Effect of older maternal age on birth outcomes in twin pregnancies: a population-based study.

OBJECTIVE: We compared perinatal mortality, preterm birth (<37, <33 and <28 weeks), small for gestational age (SGA), Apgar score (<4), mechanical ventilation (1 days) and prolonged neonatal intensive care unit (NICU) hospitalization (13 days) between twins of 25 to 34 and >35-year-old women. Further, we examined whether older maternal age effects were modified by parity or otherwise affected by chorionicity. STUDY DESIGN: We carried out a population-based retrospective cohort study including all twin births in British Columbia (BC), Canada, from 1999 to 2003. The BC perinatal database registry was used to obtain clinical, behavioral and demographic data. Adjusted odds ratios (OR) with 95% confidence intervals (CI) were calculated using generalized estimating equation models. RESULT: Overall, twins of older women were more likely to be born preterm (<37 weeks), but not very or extremely preterm (<33 weeks). These twins were not at increased risk of perinatal death, mechanical ventilation or were not SGA compared with twins of younger women. Twins of older primiparous women did not have an elevated risk of NICU hospitalization; twins born to older multiparous women had higher risk (OR=1.8; 95% CI: 1.2 to 2.6). Analyses restricted to opposite-sex (dichorionic) twins showed that perinatal death, mechanical ventilation and very preterm birth occur less likely among older women (OR=0.2 (95% CI: 0.0 to 0.8), OR=0.3 (95% CI: 0.1 to 0.7) and OR=0.4 (95% CI: 0.2 to 0.7), respectively). Further, the risk of late preterm birth was increased and NICU hospitalization was reduced among opposite-sex twins born to older compared with younger primiparous women (OR=1.9 (95% CI: 1.3 to 2.8) and OR=0.2 (95% CI: 0.1 to 0.5), respectively). CONCLUSION: Twins of older mothers did not have an elevated risk for most adverse birth outcomes, except for late preterm birth. Risks of neonatal care admission may be elevated among older multiparous women.

Neovascular AMD: an overlooked risk factor for injurious falls.

UNLABELLED: While those with neovascular age-related macular degeneration (NV-AMD) may be at increased risk of injurious falls risk due to poor central vision and suboptimal responses when falling, preserved peripheral vision and decreased activity levels may actually be protective. Compared with control participants, patients with NV-AMD had a significantly greater number of falls and almost twice the risk of injurious falls. INTRODUCTION: Impaired vision, particularly peripheral visual function, is a key risk factor for injurious falls. NV-AMD is a leading cause of severely impaired vision among older adults but is associated with a profound central, rather than peripheral, deficit. The objective was to determine whether older women with NV-AMD are at an increased risk of falls or injurious falls. METHODS: We conducted a 12-month prospective cohort study of community-dwelling older (>or=70 years) women, enrolling 114 with NV-AMD and 132 without from a retinal clinic in Vancouver, Canada. Fall incidence was determined through monthly telephone follow-up, with fall severity classified by a blinded reviewer. We compared mean injurious falls per person-year between groups using negative binomial regression. RESULTS: A mean of 0.37 injurious falls per person-year were experienced among NV-AMD participants, compared to 0.16 injurious falls per person-year among non-NV-AMD participants (p = 0.006). The age-adjusted incidence rate ratio for injurious falls, for an individual with NV-AMD compared to without, was 1.77 (1.07-3.02). CONCLUSIONS: Older women with NV-AMD are at almost twice the risk of injurious falls compared to those without. Clinicians caring for older adults should recognise NV-AMD as an important risk factor for injurious falls.

Statistical properties of directional ocean waves: the role of the modulational instability in the formation of extreme events.

We discuss two independent, large scale experiments performed in two wave basins of different dimensions in which the statistics of the surface wave elevation are addressed. Both facilities are equipped with a wave maker capable of generating waves with prescribed frequency and directional properties. The experimental results show that the probability of the formation of large amplitude waves strongly depends on the directional properties of the waves. Sea states characterized by long-crested and steep waves are more likely to be populated by freak waves with respect to those characterized by a large directional spreading.

Effects of an intervention aimed at reducing night waking and signaling in 6- to 12-month-old infants.

This quasi-experimental one-group pre- and posttest pilot study evaluated an intervention aimed at reducing night waking and signaling for infants between 6 and 12 months of age. Thirty-nine healthy infants and their parents were recruited. Thirty-five infants completed the intervention and data collection. Both parents participated in a group teaching session with telephone follow-up for 2 weeks. Actigraphy and sleep diary data were collected at baseline and 6 and 16 weeks postintervention. We hypothesized a decrease in length and number of infant waking and crying periods and an increase in longest night sleep and nap time. Following the intervention, infants had significantly reduced length of night crying and number of wakes and longer night sleep periods. The intervention warrants evaluation with a randomized controlled design.

