Erratum to: Association between Modifiable Risk Factors and Levels of Blood-Based Biomarkers of Alzheimer's and Related Dementias in the Look AHEAD Cohort.

[This corrects the article DOI: 10.14283/jarlife.2024.1.].

Association between Modifiable Risk Factors and Levels of Blood-Based Biomarkers of Alzheimer's and Related Dementias in the Look AHEAD Cohort.

Background: Emerging evidence suggests that a number of factors can influence blood-based biomarker levels for Alzheimer's disease (AD) and Alzheimer's related dementias (ADRD). We examined the associations that demographic and clinical characteristics have with AD/ADRD blood-based biomarker levels in an observational continuation of a clinical trial cohort of older individuals with type 2 diabetes and overweight or obesity. Methods: Participants aged 45-76 years were randomized to a 10-year Intensive Lifestyle Intervention (ILI) or a diabetes support and education (DSE) condition. Stored baseline and end of intervention (8-13 years later) plasma samples were analyzed with the Quanterix Simoa HD-X Analyzer. Changes in Aß42, Aß40, Aß42/Aß40, ptau181, neurofilament light chain (NfL), and glial fibrillary acidic protein (GFAP) were evaluated in relation to randomization status, demographic, and clinical characteristics. Results: In a sample of 779 participants from the Look AHEAD cohort, we found significant associations between blood-based biomarkers for AD/ADRD and 15 of 18 demographic (age, gender, race and ethnicity, education) and clinical characteristics (APOE, depression, alcohol use, smoking, body mass index, HbA1c, diabetes duration, diabetes treatment, estimated glomerular filtration rate, hypertension, and history of cardiovascular disease) . Conclusions: Blood-based biomarkers of AD/ADRD are influenced by common demographic and clinical characteristics. These factors should be considered carefully when interpreting these AD/ADRD blood biomarker values for clinical or research purposes.

Influence of early-life nutritional stress on songbird memory formation.

In birds, vocal learning enables the production of sexually selected complex songs, dialects and song copy matching. But stressful conditions during development have been shown to affect song production and complexity, mediated by changes in neural development. However, to date, no studies have tested whether early-life stress affects the neural processes underlying vocal learning, in contrast to song production. Here, we hypothesized that developmental stress alters auditory memory formation and neural processing of song stimuli. We experimentally stressed male nestling zebra finches and, in two separate experiments, tested their neural responses to song playbacks as adults, using either immediate early gene (IEG) expression or electrophysiological response. Once adult, nutritionally stressed males exhibited a reduced response to tutor song playback, as demonstrated by reduced expressions of two IEGs (Arc and ZENK) and reduced neuronal response, in both the caudomedial nidopallium (NCM) and mesopallium (CMM). Furthermore, nutritionally stressed males also showed impaired neuronal memory for novel songs heard in adulthood. These findings demonstrate, for the first time, that developmental conditions affect auditory memories that subserve vocal learning. Although the fitness consequences of such memory impairments remain to be determined, this study highlights the lasting impact early-life experiences can have on cognitive abilities.

Single-dose aprepitant vs ondansetron for the prevention of postoperative nausea and vomiting: a randomized, double-blind phase III trial in patients undergoing open abdominal surgery.

BACKGROUND: The neurokinin(1) antagonist aprepitant is effective for prevention of chemotherapy-induced nausea and vomiting. We compared aprepitant with ondansetron for prevention of postoperative nausea and vomiting. METHODS: Nine hundred and twenty-two patients receiving general anaesthesia for major abdominal surgery were assigned to receive a single preoperative dose of oral aprepitant 40 mg, oral aprepitant 125 mg, or i.v. ondansetron 4 mg in a randomized, double-blind trial. Vomiting episodes, use of rescue therapy, and nausea severity (verbal rating scale) were documented for 48 h after surgery. Primary efficacy endpoints were complete response (no vomiting and no use of rescue therapy) 0-24 h after surgery and no vomiting 0-24 h after surgery. The secondary endpoint was no vomiting 0-48 h after surgery. RESULTS: Aprepitant at both doses was non-inferior to ondansetron for complete response 0-24 h after surgery (64% for aprepitant 40 mg, 63% for aprepitant 125 mg, and 55% for ondansetron, lower bound of 1-sided 95% CI > 0.65), superior to ondansetron for no vomiting 0-24 h after surgery (84% for aprepitant 40 mg, 86% for aprepitant 125 mg, and 71% for ondansetron; P < 0.001), and superior for no vomiting 0-48 h after surgery (82% for aprepitant, 40 mg, 85% for aprepitant, 125 mg, and 66% for ondansetron; P < 0.001). The distribution of peak nausea scores was lower in both aprepitant groups vs ondansetron (P < 0.05). CONCLUSIONS: Aprepitant was non-inferior to ondansetron in achieving complete response for 24 h after surgery. Aprepitant was significantly more effective than ondansetron for preventing vomiting at 24 and 48 h after surgery, and in reducing nausea severity in the first 48 h after surgery. Aprepitant was generally well tolerated.

