Acrobat
MS Word
PowerPoint
Volume 6, No. 9, September 2008
Hot Topics
Obstetrics | Gynecology | Child Health | Chronic Disease and Illness
Obstetrics
Highlights from the International Workshop Conference on Gestational Diabetes Diagnosis and Classification held June 11-13, 2008
209 registrants from the International Association of Diabetes and Pregnancy Study Groups convened in Pasadena, California to review the results of the HAPO study (Hyperglycemia and Pregnancy Outcomes) published May 8 2008 in the NEJM (citation below). The Indian Health system sent two representatives to the Workshop / Conference.
The primary focus of the conference was to review the population-based data which link maternal glucose levels to fetal, neonatal, childhood, and maternal outcomes. The purpose of the conference was to analyze these data with a view to developing a world-wide consensus on the diagnosis of GDM or glucose intolerance of pregnancy.
A total of 25,505 pregnant women at 15 centers in nine countries underwent 75-g oral glucose-tolerance testing at 24 to 32 weeks of gestation. Data remained blinded if the fasting plasma glucose level was 105 mg per deciliter or less and the 2-hour plasma glucose level was 200 mg per deciliter or less. Primary outcomes were birth weight above the 90th percentile for gestational age, primary cesarean delivery, clinically diagnosed neonatal hypoglycemia, and cord-blood serum C-peptide level above the 90th percentile. Secondary outcomes were delivery before 37 weeks of gestation, shoulder dystocia or birth injury, need for intensive neonatal care, hyperbilirubinemia, and preeclampsia.
RESULTS
For the 23,316 participants with blinded data, we calculated
adjusted odds ratios for adverse pregnancy outcomes associated with an increase
in the fasting plasma glucose level of 1 SD (6.9 mg per deciliter [0.4 mmol per
liter]), an increase in the 1-hour plasma glucose level of 1 SD (30.9 mg per
deciliter [1.7 mmol per liter]), and an increase in the 2-hour plasma glucose
level of 1 SD (23.5 mg per deciliter [1.3 mmol per liter]). For birth weight
above the 90th percentile, the odds ratios were 1.38 (95% confidence interval
[CI], 1.32 to 1.44), 1.46 (1.39 to 1.53), and 1.38 (1.32 to 1.44), respectively;
for cord-blood serum C-peptide level above the 90th percentile, 1.55 (95% CI,
1.47 to 1.64), 1.46 (1.38 to 1.54), and 1.37 (1.30 to 1.44); for primary cesarean
delivery, 1.11 (95% CI, 1.06 to 1.15), 1.10 (1.06 to 1.15), and 1.08 (1.03 to
1.12); and for neonatal hypoglycemia, 1.08 (95% CI, 0.98 to 1.19), 1.13 (1.03
to 1.26), and 1.10 (1.00 to 1.12). There were no obvious thresholds at
which risks increased. Significant associations were also observed for secondary
outcomes, although these tended to be weaker.
CONCLUSIONS
The results indicate strong, continuous associations of maternal glucose levels
below those diagnostic of diabetes with increased birth weight and increased
cord-blood serum C-peptide levels.
Some interesting findings:
C-peptide was selected as a primary outcome variable because in theory
the higher the cord insulin the more likely it is that mother had high glucose
concentrations which crossed to the fetus. Insulin levels were not used because
hemolysis lowers plasma insulin concentrations, whereas it does not affect c-peptide.
About 15% of cord specimens will hemolyze. There is a strong correlation between
c-peptide (the part of the insulin molecule that links the a-chain with the b-chain)
and insulin. Therefore, cord c-peptide levels serve as a proxy for fetal insulinemia.
There was a strong association between increasing maternal OGTT results
at all three times; fasting, 1-hr, and 2 -hr and cord c-peptide
levels in the neonate but the highest correlation was with fasting
and the 1hour after the load.
The high c-peptide production was associated with neonatal
hypoglycemia following birth.
There appeared to be agreement that the 75 gm (rather than the 100 gm)
OGTT may be preferred for GDM diagnosis through out the world and that only 1
abnormal result maybe needed to diagnose GDM.
There was no consensus on whether the diagnostic test should include the fasting
and 1-hr or fasting and 1-hr and 2-hr. (i.e. whether the test should be 1 or
2 hours after the glucose load)
Pregnant Fasting Plasma Glucose (FPG) less than 80 mg/dl had the least correlation
with adverse outcomes but still had some correlation. Pregnant FPG > 90 had
the highest correlation with adverse outcomes.
One hour after a 75 gm load greater than 179 was associated with a significantly
increased risk of adverse outcomes. Two hours after the 75 gm load greater than
140 was also associated with a significantly increased risk of adverse outcomes.
There was also a majority opinion that within the definition of GDM there should
be a designation of those who have overt DM (eg FPG >126).Thus we should be
able to diagnose type 2 (and rarely type 1) during pregnancy.
Special thanks to David Sacks for this thoughtful recap of the Workshop/Conference
Editorial Comment (Neil Murphy, Southcentral Foundation; ANMC):
Still waiting for translation into practice guidelines
A writing committee will convene to determine how to translate these research
findings into a draft of clinical recommendations. Also, the calculations
will be redone, using the mean or median glucose value rather than the lowest
category of glucose results as the reference group.
Our hope is the screening / diagnosis process will be made as simple as possible. One possible scenario would have a one step test composed of a fasting and either a one or a two hour determination. Stay tuned!
Resources:
HAPO
Study Cooperative Research Group Hyperglycemia and adverse pregnancy outcomes.