Improving QSAR models for the biological activity of HIV Reverse Transcriptase inhibitors: Aspects of outlier detection and uninformative variable elimination.

The goal of this study is to derive a methodology for modeling the biological activity of non-nucleoside HIV Reverse Transcriptase (RT) inhibitors. The difficulties that were encountered during the modeling attempts are discussed, together with their origin and solutions. With the selected multivariate techniques: robust principal component analysis, partial least squares, robust partial least squares and uninformative variable elimination partial least squares, it is possible to explore and to model the contaminated data satisfactory. It is shown that these techniques are versatile and valuable tools in modeling and exploring biochemical data.

Identifying women at-risk for postpartum depression in the immediate postpartum period.

OBJECTIVE: To develop a multifactorial predictive model of depressive symptomatology in the first week postpartum in order to assist in targeted screening procedures. METHOD: As part of a longitudinal study, a population-based sample of 594 mothers in a health region near Vancouver, British Columbia completed a mailed questionnaire at 1-week postpartum that included diverse risk factors from the following domains: sociodemographic, biological, pregnancy-related, life stressors, social support, obstetric and adjustment to motherhood. Following univariate analysis, sequential regression analysis was completed to develop a multifactorial predictive model. RESULTS: In the multivariate model, the factors predictive of depressive symptomatology at 1-week postpartum included immigration within the last 5 years, history of depression independent of childbirth, diagnosis of pregnancy-induced hypertension, vulnerable personality style, stressful life events, lack of perceived support, lack of readiness for hospital discharge and dissatisfaction with infant feeding method. CONCLUSION: The findings suggest that several risk factors for depressive symptomatology in the immediate postpartum period are consistent with previously identified factors but other factors such as recent immigrant status, feeling unready for hospital discharge, dissatisfaction with their infant feeding method, and pregnancy-induced hypertension should also be examined.

Classification and regression trees--studies of HIV reverse transcriptase inhibitors.

In this paper, the application of Classification And Regression Trees (CART) is presented for the analysis of biological activity of Non-Nucleoside Reverse Transcriptase Inhibitors (NNRTIs). The data consist of the biological activities, expressed as pIC50, of 208 NNRTIs against wild-type HIV virus (HIV-1) and four mutant strains (181C, 103N, 100I, 188L) and the computed interaction energies with the Reverse Transcriptase (RT) binding pocket. CART explains the observed biological activity of NNRTIs in terms of interactions with individual amino acids in the RT binding pocket, i.e., the original data variables.

Inhibition and substrate recognition--a computational approach applied to HIV protease.

We have developed a computational approach in which an inhibitor's strength is determined from its interaction energy with a limited set of amino acid residues of the inhibited protein. We applied this method to HIV protease. The method uses a consensus structure built from X-ray crystallographic data. All inhibitors are docked into the consensus structure. Given that not every ligand-protein interaction causes inhibition, we implemented a genetic algorithm to determine the relevant set of residues. The algorithm optimizes the q2 between the sum of interaction energies and the observed inhibition constants. The best possible predictive model resulting has a q2 of 0.63. External validation by examining the predictivity for compounds not used in derivation of the model leads to a prediction accuracy between 0.9 and 1.5 log10 unit. Out of 198 residues in the whole protein, the best internally predictive model defines a subset of 20 residues and the best externally predictive model one of 9 residues. These residues are distributed over the subsites of the enzyme. This approach provides insight in which interactions are important for inhibiting HIV protease and it allows for quantitative prediction of inhibitor strength.

Ibuprofen versus acetaminophen with codeine for the relief of perineal pain after childbirth: a randomized controlled trial.

BACKGROUND: Pain from episiotomy or tearing of perineal tissues during childbirth is often poorly treated and may be severe. This randomized double-blind controlled trial was performed to compare the effectiveness, side effects and cost of, and patient preference for, 2 analgesics for the management of postpartum perineal pain. METHODS: A total of 237 women who gave birth vaginally with episiotomy or a third- or fourth-degree tear between August 1995 and November 1996 at a tertiary-level teaching and referral centre for obstetric care in Vancouver were randomly assigned to receive either ibuprofen (400 mg) (n = 127) or acetaminophen (600 mg) with codeine (60 mg) and caffeine (15 mg) (Tylenol No. 3) (n = 110), both given orally every 4 hours as necessary. Pain ratings were recorded before the first dose and at 1, 2, 3, 4, 12 and 24 hours after the first dose on a 10-cm visual analogue scale. Side effects and overall opinion were assessed at 24 hours. RESULTS: Ibuprofen and acetaminophen with codeine had similar analgesic properties in the first 24 hours post partum (mean pain rating 3.4 and 3.3, mean number of doses in 24 hours 3.4 and 3.3, and proportion of treatment failures 13.8% [16/116] and 16.0% [16/100] respectively). Significantly fewer subjects in the ibuprofen group than in the acetaminophen with codeine group experienced side effects (52.4% v. 71.7%) (p = 0.006). There were no significant differences in overall patient satisfaction between the 2 groups. The major determinant of pain intensity was forceps-assisted delivery. Overall, 78% of the treatment failures were in women with forceps-assisted deliveries. INTERPRETATION: Since the 2 analgesics were rated similarly, ibuprofen may be the preferred choice because it is less expensive and requires less nursing time to dispense. Further studies need to address improved analgesia for women with forceps-assisted deliveries.

