Vitamin A and its derivatives in experimental photocarcinogenesis: preventive effects and relevance to humans.

The 1925 classical observation that vitamin A deficiency leads to squamous metaplasia and epithelial keratinization, coupled with the later finding that excess vitamin A inhibits keratinization of chick embryo skin, set the foundation for the potential therapeutic use of retinoids in cutaneous conditions of keratinization. Significant progress has since been made understanding the molecular biology, biochemistry, pharmacology, and toxicology of vitamin A and its derivatives, collectively named retinoids. Natural and synthetic retinoids are now routinely used to treat acne, psoriasis, skin keratinization disorders, and photodamage. Retinoids also inhibit tumor formation and skin cancer development in experimental systems and in humans. Retinol and retinyl palmitate (RP) are found in cosmetic products and in foods and dietary supplements, which are all considered safe, by inclusion in the Generally Recognized as Safe Substances Database. However, the safety of topical retinoids was questioned in one publication and in a recent National Toxicology Program report of RP-containing topical preparations, suggesting the possible earlier onset of ultraviolet-induced squamous cell carcinomas in the hairless mouse photocarcinogenesis model. This suggestion contradicts a large body of data indicating that topical retinoids are chemoprotective in humans, and it was immediately challenged by new reviews on the safety of RP in general and within sunscreens. This paper will review the preclinical and clinical data supporting the safety and chemopreventive activity of retinoids, with an emphasis on RP, and will examine the experimental systems used to evaluate the safety of topical vitamin A preparations in order to provide perspective relative to human skin.

Use of topical tretinoin and the development of noncutaneous adverse events: evidence from a systematic review of the literature.

BACKGROUND: Topical retinoids have been in clinical use for the treatment of chronic skin conditions, including acne, photodamage, and psoriasis, for 30 years. OBJECTIVE: A systematic literature review was conducted to assess the incidence of noncutaneous adverse events (AE) among patients treated with topical retinoids with a focus on topical tretinoin studies reported before the Veterans Affairs Topical Tretinoin Chemoprevention trial. METHODS: Electronic literature searches were conducted in Embase and MEDLINE for literature reporting development of nonteratogenic, noncutaneous AE among patients treated with topical retinoids published through September 2008. RESULTS: The search yielded 2778 citations, of which 20 studies met inclusion criteria. Tretinoin was used in 14 of the studies. Other retinoids assessed included isotretinoin, adapalene, alitretinoin, and tazarotene. Within patients receiving topical tretinoin, 27.9% reported the occurrence of at least one noncutaneous AE. The majority of noncutaneous AE were transient and judged not to be related to tretinoin treatment. LIMITATIONS: The conclusions of this study apply largely to tretinoin compared with other topical retinoids. Many of the included trials were designed to evaluate the efficacy of topical treatment and reporting of safety events concentrated on incidence of localized AE, rather than systemic or noncutaneous events. CONCLUSION: We found no clear evidence of a relationship between the use of topical tretinoin and the development of noncutaneous AE before a recent report of excess mortality in a clinical trial. The majority of noncutaneous AE reported by patients receiving topical retinoids consisted of nonsevere, nonspecific symptoms that were judged not to be related to treatment.

A randomized breast-feeding promotion intervention did not reduce child obesity in Belarus.

The evidence that breast-feeding protects against obesity is based on observational studies, with potential for confounding and selection bias. This article summarizes a previously published study in which we assessed whether an intervention designed to promote exclusive and prolonged breast-feeding affects children's height, weight, adiposity, and blood pressure (BP) at age 6.5 y. The Promotion of Breastfeeding Intervention Trial (PROBIT) is a cluster-randomized trial of a breast-feeding promotion intervention based on the WHO/UNICEF Baby-Friendly Hospital Initiative. A total of 17,046 healthy breast-fed infants were enrolled from 31 Belarussian maternity hospitals and affiliated clinics, of whom 13,889 (81.5%) were followed up at 6.5 y with duplicate measurements of height, weight, waist circumference, triceps and subscapular skinfold thicknesses, systolic and diastolic BP. Analysis was based on intention to treat, with statistical adjustment for clustering within hospitals/clinics to permit inferences at the individual level. The experimental intervention led to a large increase in exclusive breast-feeding at 3 mo (43.3% vs. 6.4%, P < 0.001) and a significantly higher prevalence of any breast-feeding throughout infancy. No significant intervention effects were observed on height, BMI, adiposity measures, or BP. The breast-feeding promotion intervention resulted in substantial increases in the duration and exclusivity of breast-feeding yet did not reduce measures of adiposity at age 6.5 y. Previous reports of protective effects against obesity may reflect uncontrolled bias caused by confounding and selection.