N Engl J Med. 2008 May 8;358(19):1991-2002.
http://www.ncbi.nlm.nih.gov/pubmed/18463375
Ecker
JL, Greene
MF. Gestational diabetes--setting limits, exploring treatments. N Engl J
Med. 2008 May 8;358(19):2061-3.
http://www.ncbi.nlm.nih.gov/pubmed/18463383
Preeclampsia and the risk of end-stage renal disease
BACKGROUND:
It is unknown whether preeclampsia is a risk marker for subsequent end-stage
renal disease (ESRD).
METHODS: We linked data from the Medical Birth Registry of Norway, which contains
data on all births in Norway since 1967, with data from the Norwegian Renal Registry,
which contains data on all patients receiving a diagnosis of end-stage renal
disease (ESRD) since 1980, to assess the association between preeclampsia in
one or more pregnancies and the subsequent development of ESRD. The study population
consisted of women who had had a first singleton birth between 1967 and 1991;
we included data from up to three pregnancies.
RESULTS: ESRD developed in 477 of 570,433 women a mean (+/-SD) of 17+/-9 years
after the first pregnancy (overall rate, 3.7 per 100,000 women per year). Among
women who had been pregnant one or more times, preeclampsia during the first
pregnancy was associated with a relative risk of ESRD of 4.7 (95% confidence
interval [CI], 3.6 to 6.1). Among women who had been pregnant two or more times,
preeclampsia during the first pregnancy was associated with a relative risk of
ESRD of 3.2 (95% CI, 2.2 to 4.9), preeclampsia during the second pregnancy with
a relative risk of 6.7 (95% CI, 4.3 to 10.6), and preeclampsia during both pregnancies
with a relative risk of 6.4 (95% CI, 3.0 to 13.5). Among women who had been pregnant
three or more times, preeclampsia during one pregnancy was associated with a
relative risk of ESRD of 6.3 (95% CI, 4.1 to 9.9), and preeclampsia during two
or three pregnancies was associated with a relative risk of 15.5 (95% CI, 7.8
to 30.8). Having a low-birth-weight or preterm infant increased the relative
risk of ESRD. The results were similar after adjustment for possible confounders
and after exclusion of women who had kidney disease, rheumatic disease, essential
hypertension, or diabetes mellitus before pregnancy.
CONCLUSIONS: Although the absolute risk of ESRD in women who have had preeclampsia
is low, preeclampsia is a marker for an increased risk of subsequent ESRD.
Vikse BE, Irgens LM, Leivestad T, Skjaerven R, Iversen BM. Preeclampsia and the risk of end-stage renal disease. N Engl J Med. 2008 Aug 21;359(8):800-9. http://www.ncbi.nlm.nih.gov/pubmed/18716297
Recurrence of group B streptococci colonization in subsequent pregnancy
OBJECTIVE:
To estimate the prevalence of group B streptococci (GBS) colonization in a subsequent
pregnancy in women with and without GBS colonization in an index pregnancy. METHODS:
A retrospective cohort study of women who had two consecutive deliveries with
the availability of GBS culture result at 35 to 37 weeks of gestation or the
diagnosis of GBS colonization by urine culture for both pregnancies was undertaken.
Women in the index pregnancy with GBS genitourinary tract colonization were compared
by culture date with the next woman that screened negative for GBS colonization.
To detect a doubling of GBS colonization from 20% to 40% would require 91 women
in each arm at P<.05 with a power of 80%. Risk factors for
GBS colonization were ascertained. Univariable and conditional logistic regression
analyses were performed. P<.05 was considered statistically significant.
RESULTS: A total of 102 women positive for GBS genitourinary colonization were
compared with controls. The rate of recurrence for GBS colonization (53%) was
significantly higher when judged against women GBS negative in their index pregnancy
(15%) (adjusted odds ratio 11.7, 95% confidence interval 3.5-38.9, P<.01).
Women who were GBS positive in the index pregnancy were more often of African-American
race and less likely to be nulliparous or smoke tobacco. CONCLUSION: Women with
GBS colonization are at increased risk of GBS colonization in a subsequent pregnancy.
Prior GBS colonization should be considered in the algorithm to treat unknown
GBS status during term labor.
Turrentine MA, Ramirez MM. Recurrence of group B streptococci colonization in
subsequent pregnancy. Obstet Gynecol. 2008 Aug;112(2 Pt 1):259-64. http://www.ncbi.nlm.nih.gov/pubmed/18669720
Maternal death in the 21st century: causes, prevention, and relationship to cesarean delivery
OBJECTIVE: We sought to examine etiology and preventability
of maternal death and the causal relationship of cesarean delivery to maternal
death in a series of approximately 1.5 million deliveries between 2000 and 2006.
STUDY DESIGN: This was a retrospective medical records extraction of data from
all maternal deaths in this time period, augmented when necessary by interviews
with involved health care providers. Cause of death, preventability, and causal
relationship to mode of delivery were examined.
RESULTS: Ninety-five maternal deaths occurred in 1,461,270 pregnancies (6.5 per
100,000 pregnancies.) Leading causes of death were complications of preeclampsia,
pulmonary thromboembolism, amniotic fluid embolism, obstetric hemorrhage, and
cardiac disease. Only 1 death was seen from placenta accreta. Twenty-seven deaths
(28%) were deemed preventable (17 by actions of health care personnel and 10
by actions of non-health care personnel). The rate of maternal death causally
related to mode of delivery was 0.2 per 100,000 for vaginal birth and 2.2 per
100,000 for cesarean delivery, suggesting that the number of annual deaths resulting
causally from cesarean delivery in the United States is about 20.