Results of a 10 week community based strength and balance training programme to reduce fall risk factors: a randomised controlled trial in 65-75 year old women with osteoporosis.

OBJECTIVE: To test the efficacy of a community based 10 week exercise intervention to reduce fall risk factors in women with osteoporosis. METHODS: Static balance was measured by computerised dynamic posturography (Equitest), dynamic balance by timed figure of eight run, and knee extension strength by dynamometry. Subjects were randomised to exercise intervention (twice weekly Osteofit classes for 10 weeks) or control groups. RESULTS: The outcome in 79 participants (39 exercise, 40 control) who were available for measurement 10 weeks after baseline measurement is reported. After confounding factors had been controlled for, the exercise group did not make significant gains compared with their control counterparts, although there were consistent trends toward greater improvement in all three primary outcome measures. Relative to the change in control subjects, the exercise group improved by 2.3% in static balance, 1.9% in dynamic balance, and 13.9% in knee extension strength. CONCLUSIONS: A 10 week community based physical activity intervention did not significantly reduce fall risk factors in women with osteoporosis. However, trends toward improvement in key independent risk factors for falling suggest that a study with greater power may show that these variables can be improved to a level that reaches statistical significance.

Single room maternity care: the nursing response.

BACKGROUND: The introduction of single room maternity care in the 1990s necessitated a new approach to nursing education and practice. A focus on perinatal nursing requires competence across the spectrum of labor, delivery, postpartum and newborn care. We sought to evaluate the nursing response to this change by comparing satisfaction with the workplace environment among single room maternity care nurses before and after they worked in the setting and among nurses working in traditional birth settings. METHODS: Six months before the opening of a pilot seven-bed single room maternity care unit, nurses who planned to work in the new unit completed a survey about their satisfaction with aspects of their work environment. Three months after the new unit opened the survey was repeated with this study group and also by a sample of nurses working in the delivery and postpartum areas. RESULTS: Responses indicated that single room maternity care nurses before and after working in the unit were significantly more satisfied with the physical setting, their ability to respond to patients' needs, their opportunity for teaching families, the nursing practice environment, peer support, and their perceived level of competency. They rated their satisfaction significantly higher than that of their colleagues in the traditional delivery and postpartum settings. CONCLUSIONS: The positive transition to single room maternity care by obstetrical nurses was demonstrated by their improved overall satisfaction with the work environment. Evaluation of the nurses' responses to changes in health care delivery has important implications for justifying new clinical approaches and planning for future changes.

Evolution of anti-HIV drug candidates. Part 1: From alpha-anilinophenylacetamide (alpha-APA) to imidoyl thiourea (ITU).

Stemming from work on a previous clinical candidate, loviride, and other alpha-APA derivatives, a new series of potent non-nucleoside reverse transcriptase inhibitors (NNRTIs) has been synthesized. The ITU analogues, which contain a unique diarylated imidoyl thiourea, are very active in inhibiting both wild-type and clinically important mutant strains of HIV-1.

Evolution of anti-HIV drug candidates. Part 2: Diaryltriazine (DATA) analogues.

A synthesis program directed toward improving the stability of imidoyl thiourea based non-nucleoside reverse transcriptase inhibitors (NNRTIs) led to the discovery of diaryltriazines (DATAs), a new class of potent NNRTIs. The synthesis and anti-HIV structure-activity relationship (SAR) studies of a series of DATA derivatives are described.

Evolution of anti-HIV drug candidates. Part 3: Diarylpyrimidine (DAPY) analogues.

The synthesis and anti-HIV-1 activity of a series of diarylpyrimidines (DAPYs) are described. Several members of this novel class of non-nucleoside reverse transcriptase inhibitors (NNRTIs) are extremely potent against both wild-type and a panel of clinically significant single- and double-mutant strains of HIV-1.

The Lys103Asn mutation of HIV-1 RT: a novel mechanism of drug resistance.

