• Saturated Fat and Disease Activity in Pediatric Multiple Sclerosis
• Obstetric Consequences of Super-Super Obesity
• Daily vs. Alternate-Day Oral Iron Therapy
• Drinking Water Before Vaccination does not Prevent Postvaccination Presyncope
• Can Medical Marijuana Help Children?
• Do Transfusions from Female Donors Increase Mortality in Male Recipients?
• NOTES Cholecystectomy: A Potentially Less Painful Alternative to
Laparoscopic Cholecystectomy
• Relative Potency of Proton-Pump Inhibitors
J Neurol Neurosurg Psychiatry 2017 Oct 9 2011 Aug 8/22; 171:1363
Saturated Fat and Disease Activity in Pediatric Multiple Sclerosis
Does eating too many cheeseburgers result in MS exacerbations?
Although obesity may be a risk factor for pediatric multiple sclerosis (MS; NEJM JW Neurol Mar 2013 and Neurology 2013 Feb 5; 80:548), the impact of diet for those with established pediatric MS has been unknown. Investigators conducted a multicenter study of 219 patients who were prospectively diagnosed with MS with disease onset before age 18 and disease duration <4 years. Patients or their caregivers completed a food frequency questionnaire at enrollment.
For each 10% increase in intake of total fat, risk for relapse increased 1.6-fold. The risk for disease activity due to fat seemed to be largely due to saturated fats. Neither total caloric intake nor sugar intake was associated with relapses. Higher vegetable intake was associated with lower relapse rates.
COMMENT: Children with MS should be encouraged to eat their vegetables and to use moderation in eating meat and dairy, particularly foods high in saturated fat (e.g., burgers, sausages, chicken skin, cheese, cream, and butter). Keeping a healthy weight by staying fit and active are also advised. More studies are required in MS patients for confirmation of this potential connection between saturated fat and worse disease. Future studies should include both adults and teenagers and evaluate other endpoints, such as disability progression and imaging evidence of disease activity. Immunologists have already identified a connection between saturated fats and a proinflammatory immune response. Several other autoimmune diseases have been linked to saturated fat consumption. More studies on nutrition and MS would be welcome — first to identify other risk factors, and then to test randomized interventions.
CITATION(S): Azary S et al. Contribution of dietary intake to relapse rate in early paediatric multiple sclerosis. J Neurol Neurosurg Psychiatry 2017 Oct 9; [e-pub].
(http://dx.doi.org/10.1136/jnnp-2017-315936)
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Obstet Gynecol 2017 Nov; 130:988
Obstetric Consequences of Super-Super Obesity
BMI ≥60 kg/m2 is an important predictor of adverse maternal and neonatal outcomes.
As the obesity epidemic escalates, its consequences in reproductive-aged women assume increasing importance. To assess the effects of extreme obesity on pregnancy outcomes, investigators at two Minnesota hospitals performed a retrospective study of women with body-mass index (BMI) ≥60 kg/m2at delivery compared with those having BMI of 30 to 39, 40 to 49, or 50 to 59.
Rates of maternal complications and neonatal morbidities were substantially higher in women with BMI ≥60 than in any of those with BMIs between 30 and 59 (see table). Composite neonatal morbidity was significantly more likely among newborns whose mothers had BMI ≥60 compared with those in the reference cohort (BMI 30–39; adjusted odds ratio, 4.5).
COMMENT: This report points to the importance of optimizing maternal BMI prior to conception. Many interventions can help with preconception weight loss, including dietary modification, exercise, and bariatric surgery. These findings should help clinicians provide counseling about maternal and neonatal outcomes associated with increased BMI with women who are pregnant or planning to be.
CITATION(S): Kim T et al. Neonatal morbidity and maternal complication rates in women with a delivery body mass index of 60 kg/m2 or higher. Obstet Gynecol 2017 Nov; 130:988.
(http://dx.doi.org/10.1097/AOG.0000000000002316)
Lancet Haematol 2017 Oct 9
Daily vs. Alternate-Day Oral Iron Therapy
A small study suggests some advantages for alternate-day dosing.
