Anti-BCMA CAR T-Cell Therapy bb2121 in Relapsed or Refractory Multiple Myeloma.

BACKGROUND: Preclinical studies suggest that bb2121, a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation antigen (BCMA), has potential for the treatment of multiple myeloma. METHODS: In this phase 1 study involving patients with relapsed or refractory multiple myeloma, we administered bb2121 as a single infusion at doses of 50×106, 150×106, 450×106, or 800×106 CAR-positive (CAR+) T cells in the dose-escalation phase and 150×106 to 450×106 CAR+ T cells in the expansion phase. Patients had received at least three previous lines of therapy, including a proteasome inhibitor and an immunomodulatory agent, or were refractory to both drug classes. The primary end point was safety. RESULTS: Results for the first 33 consecutive patients who received a bb2121 infusion are reported. The data-cutoff date was 6.2 months after the last infusion date. Hematologic toxic effects were the most common events of grade 3 or higher, including neutropenia (in 85% of the patients), leukopenia (in 58%), anemia (in 45%), and thrombocytopenia (in 45%). A total of 25 patients (76%) had cytokine release syndrome, which was of grade 1 or 2 in 23 patients (70%) and grade 3 in 2 patients (6%). Neurologic toxic effects occurred in 14 patients (42%) and were of grade 1 or 2 in 13 patients (39%). One patient (3%) had a reversible grade 4 neurologic toxic effect. The objective response rate was 85%, including 15 patients (45%) with complete responses. Six of the 15 patients who had a complete response have had a relapse. The median progression-free survival was 11.8 months (95% confidence interval, 6.2 to 17.8). All 16 patients who had a response (partial response or better) and who could be evaluated for minimal residual disease (MRD) had MRD-negative status (≤10-4 nucleated cells). CAR T-cell expansion was associated with responses, and CAR T cells persisted up to 1 year after the infusion. CONCLUSIONS: We report the initial toxicity profile of a BCMA-directed cellular immunotherapy for patients with relapsed or refractory multiple myeloma. Antitumor activity was documented. (Funded by Bluebird Bio and Celgene; CRB-401 ClinicalTrials.gov number, NCT02658929.).

Planned mode of birth after previous caesarean section and special educational needs in childhood: a population-based record linkage cohort study.

OBJECTIVE: To investigate the association between planned mode of birth after previous caesarean section and a child's risk of having a record of special educational needs (SENs). DESIGN: Population-based cohort study. SETTING: Scotland. POPULATION: A cohort of 44 892 singleton children born at term in Scotland between 2002 and 2011 to women with one or more previous caesarean sections. METHODS: Linkage of Scottish national health and education data sets. MAIN OUTCOME MEASURES: Any SENs and specific types of SEN recorded when a child was aged 4-11 years and attending a Scottish primary or special school. RESULTS: Children born following planned vaginal birth after previous caesarean (VBAC) compared with elective repeat caesarean section (ERCS) had a similar risk of having a record of any SENs (19.24 versus 17.63%, adjusted risk ratio aRR 1.04, 95% CI 0.99-1.09) or specific types of SEN. There was also little evidence that planned VBAC with or without labour induction compared with ERCS was associated with a child's risk of having a record of any SENs (21.42 versus 17.63%, aRR 1.09, 95% CI 1.01-1.17 and 18.78 versus 17.63%, aRR 1.03, 95% CI 0.98-1.08, respectively) or most types of SEN. However, an increased risk of sensory impairment was seen for planned VBAC with labour induction compared with ERCS (1.18 versus 0.78%, risk difference 0.4%, adjusted odds ratio aOR 1.60, 95% CI 1.09-2.34). CONCLUSIONS: This study provides little evidence of an association between planned mode of birth after previous caesarean and SENs in childhood beyond a small absolute increased risk of sensory impairment seen for planned VBAC with labour induction. This finding may be the result of performing multiple comparisons or residual confounding. The findings provide valuable information to manage and counsel women with previous caesarean section concerning their future birth choices. TWEETABLE ABSTRACT: There is little evidence planned mode of birth after previous caesarean section is associated with special educational needs in childhood.

