INTRODUCTION:Buprenorphine (BUP) is increasingly recognized and utilized as a valuable medication for the treatment of opioid use disorder. This article focuses on the problem of regulatory restrictions on access to buprenorphine products without naloxone (mono-product), involving patients in one geographic area, but which may represent a more general access problem in the United States.DESIGN:In response to an audit by the Tennessee Board of Pharmacy, a pharmacy in northeast Tennessee designed a questionnaire to survey patient motivation for traveling long distances to fill their prescriptions for BUP, rather than buprenorphine/naloxone (BNx, combo-product), and to document their satisfaction with treatment with the mono-product.RESULTS:Questionnaires were submitted by 194 patients, living in northeast Tennessee, southwest Virginia, and southeast Kentucky. Significant, intolerable, side effects were reported by all patients in the survey prescribed BNx, but because of legislative and regulatory restrictions in their respective states, they were unable to obtain BUP closer to home. Consequently, they were required to drive significant distances from their homes to fill their prescriptions, a median distance of 52 miles, and in some cases as far as 216 miles round trip. Intolerable reactions included severe headaches, nausea and vomiting, allergies, and severe dysphoria. All patients tolerated BUP and were clinically well maintained on the mono-product.CONCLUSION:Severe, intolerable reactions/side effects from the naloxone component of BNx are not uncommon, but legislative and regulatory restrictions on the mono-product prohibit providers and pharmacies in some states from prescribing and dispensing BUP. The participants in this qualitative study found it necessary to travel significant distances to obtain their prescribed medication, thereby potentially limiting access to this life-saving therapy.

Warner, Shirley A. DNP, FNP-C, WHNP-BC; Strickland, Daniel M. MD, FACOG Author Information

PROBLEM Drug addiction and misuse is a medical and societal problem that has exacted a heavy toll on the United States, and, indeed, the world. In the United States, opioids are currently the main driver of drug overdose deaths. Despite the proven safety and efficacy of medically assisted therapy (MAT) using buprenorphine for the treatment of opioid use disorder (OUD), as well as the fact that its use is regulated by US Federal Law, many states have enacted separate and often burdensome regulations that restrict the prescribing of buprenorphine beyond those required by the US Drug Enforcement Agency (DEA) under the provisions of the DATA 2000 Act, and unnecessarily reduce the availability of effective treatment of OUD in those states. PURPOSE The purpose of this article is to review the pharmacology of both buprenorphine (and naloxone as an additive) and the risks associated with the misuse of buprenorphine products and to consider if such additional state oversight and restrictions improves or is deleterious to public safety in the face of this national epidemic. CONCLUSION We conclude that the placing of unnecessary and unscientific restraints on the treatment of patients with OUD is inconsistent with the principles of harm reduction, and such restraints should be removed unless/until they can be supported by real evidence.

Background: The practice of anesthesia requires knowledge of procedures, patient conditions, comorbidities, and medications, as well as the ability to continually assess and respond to the patient’s status. The use of mobile anesthesia applications (apps) has become increasingly common among Certified Registered Nurse Anesthetists (CRNAs) to provide immediate access to current information regarding anesthesia administration and to support optimal patient care.The purpose of this study was to assess the use of mobile anesthesia apps used by CRNAs as point-of-care (POC) tools in their anesthesia practice.Methodology: We report data collected from a survey designed to sample CRNAs who have been in practice for three years or less (“recent” graduates) and who utilize mobile anesthesia apps. The survey was offered to members of a Facebook group called CRNAs and SRNAs.Results: A total of 160 CRNAs in practice three years or less completed the survey and reported the ways they currently use a mobile anesthesia app. In this report we quantify the various ways such apps are used and conclude that mobile apps are widely used among student and/or recent graduate CRNAs as point-of-care tools and who believe they improve the safety and efficacy of their anesthesia practice.Conclusions: The benefits to practice that users report should be encouraging to the developers of mobile health care apps and a motivating factor for more practitioners to utilize them.

