Impact of the 2022 Infant Formula Shortage on Self-Reported Rates of Anxiety and Depression: Evidence from the Household Pulse Survey.

PURPOSE: To evaluate the impact of the 2022 infant formula shortage on self-reported anxiety and depression. BACKGROUND: The US national infant formula shortage of 2022 originated from supply chain disruptions triggered by the COVID-19 pandemic, and the shortage was further compounded by a recall of tainted formula products. METHODS: We used survey-weighted data from the Household Pulse Survey (HPS) to measure self-reported anxiety and depression among individuals with formula-fed infants less than 1 year of age. We evaluated the association between 2 formula disruption variables (being impacted by the infant formula shortage or having difficulty obtaining formula in the last 7 days) with 2 mental health outcomes (anxiety and depression) using multivariable logistic regressions. RESULTS: We found increased odds of self-reported anxiety (aOR: 3.13; P < .001) and depression (aOR: 3.05; P = .005) for respondents affected by the infant formula shortage. There were no adjusted associations between having difficulty obtaining formula in the last 7 days and anxiety and depression. CONCLUSIONS: Individuals affected by the infant formula shortage had increased odds of both anxiety and depression. Continued efforts to improve food security for low-income infants is critical for ensuring equitable nutritional and health outcomes across infant populations. IMPLICATIONS FOR PRACTICE AND RESEARCH: Continued efforts to reduce food insecurity for low-income infants are critically needed, as infant nutrition impacts caregiver mental health and infant health. Efforts to improve lactation support and breastfeeding initiation are needed in addition to improvements in access to formula.

Association of the COVID-19 Pandemic With Women, Infants, and Children (WIC) Receipt Among Pregnant Individuals: United States, 2016-2022.

Objectives. To evaluate the effect of COVID-19 on Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) receipt among pregnant individuals overall and by race/ethnicity. Methods. We measured changes in WIC receipt among Medicaid-covered births (n = 10 484 697) from the US National Center for Health Statistics Natality Files (2016-2022). Our interrupted time series logistic model included a continuous monthly variable, a binary post-COVID variable, and a continuous slope shift variable. We additionally fit separate models for each race/ethnicity relative to White individuals, using interaction terms between the time series variables and race/ethnicity. Results. We found decreases in WIC receipt (adjusted odds ratio [AOR] = 0.899; P < .001) from before COVID (66.6%) to after COVID (57.9%). There were larger post-COVID decreases for American Indian/Alaska Native (AOR = 0.850; P < .001), Native Hawaiian/Other Pacific Islander (AOR = 0.877; P = .003), Black (AOR = 0.974; P < .001), and Hispanic (AOR = 0.972, P < .001) individuals relative to White individuals. Conclusions. The greater reductions in WIC receipt among minoritized individuals highlights a pathway through which the pandemic may have widened gaps in already disparate maternal and infant health. Public Health Implications. Continued efforts to increase WIC utilization are needed overall and among minoritized populations. (Am J Public Health. 2023;113(S3):S240-S247. https://doi.org/10.2105/AJPH.2023.307525).

Psychometric properties of PedsQL generic core scales for children with functional constipation in the Netherlands.