Migration, ethnicity and mental health: evidence from mothers participating in the Millennium Cohort Study.

OBJECTIVES: Over a quarter of UK births are to women who were born outside of the UK. Black and Minority Ethnic (BME) women are disproportionately affected by poor mental health and inequitable access to mental health care in the perinatal period, yet the influence of the migrant status (mothers' UK vs. non-UK birth) is poorly understood. This study aimed to explore the relationship between ethnicity, migration and mental health indicators among mothers participating in a large nationally representative cohort study. STUDY DESIGN: This is a secondary analysis of data from the Millennium Cohort Study. METHODS: Logistic regression quantified the crude and adjusted effects of self-reported ethnicity and migrant status on prevalence of psychological distress and treatment for anxiety/depression at 9-month and 5-year postpartum. RESULTS: We found substantial variation in the prevalence of distress according to ethnicity and migrant status, with Indian and Pakistani women at greatest risk. Despite equal or greater risk, BME and migrant women were less likely to report treatment for anxiety/depression. Mutually adjusted analyses showed ethnicity to be a stronger predictor of both outcomes than migrant status; however, at 5 years, being a migrant independently predicted lower odds of treatment, for a statistically similar level of distress. CONCLUSIONS: Migrant women are likely to be at high risk of poor mental health in the perinatal period and beyond, yet may face significant barriers to accessing mental health care. A better understanding of ethnicity and migration as interrelated risk factors for perinatal mental ill-health is needed to help National Health Service organisations develop policy and practice that is flexible and responsive to diversity.

Long-term cognitive and school outcomes of late-preterm and early-term births: a systematic review.

BACKGROUND: Children born before full term (39-41 weeks' gestation) are at increased risk of adverse cognitive outcomes. Risk quantification is important as late-preterm (LPT; 34-36 weeks) and early-term (ET; 37-38 weeks) births are common. METHOD: This review analyses the effect of LPT and ET births on long-term cognitive and educational outcomes. The primary outcome was general cognitive ability. Secondary outcomes included verbal/non-verbal intelligence quotient, subject-specific school performance and special educational needs. The search strategy included Medline and Embase from January 1975 to June 2013. Eligible studies investigated specified outcomes and included suitable gestational age participants assessed at 2 years and older. Outcome measures and socio-demographic descriptors were extracted, and data meta-analysed where possible. RESULTS: Eight studies compared ET birth with full-term birth. Fourteen studies compared LPT birth with either term birth (>37 weeks, n = 12 studies) or full-term birth (39-41 weeks, n = 2 studies). Substantial between-study heterogeneity existed. LPT and ET children underperformed in most outcomes compared with their term/full-term counterparts, respectively. For example, LPT children had an increased risk of lower general cognitive ability (adjusted risk ratio 1.38 [95% confidence interval 1.06-1.79]), and full-term children performed 5% of a standard deviation higher (z-score 0.05 [0.02, 0.08]) than ET children. Poorer outcomes persist into adulthood; term cohorts performed 5% of a standard deviation higher than LPT cohorts (z-score 0.05 [0.04, 0.07]), and full-term cohorts performed 3% of a standard deviation higher than ET cohorts (z-score 0.03 [0.02, 0.04]). CONCLUSION: This review critically examines the knowledge around long-term cognitive outcomes of LPT and ET births, demonstrating multiple, small, adverse differences between LPT/ET and term/full-term births.

The impact of the Covid-19 pandemic on postnatal anxiety and posttraumatic stress: Analysis of two population-based national maternity surveys in England.