Background and Objectives: The combination of buprenorphine and naloxone (combo product) is a medication that is administered sublingually to treat opioid use disorder as part of medication assisted treatment. The naloxone component is believed to deter inappropriate use of the medication. True allergies to naloxone are infrequent, but many patients experience severe, unpleasant side effects that they associate with the combo product but not with the formulation containing buprenorphine alone (mono product). It is commonly contended that naloxone is poorly absorbed sublingually, so we sought to test the validity of that belief. Methods: Using a sensitive LC-MS assay, we quantified the concentration of naloxone in the urine of 61 patients (Total specimens=686) prescribed the combo product. Because this study was retrospective it was neither intended nor possible to compare adverse side effects between patients prescribed mono versus combo products. Results: We found that 92.7% of the patients prescribed the combo product had significant quantifiable concentrations of naloxone in their urine drug screens. Conclusions and Scientific Significance: Contrary to popular belief, naloxone is absorbed sublingually. Such absorption may account for some of the unpleasant side effects experienced by patients treated with the combo products, but it was not possible to compare or quantify side effects in this retrospective study. We feel it is important that clinicians be aware of the possibility of significant sublingual absorption of naloxone when choosing therapeutic modalities for their patients.

The growth of breast cancer may be mediated by endogenous or exogenous sex steroid hormones, particularly estrogen. However, neither contraceptive nor noncontraceptive estrogen use has been associated definitively with an increased risk of developing breast cancer. In this study, we addressed a corollary question: If a postmenopausal woman develops carcinoma of the breast, is her survival affected by previous use of replacement estrogen? Two hundred fifty-six postmenopausal women with breast cancer entered our Tumor Registry between 1972-1981, inclusive. Of these, 174 took no replacement estrogen before the diagnosis (never-users), 21 had used estrogen previously (past users), and 61 were taking estrogen at the time of diagnosis (current users). Survival analysis revealed a median survival of less than 84 months after diagnosis for never- and past users and greater than 143 months for current users, but these differences were not significant when controlled for stage of disease at diagnosis. We conclude that prior postmenopausal estrogen replacement therapy does not compromise survival in women who subsequently develop carcinoma of the breast.

Unrecognized assay drift that may occur during low-volume (fewer than 500 specimens per week) maternal serum alpha-fetoprotein testing could result in either underestimation or overestimation of the number of pregnant women who are at increased risk of fetal malformations and genetic anomalies. Quality control software programs that incorporate the use of a multirule Shewhart chart are designed to detect assay drift. Careful selection of quality control sera for inclusion in analytic assays and appropriate application of a multirule quality control procedure to values that are obtained on these control materials should detect assay drift, regardless of the volume of patients' specimens in the run.

Predictive value: Symptoms of preterm laborTo the Editors: Preterm birth is the greatest single cause of neonatal morbidity and mortality in the United States, I and as such deserves a concerted effort directed toward its prevention.The well-known continuing efforts of Drs.Robert Creasy and Michael Katz to sensitize obstetricians to the problem of preterm labor are commendable.However, their recent article, which describes early signs and symptoms of preterm labor (Katz M, Goodyear K, Creasy RK.Early signs and symptoms of pre-

Using a pregnant goat (Capra hircus) model to study the in vivo effects of hypermagnesemia on serum osteocalcin concentration, magnesium sulfate infusion has been shown to increase circulating levels of osteocalcin. At 2 h after the administration of magnesium sulfate, a 98% increase in Mg2+ concentration over the basal level resulted in: a 38% increase in serum osteocalcin concentration over baseline; a 22% decrease in PTH concentration, and no change in total and ionized calcium concentrations. These in vivo data support previous in vitro results demonstrating that Mg2+ is a potent inhibitor of osteocalcin binding to hydroxyapatite.

Maternal serum alpha-fetoprotein (MSAFP) screening of all pregnant women between 15 and 20 weeks gestational age is generally recognized as a standard of care in current obstetric practice. There are many factors to consider when deciding to establish MSAFP testing as an in-house procedure versus ship-out testing by a reference laboratory at fee-for-service cost. In this report, we review clinical and analytical aspects of MSAFP testing, along with appropriate guidelines for establishing an on-site MSAFP screening program.