Combined data from two phase III trials of the NK1 antagonist aprepitant plus a 5HT 3 antagonist and a corticosteroid for prevention of chemotherapy-induced nausea and vomiting: effect of gender on treatment response.

GOALS OF WORK: Prevention of chemotherapy-induced nausea and vomiting (CINV) with standard antiemetics has been more difficult to achieve in female patients. Data from two phase III trials of the NK1 antagonist aprepitant were assessed for potential effect of gender on treatment response. PATIENTS AND METHODS: 1,044 patients receiving cisplatin (> or = 70 mg/m2) were randomly assigned to control regimen [ondansetron (O) 32 mg i.v. and dexamethasone (D) 20 mg p.o. on day 1; D 8 mg twice daily on days 2-4] or aprepitant (A) regimen (A 125 mg p.o. plus O 32 mg and D 12 mg on day 1; A 80 mg and D 8 mg once daily on days 2-3; and D 8 mg on day 4). The primary endpoint was overall complete response (no emesis and no rescue therapy over days 1-5). Data were analyzed by a modified intent-to-treat approach. Between-treatment comparisons for each gender were made using logistic regression. MAIN RESULTS: Women comprised 42 and 43% of the aprepitant and control groups, respectively. In the control group, 41% of women had overall complete response compared with 53% of men. In the aprepitant group, 66% of women had overall complete response compared with 69% of men. CONCLUSION: The addition of aprepitant may negate the adverse prognostic effect of female gender on the prevention of CINV in patients receiving highly emetogenic chemotherapy.

The oral NK(1) antagonist, aprepitant, given with standard antiemetics provides protection against nausea and vomiting over multiple cycles of cisplatin-based chemotherapy: a combined analysis of two randomised, placebo-controlled phase III clinical trials.

In early clinical trials, the NK(1) receptor antagonist, aprepitant (EMEND(R)) was shown to improve the protection provided by the best available therapy (hereafter referred to as 'standard therapy': a 5-HT(3) receptor antagonist and dexamethasone) against chemotherapy-induced nausea and vomiting over multiple cycles of cisplatin-based chemotherapy. To further study the sustainment of antiemetic efficacy of aprepitant plus standard therapy over more than one cycle of chemotherapy, we examined combined data from the multiple cycles extensions of two phase III clinical trials of oral aprepitant plus standard therapy for the prevention of chemotherapy-induced nausea and vomiting. Data were pooled from two multicentre, randomised, double-blind, placebo-controlled studies with identical design and treatment regimens. Cancer patients receiving a first cycle of cisplatin-based (>or=70 mg/m(2)) chemotherapy were randomised to one of two treatment groups as follows: the standard therapy group received ondansetron 32 mg intravenously (i.v.) and dexamethasone 20 mg on day 1 and dexamethasone 8 mg twice daily (b.i.d.) on days 2-4. The aprepitant group received aprepitant 125 mg, ondansetron 32 mg i.v., and dexamethasone 12 mg on day 1, aprepitant 80 mg and dexamethasone 8 mg on days 2-3, and dexamethasone 8 mg on day 4. Patients had the option to receive the same blinded treatment for up to five additional cycles. The analysis used a combined exploratory endpoint of no emesis and no significant nausea (i.e. nausea which interfered with a patient's normal activities) over the 5 days following cisplatin, for up to six cycles of chemotherapy. A cumulative probabilities approach incorporating a model for transitional probabilities was used to analyse the data. Tolerability was assessed by reported adverse events and physical and laboratory assessments. Baseline characteristics, reasons for discontinuation, and drop-out rates were similar between groups. In every cycle, the estimated probabilities (rates) of no emesis and no significant nausea were significantly higher (P<0.006) in the aprepitant group: in the first cycle, rates were 61% in the aprepitant group (N=516) and 46% in the standard therapy group (N=522), and thereafter, rates for the aprepitant regimen remained higher throughout (59% (N=89) versus 40% (N=78) for the standard therapy, by cycle 6). Repeated dosing with aprepitant over multiple cycles was generally well tolerated. Compared with patients who received standard therapy alone (a 5-HT(3) antagonist plus dexamethasone), those who received aprepitant in addition to standard therapy had consistently better antiemetic protection that was well maintained over multiple cycles of highly emetogenic chemotherapy