BACKGROUND: Few studies have evaluated postnatal anxiety and posttraumatic stress (PTS) before and during the Covid-19 pandemic using comparable data across time. We used data from two national maternity surveys in England to explore the impact of the pandemic on prevalence and risk factors for postnatal anxiety and PTS. METHODS: Analysis was conducted using population-based surveys carried out in 2018 (n = 4509) and 2020 (n = 4611). Weighted prevalence estimates for postnatal anxiety and PTS were compared across surveys. Adjusted risk ratios (aRR) were estimated for the association between risk factors and postnatal anxiety and PTS. FINDINGS: Prevalence of postnatal anxiety increased from 13.7 % in 2018 to 15.1 % in 2020 (+1.4 %(95%CI:-0.4-3.1)). Prevalence of postnatal PTS increased from 9.7 % in 2018 to 11.5 % in 2020 (+1.8 %(95%CI:0.3-3.4)), due to an increase in PTS related to birth trauma from 2.5 % to 4.3 % (+1.8 %(95%CI:0.9-2.6); there was no increase in PTS related to non-birth trauma. Younger age (aRR = 1.31-1.51), being born in the UK (aRR = 1.29-1.59), long-term physical or mental health problem(s) (aRR = 1.27-1.94), and antenatal anxiety (aRR = 1.97-2.22) were associated with increased risk of postnatal anxiety and PTS before and during the pandemic, whereas higher satisfaction with birth (aRR = 0.92-0.94) and social support (aRR = 0.81-0.82) were associated with decreased risk. INTERPRETATION: Prevalence of postnatal PTS was significantly higher during the pandemic, compared to before the pandemic, due to an increase in PTS related to birth trauma. Prevalence of postnatal anxiety was not significantly higher during the pandemic. Risk factors for postnatal anxiety and PTS were similar before and during the pandemic.

Persistent effects of women's parity and breastfeeding patterns on their body mass index: results from the Million Women Study.

OBJECTIVE: To explore the long-term effects of women's childbearing patterns on their body mass index. DESIGN: Cross-sectional analysis. SETTING: Population-based study of UK women. PARTICIPANTS: 740 628 postmenopausal participants in the Million Women Study who reported their height, weight, reproductive histories and other relevant factors. MAIN OUTCOME MEASURES: Standardized mean BMI (kg m(-2)) in groups defined by their parity and breastfeeding history. RESULTS: Women were aged 57.5 (s.d. 4) years on average, and had a mean BMI of 26.2 kg m(-2) (s.d. 5); 88% were parous, with 2.1 (s.d. 1.2) children on average. The standardised mean BMI increased progressively with the number of births from 25.6 kg m(-2) (95% confidence interval (CI): 25.5-25.6) in nulliparous women up to 27.2 kg m(-2) (CI: 27.2-27.3) for women with four or more births, a difference of 1.7 kg m(-2) (CI: 1.6-1.7). Among the parous women 70% had ever breastfed and their average total duration of breastfeeding was 7.7 (s.d. 8.8) months. At every parity level the standardised mean BMI was significantly lower among women who had breastfed than those who had not, decreasing by 0.22 kg m(-2) (CI: 0.21-0.22) for every 6 months of breastfeeding, that is, women's mean BMI was 1% lower for every 6 months that they had breastfed. These associations were highly statistically significant (P<0.0001) and independent of the effects of socioeconomic group, region of residence, smoking and physical activity. CONCLUSIONS: Childbearing patterns have a persistent effect on adiposity in this population. The reduction in BMI associated with just 6 months breastfeeding in UK women could importantly reduce their risk of obesity-related disease as they age.

Asthma in children born after infertility treatment: findings from the UK Millennium Cohort Study.

