Growth and Gastrointestinal Tolerance in Healthy Term Infants Fed Milk-Based Infant Formula Supplemented with Five Human Milk Oligosaccharides (HMOs): A Randomized Multicenter Trial

Background: Five of the most abundant human milk oligosaccharides (HMOs) in human milk are 2′-fucosyllactose (2′-FL), 3-fucosyllactose (3-FL), lacto-N-tetraose (LNT), 3′-sialyllactose (3′-SL) and 6′-sialyllactose (6′-SL). Methods: A randomized, double-blind, controlled parallel feeding trial evaluated growth in healthy term infants fed a control milk-based formula (CF; n = 129), experimental milk-based formula (EF; n = 130) containing five HMOs (5.75 g/L; 2′-FL, 3-FL, LNT, 3′-SL and 6′-SL) or human milk (HM; n = 104). Results: No significant differences (all p ≥ 0.337, protocol evaluable cohort) were observed among the three groups for weight gain per day from 14 to 119 days (D) of age, irrespective of COVID-19 or combined non-COVID-19 and COVID-19 periods. There were no differences (p ≥ 0.05) among the three groups for gains in weight and length from D14 to D119. Compared to the CF group, the EF group had more stools that were soft, frequent and yellow and were similar to the HM group. Serious and non-serious adverse events were not different among groups, but more CF-fed infants were seen by health care professionals for illness from study entry to D56 (p = 0.044) and D84 (p = 0.028) compared to EF-fed infants. Conclusions: The study demonstrated that the EF containing five HMOs supported normal growth, gastrointestinal (GI) tolerance and safe use in healthy term infants.     

Loneliness before and during the COVID-19 pandemic—are unpartnered and childless older adults at higher risk?

COVID-19 mitigation efforts had the potential to exacerbate loneliness among older adults, particularly for the unpartnered or childless, yet specific studies on loneliness among these groups during the COVID-19 pandemic are lacking. Using data from the Survey of Health, Ageing and Retirement in Europe (SHARE) collected before (October 2019–March 2020) and during the pandemic (June–August 2020), we examine two loneliness outcomes: (1) “have you felt lonely recently?” (both datasets) and (2) “have you felt lonelier than before the pandemic?” (2020), and examine differences by partnership and parenthood status. Before COVID-19, those who lacked one tie but had the other (unpartnered parents or partnered childless) were at highest loneliness risk. During COVID-19, unpartnered and childless—especially unpartnered—remain at higher risk for loneliness, entering loneliness, and not “exiting” loneliness. We discuss these findings in light of family norms and needs in pandemic and non-pandemic times and provide recommendations for future research.Supplementary InformationThe online version contains supplementary material available at 10.1007/s10433-022-00718-x.     

A public–private collaboration model for clinical innovation

Launched in May 2012 as part of the New Therapeutic Uses program, the National Center for Advancing Translational Sciences (NCATS)’ National Institutes of Health (NIH)‐Industry Partnerships initiative fostered collaboration between pharmaceutical companies and the biomedical research community to advance therapeutic development. Over the 10‐year life of the initiative, the industry partners included: AstraZeneca; AbbVie (formerly Abbott); Bristol‐Myers Squibb; Eli Lilly and Company; GlaxoSmithKline; Janssen Pharmaceutical Research & Development, L.L.C.; Pfizer; Sanofi; and Mereo (out licensed assets). The initiative provided researchers at academic medical centers with a rare opportunity to propose clinical trials to test ideas for new therapeutic uses for a selection of clinic‐ready and often previously proprietary experimental pharmaceutical assets that were provided by industry partners. Here, we describe the process by which collaborations between pharmaceutical companies with viable experimental assets and academic researchers with ideas for new uses of those assets were established; and how NCATS/NIH funding supported not only phase I and II clinical trials as well as any nonclinical studies needed before testing in a new patient population, it also provided an opportunity for testing innovative outcome measures for proof‐of‐concept trials. Although the program did not demonstrate improved success rates for phase II clinical trials, this collaboration model leverages the strengths of each party and with a focus toward evaluating an innovative outcome measure, could be used to reduce patient burden and trial costs, and improve patient engagement.     