Addition of the oral NK1 antagonist aprepitant to standard antiemetics provides protection against nausea and vomiting during multiple cycles of cisplatin-based chemotherapy.

PURPOSE: This analysis evaluated whether the antiemetic efficacy of the NK1 receptor antagonist aprepitant (EMEND trade mark, Merck, Whitehouse Station, NJ) plus standard antiemetics could be sustained for up to six cycles of cisplatin-based chemotherapy. PATIENTS AND METHODS: Patients receiving cisplatin > or = 70 mg/m2 were blindly assigned to receive one of the following three regimens: (1) aprepitant 375 mg 1 hour before cisplatin on day 1 and aprepitant 250 mg on days 2 to 5 (n = 35); (2) aprepitant 125 mg before cisplatin and aprepitant 80 mg on days 2 to 5 (n = 81); or (3) placebo before cisplatin on days 2 to 5 (n = 86). All groups received ondansetron 32 mg and dexamethasone 20 mg before cisplatin, and dexamethasone 8 mg on days 2 to 5. The primary end point was complete response (no emesis and no rescue therapy) over 5 days following cisplatin in up to six cycles. A cumulative probability analysis using a model for transitional probabilities was used to analyze the data. The aprepitant 375/250-mg regimen was discontinued early in light of new pharmacokinetic data. RESULTS: In the first cycle, 64% of patients in the aprepitant group and 49% in the standard therapy group had a complete response. Thereafter, complete response rates for the aprepitant group were still 59% by cycle 6, but decreased to 34% by cycle 6 for the standard therapy group. Reasons for discontinuation were similar across treatment groups. CONCLUSION: Compared with patients who received standard therapy, those who received only the aprepitant regimen had better and more sustained protection against chemotherapy-induced nausea and vomiting over multiple cycles.

Differential involvement of neurotransmitters through the time course of cisplatin-induced emesis as revealed by therapy with specific receptor antagonists.

Advances in antiemetic therapy for chemotherapy-induced emesis have resulted in improved protection against symptoms occurring within 24 h of chemotherapy. However, the vomiting which tends to occur beyond 24 h after chemotherapy (delayed-phase vomiting) is still relatively poorly controlled by the currently available drugs, suggesting that more than one mechanism may mediate these symptoms. The standard antiemetic regimen currently recommended for prevention of chemotherapy-induced emesis includes a serotonin (5-HT(3)) antagonist and a corticosteroid. The neurokinin-1 (NK(1)) antagonist aprepitant represents a new class of antiemetic currently in clinical development. Using data obtained in 2 Phase II clinical trials of aprepitant in patients receiving chemotherapy based on the highly emetogenic chemotherapeutic agent cisplatin, we compared the time course of antiemetic effect of aprepitant, a 5-HT(3) antagonist, or a combination of both. Over the entire observation period (up to 7 days post-cisplatin), patients who received the NK(1) antagonist had a superior prevention of emesis. However, in the first 24 h after cisplatin, emesis occurred in fewer patients who received the 5-HT(3) antagonist than in patients who did not receive this class of drug. Furthermore, the majority of treatment failures in patients who received the NK(1) antagonist occurred within the first 8-12 h of chemotherapy, whereas the treatment failures in patients who received a 5-HT(3) antagonist were more evenly distributed over time. Patients who received both drugs had superior control of symptoms compared with patients who received one or the other. The difference in the time course of emesis blockade observed with two different classes of receptor antagonists provides substantial evidence for involvement of separate pathophysiological mechanisms in chemotherapy-induced vomiting. Serotonin mediates the early vomiting process that occurs within 8-12 h following cisplatin-based chemotherapy, after which time substance P acting at NK(1) receptors becomes the dominant mediator of vomiting

Effects of 6 months of moderate aerobic exercise training on immune function in the elderly.