CONCLUSION: Most maternal deaths are not preventable. Preventable deaths are
equally likely to result from actions by nonmedical persons as from provider
error. Given the diversity of causes of maternal death, no systematic reduction
in maternal death rate in the United States can be expected unless all women
undergoing cesarean delivery receive thromboembolism prophylaxis. Such a policy
would be expected to eliminate any statistical difference in death rates caused
by cesarean and vaginal delivery.
Clark SL, Belfort MA, Dildy GA, Herbst MA, Meyers JA, Hankins GD. Maternal death in the 21st century: causes, prevention, and relationship to cesarean delivery. Am J Obstet Gynecol. 2008 Jul;199(1):36.e1-5; discussion 91-2. e7-11. Epub 2008 May 2. http://www.ncbi.nlm.nih.gov/pubmed/18455140
Guidelines for computed tomography and magnetic resonance imaging use during pregnancy and lactation
There has been a substantial increase in the use of computed tomography (CT) and magnetic resonance imaging (MRI) in pregnancy and lactation. Among some physicians and patients, however, there are misperceptions regarding risks, safety, and appropriate use of these modalities in pregnancy. We have developed a set of evidence-based guidelines for the use of CT, MRI, and contrast media during pregnancy for selected indications including suspected acute appendicitis, pulmonary embolism, renal colic, trauma, and cephalopelvic disproportion. Ultrasonography is the initial modality of choice for suspected appendicitis, but if the ultrasound examination is negative, MRI or CT can be obtained. Computed tomography should be the initial diagnostic imaging modality for suspected pulmonary embolism. Ultrasonography should be the initial study of choice for suspected renal colic. Ultrasonography can be the initial imaging evaluation for trauma, but CT should be performed if serious injury is suspected. Pelvimetry now is used rarely for suspected cephalopelvic disproportion, but when required, low-dose CT pelvimetry can be performed with minimal risk. Although iodinated contrast seems safe to use in pregnancy, intravenous gadolinium is contraindicated and should be used only when absolutely essential. It seems to be safe to continue breast-feeding immediately after receiving iodinated contrast or gadolinium. Although teratogenesis is not a major concern after exposure to prenatal diagnostic radiation, carcinogenesis is a potential risk. When used appropriately, CT and MRI can be valuable tools in imaging pregnant and lactating women; risks and benefits always should be considered and discussed with patients.
Chen MM, Coakley FV, Kaimal A, Laros RK Jr. Guidelines for computed tomography and magnetic resonance imaging use during pregnancy and lactation. Obstet Gynecol. 2008 Aug;112(2 Pt 1):333-40. http://www.ncbi.nlm.nih.gov/pubmed/18669732
Gynecology
Health and economic implications of HPV vaccination in the United States
BACKGROUND: The cost-effectiveness of prophylactic vaccination
against human papillomavirus types 16 (HPV-16) and 18 (HPV-18) is an important
consideration for guidelines for immunization in the United States.
METHODS: We synthesized epidemiologic and demographic data using models of HPV-16
and HPV-18 transmission and cervical carcinogenesis to compare the health and
economic outcomes of vaccinating preadolescent girls (at 12 years of age) and
vaccinating older girls and women in catch-up programs (to 18, 21, or 26 years
of age). We examined the health benefits of averting other HPV-16-related and
HPV-18-related cancers, the prevention of HPV-6-related and HPV-11-related genital
warts and juvenile-onset recurrent respiratory papillomatosis by means of the
quadrivalent vaccine, the duration of immunity, and future screening practices.
RESULTS: On the assumption that the vaccine provided lifelong immunity, the cost-effectiveness
ratio of vaccination of 12-year-old girls was $43,600 per quality-adjusted life-year
(QALY) gained, as compared with the current screening practice. Under baseline
assumptions, the cost-effectiveness ratio for extending a temporary catch-up
program for girls to 18 years of age was $97,300 per QALY; the cost of extending
vaccination of girls and women to the age of 21 years was $120,400 per QALY,
and the cost for extension to the age of 26 years was $152,700 per QALY. The
results were sensitive to the duration of vaccine-induced immunity; if immunity
waned after 10 years, the cost of vaccination of preadolescent girls exceeded
$140,000 per QALY, and catch-up strategies were less cost-effective than screening
alone. The cost-effectiveness ratios for vaccination strategies were more favorable
if the benefits of averting other health conditions were included or if screening
was delayed and performed at less frequent intervals and with more sensitive
tests; they were less favorable if vaccinated girls were preferentially screened
more frequently in adulthood.
CONCLUSIONS: The cost-effectiveness of HPV vaccination will depend on the duration
of vaccine immunity and will be optimized by achieving high coverage in preadolescent
girls, targeting initial catch-up efforts to women up to 18 or 21 years of age,
and revising screening policies.
Kim JJ, Goldie SJ. Health and economic implications of HPV vaccination in
the United States. N Engl J Med. 2008 Aug 21;359(8):821-32. http://www.ncbi.nlm.nih.gov/pubmed/18716299
Free Full text at: http://content.nejm.org/cgi/content/full/359/8/821
Editorial: Haug CJ.Human papillomavirus vaccination--reasons for caution.