Independent effect of depression and anxiety on chronic obstructive pulmonary disease exacerbations and hospitalizations.

RATIONALE: Depression and anxiety are significant comorbid and potentially modifiable conditions in chronic obstructive pulmonary disease (COPD), but their effects on exacerbations are not clear. OBJECTIVES: To investigate the independent effect of depression and anxiety on the risk of COPD exacerbations and hospitalizations. METHODS: A multicenter prospective cohort study in 491 patients with stable COPD in China. Multivariate Poisson and linear regression analyses were used, respectively, to estimate adjusted incidence rate ratios (IRRs) and adjusted effects on duration of events. MEASUREMENTS AND MAIN RESULTS: Depression and anxiety were measured using the Hospital Anxiety and Depression Scale (HADS) at baseline. Other measurements included sociodemographic, clinical, psychosocial, and treatment characteristics. Patients were then monitored monthly for 12 months to document the occurrence and characteristics of COPD exacerbations and hospitalizations. Exacerbation was determined using both symptom-based (worsening of > or =1 key symptom) and event-based definitions (> or =1 symptom worsening plus > or =1 change in regular medications). A total of 876 symptom-based and 450 event-based exacerbations were recorded, among which 183 led to hospitalization. Probable depression (HADS depression score > or = 11) was associated with an increased risk of symptom-based exacerbations (adjusted IRR, 1.51; 95% confidence interval [CI], 1.01-2.24), event-based exacerbations (adjusted IRR, 1.56; 95% CI, 1.02-2.40), and hospitalization (adjusted IRR, 1.72; 95% CI, 1.04-2.85) compared with nondepression (score < or = 7). The duration of event-based exacerbations was 1.92 (1.04-3.54) times longer for patients with probable anxiety (HADS anxiety score > or = 11) than those with no anxiety (score < or = 7). CONCLUSIONS: This study suggests a possible causal effect of depression on COPD exacerbations and hospitalizations. Further studies are warranted to confirm this finding and to test the effectiveness of antidepressants and psychotherapies on reducing exacerbations and improving health resource utilizations.

Breastfeeding and child cognitive development: new evidence from a large randomized trial.

CONTEXT: The evidence that breastfeeding improves cognitive development is based almost entirely on observational studies and is thus prone to confounding by subtle behavioral differences in the breastfeeding mother's behavior or her interaction with the infant. OBJECTIVE: To assess whether prolonged and exclusive breastfeeding improves children's cognitive ability at age 6.5 years. DESIGN: Cluster-randomized trial, with enrollment from June 17, 1996, to December 31, 1997, and follow-up from December 21, 2002, to April 27, 2005. SETTING: Thirty-one Belarussian maternity hospitals and their affiliated polyclinics. PARTICIPANTS: A total of 17,046 healthy breastfeeding infants were enrolled, of whom 13,889 (81.5%) were followed up at age 6.5 years. INTERVENTION: Breastfeeding promotion intervention modeled on the Baby-Friendly Hospital Initiative by the World Health Organization and UNICEF. MAIN OUTCOME MEASURES: Subtest and IQ scores on the Wechsler Abbreviated Scales of Intelligence, and teacher evaluations of academic performance in reading, writing, mathematics, and other subjects. RESULTS: The experimental intervention led to a large increase in exclusive breastfeeding at age 3 months (43.3% for the experimental group vs 6.4% for the control group; P < .001) and a significantly higher prevalence of any breastfeeding at all ages up to and including 12 months. The experimental group had higher means on all of the Wechsler Abbreviated Scales of Intelligence measures, with cluster-adjusted mean differences (95% confidence intervals) of +7.5 (+0.8 to +14.3) for verbal IQ, +2.9 (-3.3 to +9.1) for performance IQ, and +5.9 (-1.0 to +12.8) for full-scale IQ. Teachers' academic ratings were significantly higher in the experimental group for both reading and writing. CONCLUSION: These results, based on the largest randomized trial ever conducted in the area of human lactation, provide strong evidence that prolonged and exclusive breastfeeding improves children's cognitive development. TRIAL REGISTRATION: isrctn.org Identifier: ISRCTN37687716.