Vital Signs: Drug Overdose Deaths,by Selected Sociodemographic and Social Determinants of Health Characteristics — 25 States and the District of Columbia, 2019–2020

Introduction: Drug overdose deaths increased approximately 30% from 2019 to 2020 in the United States. Examining rates by demographic and social determinants of health characteristics can identify disproportionately affected populations and inform strategies to reduce drug overdose deaths.Methods: Data from the State Unintentional Drug Overdose Reporting System (SUDORS) were used to analyze overdose death rates from 2019 to 2020 in 25 states and the District of Columbia. Rates were examined by race and ethnicity and county-level social determinants of health (e.g., income inequality and treatment provider availability).Results: From 2019 to 2020, drug overdose death rates increased by 44% and 39% among non-Hispanic Black (Black) and non-Hispanic American Indian or Alaska Native (AI/AN) persons, respectively. Significant disparities were found across sex, age, and racial and ethnic subgroups. In particular, the rate in 2020 among Black males aged ≥65 years (52.6 per 100,000) was nearly seven times that of non-Hispanic White males aged ≥65 years (7.7). A history of substance use was frequently reported. Evidence of previous substance use treatment was lowest for Black persons (8.3%). Disparities in overdose deaths, particularly among Black persons, were larger in counties with greater income inequality. Opioid overdose rates in 2020 were higher in areas with more opioid treatment program availability compared with areas with lower opioid treatment availability, particularly among Black (34.3 versus 16.6) and AI/AN (33.4 versus 16.2) persons.Conclusions and Implications for Public Health Practice: Health disparities in overdose rates continue to worsen, particularly among Black and AI/AN persons; social determinants of health, such as income inequality, exacerbate these inequities. Implementation of available, evidence-based, culturally responsive overdose prevention and response efforts that address health disparities impacting disproportionately affected populations are urgently needed.     

Diagnostic and management challenges from childhood,puberty through to transition in severe insulin resistance due to insulin receptor mutations

Two Caucasian girls, both of normal weight and body mass indices, were diagnosed with type A insulin resistance (IR) in childhood. Case 1 presented with premature adrenarche aged 7 years, then by age 12 years had hirsutism, acne, acanthosis nigricans, and asymptomatic diabetes. Subsequent investigation revealed raised adiponectin (15.3 mg/L) and heterozygous p.Pro1205Leu mutation in the INSR gene encoding the insulin receptor. She experienced postprandial hypoglycaemia on metformin; acarbose was trialled and discontinued aged 16 years, as she became normoglycaemic. Hirsutism was treated with topical eflornithine, oral spironolactone and flutamide, and laser therapy. Unfortunately, diabetes reemerged in young adulthood with obesity. Case 2: during an emergency admission for acute abdominal pain aged 11 years, hyperglycaemia was noted which led to further investigation. An oral glucose tolerance test showed diabetes and ultrasound showed polycystic ovaries. Further investigations revealed raised adiponectin (18 mg/L) and compound heterozygous mutations in the INSR gene: p.Pro1263Ala and p.Ser748Leu (latter probable normal variant). She was treated with metformin and experienced postprandial hypoglycaemia. Symptoms of hyperandrogenism were controlled by flutamide. She maintained a healthy weight and reassessment at young adulthood showed resolution of diabetes. Type A IR may present in childhood with overlapping features of common endocrine entities such as premature adrenarche and polycystic ovarian syndrome. Patients with abnormal glucose tolerance yet normal weight merit screening with adiponectin; raised adiponectin levels prompt insulin receptor mutational analysis. Postprandial hypoglycaemia is characteristic. Management includes optimization of glycaemic control with oral hypoglycaemic agents and maintenance of healthy weight, and controlling the effects of hyperandrogenism.     

Perinatal transmission of Trichomonas vaginalis: a case report

BACKGROUND: Trichomonas vaginalis infection is associated with increased risks of adverse pregnancy outcome. Perinatal transmission of T vaginalis from an infected, untreated, pregnant woman to her female neonate can occur. CASE: A 22-year-old woman, gravida 3, para 2, with untreated trichomoniasis had an uncomplicated spontaneous vaginal delivery of a healthy female infant. At day of life 19 the newborn was diagnosed and treated for trichomoniasis. No evidence was found consistent with child sexual abuse. CONCLUSION: Perinatal transmission of T vaginalis occurs rarely. Neonatal infection has medical and psychosocial implications. This outcome, albeit rare, should be a consideration in the decision regarding antenatal treatment of T vaginalis infection.     