N Engl J Med. 2008 Aug 21;359(8):861-2. http://www.ncbi.nlm.nih.gov/pubmed/18716305
Free Full text at: http://content.nejm.org/cgi/content/short/359/8/861
Recurrent dysplasia as high as 7% after hysterectomy for cervical dysplasia
OBJECTIVE: Hysterectomy with concomitant cervical intraepithelial
neoplasia (CIN), is often considered a definitive treatment for CIN, but development
of subsequent vaginal intraepithelial neoplasia (VAIN) is known to range from
0.9% to 6.8%.
STUDY DESIGN: In a retrospective analysis of 3030 women with CIN2+ without history
of VAIN in the University Hospital Gasthuisberg, Leuven, Belgium, from January
1989 until December 2003, we identified 125 women who underwent a hysterectomy
within 6 months after diagnosis of CIN2+ and reviewed their postoperative Papanicolaou
smears.
RESULTS: Thirty-one patients (24.8%) were lost to follow-up. Seven of the 94
women in the follow-up group (7.4%) developed VAIN2+, of which 2 were invasive
vaginal cancers. Median interval between hysterectomy and diagnosis of VAIN2+
was 35 months (5-103 months). Women with recurrence were significantly older
(P = .003).
CONCLUSION: Hysterectomy may not be considered as a definitive therapy for CIN2+
because the incidence rate of subsequent VAIN2+ is as high as 7.4%.
Schockaert S, Poppe W, Arbyn M, Verguts T, Verguts J. Incidence of vaginal intraepithelial neoplasia after hysterectomy for cervical intraepithelial neoplasia: a retrospective study. Am J Obstet Gynecol. 2008 Aug;199(2):113.e1-5. Epub 2008 May 23. http://www.ncbi.nlm.nih.gov/pubmed/18456229
Ovulation triggers in anovulatory women undergoing ovulation induction
BACKGROUND:
Anovulation is a common cause for infertility. Drugs used to treat anovulation
include selective estrogen receptor modulators, aromatase inhibitors and gonadotrophins.
Ovulation triggers are used with these drugs, in order to time intercourse. Ovulation
triggers without reliable evidence of oocyte maturity could be inappropriately
timed, increase costs and psychological stress. This review evaluates different
ovulation triggers used when treating anovulatory women with ovulation inducing
agents compared to spontaneous ovulation. OBJECTIVES: To determine the efficacy
of administering an ovulation trigger compared to spontaneous ovulation in anovulatory
women being treated with ovulation inducing agents. SEARCH STRATEGY: We searched
the Menstrual Disorders and Subfertility Group Trials Register (August week 1
2007), Cochrane Central Register of Controlled Trials (CENTRAL Cochrane library
issue 3 2007) and the electronic databases MEDLINE (1950 July week 4 2007), EMBASE(1980
to week 31 2007) and CINAHL (1982 to August week 1 2007) for studies in all languages.
SELECTION CRITERIA: Randomised controlled trials (RCT).
DATA COLLECTION AND ANALYSIS: Two authors independently selected trials, assessed
quality and extracted data. Disagreement was resolved by discussion with the
third author and by contacting trial authors. Categorical data were analysed
using relative risks and their 95% confidence intervals. A random effects model
was used in the presence of significant heterogeneity.
MAIN RESULTS: Two RCTs comparing urinary hCG versus no treatment in anovulatory
women receiving clomiphene citrate were identified. Urinary hCG did not result
in increases in the primary outcome of live birth rate over no treatment { OR
0.98, 95% CI 0.52 to 1.83}.Among the secondary outcomes, urinary hCG did not
increase ovulation rate ( OR 0.95, 95% CI 0.49 to 1.83), clinical pregnancy rate
(OR 1.02, 95% CI 0.56 to 1.88), multiple pregnancy rate (OR 0.47, 95% CI 0.05
to 4.59), miscarriage rate( OR 1.18, 95% CI 0.18 to 7.66) and preterm delivery
(OR 0.12,95% CI 0.00 to 6.29) compared to no treatment. Trials evaluating other
ovulation triggers were not identified.
AUTHORS' CONCLUSIONS: There is inadequate evidence to recommend or refute the
use of urinary hCG, as an ovulation trigger, in anovulatory women being treated
with clomiphene citrate. We did not find trials evaluating the use of ovulation
triggers in anovulatory women, being treated with other ovulation inducing agents.
George K, Nair R, Tharyan P. Ovulation triggers in anovulatory women undergoing ovulation induction. Cochrane Database Syst Rev. 2008 Jul 16;(3):CD006900. http://www.ncbi.nlm.nih.gov/pubmed/18646175
Higher Levels of Physical Activity Needed to Maintain Weight Loss in Overweight Women
BACKGROUND: Debate remains regarding the amount of
physical activity that will facilitate weight loss maintenance.
METHODS: Between December 1, 1999, and January 31, 2003, 201 overweight and obese
women (body mass index [calculated as weight in kilograms divided by height in
meters squared], 27 to 40; age range, 21-45 years) with no contraindications
to weight loss or physical activity were recruited from a hospital-based weight
loss research center. Participants were assigned to 1 of 4 behavioral weight
loss intervention groups. They were randomly assigned to groups based on physical
activity energy expenditure (1000 vs 2000 kcal/wk) and intensity (moderate vs
vigorous). Participants also were told to reduce intake to 1200 to 1500 kcal/d.
A combination of in-person conversations and telephone calls were conducted during
the 24-month study period. RESULTS: Weight loss did not differ among the randomized
groups at 6 months' (8%-10% of initial body weight) or 24 months' (5% of initial
body weight) follow-up. Post-hoc analysis showed that individuals sustaining
a loss of 10% or more of initial body weight at 24 months reported performing
more physical activity (1835 kcal/wk or 275 min/wk) compared with those sustaining
a weight loss of less than 10% of initial body weight (P < .001).