LIGR, a protease-activated receptor-2-derived peptide, enhances skin pigmentation without inducing inflammatory processes.

The protease-activated receptor-2 (PAR-2) is a seven transmembrane G-protein-coupled receptor that could be activated by serine protease cleavage or by synthetic peptide agonists. We showed earlier that activation of PAR-2 with Ser-Leu-Ile-Gly-Arg-Leu-NH(2) (SLIGRL), a known PAR-2 activating peptide, induces keratinocyte phagocytosis and increases skin pigmentation, indicating that PAR-2 regulates pigmentation by controlling phagocytosis of melanosomes. Here, we show that Leu-Ile-Gly-Arg-NH(2) (LIGR) can also induce skin pigmentation. Both SLIGRL and LIGR increased melanin deposition in vitro and in vivo, and visibly darkened human skins grafted onto severe combined immuno-deficient (SCID) mice. Both SLIGRL and LIGR stimulated Rho-GTP activation resulting in keratinocyte phagocytosis. Interestingly, LIGR activates only a subset of the PAR-2 signaling pathways, and unlike SLIGRL, it does not induce inflammatory processes. LIGR did not affect many PAR-2 signaling pathways, including [Ca(2+)] mobilization, cAMP induction, the induction of cyclooxgenase-2 (COX-2) expression and the secretion of prostaglandin E2, interleukin-6 and -8. PAR-2 siRNA inhibited LIGR-induced phagocytosis, indicating that LIGR signals via PAR-2. Our data suggest that LIGR is a more specific regulator of PAR-2-induced pigmentation relative to SLIGRL. Therefore, enhancing skin pigmentation by topical applications of LIGR may result in a desired tanned-like skin color, without enhancing inflammatory processes, and without the need of UV exposure.

Effects of prolonged and exclusive breastfeeding on child height, weight, adiposity, and blood pressure at age 6.5 y: evidence from a large randomized trial.

BACKGROUND: The evidence that breastfeeding protects against obesity and a variety of chronic diseases comes almost entirely from observational studies, which have a potential for bias due to confounding, selection bias, and selective publication. OBJECTIVE: We assessed whether an intervention designed to promote exclusive and prolonged breastfeeding affects children's height, weight, adiposity, and blood pressure at age 6.5 y. DESIGN: The Promotion of Breastfeeding Intervention Trial (PROBIT) is a cluster-randomized trial of a breastfeeding promotion intervention based on the WHO/UNICEF Baby-Friendly Hospital Initiative. A total of 17,046 healthy breastfed infants were enrolled from 31 Belarussian maternity hospitals and their affiliated clinics; of those infants, 13,889 (81.5%) were followed up at 6.5 y with duplicate measurements of anthropometric variables and blood pressure. Analysis was based on intention to treat, with statistical adjustment for clustering within hospitals or clinics to permit inferences at the individual level. RESULTS: The experimental intervention led to a much greater prevalence of exclusive breastfeeding at 3 mo in the experimental than in the control group (43.3% and 6.4%, respectively; P < 0.001) and a higher prevalence of any breastfeeding throughout infancy. No significant intervention effects were observed on height, body mass index, waist or hip circumference, triceps or subscapular skinfold thickness, or systolic or diastolic blood pressure. CONCLUSIONS: The breastfeeding promotion intervention resulted in substantial increases in the duration and exclusivity of breastfeeding, yet it did not reduce the measures of adiposity, increase stature, or reduce blood pressure at age 6.5 y in the experimental group. Previously reported beneficial effects on these outcomes may be the result of uncontrolled confounding and selection bias.

Iatrogenic risk factors for cytomegalovirus retinitis.

BACKGROUND: To determine the iatrogenic risk factors for cytomegalovirus (CMV) retinitis in patients with the acquired immunodeficiency syndrome (AIDS). METHODS: The case-control study included 120 patients with CMV retinitis and 159 patients without CMV retinitis, all of whom had AIDS and CD4 counts less than 50 cells/microL at the time of diagnosis of retinitis or at the defined corresponding date in the controls. Iatrogenic risk factors studied were corticosteroid use, treatment with chemotherapy, treatment with radiotherapy, and blood transfusions. RESULTS: Among the risk factors studied, only steroid use was predictive of CMV retinitis (odds ratio 6.41, 95% confidence interval 2.35-17.51). Based on this study, the use of steroids systemically elevated the risk of CMV retinitis.