STUDY QUESTION: Is asthma more common in children born after subfertility and assisted reproduction technologies (ART)? SUMMARY ANSWER: Yes. Asthma, wheezing in the last year and anti-asthmatic medication were all more common in children born after a prolonged time to conception (TTC). This was driven specifically by an increase in children born after ART. WHAT IS KNOWN ALREADY: Few studies have investigated any association between ART and asthma in subsequent children, and findings to date have been mixed. A large registry-based study found an increase in asthma medication in ART children but suggests underlying infertility is the putative risk factor. Little is known about asthma in children after unplanned or mistimed conceptions. STUDY DESIGN, SIZE, DURATION: The Millennium Cohort Study is a UK-wide, prospective study of 18 818 children recruited at 9 months of age. Follow-up is ongoing. This study analyses data from follow-up surveys at 5 and 7 years of age (response rates of 79 and 70%, respectively). PARTICIPANTS/MATERIALS, SETTING, METHODS: Singleton children whose natural mothers provided follow-up data were included. Mothers reported whether their pregnancy was planned; planners provided TTC and details of any ART. The population was divided into 'unplanned' (unplanned and unhappy), 'mistimed' (unplanned but happy), 'planned' (planned, TTC < 12 months), 'untreated subfertile' (planned, TTC >12 months), 'ovulation induced' (received clomiphene citrate) and 'ART' (IVF or ICSI). The primary analysis used the planned children as the comparison group; secondary analysis compared the treatment groups to the children born to untreated subfertile parents. Outcomes were parent report of asthma and wheezing at 5 and 7 years, derived from validated questions in the International Study of Asthma and Allergies in Childhood, plus use of anti-asthmatic medications. A total of 13 041 (72%) children with full data on asthma and confounders were included at 5 years of age, and 11 585 (64%) at 7 years. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with planned children, those born to subfertile parents were significantly more likely to experience asthma, wheezing and to be taking anti-asthmatics at 5 years of age [adjusted odds ratio (OR): 1.39 (95% confidence interval (CI): 1.07, 1.80), OR: 1.27 (1.00, 1.63) and OR: 1.90 (1.32,2.74), respectively]. This association was mainly related to an increase among children born after ART (adjusted OR: 2.65 (1.48, 4.76), OR: 1.97, (1.10, 3.53) and OR: 4.67 (2.20, 9.94) for asthma, wheezing and taking anti-asthmatics, respectively). The association was also present, though reduced, at the age of 7 years. LIMITATIONS, REASONS FOR CAUTION: The number of singletons born after ART was relatively small (n = 104), and as such the findings should be interpreted with caution. However, data on a wide range of possible confounding and mediating factors were available and analysed. The data were weighted for non-response to minimize selection bias. WIDER IMPLICATIONS OF THE FINDINGS: The findings add to the growing body of evidence suggesting an association between subfertility, ART and asthma in children. Further work is needed to establish causality and elucidate the underlying mechanism. These findings are generalizable to singletons only, and further work on multiples is needed.

Light drinking versus abstinence in pregnancy - behavioural and cognitive outcomes in 7-year-old children: a longitudinal cohort study.

OBJECTIVE: To assess whether light drinking in pregnancy is linked to unfavourable developmental outcomes in children. DESIGN: Prospective population-based cohort. SETTING: UK. POPULATION: Ten thousand five hundred and thirty-four 7-year-olds. METHODS: Quasi-experimental using propensity score matching (PSM) to compare children born to light (up to 2 units per week) and non-drinkers. MAIN OUTCOME MEASURES: Behavioural difficulties rated by parents and teachers; cognitive test scores for reading, maths and spatial skills. RESULTS: Ordinary least squares (OLS) regression and PSM analyses are presented. For behavioural difficulties, unadjusted estimates for percentage standard deviation (SD) score differences ranged from 2 to 14%. On adjustment for potential confounders, differences were attenuated, with a loss of statistical significance, except for teacher-rated boys' difficulties. For boys, parent-rated behavioural difficulties: unadjusted, -11.5; OLS, -4.3; PSM, -6.8; teacher-rated behavioural difficulties: unadjusted, -13.9; OLS, -9.6; PSM, -10.8. For girls, parent-rated behavioural difficulties: unadjusted, -9.6; OLS, -2.9; PSM, -4.5; teacher-rated behavioural difficulties: unadjusted, -2.4; OLS, 4.9; PSM, 3.9. For cognitive test scores, unadjusted estimates for differences ranged between 12 and 21% of an SD score for reading, maths and spatial skills. After adjustment for potential confounders, estimates were reduced, but remained statistically significantly different for reading and for spatial skills in boys. For boys, reading: unadjusted, 20.9; OLS, 8.3; PSM, 7.3; maths: unadjusted, 14.7; OLS, 5.0; PSM, 6.5; spatial skills: unadjusted, 16.2; OLS, 7.6; PSM, 8.1. For girls, reading: unadjusted, 11.6; OLS, -0.3; PSM, -0.5; maths: unadjusted, 12.9; OLS, 4.3; PSM, 3.9; spatial skills: unadjusted, 16.2; OLS, 7.7; PSM, 6.4. CONCLUSION: The findings suggest that light drinking during pregnancy is not linked to developmental problems in mid-childhood. These findings support current UK Department of Health guidelines on drinking during pregnancy.