CONCLUSIONS: The addition of 275 mins/wk of physical activity, in combination
with a reduction in energy intake, is important in allowing overweight women
to sustain a weight loss of more than 10%. Interventions to facilitate this level
of physical activity are needed.
Child Health
Association between Maternal Diabetes in Utero and Age of Offspring's Diagnosis with Type 2 Diabetes
OBJECTIVE: To examine age of diabetes
diagnosis in youth, who have a parent with diabetes, by diabetes type and whether
the parent's diabetes was diagnosed before or after the youth's birth.
RESEARCH DESIGN AND METHODS: SEARCH for Diabetes in Youth Study participants
(diabetes diagnosis 2001-2005) with a diabetic parent. SEARCH is a multicenter
survey of youth with diabetes diagnosed before age 20 years.
RESULTS: Youth with type 2 diabetes were more likely to have a parent with either
type 1 or type 2 diabetes (mother 39.3%, father 21.2%) than youth with type 1
diabetes (5.3% and 6.7%, respectively, p<0.001 for each). Type 2 diabetes
was diagnosed 1.68 years earlier among those exposed in utero (n=174) than among
those whose mothers' diabetes was diagnosed later (p=0.018, controlled for maternal
diagnosis age, paternal diabetes, sex and race/ethnicity). Age at diagnosis of
type 1 diabetes for 269 youth with and without in utero exposure did not differ
significantly (difference=0.96 years, p=0.403 after adjustment). Controlled for
the father's age of diagnosis, father's diabetes before the child's birth was
not associated with age at diagnosis (p=0.078 for type 1; p=0.140 for type 2).
CONCLUSIONS: Type 2 diabetes was diagnosed at younger ages among those exposed
to hyperglycemia in utero. Among youth with type 1 diabetes, when controlled
for the mother's age of diagnosis, the effect of the intrauterine exposure was
not significant. This study helps explain why other studies have found higher
age-specific rates of type 2 diabetes among offspring of women with diabetes.
Pettitt DJ, Lawrence JM, Beyer J, Hillier TA, Liese AD, Mayer-Davis B, Loots
B, Imperatore G, Liu L, Dolan LM, Linder B, Dabelea D. Association between Maternal
Diabetes In Utero and Age of Offspring's Diagnosis with Type 2 Diabetes. Diabetes
Care. 2008 Aug 11. [Epub ahead of print]
http://www.ncbi.nlm.nih.gov/pubmed/18694977
No increase in long-term mortality after simple febrile seizures
BACKGROUND:
No studies have had sufficient size to estimate mortality in children with febrile
seizures. We studied mortality after febrile seizures in a large population-based
cohort of children in Denmark with up to 28 years of follow-up.
METHODS: We identified 1 675 643 children born in Denmark between Jan 1, 1977,
and Dec 31, 2004, by linking information from nationwide registers for civil
service, health, and cause of death. Children were followed up from 3 months
of age, until death, emigration, or Aug 31, 2005. We estimated overall and cause-specific
mortality after first febrile seizures with survival analyses. Furthermore, we
undertook a case-control study nested within the cohort and retrieved information
from medical records about febrile seizure and neurological abnormalities for
children who died (N=8172) and individually-matched controls (N=40 860).
FINDINGS: We identified 8172 children who died, including 232 deaths in 55 215
children with a history of febrile seizures. The mortality rate ratio was 80%
higher during the first year (adjusted mortality rate ratio 1.80 [95% CI 1.31-2.40])
and 90% higher during the second year (1.89 [1.27-2.70]) after the first febrile
seizure; thereafter it was close to that noted for the general population. 132
of 100 000 children (95% CI 102-163) died within 2 years of a febrile seizure
compared with 67 (57-76) deaths per 100 000 children without a history of this
disorder. In the nested case-control study, children with simple (</=15 min
and no recurrence within 24 h) febrile seizure had a mortality rate similar to
that of the background population (adjusted mortality rate ratio 1.09 [95% CI
0.72-1.64]), whereas mortality was increased for those with complex (>15 min
or recurrence within 24 h) febrile seizures (1.99 [1.24-3.21]). This finding
was partly explained by pre-existing neurological abnormalities and subsequent
epilepsy.
INTERPRETATION: Long-term mortality is not increased in children with febrile
seizures, but there seems to be a small excess mortality during the 2 years after
complex febrile seizures. Parents should be reassured that death after febrile
seizures is very rare, even in high-risk children.
Vestergaard M, Pedersen MG, Ostergaard JR, Pedersen CB, Olsen J, Christensen J. Death in children with febrile seizures: a population-based cohort study. Lancet. 2008 Aug 9;372(9637):457-63. http://www.ncbi.nlm.nih.gov/pubmed/18692714
Duration of intrapartum prophylaxis and concentration of penicillin G in fetal serum at delivery
OBJECTIVE: Intrapartum penicillin G prophylaxis
aims to prevent early-onset group B streptococci (GBS) sepsis by interrupting
vertical transmission. We examined the relationship between duration of prophylaxis
and fetal serum penicillin G levels among fetuses exposed to fewer than 4 hours
of prophylaxis compared with longer durations.
METHODS: In this prospective cohort study, 98 laboring GBS-positive women carrying
singleton gestations at 37 weeks or greater were administered 5 million units
of intravenous penicillin G followed by 2.5 million units every 4 hours until
delivery. Umbilical cord blood samples were collected at delivery, and penicillin
G levels were measured by high-performance liquid chromatography. Intraassay
and interassay coefficients of variation were less than 3%.