The purpose of this study was to determine the effects of 6 months of moderate aerobic exercise on age-dysregulated measures of T lymphocyte and natural killer (NK) cell number and function. Previously sedentary elderly (age = 65 +/- 0.8 years) subjects were randomly assigned to supervised 3 time/week exercise intervention group (EXC, n = 14) or flexibility/toning control group (FT-CON, n = 15). Fasting resting blood samples were drawn prior to and after the 6 month intervention. The EXC group exhibited a significant (P < 0.05) 20% increase in VO2 max, whereas the FT-CON group had a smaller non-significant (P = 0.07) increase (9%). Immune results revealed that, in general, changes in immune function in response to 6 months of exercise training at an average intensity of 52% heart rate reserve (HRR) were similar when compared to FT-CON who exercised at approximately 21% HRR. There were no intervention-induced changes in total white blood cell, neutrophil, lymphocyte, monocyte, eosinophil, or basophil blood counts. Furthermore, the percentage and number of CD3+, CD4+ and CD8+ T cells in the blood remained unchanged. There was a tendency for the percentage and number of CD4+ and CD8+ näive cells (CD45RA+) to increase and for CD4+ memory cells (CD45RO+) to decrease post-intervention, especially in FT-CON. Both groups exhibited a small intervention-induced increase in the T-cell proliferative response to mitogenic stimulation: the percentage change of which was higher in the EXC group at several doses of Con A. Unstimulated NK cell cytolysis versus K562 cells tended to increase (P < 0.1) in the EXC group with little change in FT-CON. We conclude that 6 months of supervised exercise training can lead to nominal increases in some measures of immune function, while not affecting others, in previously sedentary elderly.

Differential leukocytosis and lymphocyte mitogenic response to acute maximal exercise in the young and old.

UNLABELLED: Despite the increasing use of exercise in the elderly as a means of improving muscle function, little is known regarding the effects of exercise on the senescent immune system. PURPOSE: The purpose of this study was to determine the effects of acute maximal exercise on blood leukocyte numbers, leukocyte subsets, and the T cell mitogenic response in the elderly. METHODS: Previously sedentary elderly (N = 33, 65.3 +/- 0.8 yr) and young (N = 14, 22.4 +/- 0.7 yr) subjects participated in a modified Balke maximal exercise treadmill test. Venous blood samples were collected pre-, immediately post-, and 20 min postexercise. Blood was analyzed for leukocyte counts, leukocyte subsets via immunofluorescence, and whole blood mitogenesis in response to various doses of mitogens. RESULTS: Whereas VO2max was lower in the elderly, maximal RQ, age-predicted heart rates, and times to fatigue were not different, indicating that both groups achieved relative maximal exercise intensity. There were significant exercise-induced leukocytoses in both the elderly and young made up largely of a lymphocytosis and neutrophilia. The magnitude of the leukocytosis was lower in the elderly and failed to return to pre-exercise levels by 20 min postexercise. Acute maximal exercise increased CD8+ (153% vs 112% in young and old, respectively) and CD4+ (57% vs 22% in young and old, respectively) T cells when measured immediately postexercise. By 20 min postexercise, concentrations in the young were not significantly different from baseline, whereas CD8 cell number was still elevated in the old. The elderly had significantly higher percentages of memory (i.e., CD45RO+) and significantly lower percentages of naive (i.e., CD45RA+) CD4 and CD8 T cells pre-exercise, and the young and old recruited approximately equal numbers of CD8+ naive and memory cells to the blood in response to exercise. In contrast, the aged recruited significantly fewer numbers of CD4+ naive and transitional (CD45RA+RO+) cells. At most doses of Con A and PHA, the lymphoproliferative response was lower in the elderly subjects even though they had significantly higher numbers and percentages of CD3+ cells. Interestingly, immediately postexercise, young (but not old) subjects demonstrated reduced proliferative ability on a per CD3+ cell basis. CONCLUSIONS: These data indicate that several blood leukocyte responses to maximal exercise stress are similar in the young and the old. However, the elderly demonstrate a less resilient leukocytosis and a different lympho-proliferative response following acute maximal exercise.