Prevalence and factors associated with postpartum posttraumatic stress in a population-based maternity survey in England.

BACKGROUND: Studies on prevalence and factors associated with postpartum posttraumatic stress (PTS) typically do not distinguish between PTS related to childbirth (PTS-C) and PTS related to other stressors (PTS-O). This study aimed to describe the prevalence, clinical characteristics, and factors associated with PTS-C and PTS-O in postpartum women. METHODS: The study was a cross-sectional population-based survey of 16,000 postpartum women, selected at random from birth registrations in England to receive a postal questionnaire, including the Primary Care Posttraumatic Stress Disorder Screen. RESULTS: Questionnaires were returned by 4,509 women. The median age was 32 years (IQR=29-36), 64% were married, 77% were UK-born, and 76% were White-British. Prevalence of PTS-C was 2.5% (95%CI:2.0-3.0) and prevalence of PTS-O was 6.8% (95%CI:6.0-7.8). Women with PTS-C were significantly more likely to report re-experiencing symptoms (Chi-Square=7.69,p<0.01). Factors associated with PTS-C were: higher level of deprivation, not having a health professional to talk to about sensitive issues during pregnancy, and the baby being admitted for neonatal intensive care. Factors associated with PTS-O were: age ≤24 years, depression during pregnancy, and having a pregnancy affected by long-term health problems. Factors associated with both were: living without a partner, anxiety during pregnancy, pregnancy-specific health problems, and lower birth satisfaction. CONCLUSIONS: PTS during the postpartum period is relatively common and, for many women, unrelated to childbirth. Increased awareness among health professionals of prevalence, clinical characteristics and factors associated with postpartum PTS-C and PTS-O will aid the development of appropriate management protocols to identify and support women during the perinatal period. Posttraumatic stress, posttraumatic stress disorder, postpartum PTSD/PTS, birth-related PTSD/PTS, birth trauma, perinatal mental health.

Cognitive development following ART: effect of choice of comparison group, confounding and mediating factors.

BACKGROUND: Epidemiological studies have examined the health of children born after assisted reproductive technology (ART), with contradictory results. In this article, we address the question 'Do singletons born after ART have a poorer cognitive developmental outcome at 3 years of age?' We assess the implications of using different comparison groups, and discuss appropriate analytical approaches for the control of confounding and mediating variables. METHODS: Data were drawn from the Millennium Cohort Study. Interviews captured sociodemographic, behavioural and pregnancy information. Developmental assessments conducted at age three included the British Ability Scales II Naming Vocabulary (BAS-NV) instrument. We compared ART infants (born after IVF or ICSI) to four comparison groups: a 'matched' group; a 'subfertile' group (time to conception >12 months); a 'fertile' group (time to conception <12 months); and an 'any spontaneous conceptions' group. Linear regression provided estimates of the difference in mean BAS-NV scores in the ART and comparison groups; both unadjusted estimates and those adjusted for confounding and mediating factors are presented. RESULTS: In the unadjusted analyses, ART children gained significantly better BAS-NV test results than did the comparison group children. When converted to an estimate of developmental age gap, ART children were 2.5, 2.7, 3.6 and 4.5 months ahead of the 'matched', 'subfertile', 'fertile' and 'spontaneous conception' children, respectively. After adjusting for confounding and mediating factors, the differences were reduced, and were not statistically significant. CONCLUSIONS: ART is not associated with poorer cognitive development at 3 years. We have highlighted methodological considerations for researchers planning to study the effect of infertility and ART on childhood outcomes.