Inhibitory effect of topical applications of nondenatured soymilk on the formation and growth of UVB-induced skin tumors.

Treatment of female SKH-1 hairless mice with ultraviolet B light twice a week for 20 weeks resulted in a population of tumor-free mice with a high risk of developing skin tumors during the next several months in the absence of additional UVB treatment (high-risk mice). Topical applications of nondenatured soymilk but not heat-denatured soymilk once a day, 5 days a week to these high-risk mice inhibited the formation and growth of skin tumors. Similar topical applications of soybean trypsin inhibitor or Bowman-Birk inhibitor also inhibited the formation and growth of skin tumors, but these agents were less active than nondenatured soymilk. Treatment of miniswine skin with nondenatured soymilk once a day for 5 days prior to UVB irradiation reduced or completely eliminated UVB-induced formation of thymine dimers and apoptotic cells in the epidermis. These data suggest that nondenatured soymilk could be applied to humans to prevent sunlight-induced skin damage and to reduce the risk of skin tumor formation and progression.

Clinical risk factors for cytomegalovirus retinitis in patients with AIDS.

PURPOSE: To determine the clinical risk factors for cytomegalovirus (CMV) retinitis in patients with AIDS. DESIGN: A case-control study. PARTICIPANTS: The study included 120 patients in whom CMV retinitis had been diagnosed from 1990 through 1999 (cases) and 159 patients without CMV retinitis from the same period (controls). All individuals had AIDS and CD4 counts less than 50 cells/microl at the time of diagnosis of retinitis in the cases or on the corresponding date for the controls. METHODS: Clinical risk factors were determined by history or physical examination. Confounders controlled for included CD4 count, hospital center, and a series of variables to control for confounding by drug treatment. Statistical analysis was performed by multivariate logistic regression. A systematic model-building strategy was developed from assumption testing to model building to model checking. MAIN VARIABLES MEASURED: Presence of visual symptoms, retinal microinfarctions (cotton-wool spots), history of opportunistic infections, and risk factors for human immunodeficiency virus acquisition were determined and compared in both groups. RESULTS: The following clinical risk factors were significant predictors of CMV retinitis: flashing lights or floaters (odds ratio [OR], 11.42; 95% confidence interval [CI], 3.43 to 38.01), cotton-wool spots (OR, 2.90; 95% CI, 1.01 to 8.29), number of previous opportunistic infections (OR, 1.81; 95% CI, 1.24 to 2.64), previous nonocular CMV infection (OR, 82.99; 95% CI, 6.86 to 1004.58), previous Mycobacterium infection (OR, 3.41; 95% CI, 0.99 to 11.85), and homosexuality (OR, 2.83; 95% CI, 1.13 to 7.12). CONCLUSIONS: Based on this study, clinical variables have been identified that elevate the risk of CMV retinitis. These findings may be useful to clinicians and health policy experts in developing rational guidelines for screening, examination frequency, and targeted prophylaxis for CMV retinitis in patients with AIDS.

Effectiveness of intensive rehabilitation on functional ability and quality of life after first total knee arthroplasty: A single-blind randomized controlled trial.

OBJECTIVE: To evaluate the effectiveness of a new intensive functional rehabilitation (IFR) program on functional ability and quality of life (QOL) in persons who underwent a first total knee arthroplasty (TKA). DESIGN: Randomized controlled trial. SETTING: Ambulatory care. PARTICIPANTS: Seventy-seven people with knee osteoarthritis. INTERVENTION: Two months after TKA, subjects were randomly assigned to either a group with IFR (n=38), who received 12 supervised rehabilitation sessions combined with exercises at home between months 2 and 4 after TKA, or to a control group (n=39), who received standard care. All participants were evaluated by a blind evaluator at baseline (2mo after TKA), immediately after IFR (2mo later; POST1), and 2 and 8 months later (POST2 and POST3). Main outcome measures The primary outcome measure with respect to effectiveness was the 6-minute walk test (6MWT) at POST2. Secondary outcome measures were the 6MWT at the other evaluations and the Western Ontario and McMaster Universities Osteoarthritis Index and Medical Outcomes Study 36-Item Short-Form Health Survey. RESULTS: Subjects in the IFR group walked longer distances (range, 23-26m) in 6 minutes at the 3 POST evaluations than subjects in the control group. At POST1 and POST2, they also had less pain, stiffness, and difficulty in performing daily activities. Positive changes in QOL in favor of the IFR were found only at POST2. CONCLUSIONS: The IFR was effective in improving the short-term and mid-term functional ability after uncomplicated primary TKA. The magnitude of the IFR effect on the primary outcome was modest but consistent. More intensive rehabilitation should be promoted in the subacute recovery period after TKA, to optimize functional outcomes in the first year after surgery.