Liquid compared with conventional cervical cytology: a systematic review and meta-analysis

OBJECTIVE: To compare test performance characteristics of conventional Pap tests and liquid-based cervical cytology samples. DATA SOURCES: Eligible studies, published between 1991 and 2007, were retrieved through PubMed/EmBase searching and completed by consultation of other sources. METHODS OF STUDY SELECTION: Studies were selected if a conventional and a liquid-based sample were prepared from the same woman or when one or the other type of sample was taken from a separate but similar cohort. The current systematic review and meta-analysis is restricted to studies where all subjects were submitted to gold standard verification, based on colposcopy and histology of colposcopy-targeted biopsies, allowing computation of absolute and relative test validity for cervical intraepithelial neoplasia grade 2 or worse. Randomized trials were selected as well if all test-positive cases were verified with the same gold standard, allowing computation of the relative sensitivity. Impact of study characteristics on accuracy was assessed by subgroup meta-analyses, meta-regression, and summary receiver operating characteristic curve regression. TABULATION, INTEGRATION, AND RESULTS: The relative sensitivity, pooled from eight studies, with complete gold standard verification and from one randomized clinical trial, did not differ significantly from unity. Also, the specificity, considering high-grade and low-grade squamous intraepithelial lesions as cutoff, was similar in conventional and liquid cytology. However, a lower pooled specificity was found for liquid-based cytology when presence of atypical squamous cells of undetermined significance was the cutoff (ratio 0.91, 95% confidence interval 0.84-0.98). Differences in study characteristics did not explain interstudy heterogeneity. CONCLUSION: Liquid-based cervical cytology is neither more sensitive nor more specific for detection of high-grade cervical intraepithelial neoplasia compared with the conventional Pap test.     

Noncomparative contraceptive efficacy of cellulose sulfate gel

OBJECTIVE: To estimate the 6-month cumulative probability of pregnancy, short-term adverse effects, and acceptability of cellulose sulfate vaginal contraceptive gel. METHODS: Two hundred fertile heterosexual couples were enrolled in this single-center, phase II, 6-month noncomparative study conducted at the California Family Health Council in Los Angeles, California. Couples did not desire pregnancy, were at low risk for sexually transmitted diseases, and agreed to use 3.5 mL of cellulose sulfate gel intravaginally before each coital act as their primary means of contraception. Scheduled follow-up visits took place after one menstrual cycle and at study completion, which occurred after 6 months and six menstrual cycles had elapsed. In addition, participants were instructed to call the site at the onset of each menses to review their diary cards. RESULTS: The cumulative probabilities of pregnancy during 6 months and six cycles of typical use were 13.4% (95% confidence interval [CI] 7.5-19.4%) and 13.9% (95% CI 7.7-20.2%), respectively, and during 6 cycles of correct and consistent ("perfect") use: 3.9% (95% CI 0.0-9.2%). Slightly over one fourth of the women and one man reported experiencing gel-related adverse events, two thirds of which were mild and only possibly related to the gel. Three quarters of women and men reported that they would buy cellulose sulfate gel for contraception. CONCLUSION: Cellulose sulfate vaginal gel yields pregnancy rates comparable to nonoxynol-9 and few adverse events among couples at low risk for sexually transmitted diseases.     

Individualized norms of optimal fetal growth: fetal growth potential

OBJECTIVE: To demonstrate that individualized optimal fetal growth norms, accounting for physiologic and pathologic determinants of fetal growth, better identify normal and abnormal outcomes of pregnancy than existing methods. METHODS: In a prospective cohort of 38,033 singleton pregnancies, we identified 9,818 women with a completely normal outcome of pregnancy and characterized the physiologic factors affecting birth weight using multivariable regression. We used those physiologic factors to individually predict optimal growth trajectory and its variation, growth potential, for each fetus in the entire cohort. By comparing actual birth weight with growth potential, population, ultrasound, and customized norms, we calculated for each fetus achieved percentiles, by each norm. We then compared proportions of pregnancies classified as normally grown, between 10th and 90th percentile, or aberrantly grown, outside this interval, by growth potential and traditional norms, in 14,229 complicated pregnancies, 1,518 pregnancies with diabetes or hypertensive disorders, and 1,347 pregnancies with neonatal complications. RESULTS: Nineteen physiologic factors, associated with maternal characteristics and early placental function, were identified. Growth potential norms correctly classified significantly more pregnancies than population, ultrasound, or customized norms in complicated pregnancies (26.4% compared with 18.3%, 18.7%, 22.8%, respectively, all P<.05), pregnancies with diabetes or hypertensive disorders (37.3% compared with 23.0%, 28.0%, 34.0%, respectively, all P<.05) and neonatal complications (33.3% compared with 19.7%, 24.9%, 29.8%, respectively, all P<.05). CONCLUSION: Growth potential norms based on the physiologic determinants of birth weight are a better discriminator of aberrations of fetal growth than traditional norms. LEVEL OF EVIDENCE: II.