Microbial spatial footprint as a driver of soil carbon stabilization.

Increasing the potential of soil to store carbon (C) is an acknowledged and emphasized strategy for capturing atmospheric CO2. Well-recognized approaches for soil C accretion include reducing soil disturbance, increasing plant biomass inputs, and enhancing plant diversity. Yet experimental evidence often fails to support anticipated C gains, suggesting that our integrated understanding of soil C accretion remains insufficient. Here we use a unique combination of X-ray micro-tomography and micro-scale enzyme mapping to demonstrate for the first time that plant-stimulated soil pore formation appears to be a major, hitherto unrecognized, determinant of whether new C inputs are stored or lost to the atmosphere. Unlike monocultures, diverse plant communities favor the development of 30-150 µm pores. Such pores are the micro-environments associated with higher enzyme activities, and greater abundance of such pores translates into a greater spatial footprint that microorganisms make on the soil and consequently soil C storage capacity.

Author Correction: Microbial spatial footprint as a driver of soil carbon stabilization.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

A case of an elderly adult presenting with obstructive hydrocephalus secondary to a rare hemorrhagic suprasellar pilocytic astrocytoma.

In this report, we present a 65-year-old man who presented with signs and symptoms consistent with impending brain herniation. Emergent imaging revealed a hyperdense mass in the suprasellar region. Urgent surgery was performed and final pathology eventuated a pilocytic astrocytoma. Although rare cases of suprasellar pilocytic astrocytoma in children and adults have been reported, we report an interesting case of a hemorrhagic suprasellar pilocytic astrocytoma in an elderly adult (without prior anticoagulant use) causing impending brain herniation secondary to obstructive hydrocephalus.

Exclusion of cervical spine instability in patients with blunt trauma with normal multidetector CT (MDCT) and radiography.

The objective of the study was to determine if negative multidetector computed tomography (MDCT) and lateral radiography of the cervical spine effectively excludes patients with unstable cervical spine injuries. Over a period of 40 months, 6558 people were admitted to our trauma service with blunt injury and 447 (6.8%) were found to have cervical fractures. Fractures were identified by CT and/or lateral radiography. In order to rule out clinically significant instability in the absence of fracture, we identified nine patients who required any type of stabilization of the cervical spine including anterior fusion, posterior fusion and external orthosis. These patients also underwent MR of the cervical spine. Radiography, CT, and MR images and reports of these nine patients were reviewed. Nine patients without a fracture required cervical stabilization. These patients had the following abnormalities: disc herniation with canal stenosis in three, unilateral jumped facet in three, and various other soft tissue abnormalities in three, all of which were evident on CT or radiography. All nine patients had evidence for cervical spine injury or instability by MDCT. Normal MDCT and radiography appears adequate to 'clear' the cervical spine. We recommend that patients requiring cervical spine clearance undergo a complete MDCT and lateral radiograph of the cervical spine. If these studies are entirely normal, then the cervical spine may be cleared. If any abnormalities, including disc herniation, soft tissue swelling and bony malalignments are noted by radiography and/or MDCT, further studies, including MR, are indicated prior to clearance of the cervical spine.

High-risk sexual behaviour in men attending a sexually transmitted infection clinic in Durban, South Africa.