RESULTS: Fetuses exposed to fewer than 4 hours of prophylaxis had higher penicillin
G levels than those exposed to greater than 4 hours (P=.003). In multivariable
linear regression analysis, fetal penicillin G levels were determined by duration
of exposure, time since last dose, dosage, and number of doses, but not maternal
body mass index. Penicillin G levels increased linearly until 1 hour (R(2)=.40)
and then decreased rapidly according to a power-decay model (R(2)=.67). All subgroups
analyzed were above the minimal inhibitory concentration (MIC) for GBS (0.1 micrograms/mL)(P<.002).
Individual samples were 10-179-fold above the MIC. In patients receiving maintenance
dosing, penicillin G did not accumulate in the cord blood and returned to baseline
after each 4-hour interval.
CONCLUSION: Short durations of prophylaxis achieved levels significantly above
the MIC, suggesting a benefit even in precipitous labors. The designation of
infants exposed to fewer than 4 hours of prophylaxis as particularly at risk
for GBS sepsis may be pharmacokinetically inaccurate.
Barber EL, Zhao G, Buhimschi IA, Illuzzi JL. Duration of intrapartum prophylaxis and concentration of penicillin G in fetal serum at delivery. Obstet Gynecol. 2008 Aug;112(2 Pt 1):265-70. http://www.ncbi.nlm.nih.gov/pubmed/18669721
Blood pressure variability and classification of prehypertension and hypertension in adolescence
OBJECTIVE: There is little information in
pediatrics on the persistence of the prehypertension and hypertension classifications
or on the progression of prehypertension to hypertension. This study aimed to
examine those issues.
METHODS: An analysis of data from the National Childhood Blood Pressure database
was conducted to examine the longitudinal blood pressure outcomes for adolescents
classified after a single measurement of blood pressure. Adolescent subjects
(N = 8535) for whom serial single blood pressure measurements were obtained at
intervals of 2 years were identified. Subjects were stratified according to blood
pressure status at the initial measurement, as having normotension, prehypertension,
or hypertension.
RESULTS: Among subjects designated as having prehypertension (n = 1470), 14%
of boys and 12% of girls had hypertension 2 years later. Among subjects designated
as having hypertension, 31% of boys and 26% of girls continued to exhibit hypertension,
and 47% of boys and 26% of girls had blood pressure values in the prehypertensive
range. Regression models showed no significant effect of race on blood pressure
changes but significant effects of initial BMI and changes in BMI.
CONCLUSIONS: These data indicated that the rate of progression of prehypertension
to hypertension was approximately 7% per year. Prehypertension can be predictive
of future hypertension and may benefit from preventive interventions, especially
lifestyle changes.
Falkner B, Gidding SS, Portman R, Rosner B. Blood pressure variability and classification of prehypertension and hypertension in adolescence. Pediatrics. 2008 Aug;122(2):238-42. http://www.ncbi.nlm.nih.gov/pubmed/18676538
Care of the adolescent sexual assault victim
Sexual assault is a broad-based term that encompasses a wide range of sexual victimizations including rape. Since the American Academy of Pediatrics published its last policy statement on sexual assault in 2001, additional information and data have emerged about sexual assault and rape in adolescents and the treatment and management of the adolescent who has been a victim of sexual assault. This report provides new information to update physicians and focuses on assessment and care of sexual assault victims in the adolescent population.
Kaufman M; and the Committee on Adolescence. Care of the adolescent sexual assault victim. Pediatrics. 2008 Aug;122(2):462-70. http://www.ncbi.nlm.nih.gov/pubmed/18676568
Full text at: http://pediatrics.aappublications.org/cgi/reprint/122/2/462
Chronic Disease and Illness
Naltrexone alone and with sertraline for the treatment of alcohol dependence in Alaska natives and non-natives residing in rural settings: a randomized controlled trial
BACKGROUND: Access to specialty alcoholism treatment in rural environments is limited and new treatment approaches are needed. The objective was to evaluate the efficacy of naltrexone alone and in combination with sertraline among Alaska Natives and other Alaskans living in rural settings. An exploratory aim examined whether the Asn40Asp polymorphism of the mu-opioid receptor gene (OPRM1) predicted response to naltrexone, as had been reported in Caucasians. METHODS: Randomized, controlled trial enrolling 101 Alaskans with alcohol dependence, including 68 American Indians/Alaska Natives. Participants received 16 weeks of either (1) placebo (placebo naltrexone + placebo sertraline), (2) naltrexone monotherapy (50 mg naltrexone + sertraline placebo) and (3) naltrexone + sertraline (100 mg) plus nine sessions of medical management and supportive advice. Primary outcomes included Time to First Heavy Drinking Day and Total Abstinence. RESULTS: Naltrexone monotherapy demonstrated significantly higher total abstinence (35%) compared with placebo (12%, p = 0027) and longer, but not statistically different, Time to First Heavy Drinking Day (p = 0.093). On secondary measures, naltrexone compared with placebo demonstrated significant improvements in percent days abstinent (p = 0.024) and drinking-related consequences (p = 0.02). Combined sertraline and naltrexone did not differ from naltrexone alone. The pattern of findings was generally similar for the American Indian/Alaska Native subsample. Naltrexone treatment response was significant within the group of 75 individuals who were homozygous for OPRM1 Asn40 allele. There was a small number of Asp40 carriers, precluding statistical testing of the effect of this allele on response. CONCLUSIONS: Naltrexone can be used effectively to treat alcoholism in remote and rural communities, with evidence of benefit for American Indians and Alaska Natives. New models of care incorporating pharmacotherapy could reduce important health disparities related to alcoholism.