Effects of maximal exercise on natural killer (NK) cell cytotoxicity and responsiveness to interferon-alpha in the young and old.

We investigated the effects of a graded maximal exercise treadmill test on natural killer (NK) cell number, activity, and responsiveness to interferon-alpha (IFN-alpha) in young (22+/-0.7 yrs) and elderly (65+/-0.8 yrs) sedentary subjects. NK cell cytotoxicity (NKCC) was determined using Ficoll purified peripheral blood mononuclear cells (PBMCs) by a 51Cr release assay against NK-sensitive (K562) and NK-insensitive (Daudi) target cells at various effector:target (E:T) ratios before and immediately after exercise. PBMCs were incubated with rhu IFN-alpha (125 and 250u/10(6) PBMCs) or without for 2 hrs before addition to the 51Cr release assay. There were no differences in unstimulated NKCC against K562 or Daudi targets between the old and the young despite significantly (p=.01) higher percentages of CD56+ NK cells (21.1+/-2.3% in old vs 12.5+/-2.5% in young, pre-exercise). IFN-alpha increased NKCC versus both targets, and NK cells from old subjects were hyporesponsive to IFN-alpha stimulation; this was especially evident at low E:T ratios versus Daudi cells. Maximal exercise significantly increased (50-200%) unstimulated NKCC versus K562 and Daudi targets similarly in both young and old and increased the percentage of CD56+ cells in the PBMC fraction to 33.3+/-3.7% and 23.3+/-3.6% in old and young, respectively. We found a significant correlation between %CD56+ and basal NKCC versus K562s and Daudi cells in the young (i.e., r=.55; p=.02 vs K562s), but not the old (i.e., r=.20; p=.29 vs K562s) subjects. This indicates that, in the young, part of the exercise-induced increase in NKCC is due to an increase in NK cell number. Maximal exercise did not affect unstimulated per cell killing of K562s, but tended to increase per cell killing of Daudis. These results indicate that CD56+ cells from old subjects have an intrinsic defect in their ability to perform cytolysis and respond to IFN-alpha. Furthermore, a single bout of maximal exercise increases NKCC and CD56+ cell number similarly in both young and old subjects regardless of the target cell used.

Predictors of the progression of renal insufficiency in patients with insulin-dependent diabetes and overt diabetic nephropathy. The Collaborative Study Group.

We designed a prospective, double-blind controlled trial to determine predictors of loss of renal function in patients with insulin dependent diabetes and established nephropathy. A total of 409 insulin-dependent diabetic patients with established nephropathy enrolled in a trial on the effect of Captopril on the rate of progression of renal disease. Baseline demographic, clinical (history and physical) and laboratory parameters were analyzed as risk factors for time to progression. Dichotomous characteristics were compared by Fisher's exact test and continuous characteristics with the Wilcoxon rank-sum test. Univariate proportional hazards regression analysis was used to estimate relative risk of nephropathy progression, and bivariate proportional hazard regression to identify interactions with the treatment group assignment. Multivariate proportional hazard regression was employed to determine which characteristics were independent risk factors. We found that a number of demographic and clinical characteristics were significantly associated with nephropathy progression even after adjustment for treatment group. However, after multivariate analysis, the risk factors that independently predicted progression were onset of IDDM later in life, parental diagnosis of IDDM, the presence of edema, increased mean arterial pressure, and an abnormal electrocardiogram. Likewise, a number of laboratory characteristics were also predictive of nephropathy progression. A low hematocrit, high blood sugar, and higher protein excretion predicted nephropathy progression as did a higher serum creatinine, particularly in the face of a normal serum albumin. In conclusion, this study identifies a number of clinical and laboratory risk factors that can predict which patients with insulin-dependent diabetes with established nephropathy are more likely to sustain a clinically important decrease in renal function over a median follow-up of three years.

