: Monitoring electronic patient-reported outcomes (ePRO) can provide various benefits to cancer patients, such as enhanced quality of life, reduction of hospital admissions, and even prolonged survival. Furthermore, ePRO might offer significant benefits to patients under antineoplastic treatment in the context of the current COVID-19 pandemic. However, evidence on feasibility of ePRO in routine cancer care and barriers met in a real-life setting remains limited. Subject and methods: We conducted a feasibility study among patients diagnosed with multiple myeloma currently under antineoplastic treatment. Patients filled out weekly ePRO questionnaires and were followed up for 6 months. In case of adverse events, an alert was sent to the clinic. We assessed uptake and adherence, as well as subjective perceptions of patients and clinic staff. A semi-structured literature review was conducted to contextualize results. Results: Eleven patients were recruited and followed up for 6 months. Overall adherence was found at a high level and remained stable throughout the study period. Feedback from patients was positive; however, clinic staff expressed disappointment and frustration, criticising an increase of workload while not perceiving any benefit to the oncological treatment. Both findings were backed by evidence we found in literature. Conclusions: Implementation of ePRO monitoring to routine cancer treatment seems to be feasible regarding patients' acceptance and compliance. However, integration of the tool into clinical workflow without increasing workload and deterring clinicians proves to be a major challenge. Supplementary Information: The online version contains supplementary material available at 10.1007/s10389-022-01767-3.

Prevention of mother-to-child transmission of HIV: Postpartum adherence to Option B+ until 18 months in Western Uganda.

Since 2012, the WHO recommends Option B+ for the prevention of mother-to-child transmission of HIV. This approach entails the initiation of lifelong antiretroviral therapy in all HIV-positive pregnant women, also implying protection during breastfeeding for 12 months or longer. Research on long-term adherence to Option B+ throughout breastfeeding is scarce to date. Therefore, we conducted a prospective observational cohort study in Fort Portal, Western Uganda, to assess adherence to Option B+ until 18 months postpartum. In 2013, we recruited 67 HIV-positive, Option B+ enrolled women six weeks after giving birth and scheduled them for follow-up study visits after six, twelve and 18 months. Two adherence measures, self-reported drug intake and amount of drug refill visits, were combined to define adherence, and were assessed together with feeding information at all study visits. At six months postpartum, 51% of the enrolled women were considered to be adherent. Until twelve and 18 months postpartum, adherence for the respective follow-up interval decreased to 19% and 20.5% respectively. No woman was completely adherent until 18 months. At the same time, 76.5% of the women breastfed for ≥12 months. Drug adherence was associated with younger age (p<0.01), lower travel costs (p = 0.02), and lower number of previous deliveries (p = 0.04). Long-term adherence to Option B+ seems to be challenging. Considering that in our cohort, prolonged breastfeeding until ≥12 months was widely applied while postpartum adherence until the end of breastfeeding was poor, a potential risk of postpartum vertical transmission needs to be taken seriously into account for Option B+ implementation.

Decreased emergence of HIV-1 drug resistance mutations in a cohort of Ugandan women initiating option B+ for PMTCT.