OBJECTIVES: The aim of the study was to evaluate the psychometric properties of the Dutch translation of the Pediatric Quality of Life Inventory version 4.0 Generic Core Scales (PedsQL) in children with functional constipation (FC). METHODS: The PedsQL was completed by children with FC ages 5 to 18 years and by the parents of children ages 2 to 18 years. To assess construct validity, all of the parents and children completed the PedsQL Gastrointestinal Symptoms Module (GI module) and children ages 8 to 18 years completed the defecation disorder list. Item response distributions, internal consistency reliability, patient-parent agreement, and discriminating ability were evaluated. RESULTS: Overall, 269 children were enrolled. The PedsQL showed minimal missing responses (self-report: 5.3% with >50% missing, parent report: 2.6% with >50% missing) and achieved satisfactory internal consistency for the total (self-report: α = 0.86, parent report: α = 0.88), physical health (self-report: α = 0.75, parent report α = 0.83), and psychosocial health (self-report: α = 0.80; parent report: α = 0.85) scores. Internal consistency was less convincing for those ages 5 to 7 years (α = 0.53-0.77) than for older individuals. Self-reported health-related quality of life was lower than parent reported, with the exception of children ages 5 to 7 years. Interrater reliability intraclass correlations were 0.52 to 0.61 for the overall population. Correlations among the PedsQL, GI module, and defecation disorder list were consistent with a priori hypotheses and generally supported construct validity. The PedsQL distinguished between a previously published healthy reference sample and children with FC, and between those with mild and severe symptoms (P < 0.05). CONCLUSIONS: The self-reported and proxy reported PedsQL demonstrated satisfactory measurement properties in Dutch children with FC ages 8 to 18 years. Further research is needed to establish internal consistency and validity in those ages 5 to 7 years.

Predictive markers for pathological complete response (pCR) after neo-adjuvant chemotherapy in HER2-positive breast carcinoma.

OBJECTIVES: Patients with HER2-positive invasive breast cancer that is node-positive and/or larger than 3 cm are generally treated with neoadjuvant chemotherapy (NAC). We aimed to identify predictive markers for pathological complete response (pCR) after NAC in HER2-positive breast carcinoma. METHODS: Hematoxylin/eosin-stained slides of 43 HER2-positive breast carcinoma biopsies were histopathologically reviewed. Immunohistochemistry (IHC) was performed on pre-NAC biopsies, comprising HER2, estrogen receptor (ER), progesterone receptor (PR), Ki-67, epidermal growth factor receptor (EGFR), mucin-4 (MUC4), p53 and p63. Dual-probe HER2 in situ hybridization (ISH) was performed to study the mean HER2 and CEP17 copy numbers. ISH and IHC data were retrospectively collected for a validation cohort, comprising 33 patients. RESULTS: Younger age at diagnosis, 3+ HER2 IHC scores, high mean HER2 copy numbers and high mean HER2/CEP17 ratios were significantly associated with an increased chance of achieving a pCR, and the latter two associations were confirmed in the validation cohort. No other immunohistochemical or histopathological markers were associated with pCR. CONCLUSIONS: This retrospective study of two community-based NAC-treated HER2-positive breast cancer patient cohorts identified high mean HER2 copy numbers as a strong predictor for pCR. Further studies on larger cohorts are required to determine a precise cut-point for this predictive marker.

Effects of etravirine versus placebo on health-related quality of life in treatment-experienced HIV patients as measured by the functional assessment of human immunodeficiency virus infection (FAHI) questionnaire in the DUET trials.

PURPOSE: To study the effects of etravirine versus placebo on the health-related quality of life (HRQL) of HIV-infected patients. METHOD: HRQL of HIV-infected patients was measured using the Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) questionnaire in two identically designed phase III clinical trials investigating efficacy and safety of etravirine as part of highly active antiretroviral therapy. Pooled analyses of covariance, adjusted for treatment group, baseline FAHI score, CD4 cell count, viral load, and enfuvirtide use helped investigate changes in FAHI scores between baseline and Week 24 in etravirine-treated (n = 599) and placebo-treated (n = 604) subjects. Responder analyses were also conducted. RESULTS: Significant improvements with etravirine treatment were observed for FAHI physical, functional, emotional, and total scores (P < .001). These improvements were greater and statistically different from those with placebo (.013

Psychometric evaluation of the functional assessment of HIV Infection (FAHI) questionnaire and its usefulness in clinical trials.