Emergency hormonal contraception usage in genitourinary medicine clinic attenders.

OBJECTIVE: To assess the indications for usage of emergency hormonal contraception amongst a population of London genitourinary medicine clinic attenders. METHODS: In a prospective study, 150 consecutive women receiving emergency hormonal contraception (EHC) were enrolled. The attending doctor completed a questionnaire of patient details and prescribed EHC with prophylactic prochlorperazine. Follow-up was arranged three weeks later, at which time outcomes and side-effects of therapy were recorded. For those women who did not reattended as planned case notes were reviewed at three months. RESULTS: Of 150 women surveyed, 100 (66%) reported contraceptive method failure, 48 (32%) had used no contraception at the time of last sexual intercourse and two requested EHC after sexual assault. Ninety three (62%) reported condom failure, 7 (5%) oral contraceptive pill failure. Seventy five (50%) had used EHC before (range 1-10 times). Seventy one (47%) women reattended within three months. Five (3.3%) of the 150 women were pregnant; none of these cases had experienced nausea or vomiting whilst taking EHC. Side-effects were reported by 22 (31%) of the 71 patients who reattended. Nine (6%) women had been followed-up in the family planning advisory clinic. Of the 71 women who reattended, 39 (55%) reported that their preferred future method of contraception would be condoms. Of the 150 women 19 (13%) underwent tests for sexually transmissible infections within one month of presentation. CONCLUSIONS: EHC usage in this population was associated with a failure rate of at least 3.3% and an overall side effect rate of 31%. Despite requests for emergency contraception because of condom failure many elected to continue using condoms as their preferred method of contraception. The majority of women (53%) did not return for follow-up or family planning advice, and so we believe that future contraceptive plans must be addressed at the time EHC is prescribed.

PIP: In England, health providers conducted a prospective study of 150 consecutive women 14-43 years old who sought emergency hormonal contraception (EHC) (50 mcg ethinyl estradiol + 500 mcg norgestrel) at the genitourinary medicine clinic of The Royal London Hospital in the Whitechapel section of London. 50% had also used EHC in the past. 23% had experienced at least 1 induced abortion. The reasons for EHC use were contraceptive failure for 100 (66%) women, unprotected sexual intercourse for 48 (32%) women, and rape for 2 women. 93% of the women reporting contraceptive failure were using a condom during the index sexual intercourse. The remaining women recognized the possibility of failure of their oral contraceptives (e.g., concurrent use of an antibiotic and forgotten pill). 50 (33%) and 21 (14%) women returned to the clinic for follow-up within 1 month and 1-3 months of initial presentation, respectively. Nine of these women had attended the family planning advisory clinic. 3.3% of the 71 women who returned to the clinic were pregnant. 22 (31%) of the women who returned to the clinic reported side effects (10 nausea and vomiting, 9 nausea, 5 abdominal pain, 1 breast tenderness, and 1 a panic attack). More than 31% of returning women reported an abnormal period after using EHC. 51% of returning women said that their preferred future method of contraception would be condoms. 10% either had not yet decided to use contraception or were planning to become pregnant. Clinic staff screened only 13% of all 150 women for sexually transmitted diseases (STDs) within 1 month of unprotected intercourse. None of them had an STD. Six of the 150 women returned for a second EHC prescription within 3 months. These findings indicate the need for clinicians to address future contraceptive plans at the time of EHC prescription, since most women did not return for follow-up or family planning advice. They should also screen for STDs during this initial contact considering the high rate of unprotected intercourse.

Determinants of preterm delivery in low-risk pregnancies. The RADIUS Study Group.