Oral iron therapy is plagued by relatively poor absorption and gastrointestinal side effects. In a previous 2-day study, researchers demonstrated that fractional iron absorption is suppressed by high doses of oral iron (compared with lower doses) and by twice-daily dosing (compared with once-daily dosing; NEJM JW Gen Med Dec 1 2015 and Blood 2015; 126:1981). Now, the researchers have extended their previous observations.
They recruited healthy young Swiss women with low or low-normal iron stores (serum ferritin levels, ≤25 μg/L) and normal or only mildly low hemoglobin levels. In one experiment, 40 participants were randomized to receive 60 mg of iron (as ferrous sulfate) either every morning for 14 days or on alternate mornings for 28 days. At the end of these dosing periods, both fractional absorption and cumulative total absorption of iron were significantly greater in the alternate-day group than in the daily group.
In a second experiment, 20 women received either 120 mg of iron once daily or 60 mg twice daily for 3 days; after a 2-week washout period, each participant crossed over to the other regimen. The two regimens did not differ in fractional or total iron absorption, but with both regimens, absorption was higher on the first day than on the second and third days.
COMMENT: Alternate-day oral iron dosing is associated with better fractional absorption of iron than is daily dosing; the presumed mechanism is that iron intake raises levels of hepcidin (which blocks the absorption of iron given the following day). This study was too small and too short to allow reliable assessment of side effects, but gastrointestinal tolerability likely would be enhanced with alternate-day dosing. The next step will be to compare daily and alternate-day regimens in patients with substantial iron deficiency anemia.
CITATION(S): Stoffel NU et al. Iron absorption from oral iron supplements given on consecutive versus alternate days and as single morning doses versus twice-daily split dosing in iron-depleted women: Two open-label, randomised controlled trials. Lancet Haematol 2017 Oct 9; [e-pub].
(http://dx.doi.org/10.1016/S2352-3026(17)30182-5)
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Pediatrics 2017 Oct 23
Drinking Water Before Vaccination Does Not Prevent Postvaccination Presyncope
Even drinking 500 mL of water before vaccination did not reduce risk for presyncope in adolescents.
Presyncope (and more serious but less common, syncope) can occur postvaccination. Drinking water before blood donation has been shown to ameliorate these negative reactions in adolescents. To determine if water consumption also reduces postvaccination symptoms, researchers randomized 1800 adolescents (ages 11–21 years) scheduled for one or more intramuscular vaccinations to receive usual care or to consume as much water as they could from a 500-mL bottle. After vaccination, patients were observed for 20 minutes and completed a symptom survey.
Almost two thirds of patients drank 500 mL and three quarters consumed more than 250 mL. No instances of syncope occurred in either group. There were no significant differences in rates of presyncope between intervention and control groups when either a liberal (37% and 35%) or restrictive (9% and 7%) definition of presyncope was used. Rates were also comparable between groups when the analysis was limited to patients who consumed 500 mL and were vaccinated within 10 to 60 minutes. In multivariable analyses, age <15 years, history of presyncope/syncope, receiving more than one vaccine, and higher levels of prevaccination anxiety and postvaccine pain were associated with greater risk for presyncope.
COMMENT: These results are disappointing. It may be that the physiology of postvaccination- and phlebotomy-associated presyncope is sufficiently different that hydration would not work in both situations. Some of my patients present for vaccination not having eaten for 8–10 hours, so I wonder if the results might have differed if a caloric beverage had been used. In the meantime, we can concentrate prevention efforts on ameliorating modifiable risk factors, such as anxiety and pain, and urging patients to wait at least 20 minutes before leaving the office.
CITATION(S): Kemper AR et al. Drinking water to prevent postvaccination presyncope in adolescents: A randomized trial. Pediatrics 2017 Oct 23; [e-pub].
(http://dx.doi.org/10.1542/peds.2017-0508)
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Pediatrics 2017 Oct 23
Can Medical Marijuana Help Children?
A systematic review shows evidence of therapeutic potential of cannabinoids in children and underscores the need for dedicated research in this area.