PURPOSE: To evaluate psychometric properties of the Functional Assessment of Human Immunodeficiency Virus Infection (FAHI) questionnaire, a 47-item disease-specific instrument evaluating Health-Related Quality of Life (HRQL) in human immunodeficiency virus (HIV)-infected patients. METHODS: Treatment-experienced HIV-infected patients from two clinical programmes (N = 565; N = 1,096) completed the FAHI at Baseline and after 24 weeks of treatment. Psychometric properties of the FAHI were assessed in both trial populations, including minimal important differences (MIDs) calculations. Links between HRQL assessed by FAHI Total score, and biological endpoints were explored by regression analysis and mean score comparisons. RESULTS: Cronbach's alphas ranged from 0.72 to 0.94. Most items met convergent and discriminant validity criteria. Better FAHI scores were seen for patients in earlier HIV stages. Responsiveness was demonstrated with changes in FAHI scores significantly linked to change in EQ-5D score. Depending on methods used, MIDs ranged from 3.2 to 14 for FAHI Total score. Small association was found between FAHI Total score and CD4 count and viral load (r-square < 3%). Mean changes in FAHI scores were not statistically related to viral response. CONCLUSIONS: The FAHI demonstrated acceptable psychometric properties in two independent populations. HRQL assessment enabled detection of changes in patients' health status not revealed by traditional efficacy endpoints.

Community subgroups in dyspepsia and their association with weight loss.

OBJECTIVE: A link between dyspepsia symptoms and weight loss is controversial. We aimed to determine whether or not weight loss is a marker of dyspepsia. METHODS: Independent community-based cross-sectional studies. Subjects were randomly selected from the general population in Sydney, Australia. All subjects completed validated community health surveys. Two distinct data collections were used; the first as a training sample (N = 888) and the second as a validation sample to confirm the findings of the first (N = 2,907). The study was focused on weight loss, which was categorized as (a) any weight loss, (b) substantive weight loss (> or =3 kg), and (c) weight loss expressed as percentage of body weight. RESULTS: All dyspepsia symptoms studied were positively associated with weight loss although the strength of association did vary. Nausea and vomiting were most strongly associated with weight loss as were meal-related complaints such as postprandial fullness. Similarly, clusters formed based on symptoms were strongly differentiated in terms of weight loss with clusters characterized by nausea, vomiting, and early satiety/postprandial fullness reporting 25-30% weight loss prevalence over the previous 3 months compared with around 10% prevalence in clusters characterized by low dyspepsia symptom burden. Weight loss > or =3 kg followed a similar pattern but with a prevalence approximately half that of any weight loss, while weight loss expressed as percentage of body weight followed the same pattern. CONCLUSIONS: Dyspepsia symptoms are clearly and, in some cases, strongly associated with weight loss, both any loss of weight and substantive weight loss. Weight loss should be considered a warning symptom of dyspepsia.

The Shared Ethical Responsibility of Medically and Non-medically Qualified Experts in Human Drug Development Teams.

The complexity of developing and applying increasingly sophisticated new medicinal products has led to the participation of many non-medically qualified scientists in multi-disciplinary non-clinical and clinical drug development teams world-wide. In this introductory paper to the "IFAPP International Ethics Framework for Pharmaceutical Physicians and Medicines Development Scientists" it is argued that all members of such multidisciplinary teams must share the scientific and ethical responsibilities since they all influence directly or indirectly both the outcome of the various phases of the medicines development projects and the safety of the research subjects involved. The participating medical practitioner retains the overriding responsibility and the final decision to stop a trial if the well-being of the research subjects is seriously endangered. All the team members should follow the main ethical principles governing human research, the respect for autonomy, justice, beneficence and non-maleficence. Nevertheless, the weighing of these principles might be different under various conditions according to the specialty of the members.

Patient-reported outcomes helped predict survival in multiple myeloma using partial least squares analysis.