O'Malley SS, Robin RW, Levenson AL, GreyWolf I, Chance LE, Hodgkinson CA, Romano D, Robinson J, Meandzija B, Stillner V, Wu R, Goldman D. Naltrexone alone and with sertraline for the treatment of alcohol dependence in Alaska natives and non-natives residing in rural settings: a randomized controlled trial. Alcohol Clin Exp Res. 2008 Jul;32(7):1271-83. http://www.ncbi.nlm.nih.gov/pubmed/18482155
Naltrexone for the Management of Alcohol Dependence
The New England Journal of Medicine has published a case-based article in their Clinical Therapeutics series that covers the use of naltrexone well. The article begins:
A 44-year-old businessman with a history of hypertension presents for evaluation
with a report of being under stress at work and home, which has led to "unsatisfactory" sleep.
Although there is some despondency, screening for depression is negative. His .
. .
Anton RF. Naltrexone for the management of alcohol dependence. N Engl J Med.
2008 Aug 14;359(7):715-21. http://www.ncbi.nlm.nih.gov/pubmed/18703474
FDA MedWatch-Vivitrol (naltrexone) - Serious Injection Site Reactions May Occur
FDA informed healthcare professionals of the risk of adverse injection site reactions in patients receiving naltrexone. Naltrexone is indicated for the treatment of alcohol dependence in patients who are able to abstain from alcohol in an outpatient setting prior to initiation of treatment. Naltrexone is administered as an intramuscular gluteal injection and should not be administered intravenously, subcutaneously, or inadvertently into fatty tissue. Physicians should instruct patients to monitor the injection site and contact them if they develop pain, swelling, tenderness, induration, bruising, pruritus, or redness at the injection site that does not improve or worsens within two weeks. Physicians should promptly refer patients with worsening injection site reactions to a surgeon.
Read the entire MedWatch Safety Summary, including a link to the FDA Drug Information Page regarding this issue at: http://www.fda.gov/medwatch/safety/2008/safety08.htm#naltrexone
Comprehensive treatment of extensively drug-resistant tuberculosis
BACKGROUND:
Extensively drug-resistant tuberculosis has been reported in 45 countries, including
countries with limited resources and a high burden of tuberculosis. We describe
the management of extensively drug-resistant tuberculosis and treatment outcomes
among patients who were referred for individualized outpatient therapy in Peru.
METHODS: A total of 810 patients were referred for free individualized therapy,
including drug treatment, resective surgery, adverse-event management, and nutritional
and psychosocial support. We tested isolates from 651 patients for extensively
drug-resistant tuberculosis and developed regimens that included five or more
drugs to which the infecting isolate was not resistant.
RESULTS: Of the 651 patients tested, 48 (7.4%) had extensively drug-resistant
tuberculosis; the remaining 603 patients had multidrug-resistant tuberculosis.
The patients with extensively drug-resistant tuberculosis had undergone more
treatment than the other patients (mean [+/-SD] number of regimens, 4.2+/-1.9
vs. 3.2+/-1.6; P<0.001) and had isolates that were resistant to more drugs
(number of drugs, 8.4+/-1.1 vs. 5.3+/-1.5; P<0.001). None of the patients
with extensively drug-resistant tuberculosis were coinfected with the human immunodeficiency
virus (HIV). Patients with extensively drug-resistant tuberculosis received daily,
supervised therapy with an average of 5.3+/-1.3 drugs, including cycloserine,
an injectable drug, and a fluoroquinolone. Twenty-nine of these patients (60.4%)
completed treatment or were cured, as compared with 400 patients (66.3%) with
multidrug-resistant tuberculosis (P=0.36).
CONCLUSIONS: Extensively drug-resistant tuberculosis can be cured in HIV-negative
patients through outpatient treatment, even in those who have received multiple
prior courses of therapy for tuberculosis.
Mitnick CD, et al. Comprehensive treatment of extensively drug-resistant tuberculosis.
N Engl J Med. 2008 Aug 7;359(6):563-74.
PubMed Citation: http://www.ncbi.nlm.nih.gov/pubmed/18687637
Free Full Text at NEJM: http://content.nejm.org/cgi/content/full/359/6/563
Editorial:
Raviglione MC. Facing extensively drug-resistant tuberculosis--a hope and a challenge. N
Engl J Med. 2008 Aug 7;359(6):636-8.
PubMed Citation: http://www.ncbi.nlm.nih.gov/pubmed/18687645
Free Full Text at NEJM: http://content.nejm.org/cgi/content/full/359/6/636
Weight loss with a low-carbohydrate, Mediterranean, or low-fat diet
BACKGROUND:
Trials comparing the effectiveness and safety of weight-loss diets are frequently
limited by short follow-up times and high dropout rates.
METHODS: In this 2-year trial, we randomly assigned 322 moderately obese subjects
(mean age, 52 years; mean body-mass index [the weight in kilograms divided by
the square of the height in meters], 31; male sex, 86%) to one of three diets:
low-fat, restricted-calorie; Mediterranean, restricted-calorie; or low-carbohydrate,
non-restricted-calorie.