Laboratory-based risk factors for cytomegalovirus retinitis.

BACKGROUND: Very few studies have investigated risk factors for cytomegalovirus (CMV) retinitis. Identifying these risk factors will have many benefits, including helping establish screening regimens, examination frequency regimens, and targeted prophylaxis with oral therapy with valganciclovir or other anti-CMV agents. The purpose of this study was to determine the laboratory-based risk factors for CMV retinitis in patients with AIDS. METHODS: We conducted a case-control study involving 120 patients in whom CMV retinitis had been diagnosed in 1990-99 and 159 patients without CMV retinitis from the same period. The sampling was from a primary study base in eastern Ontario and western Quebec of patients with AIDS and CD4 counts less than 50 cells/microL at the time of diagnosis of retinitis in the case subjects or an analogous date for the control subjects. There were two components to the study. In the first component (n = 279) we examined standard-of-care laboratory tests (hematologic and nutrition variables) done during the study period. In the second component (n = 57), which was a subset of the first, we examined laboratory tests (HLA type, qualitative and quantitative CMV polymerase chain reaction [PCR] and HIV load) on stored blood samples from the eastern Ontario site. Multivariate logistic regression was used to model the data and control for confounding. We developed a systematic model-building strategy, from assumption testing to model building to model checking. RESULTS: A low hemoglobin concentration was a statistically significant predictor of CMV retinitis (odds ratio [OR] 0.96, 95% confidence interval [CI] 0.94-0.98). Both qualitative CMV PCR (OR 21.71, 95% CI 1.80-261.67) and quantitative CMV PCR (OR 33.03,95% CI 2.32-469.39) were strong predictors of CMV retinitis. Among the 80 HLA types tested, HLA-Bw4 (OR 11.68, 95% CI 1.29-105.82) and HLA-DRB115 (OR 9.34, 95% CI 1.14-76.41) were significant predictors of CMV retinitis, whereas HLA-Cw7 was protective against CMV retinitis (OR 0.09, 95% CI 0.01-0.67). INTERPRETATION: We have identified laboratory variables that elevate (or decrease) the risk of CMV retinitis. These findings may be useful to clinicians and health policy experts in developing rational guidelines for screening, examination frequency and targeted prophylaxis for patients with AIDS.

Oral health status and treatment satisfaction with mandibular implant overdentures and conventional dentures: a randomized clinical trial in a senior population.

PURPOSE: The purpose of this study was to compare elderly patients' satisfaction and oral health-related quality of life with mandibular two-implant overdentures and conventional dentures. MATERIALS AND METHODS: Sixty edentulous subjects aged 65 to 75 years were randomly assigned to two groups treated with maxillary conventional dentures and either a mandibular conventional denture (n = 30) or an overdenture supported by two implants with ball retainers (n = 30). Subjects rated their general satisfaction, as well as other features of their dentures (comfort, stability, ability to chew, speech, esthetics, and cleaning ability), prior to treatment and 2 months postdelivery. Changes in ratings on the original Oral Health Impact Profile (OHIP) and its short form (OHIP-EDENT) were also used as indicators of oral health-related quality of life. RESULTS: The primary outcome of this study, ratings of general satisfaction 2 months postdelivery, was significantly better in the group treated with mandibular two-implant overdentures (P = .001). In addition, the implant group gave significantly higher ratings on comfort, stability, and ability to chew. Furthermore, using OHIP-EDENT, subjects who received mandibular two-implant overdentures had significantly fewer oral health-related quality of life problems than did the conventional group. CONCLUSION: These short-term results suggest that mandibular two-implant overdentures combined with maxillary conventional dentures provide better function and oral health-related quality of life than conventional dentures.