Some studies suggest that cannabinoids may help treat seizure disorders and chemotherapy-induced nausea and vomiting in children, but the data are very limited.
To better characterize the evidence to date, investigators conducted a systematic review of articles published between 1948 and 2017. Twenty-two studies involving 795 participants met inclusion criteria. Only 5 studies were randomized, controlled trials; the remainder were retrospective chart reviews (5), case reports (5), open-label trials (4), parent surveys (2) and 1 case series. Only 9 studies included more than 20 patients. The most commonly studied indications were seizure disorders (11 studies) and chemotherapy-induced nausea and vomiting (CINV; 6 studies). Results were as follows:
- Nabilone was superior to domperidone, metoclopramide, and prochlorperazine for treatment of CINV (4 randomized trials of sample sizes <30).
- Cannabidiol or oral cannabis products reduced seizure frequency in multiple studies, but only one was a randomized trial (sample size, 61).
- In a palliative care setting, dronabinol reduced spasticity in 12 of 16 children.
Studies were heterogeneous with regard to cannabinoid type and dosage, and few were powered to test treatment efficacy. However, the five randomized, controlled trials all showed benefit from cannabidiol treatment for the primary outcome.
COMMENT: It is ironic and unfortunate that while cannabis is becoming increasingly available to adults for both medical and recreational uses, the drug remains classified as schedule I, limiting its availability for pediatric research purposes. There is some evidence that cannabinoids might benefit children, but unless we advocate for a vigorous pediatric medical marijuana research agenda (helped by a change in its classification), we will continue to wonder whether and how best to use it.
CITATION(S): Wong SS and Wilens TE.Medical cannabinoids in children and adolescents: A systematic review.Pediatrics 2017 Oct 23; [e-pub].
(http://dx.doi.org/10.1542/peds.2017-1818)
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JAMA 2017 Oct 17; 318:1471
Do Transfusions from Female Donors Increase Mortality in Male Recipients?
Deaths were more frequent in male patients who received red cells from an ever-pregnant female donor than from a male donor.
Immunologic reactions due to donor–recipient mismatch occasionally complicate blood transfusions and are usually prevented by meticulous red cell typing and cross-matching. But is it safe for male recipients to receive blood from female donors that might contain cytotoxic antibodies from previous pregnancies?
To answer this question, investigators conducted a retrospective review of 31,118 patients (median age, 65 years; 52% female) in six Dutch hospitals who received a total of 59,320 red cell transfusions. The red cells were from one of three types of donors: men (88%), women with previous pregnancies (6%), and women who had never been pregnant (6%). All units were leukocyte-reduced and ABO-rhD identical.
At a median follow-up of 245 days, 13% of patients had died. Deaths were more frequent in male patients who received a unit of red cells from an ever-pregnant female donor than from a male donor (101 vs. 80 per 1000 patient-years; hazard ratio, 1.13; 95% confidence interval; 1.01–1.26). The highest HRs were observed in male recipients ≤50 years of age. HRs were not increased if transfusions were from a never-pregnant female donor or an ever-pregnant female donor to a female recipient.
COMMENT: This study questions the safety of transfusing male recipients with red cells from previously pregnant female donors. The presumption is that preformed cytotoxic antibodies in the blood product contributed to the death of the recipients, but neither the indications for transfusion nor the causes of death were reported. Therefore, further investigation is needed to confirm the findings and elucidate the pathogenesis.
CITATION(S): Caram-Deelder C et al. Association of blood transfusion from female donors with and without a history of pregnancy with mortality among male and female transfusion recipients. JAMA 2017 Oct 17; 318:1471.
(https://jamanetwork.com/journals/jama/article-abstract/2657377)
Cable RG and Edgren G.Blood transfusions from previously pregnant women and mortality: Interpreting the evidence. JAMA 2017 Oct 17; 318:1445.
(https://jamanetwork.com/journals/jama/article-abstract/2657356)
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Gastrointest Endosc 2017 Oct 6
NOTES Cholecystectomy: A Potentially Less Painful Alternative to
Laparoscopic Cholecystectomy
Postoperative pain scores and analgesic use were significantly lower in women undergoing transvaginal NOTES versus laparoscopic cholecystectomy.