OBJECTIVE: The prognostic value of Patient-Reported Outcomes (PRO) in predicting mortality during treatment of multiple myeloma (MM) patients was assessed using partial least square (PLS) regression, a statistical method that is well-adapted for highly correlated data. STUDY DESIGN AND SETTING: Four PRO measures, The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30, the EORTC QLQ-MY24, the FACIT-Fatigue scale, and the FACT/GOG-Ntx scale, were administered during a trial designed to evaluate the efficacy and safety of bortezomib (VELCADE 1.3mg/m(2)) in MM patients (N=202). Clinical and PRO data were analyzed for predictive value by univariate and multivariate logistic regression methods and then by PLS regression. RESULTS: Fifteen baseline PRO parameters were significant in predicting mortality during treatment when univariate logistic regression was used. In contrast, only two variables were retained in the multivariate analysis, as correlated variables were excluded from the model. Using PLS regression, 14 of the 21 PRO predictors were significant in predicting mortality. Clinical and PRO data used together increased the predictive power of all models compared to clinical data alone. CONCLUSION: The prognostic value of PRO was established and was more informative using PLS regression. PLS regression may therefore be a valuable method for analyzing PRO data.

Use of patient-reported sleep measures in clinical trials of pain treatment: a literature review and synthesis of current sleep measures and a conceptual model of sleep disturbance in pain.

BACKGROUND: Despite the strong relationship between sleep-related problems and chronic pain, no measures have been developed specifically for the assessment of sleep disorders in patients with chronic pain. In addition, there are no explicit guidelines to suggest which of the existing self-reported measures of sleep disorders best capture the sleep disorders pertinent to patients with chronic pain. OBJECTIVE: The objective of this paper was to examine the fit between current sleep measures that capture areas of sleep disturbance important to patients with pain and to develop a conceptual model of sleep disturbance in these patients. METHODS: A conceptual framework describing the associations between patient-reported experiences of pain and sleep problems was constructed based on a review of the published peer-reviewed literature. The online OVID/MEDLINE and PubMed databases were searched for articles in English published between 1995 and June 2007. Additional relevant material was identified by searching the reference lists of systematic review articles. The literature review and conceptual framework were used to determine the sleep domains that are most relevant to the study of patients with chronic pain. The patient-reported sleep measures most frequently used in pain clinical trials were identified and characterized psychometrically, along with how well they captured the relevant sleep domains. RESULTS: Fourteen pain trials were identified in which sleep instruments were used. A review of the characteristics of the sleep-assessment instruments indicated that both the Medical Outcomes Study (MOS) Sleep Scale and the Pittsburgh Sleep Quality Index (PSQI) are well suited to measuring aspects of sleep that are of particular importance in the study of pain. The PSQI was used more frequently in the identified literature, but the MOS Sleep Scale was also well represented. The MOS Sleep Scale has fewer items than the PSQI, and its scoring system has a better psychometric fit with its conceptual framework. CONCLUSIONS: Sleep disturbance was found to be an essential element of the conceptual model for sleep-related problems in patients with pain. Of several sleep-quality instruments that have been used in pain clinical trials, the MOS Sleep Scale was found to be the best option. The PSQI, which was useful in many respects, may have a questionable factor structure. More research is needed comparing the scoring invariance on sleep scales between individuals with sleep disturbance in the general population and patients with pain.

Validation of the PAC-SYM questionnaire for opioid-induced constipation in patients with chronic low back pain.

BACKGROUND: The Patient Assessment of Constipation Symptoms (PAC-SYM) questionnaire is a 12-item self-report instrument divided into abdominal, rectal and stool domains. AIMS: This study aimed to (1) evaluate the psychometric properties of PAC-SYM in assessing the symptoms and severity of opioid-induced constipation; (2) test for differences in opioid-induced constipation between Durogesic fentanyl transdermal reservoir (TDF) and oral sustained-release morphine (SRM) in patients with chronic low back pain (CLBP). METHODS: In a 13-month, open-label, parallel-group study, 680 patients were randomised to receive either TDF (n=338) or SRM (n=342) for CLBP. Assessments were recorded at Visit 1 (baseline), Visit 5 (Day 29) and Visit 17 (Month 13). Concurrent validity, clinical validity and responsiveness of PAC-SYM were determined based on patients' confirmation of constipation (CC) scores. Differences in PAC-SYM scores between treatment groups were also evaluated. RESULTS: The study included 677 patients, of whom 638 were opioid-naïve. Mean PAC-SYM scores for constipated patients were substantially higher than for non-constipated patients, demonstrating good clinical validity for PAC-SYM. The PAC-SYM could detect changes in bowel function over the treatment period, indicating responsiveness. Homogeneity of each symptom domain exceeded Cronbach's alpha coefficient of 0.70, suggesting good internal consistency and reliability. Changes in mean PAC-SYM scores from baseline to Visit 5 and Visit 17 were significantly lower for the TDF group than for the SRM group, indicating that the TDF group experienced less severe constipation. CONCLUSION: PAC-SYM is a reliable, valid and responsive measure of the presence and severity of opioid-induced constipation symptoms.