BACKGROUND: Since 2012, WHO guidelines for the prevention of mother-to-child transmission (PMTCT) of HIV-1 in resource-limited settings recommend the initiation of lifelong antiretroviral combination therapy (cART) for all pregnant HIV-1 positive women independent of CD4 count and WHO clinical stage (Option B+). However, long-term outcomes regarding development of drug resistance are lacking until now. Therefore, we analysed the emergence of drug resistance mutations (DRMs) in women initiating Option B+ in Fort Portal, Uganda, at 12 and 18 months postpartum (ppm). METHODS AND FINDINGS: 124 HIV-1 positive pregnant women were enrolled within antenatal care services in Fort Portal, Uganda. Blood samples were collected at the first visit prior starting Option B+ and postpartum at week six, month six, 12 and 18. Viral load was determined by real-time RT-PCR. An RT-PCR covering resistance associated positions in the protease and reverse transcriptase HIV-1 genomic region was performed. PCR-positive samples at 12/18 ppm and respective baseline samples were analysed by next generation sequencing regarding HIV-1 drug resistant variants including low-frequency variants. Furthermore, vertical transmission of HIV-1 was analysed. 49/124 (39.5%) women were included into the DRM analysis. Virological failure, defined as >1000 copies HIV-1 RNA/ml, was observed in three and seven women at 12 and 18 ppm, respectively. Sequences were obtained for three and six of these. In total, DRMs were detected in 3/49 (6.1%) women. Two women displayed dual-class resistance against all recommended first-line regimen drugs. Of 49 mother-infant-pairs no infant was HIV-1 positive at 12 or 18 ppm. CONCLUSION: Our findings suggest that the WHO-recommended Option B+ for PMTCT is effective in a cohort of Ugandan HIV-1 positive pregnant women with regard to the low selection rate of DRMs and vertical transmission. Therefore, these results are encouraging for other countries considering the implementation of lifelong cART for all pregnant HIV-1 positive women.

Option B+ for prevention of vertical HIV transmission has no influence on adverse birth outcomes in a cross-sectional cohort in Western Uganda.

BACKGROUND: While most Sub-Saharan African countries are now implementing the WHO-recommended Option B+ protocol for prevention of vertical HIV transmission, there is a lack of knowledge regarding the influence of Option B+ exposure on adverse birth outcomes (ABOs). Against this background, we assessed ABOs among delivering women in Western Uganda. METHODS: A cross-sectional, observational study was performed within a cohort of 412 mother-newborn-pairs in Virika Hospital, Fort Portal in 2013. The occurrence of stillbirth, pre-term delivery, and small size for gestational age (SGA) was analysed, looking for influencing factors related to HIV-status, antiretroviral drug exposure and duration, and other sociodemographic and clinical parameters. RESULTS: Among 302 HIV-negative and 110 HIV-positive women, ABOs occurred in 40.5%, with stillbirth in 6.3%, pre-term delivery in 28.6%, and SGA in 12.2% of deliveries. For Option B+ intake (n = 59), no significant association was found with stillbirth (OR 0.48, p = 0.55), pre-term delivery (OR 0.97, p = 0.92) and SGA (OR 1.5, p = 0.3) compared to seronegative women. Women enrolled on antiretroviral therapy (ART) before conception (n = 38) had no different risk for ABOs than women on Option B+ or HIV-negative women. Identified risk factors for stillbirth included lack of formal education, poor socio-economic status, long travel distance, hypertension and anaemia. Pre-term delivery risk was increased with poor socio-economic status, primiparity, Malaria and anaemia. The occurrence of SGA was influenced by older age and Malaria. CONCLUSION: In our study, women on Option B+ showed no difference in ABOs compared to HIV-negative women and to women on ART. We identified several non-HIV/ART-related influencing factors, suggesting an urgent need for improving early risk assessment mechanisms in antenatal care through better screening and triage systems. Our results are encouraging with regard to continued universal scale-up of Option B+ and ART programmes.

Prevention of Mother-to-Child Transmission of HIV in Option B+ Era: Uptake and Adherence During Pregnancy in Western Uganda.