Early-onset neonatal group B streptococci infection occurs in two cases per 1000 live births in the United States and is associated with a mortality rate greater than 20%. Nearly 30% of infected infants have concomitant meningitis and half suffer permanent neurologic damage. Group B streptococci also account for at least 20% of postpartum metritis. The annual cost of group B streptococci infection in the United States is conservatively estimated at nearly 2000 neonatal deaths and greater than $500 million, excluding the costs of long-term neurologic handicaps. Intrapartum chemoprophylaxis with ampicillin is effective in curtailing transmission of group B streptococci from mother to infant. Methods have been developed to identify maternal colonization before delivery. We applied principles of decision analysis to evaluate cost-effectiveness of intrapartum screening for maternal group B streptococci colonization with various reported methods in cohorts of low- and high-risk women. In the United States intrapartum screening for group B streptococci is cost-effective and offers the potential to avert a significant number of neonatal deaths and postpartum infections.

Biological fluids from several sources (e.g. blood, fertal urine, amniotic fluid) have been shown to contain factors that modulate prostaglandin (PG) synthesis. In this study, we investigated the possibility that peritoneal fluid contains substances that may regulate PG synthesis. Peritoneal fluids were obtained from women undergoing diagnostic laparoscopy for infertility. Fluids from women without evident pelvic pathology were incubated with prostaglansin synthase prepared from bull seminal vesicles in the presence of excess arachidonic acid, and the production of PGE2, PGF2α, and 6-keto-PGF1α was quantified by specific radioimmunoassay.

Maternal height, maternal weight, infant weight, and maternal weight gain during pregnancy were examined as factors associated with the likelihood of delivery by cesarean section for cephalopelvic disproportion (CPD). Sixty-four women, delivered by cesarean section for CPD, were compared with matched controls who delivered vaginally. The only factor associated with an increased risk of cesarean section for CPD was short stature: women shorter than 63 inches were 4.9 times more likely to have CPD than taller women.

Endometrial biopsy specimens (n = 62) were evaluated by five pathologists to assess the effect of interobserver variation on histologic dating of the endometrium. The potential effect of this variation on the diagnosis of luteal phase defects (LPDs) and resulting clinical management was also determined. Mean (+/- standard error) interobserver variation was 0.96 +/- 0.08 days, comparable to results reported by other investigators. The magnitude of the variation was not affected by whether the biopsy specimen was obtained in the mid or late luteal phase, the degree of lag between the dating and subsequent menses, or the presence of an LPD. Redating of a specimen by another pathologist would have resulted in a change in the determination of "in" or "out" of phase in 22% of cases. The subsequent probability of changing patient management altered ranged from 22% to 39% depending on the clinical setting.

One hundred women between ages 15 and 19 were evaluated for chronic pelvic pain. At laparoscopy, 46 had a normal pelvis, 29 had evidence of pelvic inflammatory disease, 12 had endometriosis, and 13 had other pelvic pathology. Diagnostic laparoscopy may be of significant value in the evaluation of adolescent women with chronic pelvic pain of uncertain etiology that fails conservative medical therapy.

The bleeding time test quantifies the duration of bleeding from a standardized skin wound. The test measures in vivo function of the platelet capacity to respond to injury, vascular function, and the presence of von Willebrand÷s factor. This study compared the range of test results in time, safety of technique to the technician and patient, patient preference in relation to pain, scarring potential, and cost-effectiveness of three bleeding time devices usedto assess platelet function. The three devices evaluated were the Simplate by General Diagnostics (Organon-Teknika), Surgicutt by International Technidyne Corporation, and the Mayo Clinic Automatic Lancet available through V. Mueller Co.

We studied the effects of human amniotic fluid (HAF) on the production of prostaglandin E (PGE) by amnion tissues using a technique of fresh-tissue superfusion. The production of PGE was linear with time for 4.5 h by amnion tissues superfused either with medium alone or with medium plus HAF (30% v/v). Tissues superfused with medium plus HAF produced significantly more PGE than tissues superfused with medium alone. Additionally, amnion tissue obtained at cesarean section, prior to labor, displayed a greater responsiveness to HAF than did amnion obtained after spontaneous labor.