Fostering Competence in Medicines Development: The IFAPP Perspective.

IFAPP (International Federation of Associations of Pharmaceutical Physicians and Pharmaceutical Medicine) is a nonprofit organization with the mission to promote Pharmaceutical Medicine & Medicines Development (PM&MD) by enhancing the competencies and maintaining high research ethical standards of Pharmaceutical Physicians and other professionals involved in medicines development worldwide, leading to the availability and appropriate use of medicines for the benefit of patients and society. About 30 national professional associations related to PM&MD, involving 7000 professionals, are affiliated to IFAPP. Medicines development has traditionally been a challenging enterprise, with high risk, high investment, and potentially high returns in the lengthy and complex process of identifying a new chemical entity as a candidate for development and possibly succeeding in bringing it as a pharmaceutical product to the market. However, the emergence of genomics, translational research, biomarkers, and precision medicine pose challenges going forward involving allocation of resources, price, market access, and cost-effectiveness as opposed to the traditional concepts of "efficacy" and "safety." Education and Continuing Professional Development (CPD) are a major focus of IFAPP. The International Conference on Pharmaceutical Medicine (ICPM) is the largest event for our organization; ICPM is held every 2 or 3 years and is aimed to provide the state of the art in key areas for our discipline and profession. The paper is a reflection on the role of competency-based education and training for Pharmaceutical Physicians and medicines development scientists, as was discussed during the recent ICPM 2016 held in Sao Paulo, Brazil on April 18-19, with the support of the Brazilian Association of Pharmaceutical Medicine, and gathered around 200 representatives from the pharmaceutical, clinical research and regulatory arenas from all over the world,.

Economic analysis of on-demand maintenance therapy with proton pump inhibitors in patients with non-erosive reflux disease.

AIM: To evaluate the costs and effectiveness of on-demand maintenance therapy with oral esomeprazole, lansoprazole, omeprazole, pantoprazole or rabeprazole in patients with endoscopy-confirmed non-erosive reflux disease (NERD) in the UK. METHODS: A probabilistic model was developed to compare the costs and effectiveness of five proton pump inhibitors (PPIs) in endoscopy-negative, symptomatic NERD patients who had complete resolution of heartburn symptoms following 4 weeks of open-label acute PPI treatment. The total annual expected costs (euro, 2003 values) and utilities gained per patient were measured over a 1-year horizon from the perspective of the UK NHS. Model uncertainty was addressed by sensitivity analyses. RESULTS: The base-case annual median costs and utilities gained with on-demand PPI therapy were: 123 euro and 0.89 for rabeprazole 10mg; 176 euro and 0.90 for pantoprazole 20mg; 190 euro and 0.89 for esomeprazole 20mg; 195 euro and 0.91 for lansoprazole 15mg; 201 euro and 0.90 for omeprazole 20mg; and 210 euro and 0.91 for omeprazole 10mg. Differences in costs, but not in outcomes, were statistically significant. The results were robust to sensitivity analyses. CONCLUSIONS: In this analysis, on-demand use of rabeprazole for the management of NERD incurred the least cost in comparison with the other PPIs evaluated. Utility gains were comparable for all on-demand PPIs. The place of on-demand PPIs in therapy, however, requires further evaluation.

Assessing the impact of dietary habits on health-related quality of life requires contextual measurement tools.