Since 2012, lifelong antiretroviral therapy for all HIV-positive pregnant women ("Option B+") is recommended by WHO for the prevention of mother-to-child transmission of HIV (PMTCT). Many sub-Saharan African countries have since introduced this regimen, but to date, longer-term outcome evaluations are scarce. We conducted an observational study in Fort Portal Municipality, Uganda, to describe uptake and adherence of Option B+ during pregnancy. HIV-positive women approaching antenatal care (ANC) services in two hospitals were enrolled and followed-up at monthly routine ANC visits until delivery. At each visit, next to sociodemographic and clinical data, we assessed drug adherence through pill counts. In total, 124 HIV-positive pregnant women were enrolled in our study; from these, 80.8% had not been aware of their positive serostatus before. Forty-five PMTCT clients (36.3%) never returned to ANC after their first visit. Protective factors (p < 0.05) for immediate loss to care included previous HIV status knowledge, status disclosure before or at first ANC visit, and tertiary education. Among those clients starting Option B+, the median adherence during pregnancy was 95.7% pill intake. Rather low adherence (<80%) was observed in 21.1% of clients, while more than half achieved an adherence level of ≥95%, with 40.8% of all clients being 100% adherent. The cohort's median adherence remained stable throughout the course of pregnancy. Healthcare providers should place high emphasis on individual PMTCT counseling at first ANC encounter, and pay special attention to those women previously unaware of their HIV status. However, after initial uptake, high adherence seems to be feasible for Option B+.

Lack of effect of intermittent preventive treatment for malaria in pregnancy and intense drug resistance in western Uganda.

BACKGROUND: Intermittent preventive treatment in pregnancy (IPTp) with sulfadoxine-pyrimethamine (SP) is widely implemented in sub-Saharan Africa for the prevention of malaria in pregnancy and adverse birth outcomes. However, in areas of intense SP resistance, the efficacy of IPTp may be compromised. METHODS: A cross-sectional study among 915 delivering women (728 analysable live singleton deliveries) was conducted in Fort Portal, western Uganda, to assess associations of reported IPTp use, Plasmodium falciparum infection, maternal anaemia, low birth weight, and preterm delivery, and to estimate the degree of SP resistance as reflected by pfdhfr/pfdhps mutations. RESULTS: Plasmodium falciparum infection was detected by PCR in 8.9 % and by microscopy of placental blood samples in 4.0 %. Infection was significantly associated with stillbirth, early neonatal death, anaemia, low birth weight, and pre-term delivery. Eighty percent of the women had taken at least one dose of IPTp, and more than half had taken two doses. As compared to women without chemoprophylaxis against malaria, IPTp had no significant influence on the presence of P. falciparum infection (13.8 vs. 9.6 %, P = 0.31). Nor was it associated with reductions in anaemia, low birth weight or preterm delivery. P. falciparum with intense SP resistance (pfdhfr/pfdhps quintuple or sextuple mutations) were observed in 93 % (pfdhps 581G, 36 %), and the additional high resistance allele pfhdr 164L in 36 %. CONCLUSIONS: In Fort Portal, Uganda, reported use of IPTp with SP does not provide an observable benefit. The molecular markers of P. falciparum indicate high grade SP resistance reaching the threshold set by WHO for the discontinuation of IPTp with SP. Alternative approaches for the prevention of malaria in pregnancy are urgently needed.

Perceptual instability in schizophrenia: Probing predictive coding accounts of delusions with ambiguous stimuli.

BACKGROUND: Delusions, a core symptom of schizophrenia, are thought to arise from an alteration in predictive coding mechanisms that underlie perceptual inference. Here, we aimed to empirically test the hypothesized link between delusions and perceptual inference. METHOD: 28 patients with schizophrenia and 32 healthy controls matched for age and gender took part in a behavioral experiment that assessed the influence of stabilizing predictions on perception of an ambiguous visual stimulus. RESULTS: Participants with schizophrenia exhibited a weaker tendency towards percept stabilization during intermittent viewing of the ambiguous stimulus compared to healthy controls. The tendency towards percept stabilization in participants with schizophrenia correlated negatively with delusional ideation as measured with a validated questionnaire. CONCLUSION: Our results indicate an association between a weakened effect of sensory predictions in perceptual inference and delusions in schizophrenia. We suggest that attenuated predictive signaling during perceptual inference in schizophrenia may yield the experience of aberrant salience, thereby providing the starting point for the formation of delusions.