From 14,948 low-risk singleton pregnancies, we calculated incidence, risk ratios, and attributable risks for characteristics associated with spontaneous and medically induced preterm delivery. There were 754 women who gave birth prior to 37 weeks of gestation (50.4/1000 deliveries). The greatest fraction of the incidence of prematurity among low-risk pregnancies was due to unknown factors associated with carrying a first live birth, regardless of preterm delivery mechanism (i.e., spontaneous labor, PROM, medical intervention), with population-attributable risk percents (PAR%) ranging from 16.0 to 30.5%. Other than nulliparity, male sex of the fetus accounted for the greatest fraction of spontaneous labor-induced prematurity incidence (PAR% = 13.6%), and maternal age greater than 30 years or a positive urine culture accounted for the greatest fraction of PROM-induced prematurity incidence (PAR% = 7.9 and 6.7, respectively). All other risk factors for either preterm labor or PROM accounted for less than 5% of the incidence. Three characteristics explained a large fraction of medically induced prematurity: women over 150 pounds at the onset of pregnancy (PAR% = 23.8), a > or = 2+ prenatal urine protein (PAR% = 18.7%), and cigarette smoking during the first trimester (PAR% = 8.6). Our results suggest known risk factors may explain only a small fraction of spontaneous preterm delivery incidence in low-risk pregnancies.

Incidence of symptomatic urinary tract infections in HIV seropositive patients and the use of cotrimoxazole as prophylaxis against Pneumocystis carinii pneumonia.

OBJECTIVES: To determine the incidence of symptomatic urinary tract infections in HIV seropositive patients and to assess whether this varies with stage of disease, risk group or the use of co-trimoxazole as prophylaxis against Pneumocystis carinii pneumonia. METHODS: A retrospective case note review of 175 HIV-infected patients attending The Royal London Hospital between July 1988 and December 1992 was performed. A urinary tract infection was defined as a pure culture of > or = 10(5) colony forming units in a mid-stream specimen of urine from a patient with symptoms consistent with a urinary tract infection. RESULTS: Urinary tract infections occurred in 10 (5.7%) of 175 patients, with an incidence of 1.49 per hundred patient years. Urinary tract infections were significantly more common in patients with AIDS or a CD4 lymphocyte count below 0.2 x 10(9)/l (or both) when compared to those without AIDS and a CD4 lymphocyte count above 0.2 x 10(9)/l (5.4 vs. 0.5 urinary tract infections per hundred patient years, p = 0.00005). Women with AIDS or a CD4 count below 0.2 x 10(9)/l (or both) had an incidence of urinary tract infection of 18.5 per hundred patient years. No significant difference was found between the incidence of urinary tract infections in those taking co-trimoxazole as Pneumocystis carinii pneumonia prophylaxis and those taking alternative or no prophylaxis (2.6 vs 6.4 per hundred patient years, p = 0.39). CONCLUSIONS: Urinary tract infection represents a considerable health problem amongst HIV infected patients. Our data show that urinary tract infections are more common in patients with advanced compared with early HIV infection. Cotrimoxazole, when taken by patients as prophylaxis against Pneumocystis carinii pneumonia did not appear to reduce the incidence of urinary tract infection.

Is smoking an indication for prenatal ultrasonography? RADIUS Study Group.

OBJECTIVE: To evaluate whether ultrasound screening during pregnancy decreases the frequency of smoking in women who present with a history of smoking. DESIGN: The Routine Antenatal Diagnostic Imaging with Ultrasound Study was a multicenter, randomized clinical trial of ultrasound screening during pregnancy. We obtained information on smoking habits during pregnancy from birth certificate records for the subset of women who were delivered of a neonate in Missouri hospitals, and determined the effect of ultrasound screening on smoking habits during pregnancy. SETTING: The study was conducted in multiple practices in six states. PARTICIPANTS: Women who registered for prenatal care at participating practices. INTERVENTION: Women in the screened group were routinely scheduled for ultrasound screening at 16 to 22 weeks' gestation and at 31 to 35 weeks' gestation. Those in the control group received ultrasound screening only for medical indications, as determined by their physicians. MAIN OUTCOME MEASURE: Smoking habits were measured by the number of cigarettes smoked per day. RESULTS: There was no difference in the rates of smoking cessation between the screened group and the control group. For those who continued smoking, the mean number of cigarettes smoked per day, as reported at the time of delivery, was slightly higher in the screened group. CONCLUSION: Ultrasound screening does not reduce the frequency of smoking during pregnancy.

Analgesia for the reduction of fractures in children: a comparison of nitrous oxide with intramuscular sedation.