OBJECTIVES: A study of men with genital ulcer disease (GUD) in Durban, South Africa, at the start of the local HIV epidemic in 1988/1989 found that 36% of men with GUD continued with sexual intercourse despite symptoms. The aim of this study was to determine whether this high-risk behaviour was still prevalent and to enquire about similar risk behaviours with other sexually transmitted infection (STI)-related problems. METHODS: 650 Men attending the main Durban STI clinic with a new complaint were enrolled. A standard questionnaire was administered. Polymerase chain reaction (PCR) tests were performed to diagnose genital herpes from ulcer specimens and gonorrhoea and chlamydia from those with urethral discharge and/or dysuria. Serology tests were performed for HIV, herpes simplex virus type 2 (HSV-2) and syphilis. RESULTS: Sex since the start of symptoms was reported by between 33.3% and 43.9% of men with GUD, herpetic ulcers, gonorrhoea and/or chlamydia or dysuria. The incidence of condom use was very low in all groups having sex despite symptoms. In 87 men with genital ulcers confirmed positive for genital herpes by PCR testing, 30 (34.4%) had had sex since the start of symptoms, 28 (93.3%) of whom had had unprotected sex. CONCLUSIONS: There is a high level of risk behaviour in this group of men in whom genital herpes is the most common cause of GUD. This risky sexual behaviour could reflect disinhibition, possibly because so many have already been infected with HSV-2, lack of education or other unknown factors. Syndromic STI management should be strengthened with intensive health education to promote community awareness of both genital ulceration and genital herpes and their role in facilitating HIV transmission. The low level of condom use indicates that condom promotion programmes still have much to achieve.

Formula milk versus donor breast milk for feeding preterm or low birth weight infants.

BACKGROUND: When sufficient maternal breast milk is not available, the alternative sources of enteral nutrition for preterm or low birth weight infants are donor breast milk or artificial formula milk. Feeding preterm or low birth weight infants with formula milk might increase nutrient input and growth rates. However, since feeding with formula milk may be associated with a higher incidence of feeding intolerance and necrotising enterocolitis, this may adversely affect growth and development. OBJECTIVES: To determine the effect of formula milk compared with donor human breast milk on growth and development in preterm or low birth weight infants. SEARCH STRATEGY: The standard search strategy of the Cochrane Neonatal Review Group was used. This included electronic searches of the Cochrane Central Register of Controlled Trials (CENTRAL, The Cochrane Library, Issue 2, 2007), MEDLINE (1966 - May 2007), EMBASE (1980 - May 2007), CINAHL (1982 - May 2007), conference proceedings, and previous reviews. SELECTION CRITERIA: Randomised controlled trials comparing feeding with formula milk versus donor breast milk in preterm or low birth weight infants. DATA COLLECTION AND ANALYSIS: Data were extracted using the standard methods of the Cochrane Neonatal Review Group, with separate evaluation of trial quality and data extraction by two reviewer authors, and synthesis of data using relative risk, risk difference and weighted mean difference. MAIN RESULTS: Eight trials fulfilled the inclusion criteria. Only one trial used nutrient-fortified donor breast milk. Enteral feeding with formula milk compared with donor breast milk resulted in higher rates of growth in the short term. There was no evidence of an effect on long-term growth rates or neurodevelopmental outcomes. Meta-analysis of data from five trials demonstrated a statistically significantly higher incidence of necrotising enterocolitis in the formula fed group: typical relative risk 2.5 (95% confidence interval 1.2, 5.1); typical risk difference: 0.03 (95% confidence interval 0.01, 0.06; number needed to harm: 33 (95% confidence interval 17, 100). AUTHORS' CONCLUSIONS: In preterm and low birth weight infants, feeding with formula milk compared with donor breast milk results in a higher rate of short-term growth but also a higher risk of developing necrotising enterocolitis. There are only limited data on the comparison of feeding with formula milk versus nutrient-fortified donor breast milk. This limits the applicability of the findings as nutrient fortification of breast milk is now a common practice in neonatal care. Future trials may compare growth, development and adverse outcomes in infants who receive formula milk versus nutrient-fortified donor breast milk given as a supplement to maternal expressed breast milk or as a sole diet.