RESULTS: The rate of adherence to a study diet was 95.4% at 1 year and 84.6%
at 2 years. The Mediterranean-diet group consumed the largest amounts of dietary
fiber and had the highest ratio of monounsaturated to saturated fat (P<0.05
for all comparisons among treatment groups). The low-carbohydrate group consumed
the smallest amount of carbohydrates and the largest amounts of fat, protein,
and cholesterol and had the highest percentage of participants with detectable
urinary ketones (P<0.05 for all comparisons among treatment groups). The mean
weight loss was 2.9 kg for the low-fat group, 4.4 kg for the Mediterranean-diet
group, and 4.7 kg for the low-carbohydrate group (P<0.001 for the interaction
between diet group and time); among the 272 participants who completed the intervention,
the mean weight losses were 3.3 kg, 4.6 kg, and 5.5 kg, respectively. The relative
reduction in the ratio of total cholesterol to high-density lipoprotein cholesterol
was 20% in the low-carbohydrate group and 12% in the low-fat group (P=0.01).
Among the 36 subjects with diabetes, changes in fasting plasma glucose and insulin
levels were more favorable among those assigned to the Mediterranean diet than
among those assigned to the low-fat diet (P<0.001 for the interaction among
diabetes and Mediterranean diet and time with respect to fasting glucose levels).
CONCLUSIONS: Mediterranean and low-carbohydrate diets may be effective alternatives
to low-fat diets. The more favorable effects on lipids (with the low-carbohydrate
diet) and on glycemic control (with the Mediterranean diet) suggest that personal
preferences and metabolic considerations might inform individualized tailoring
of dietary interventions.
Shai I, Schwarzfuchs D, Henkin Y, et al., Weight loss with a low-carbohydrate,
Mediterranean, or low-fat diet. N Engl J Med. 2008 Jul 17;359(3):229-41.
PubMed citation: http://www.ncbi.nlm.nih.gov/pubmed/18635428
Free Full Text at NEJM: http://content.nejm.org/cgi/content/full/359/3/229
Screening for type 2 diabetes mellitus in adults with hypertension: U.S. Preventive
Services Task Force recommendation statement
DESCRIPTION: Updated U.S. Preventive Services Task Force (USPSTF) recommendation
about screening for type 2 diabetes mellitus in adults.
METHODS: To estimate the balance of benefits and harms of screening, the USPSTF
updated its 2003 evidence review, adding evidence from new trials as well as
updates on earlier studies. The review for this current recommendation focused
on evidence that early treatment prevented long-term adverse outcomes of diabetes,
including cardiovascular events, visual impairment, renal failure, and amputation.
RECOMMENDATIONS: Screen for type 2 diabetes in asymptomatic adults with sustained
blood pressure (either treated or untreated) greater than 135/80 mm Hg. (B recommendation)
Current evidence is insufficient to assess the balance of benefits and harms
of routine screening in asymptomatic adults with blood pressure of 135/80 mm
Hg or lower. (I statement).
U.S. Preventive Services Task Force. Screening for type 2 diabetes mellitus in adults: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med. 2008 Jun 3;148(11):846-54. http://www.ncbi.nlm.nih.gov/pubmed/18519930
Effect of PCI on Quality of Life in Patients with Stable Coronary Disease
BACKGROUND: It has not been clearly established whether percutaneous
coronary intervention (PCI) can provide an incremental benefit in quality of
life over that provided by optimal medical therapy among patients with chronic
coronary artery disease.
METHODS: We randomly assigned 2287 patients with stable coronary disease to PCI
plus optimal medical therapy or to optimal medical therapy alone. We assessed
angina-specific health status (with the use of the Seattle Angina Questionnaire)
and overall physical and mental function (with the use of the RAND 36-item health
survey [RAND-36]).
RESULTS: At baseline, 22% of the patients were free of angina. At 3 months, 53%
of the patients in the PCI group and 42% in the medical-therapy group were angina-free
(P<0.001). Baseline mean (+/-SD) Seattle Angina Questionnaire scores (which
range from 0 to 100, with higher scores indicating better health status) were
66+/-25 for physical limitations, 54+/-32 for angina stability, 69+/-26 for angina
frequency, 87+/-16 for treatment satisfaction, and 51+/-25 for quality of life.
By 3 months, these scores had increased in the PCI group, as compared with the
medical-therapy group, to 76+/-24 versus 72+/-23 for physical limitation (P=0.004),
77+/-28 versus 73+/-27 for angina stability (P=0.002), 85+/-22 versus 80+/-23
for angina frequency (P<0.001), 92+/-12 versus 90+/-14 for treatment satisfaction
(P<0.001), and 73+/-22 versus 68+/-23 for quality of life (P<0.001). In
general, patients had an incremental benefit from PCI for 6 to 24 months; patients
with more severe angina had a greater benefit from PCI. Similar incremental benefits
from PCI were seen in some but not all RAND-36 domains. By 36 months, there was
no significant difference in health status between the treatment groups.
CONCLUSIONS: Among patients with stable angina, both those treated with PCI and
those treated with optimal medical therapy alone had marked improvements in health
status during follow-up. The PCI group had small, but significant, incremental
benefits that disappeared by 36 months.
From Your Colleagues ‹ Previous | Next › Features
OB/GYN
Jean Howe, MD, MPH is the Obstetrics and Gynecology Chief Clinical Consultant (OB/GYN C.C.C.). Dr. Howe is very interested in establishing a dialogue and/or networking with anyone involved in women's health or maternal child health, especially as it applies to American Indian and Alaska Native women and also indigenous peoples around the world. Please don't hesitate to contact her by e-mail (jean.howe@ihs.gov) or phone at (928) 674-7422.