A prospective, randomized study was undertaken to compare the effectiveness of nitrous oxide with intramuscular sedation (meperidine and promethazine) in providing analgesia and amnesia during the reduction and treatment of children's fractures in an outpatient clinic setting. Fifteen patients received a 50:50 mixture of nitrous oxide and oxygen, and 15 received intramuscular injection. The two groups were similar in regard to gender distribution, age, and fracture types. Pain response was recorded using the Children's Hospital of Eastern Ontario (Canada) Pain Scale (CHEOPS) at the time of fracture reduction and 30 min postreduction. At the first follow-up visit a questionnaire regarding the patient's memory and subjective experience of the fracture reduction was answered. Data between the two groups were compared using the Mann-Whitney test. The CHEOPS scores, and the memory and subjective experience of the fracture reduction were similar between the two groups. Time in the outpatient department averaged 83 min for the intramuscular group and 30 min for the nitrous oxide group (p < 0.01). All of the nitrous oxide patients stated they would use nitrous oxide again, whereas only eight of 15 intramuscular patients stated they would try intramuscular sedation again. Nitrous oxide is as effective as intramuscular sedation in providing analgesia and amnesia in the treatment of children's fractures while having a more rapid onset and a shorter recovery period with greater patient acceptance.

Epidemiologic predictors of cesarean section in nulliparous patients at low risk. RADIUS Study Group. Routine Antenatal Diagnostic Imaging with Ultrasound Study.

OBJECTIVES: We sought to determine whether certain maternal and fetal characteristics influenced the risk of maternal- and fetal-indicated cesarean sections in pregnant women at low risk for adverse perinatal outcomes. STUDY DESIGN: From a cohort of 6393 low-risk nulliparous patients maternal and fetal indicated cesarean section rates with 95% confidence intervals were calculated and stratified by demographic, anthropometric, and clinical tests and measurements. The strongest risk factors were modeled by means of multiple logistic regression. RESULTS: Few risk factors distinguished maternal from fetal characteristics preceding cesarean delivery. Maternal age was associated with increased cesarean section risk in the tallest group of women only, and cesarean section rates decreased with increasing height, increased with higher prepregnancy weights, and was highest in women carrying male fetuses. Higher first prenatal visit diastolic blood pressure, increasing numbers of nonstress tests, > or = 2+ prenatal urine protein, late sonograms, geographic region, and practice type were statistically significant risk factors as well. Interestingly, results of prenatal visit tests and measurements contributed less to the prevalence of cesarean section than did age, fetal sex, and anthropometric parameters. However, the generalizability of these results is limited to low-risk (predominantly white) populations. CONCLUSIONS: Of the risk factors we were able to assess, a large proportion of the incidence of cesarean section in this population of nulliparous patients at low risk was attributable to age, sex of fetus, and anthropometric patient profiles.

A randomized trial of prenatal ultrasonographic screening: impact on the detection, management, and outcome of anomalous fetuses. The RADIUS Study Group.

OBJECTIVE: The objective of this randomized clinical trial was to test the hypothesis that ultrasonographic screening would significantly alter perinatal outcome as a result of the antenatal detection of fetal congenital malformations. STUDY DESIGN: Pregnant women without a specific indication for ultrasonography were randomly assigned to have either two screening sonograms (15 to 22 weeks and 31 to 35 weeks) or conventional obstetric care with ultrasonography used only as determined by the clinical judgment of the patient's physician. The frequency of birth defect detection in the screened and control populations was compared, as was the impact of discovery on pregnancy outcome. RESULTS: Major congenital malformations occurred in 2.3% of the 15,281 fetuses and infants in this study. Antenatal ultrasonography detected 35% of the anomalous fetuses in the screened group versus only 11% in the control population (relative detection rate 3.1; 95% confidence interval 2.0 to 5.1). Ultrasonography screening did not, however, significantly influence the management or outcome of pregnancies complicated by congenital malformations. Specifically, only 9 abortions were performed for anomalies among 7685 fetuses in the screened group whereas 4 pregnancies were terminated for fetal anomalies detected among 7596 control subjects. Ultrasonography screening also had no significant impact on survival rates among infants with potentially treatable, life-threatening anomalies despite the opportunity to take precautionary measures such as delivery in a tertiary center. CONCLUSIONS: Ultrasonography screening in a low-risk pregnant population had no significant impact on the frequency of abortion for fetal anomalies. Survival rates for anomalous fetuses were also unaffected by screening.