Surgery versus collagen for female stress urinary incontinence: economic assessment in Ontario and Quebec.

INTRODUCTION AND OBJECTIVE: The purpose of this study was to evaluate the cost-effectiveness of surgery versus collagen injection to treat female stress urinary incontinence after the failure of initial surgical treatment. The analysis was conducted from the health care system perspectives of Ontario and Quebec. MATERIALS AND METHODS: A decision-tree was constructed to compare each of three surgeries (i.e., retropubic suspension, transvaginal suspension, sling procedures) with collagen. An average cost estimate was generated for each intervention, as was an incremental cost-effectiveness ratio for each surgery-collagen comparison. RESULTS: In both Ontario and Quebec, the treatment with the lowest average cost was collagen (Ontario: collagen = 2695 dollars; Quebec: collagen = 2718 dollars). However, the surgeries had higher probabilities of success (defined as 'cure' - no urine leakage during follow-up examinations), with point estimates of at least.79 (.53 for collagen). Incremental cost-effectiveness ratios for the base case analyses of all treatment comparisons indicated that the cost to cure an additional patient with surgery could range from 1824 dollars to 6814 dollars in Ontario and 1388 dollars to 3008 dollars in Quebec. These ratios were sensitive to changes in the mean number of injections for collagen patients and to a reduction in the length of hospital stay for surgery to 1 day. CONCLUSIONS: Collagen injection may be cost-effective as a follow-up treatment to initial surgical failure in both Ontario and Quebec when the number of injections is kept to a minimum and hospital stays after surgery are relatively lengthy. Otherwise, surgery may be cost-effective.

Infant growth and health outcomes associated with 3 compared with 6 mo of exclusive breastfeeding.

BACKGROUND: Opinions and recommendations about the optimal duration of exclusive breastfeeding have been strongly divided, but few published studies have provided direct evidence on the relative risks and benefits of different breastfeeding durations in recipient infants. OBJECTIVE: We examined the effects on infant growth and health of 3 compared with 6 mo of exclusive breastfeeding. DESIGN: We conducted an observational cohort study nested within a large randomized trial in Belarus by comparing 2862 infants exclusively breastfed for 3 mo (with continued mixed breastfeeding through >/= 6 mo) with 621 infants who were exclusively breastfed for >/= 6 mo. Regression to the mean, within-cluster correlation, and cluster- and individual-level confounding variables were accounted for by using multilevel regression analyses. RESULTS: From 3 to 6 mo, weight gain was slightly greater in the 3-mo group [difference: 29 g/mo (95% CI: 13, 45 g/mo)], as was length gain [difference: 1.1 mm (0.5, 1.6 mm)], but the 6-mo group had a faster length gain from 9 to 12 mo [difference: 0.9 mm/mo (0.3, 1.5 mm/mo)] and a larger head circumference at 12 mo [difference: 0.19 cm (0.07, 0.31 cm)]. A significant reduction in the incidence density of gastrointestinal infection was observed during the period from 3 to 6 mo in the 6-mo group [adjusted incidence density ratio: 0.35 (0.13, 0.96)], but no significant differences in risk of respiratory infectious outcomes or atopic eczema were apparent. CONCLUSIONS: Exclusive breastfeeding for 6 mo is associated with a lower risk of gastrointestinal infection and no demonstrable adverse health effects in the first year of life.

Healthcare utilization by women in a comprehensive managed care population subsequent to diagnosis of a sexually transmitted disease.

BACKGROUND: Healthcare utilization (HCU) following a sexually transmitted disease (STD) diagnosis is poorly characterized. GOAL: The goal was to quantify HCU for new/recurrent STDs and other relevant Ob-Gyn and mental health problems in the 18 months subsequent to an STD diagnosis. STUDY DESIGN: We compared HCU between a group of females aged 18 to 45 years who were Kaiser Permanente Medical Program members with a diagnosed STD (n = 1,205) and a medical center- and age group-matched sample of women seen for a non-STD diagnosis in the same time period (n = 4820), with controlling where appropriate for age, medical center, and chronic disease status. RESULTS: An STD diagnosis was associated with significantly greater likelihood of subsequent visits for STDs (relative risk [RR] = 3.8), pelvic inflammatory disease/endometritis (RR = 2.9), candidiasis (RR = 2.0), vaginitis (RR = 2.4), cervical dysplasia (RR = 1.7), menstrual disorders/abnormal bleeding (RR = 1.3), high risk/complicated/ectopic pregnancy (RR = 1.5), and behavioral/mental health problems (RR = 1.3) than for women seen for a non-STD diagnosis. CONCLUSION: Detrimental sequelae of STDs are reflected in substantially elevated near-term HCU following an STD diagnosis.