Natural orifice transluminal endoscopic surgery (NOTES) was once a red-hot area of study, offering the promise of incisionless endoscopic surgery as an alternative to standard laparotomy or laparoscopic surgery. While in great part NOTES has not lived up to its potential, some topics have been investigated in detail, such as NOTES cholecystectomy (by the transgastric or transvaginal route).
In a recent single-center study, researchers compared postoperative pain and adverse events between 226 female patients undergoing laparoscopic cholecystectomy (LC) and 90 undergoing NOTES transvaginal cholecystectomy (TVC) for treatment of symptomatic cholelithiasis. Patients selected the procedure of their choice, and all procedures were performed by one surgeon.
Postoperative pain scores on a visual analog scale strongly favored TVC. Overall consumption of nonsteroidal anti-inflammatory drugs was significantly lower in the TVC group compared with the LC group. Notably, one quarter of the patients in the TVC group did not require any postoperative analgesics at all. Strikingly, no intraoperative adverse events occurred during any LCs, but three patients experienced adverse events during TVC (bleeding in two patients, gallbladder rupture in one). No postoperative adverse events occurred in either group.
COMMENT: This study can be seen, to some extent, as a validation of the NOTES model for “incisionless” surgery. The lower levels of postoperative pain among the NOTES patients is perhaps the most notable feature of this study. Though these results are encouraging, NOTES cholecystectomies are still experimental procedures at this time and further research is needed before their widespread adoption becomes a reality.
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
CITATION(S): Benhidjeb T et al. Laparoscopic cholecystectomy versus transvaginal natural orifice transluminal endoscopic surgery cholecystectomy: Results of a prospective-comparative single-center study.Gastrointest Endosc 2017 Oct 6; [e-pub].
(http://dx.doi.org/10.1016/j.gie.2017.09.039)
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Clin Gastroenterol Hepatol 2017 Sep 27
Relative Potency of Proton-Pump Inhibitors
Very high PPI doses and three times daily administration do not increase the duration of gastric acid suppression.
Various proton-pump inhibitors (PPIs) are used in different doses to achieve similar clinical results. To suggest ideal dosing regimens of different PPIs, investigators performed a meta-analysis of 56 randomized trials that compared PPI doses to changes in gastric pH.
The analysis included a total of 3713 patients in 146 study groups who took PPIs once daily (116 groups), twice daily (25 groups), or three times daily (5 groups). Median daily time with a gastric pH ≤4 (pH4 time) was compared among the groups after 5 days of oral PPI administration. Data were reviewed based on previously determined omeprazole equivalents (OEs; Eur J Clin Pharmacol 2009; 65:19), ranging from 4.5 mg of pantoprazole to 36 mg of rabeprazole being equivalent to 20 mg of omeprazole.
Increasing once daily doses of PPIs from 9 mg OE to 60 mg OE increased the pH4 time linearly from 10 hours to 18.5 hours, with no advantage for doses higher than 60 mg OE. Twice or three times daily PPI dosing increased median pH4 time linearly from 15.8 to 21 hours. There was no advantage of three times a day dosing versus twice daily. The authors noted that generic forms of PPIs were the most cost-effective. They conclude that the use of OEs and these data allow clinicians to tailor PPI choice and dosing to provide the lowest effective dose.
COMMENT: Gastric acid secretion has long been used as a surrogate marker for efficacy of PPIs. We must remember that changes in gastric pH do not always correlate with clinical results. These results show that very high OEs (over 60 mg) do not provide better acid suppression and that three times daily dosing has no benefit over twice daily dosing.
Note to readers: At the time we reviewed this paper, its publisher noted that it was not in final form and that subsequent changes might be made.
CITATION(S): Graham DY and Tansel A.Interchageable use of proton pump inhibitors based on relative potency. Clin Gastroenterol Hepatol 2017 Sep 27; [e-pub].
(http://dx.doi.org/10.1016/j.cgh.2017.09.033)
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