Inhibitors of human immunodeficiency virus (HIV) reverse transcriptase (RT) are widely used in the treatment of HIV infection. Loviride (an alpha-APA derivative) and HBY 097 (a quinoxaline derivative) are two potent non-nucleoside RT inhibitors (NNRTIs) that have been used in human clinical trials. A major problem for existing anti-retroviral therapy is the emergence of drug-resistant mutants with reduced susceptibility to the inhibitors. Amino acid residue 103 in the p66 subunit of HIV-1 RT is located near a putative entrance to a hydrophobic pocket that binds NNRTIs. Substitution of asparagine for lysine at position 103 of HIV-1 RT is associated with the development of resistance to NNRTIs; this mutation contributes to clinical failure of treatments employing NNRTIs. We have determined the structures of the unliganded form of the Lys103Asn mutant HIV-1 RT and in complexes with loviride and HBY 097. The structures of wild-type and Lys103Asn mutant HIV-1 RT in complexes with NNRTIs are quite similar overall as well as in the vicinity of the bound NNRTIs. Comparison of unliganded wild-type and Lys103Asn mutant HIV-1 RT structures reveals a network of hydrogen bonds in the Lys103Asn mutant that is not present in the wild-type enzyme. Hydrogen bonds in the unliganded Lys103Asn mutant but not in wild-type HIV-1 RT are observed between (1) the side-chains of Asn103 and Tyr188 and (2) well-ordered water molecules in the pocket and nearby pocket residues. The structural differences between unliganded wild-type and Lys103Asn mutant HIV-1 RT may correspond to stabilization of the closed-pocket form of the enzyme, which could interfere with the ability of inhibitors to bind to the enzyme. These results are consistent with kinetic data indicating that NNRTIs bind more slowly to Lys103Asn mutant than to wild-type HIV-1 RT. This novel drug-resistance mechanism explains the broad cross-resistance of Lys103Asn mutant HIV-1 RT to different classes of NNRTIs. Design of NNRTIs that make favorable interactions with the Asn103 side-chain should be relatively effective against the Lys103Asn drug-resistant mutant.

Differences in institutional cesarean delivery rates-the role of pain management.

BACKGROUND: The objective of our study was to compare cesarean delivery rates for low-risk nulliparous women in a community hospital and a tertiary-level maternity hospital and to determine factors influencing those rates. METHODS: We performed a retrospective cohort study of 857 women who did not have obstetric risk factors. The association between hospital and cesarean delivery rate was examined in a multivariate analysis using logistic regression. In a follow-up cohort study, we observed labor management for 24 couples in the community and 26 in the tertiary hospital. RESULTS: The odds of having a cesarean birth (age-adjusted) at the tertiary center were 3.4 (95% confidence interval, 2.1-5.4) compared with the community hospital. Maternal age, cervical dilatation on first examination, and use of epidural analgesia were the primary factors associated with the difference in cesarean delivery rates, with epidural analgesia having the largest effect. Labor support between the 2 hospitals appeared to be similar with the exception of increased use of ambulation in the community hospital and fewer numbers of caregivers for each woman in labor. Women in the tertiary center were more often offered epidural analgesia. CONCLUSIONS: Differences in use of epidural analgesia may contribute to differences in institutional rates of cesarean delivery. Use of epidural analgesia may be related to use of ambulation, consistency of caregiver during labor, availability of epidural, and suggestion for its use by caregivers.

Single room maternity care and client satisfaction.

BACKGROUND: Single room maternity care is the provision of intrapartum and postpartum care in a single room. It promotes a philosophy of family centered care in which one nurse cares for the family consistently throughout the intrapartum and postpartum periods. At B.C. Women's Hospital, a tertiary level obstetric teaching hospital in Vancouver, British Columbia, a seven-bed, single room maternity care unit was developed and opened as a demonstration project. As part of the evaluation of this unit, client satisfaction was compared between women enrolled in single room maternity care and those in a traditional setting. METHOD: The study group included 205 women who were admitted to the single room maternity care unit after meeting the low-risk criteria. Their responses on a satisfaction survey were compared with those of a historical comparison group of 221 women meeting the same eligibility criteria who were identified through chart audits 3 months before the single room maternity care unit was opened. A second, concurrent comparison group comprised 104 women who also met eligibility criteria. RESULTS: Study group women were more satisfied than comparison groups in all areas evaluated, including provision of information and support, physical environment, nursing care, patient education, assistance with infant feeding, respect for privacy, and preparation for discharge. CONCLUSIONS: Single room maternity care was associated with a significant improvement in client satisfaction because of many factors, including the physical setting itself, avoidance of transfers, and improved continuity of nursing care.