Breastfeeding and infant growth: biology or bias?

BACKGROUND: Available evidence suggests that prolonged and exclusive breastfeeding is associated with lower infant weight and length by 6 to 12 months of age. This evidence, however, is based on observational studies, which are unable to separate the effects of feeding mode per se from selection bias, reverse causality, and the confounding effects of maternal attitudinal factors. DESIGN/METHODS: A cluster-randomized trial in the Republic of Belarus of a breastfeeding promotion intervention modeled on the World Health Organization (WHO)/UNICEF Baby-Friendly Hospital Initiative versus control (then current) infant feeding practices. Healthy, full-term, singleton breastfed infants (n = 17 046) weighing > or =2500 g were enrolled soon after birth and followed up at 1, 2, 3, 6, 9, and 12 months old for measurements of weight, length, and head circumference. Data were analyzed according to intention-to-treat, while accounting for within-cluster correlation. To assess the potential for bias in observational studies of breastfeeding, we also analyzed our data as if we had conducted an observational study by ignoring treatment, combining the 2 randomized groups, and comparing 1378 infants weaned in the first month and those breastfed for the full 12 months of follow-up with either > or =3 months (n = 1271) or > or =6 months (n = 251) of exclusive breastfeeding. RESULTS: Infants from the experimental sites were significantly more likely to be breastfed (to any degree) at 3, 6, 9, and 12 months and were far more likely to be exclusively breastfed at 3 months (43.3% vs 6.4%). Mean birth weight was nearly identical in the 2 groups (3448 g, experimental; 3446 g, control). Mean weight was significantly higher in the experimental group by 1 month of age (4341 vs 4280 g). The difference increased through 3 months (6153 g vs 6047 g), declined slowly thereafter, and disappeared by 12 months (10564 g vs 10571 g). Analysis by z scores confirmed that infants in both groups gained more weight than the WHO/Centers for Disease Control and Prevention reference, with no evidence of undernutrition in the control group. Length followed a similar pattern. In the observational analyses, infants weaned in the first month were slightly lighter and shorter at birth and their weight-for-age and length-for-age z scores declined by 1 month, but they caught up to both experimental and the other observational groups by 6 months and were heavier and longer by 12 months. Among infants in the 2 prolonged and exclusive breastfeeding groups, weight-for-age z scores fell slightly between 3 and 12 months; length-for-age fell below the reference by 6 months with catch-up to the reference by 12 months. Head circumference showed no significant differences at any age between the 2 trial groups or among the observational groups. CONCLUSIONS: Our data, the first in humans based on a randomized experiment, suggest that prolonged and exclusive breastfeeding may actually accelerate weight and length gain in the first few months, with no detectable deficit by 12 months old. These results add support to current WHO and UNICEF feeding recommendations. Our observational analysis showing faster weight and length gains with early weaning and slower gains with prolonged and exclusive breastfeeding may reflect unmeasured confounding differences or a true biological effect of formula feeding.

Medical care capacity for influenza outbreaks, Los Angeles.

In December 1997, media reported hospital overcrowding and "the worst [flu epidemic] in the past two decades" in Los Angeles County (LAC). We found that rates of pneumonia and influenza deaths, hospitalizations, and claims were substantially higher for the 1997-98 influenza season than the previous six seasons. Hours of emergency medical services (EMS) diversion (when emergency departments could not receive incoming patients) peaked during the influenza seasons studied; the number of EMS diversion hours per season also increased during the seasons 1993-94 to 1997-98, suggesting a decrease in medical care capacity during influenza seasons. Over the seven influenza seasons studied, the number of licensed beds decreased 12%, while the LAC population increased 5%. Our findings suggest that the capacity of health-care systems to handle patient visits during influenza seasons is diminishing.