The increase of non-communicable diseases at all ages has fostered the general concern for sustaining population health worldwide. Unhealthy lifestyles and dietary habits impacting physical and psycho-social health are well known risk factors for developing life threatening diseases. Identifying the determinants of quality of life is an important task from a Public Health perspective. Consumer-Reported Outcome measures of health-related quality of life (HRQoL) are becoming increasingly necessary and relevant in the field of nutrition. However, quality of life questionnaires are seldom used in the nutrition field. We conducted a scientific literature search to find out the questionnaires used to determine the association between dietary habits and quality of life. A total of 13 studies were eligible for inclusion. Across these studies the short form-36, a generic (non-disease specific) HRQoL measurement instrument was the most widely used. However, generic measures may have limited content validity in the context of dietary habits interventions. We recommend additional contextual diet-specific HRQoL measures are also needed for evaluating the impact of diet habits on daily life functioning and well-being.

Cost-effectiveness of prucalopride in the treatment of chronic constipation in the Netherlands.

OBJECTIVE: To assess the cost-effectiveness of prucalopride vs. continued laxative treatment for chronic constipation in patients in the Netherlands in whom laxatives have failed to provide adequate relief. METHODS: A Markov model was developed to estimate the cost-effectiveness of prucalopride in patients with chronic constipation receiving standard laxative treatment from the perspective of Dutch payers in 2011. Data sources included published prucalopride clinical trials, published Dutch price/tariff lists, and national population statistics. The model simulated the clinical and economic outcomes associated with prucalopride vs. standard treatment and had a cycle length of 1 month and a follow-up time of 1 year. Response to treatment was defined as the proportion of patients who achieved "normal bowel function". One-way and probabilistic sensitivity analyses were conducted to test the robustness of the base case. RESULTS: In the base case analysis, the cost of prucalopride relative to continued laxative treatment was € 9015 per quality-adjusted life-year (QALY). Extensive sensitivity analyses and scenario analyses confirmed that the base case cost-effectiveness estimate was robust. One-way sensitivity analyses showed that the model was most sensitive in response to prucalopride; incremental cost-effectiveness ratios ranged from € 6475 to 15,380 per QALY. Probabilistic sensitivity analyses indicated that there is a greater than 80% probability that prucalopride would be cost-effective compared with continued standard treatment, assuming a willingness-to-pay threshold of € 20,000 per QALY from a Dutch societal perspective. A scenario analysis was performed for women only, which resulted in a cost-effectiveness ratio of € 7773 per QALY. CONCLUSION: Prucalopride was cost-effective in a Dutch patient population, as well as in a women-only subgroup, who had chronic constipation and who obtained inadequate relief from laxatives.

Education and training for medicines development, regulation, and clinical research in emerging countries.

The aim of this satellite workshop held at the 17th World Congress of Basic and Clinical Pharmacology (WCP2014) was to discuss the needs, optimal methods and practical approaches for extending education and teaching of medicines development, regulation, and clinical research to Low and Middle Income Countries (LMICs). It was generally agreed that, for efficiently treating the rapidly growing number of patients suffering from non-communicable diseases, modern drug therapy has to become available more widely and with a shorter time lag in these countries. To achieve this goal many additional experts working in medicines development, regulation, and clinical research have to be trained in parallel. The competence-oriented educational programs designed within the framework of the European Innovative Medicine Initiative-PharmaTrain (IMI-PhT) project were developed with the purpose to cover these interconnected fields. In addition, the programs can be easily adapted to the various local needs, primarily due to their modular architecture and well defined learning outcomes. Furthermore, the program is accompanied by stringent quality assurance standards which are essential for providing internationally accepted certificates. Effective cooperation between international and local experts and organizations, the involvement of the industry, health care centers and governments is essential for successful education. The initiative should also support the development of professional networks able to manage complex health care strategies. In addition it should help establish cooperation between neighboring countries for jointly managing clinical trials, as well as complex regulatory and ethical issues.