An evaluation of community-based cognitive stimulation therapy: a pilot study with an Irish population of people with dementia.

OBJECTIVES: Research shows that cognitive stimulation therapy (CST) improves cognitive function, quality of life, and well-being of people with mild-moderate dementia. Despite consistent evidence and recommendations, CST is not routinely available in Ireland post-diagnosis. The aim of the current research was to develop and evaluate community-based CST for people with mild-moderate dementia, run by the Alzheimer Society of Ireland across four pilot sites in Ireland. METHODS: Participants with mild-moderate dementia attended once weekly CST sessions for 14 weeks. Baseline and post-intervention assessments were completed by CST participants, carers, and CST facilitators. Primary outcomes of interest for CST participants included quality of life (Quality of Life in Alzheimer Disease Scale), cognitive function (Montreal Cognitive Assessment), and subjective cognitive function (Memory Awareness Rating Scale-Functioning Subscale). Secondary outcomes included well-being, cognitive ability, satisfaction with cognitive performance, and engagement and confidence of CST participants; well-being of carers; and job satisfaction of facilitators. Post-intervention interviews supplemented quantitative analyses. RESULTS: In total, 20 CST participants, 17 carers, and six CST facilitators completed evaluation assessments. Results showed that CST improved participants' satisfaction with cognitive performance (p=0.002), level of engagement (p=0.046), level of confidence (p=0.026). Improvements on subjective cognitive function just fell short of significance (p=0.055). Qualitative analysis of interview data identified consistent themes of cognitive and overall benefits of CST; and provided support for quantitative data. CONCLUSIONS: Community-based CST positively impacted the lives of people with dementia and their families. This study supports prior recommendations that CST should be made routinely available to people with mild-moderate dementia, particularly in light of the lack of post-diagnostic interventions currently offered in Ireland.

Ecteinascidin-743 (ET-743) for chemotherapy-naive patients with advanced soft tissue sarcomas: multicenter phase II and pharmacokinetic study.

PURPOSE: To evaluate the response rate, toxicity profile, and pharmacokinetics of ecteinascidin-743 (ET-743) as first-line therapy in patients with unresectable advanced soft tissue sarcoma (STS). PATIENTS AND METHODS: Thirty-six patients with STS were enrolled onto the study between September 1999 and August 2000. Patients were treated with 1.5 mg/m2 of ET-743 given as a 24-hour continuous intravenous (IV) infusion every 21 days. Pharmacokinetic sampling was performed in 23 patients. RESULTS: One complete and five partial responses were achieved in 35 assessable patients for an overall response rate of 17.1% (95% CI, 6.6% to 33.6%). In addition, one patient had a minor response, leading to an overall clinical benefit of 20%. Neutropenia and transaminitis were the main grade 3 to 4 toxicities, which occurred in 33% and 36% of the patients. The estimated 1-year progression-free and overall survival rates were 21% (95% CI, 11% to 41%) and 72% (95% CI, 59% to 88%), respectively. Total body clearance (L/h) was not significantly correlated with body-surface area (r = -0.28; P = .21). Mild hepatic impairment or the extent of prior cytotoxic therapy does not seem to contribute significantly to the high interpatient variability (49%) in the clearance of this drug. Severity of treatment-related toxicity was not correlated with pharmacokinetic variables. CONCLUSION: ET-743 demonstrates clinical activity as first-line therapy against STS with acceptable toxicity. Additional studies to establish empirical dosing guidelines may be necessary to improve the safety of the drug in patients with varying degrees of hepatic dysfunction and definitively establish the role of ET-743 for patients with these malignancies.