Integrating Alcohol-Related Prevention and Treatment Into Primary Care: A Cluster Randomized Implementation Trial.

Importance: Unhealthy alcohol use is common and affects morbidity and mortality but is often neglected in medical settings, despite guidelines for both prevention and treatment. Objective: To test an implementation intervention to increase (1) population-based alcohol-related prevention with brief interventions and (2) treatment of alcohol use disorder (AUD) in primary care implemented with a broader program of behavioral health integration. Design, Setting, and Participants: The Sustained Patient-Centered Alcohol-Related Care (SPARC) trial was a stepped-wedge cluster randomized implementation trial, including 22 primary care practices in an integrated health system in Washington state. Participants consisted of all adult patients (aged ≥18 years) with primary care visits from January 2015 to July 2018. Data were analyzed from August 2018 to March 2021. Interventions: The implementation intervention included 3 strategies: practice facilitation; electronic health record decision support; and performance feedback. Practices were randomly assigned launch dates, which placed them in 1 of 7 waves and defined the start of the practice's intervention period. Main Outcomes and Measures: Coprimary outcomes for prevention and AUD treatment were (1) the proportion of patients who had unhealthy alcohol use and brief intervention documented in the electronic health record (brief intervention) for prevention and (2) the proportion of patients who had newly diagnosed AUD and engaged in AUD treatment (AUD treatment engagement). Analyses compared monthly rates of primary and intermediate outcomes (eg, screening, diagnosis, treatment initiation) among all patients who visited primary care during usual care and intervention periods using mixed-effects regression. Results: A total of 333 596 patients visited primary care (mean [SD] age, 48 [18] years; 193 583 [58%] female; 234 764 [70%] White individuals). The proportion with brief intervention was higher during SPARC intervention than usual care periods (57 vs 11 per 10 000 patients per month; P < .001). The proportion with AUD treatment engagement did not differ during intervention and usual care (1.4 vs 1.8 per 10 000 patients; P = .30). The intervention increased intermediate outcomes: screening (83.2% vs 20.8%; P < .001), new AUD diagnosis (33.8 vs 28.8 per 10 000; P = .003), and treatment initiation (7.8 vs 6.2 per 10 000; P = .04). Conclusions and Relevance: In this stepped-wedge cluster randomized implementation trial, the SPARC intervention resulted in modest increases in prevention (brief intervention) but not AUD treatment engagement in primary care, despite important increases in screening, new diagnoses, and treatment initiation. Trial Registration: ClinicalTrials.gov Identifier: NCT02675777.

Preclinical characterization of AB-506, an inhibitor of HBV replication targeting the viral core protein.

AB-506, a small-molecule inhibitor targeting the HBV core protein, inhibits viral replication in vitro (HepAD38 cells: EC50 of 0.077 µM, CC50 > 25 µM) and in vivo (HBV mouse model: ∼3.0 log10 reductions in serum HBV DNA compared to the vehicle control). Binding of AB-506 to HBV core protein accelerates capsid assembly and inhibits HBV pgRNA encapsidation. Furthermore, AB-506 blocks cccDNA establishment in HBV-infected HepG2-hNTCP-C4 cells and primary human hepatocytes, leading to inhibition of viral RNA, HBsAg, and HBeAg production (EC50 from 0.64 µM to 1.92 µM). AB-506 demonstrated activity across HBV genotypes A-H and maintains antiviral activity against nucleos(t)ide analog-resistant variants in vitro. Evaluation of AB-506 against a panel of core variants showed that T33N/Q substitutions results in >200-fold increase in EC50 values, while L30F, L37Q, and I105T substitutions showed an 8 to 20-fold increase in EC50 values in comparison to the wild-type. In vitro combinations of AB-506 with NAs or an RNAi agent were additive to moderately synergistic. AB-506 exhibits good oral bioavailability, systemic exposure, and higher liver to plasma ratios in rodents, a pharmacokinetic profile supporting clinical development for chronic hepatitis B.

The Role of Vitamin B6 in Women's Health.

Vitamin B6, a cofactor in many biochemical reactions in the cells of living organisms, is an essential coenzyme for various catabolic and anabolic processes. Although vitamin B6 deficiency in young healthy women with a balanced diet is thought to be unusual, it can be seen with certain medications, health conditions, and dietary deficits, as well as aging. Vitamin B6 deficiency is associated with a variety of ill health effects, and correction of deficiency is considered beneficial. Women particularly are affected by unique health issues that are part of the array of disorders potentially alleviated through vitamin B6 supplementation.

Costs of using evidence-based implementation strategies for behavioral health integration in a large primary care system.

OBJECTIVE: To describe the cost of using evidence-based implementation strategies for sustained behavioral health integration (BHI) involving population-based screening, assessment, and identification at 25 primary care sites of Kaiser Permanente Washington (2015-2018). DATA SOURCES/STUDY SETTING: Project records, surveys, Bureau of Labor Statistics compensation data. STUDY DESIGN: Labor and nonlabor costs incurred by three implementation strategies: practice coaching, electronic health records clinical decision support, and performance feedback. DATA COLLECTION/EXTRACTION METHODS: Personnel time spent on these strategies was estimated for five broad roles: (a) project leaders and administrative support, (b) practice coaches, (c) clinical decision support programmers, (d) performance metric programmers, and (e) primary care local implementation team members. PRINCIPAL FINDING: Implementation involved 286 persons, 18 131 person-hours, costing $1 587 139 or $5 per primary care visit with screening or $38 per primary care visit identifying depression, suicidal thoughts and/or alcohol or substance use disorders, in a single year. The majority of person-hours was devoted to project leadership (35%) and practice coaches (34%), and 36% of costs were for the first three sites. CONCLUSIONS: When spread across patients screened in a single year, BHI implementation costs were well within the range for commonly used diagnostic assessments in primary care (eg, laboratory tests). This suggests that implementation costs alone should not be a substantial barrier to population-based BHI.

Interactions between genetics and environment shape Camelina seed oil composition.

BACKGROUND: Camelina sativa (gold-of-pleasure) is a traditional European oilseed crop and emerging biofuel source with high levels of desirable fatty acids. A twentieth century germplasm bottleneck depleted genetic diversity in the crop, leading to recent interest in using wild relatives for crop improvement. However, little is known about seed oil content and genetic diversity in wild Camelina species. RESULTS: We used gas chromatography, environmental niche assessment, and genotyping-by-sequencing to assess seed fatty acid composition, environmental distributions, and population structure in C. sativa and four congeners, with a primary focus on the crop's wild progenitor, C. microcarpa. Fatty acid composition differed significantly between Camelina species, which occur in largely non-overlapping environments. The crop progenitor comprises three genetic subpopulations with discrete fatty acid compositions. Environment, subpopulation, and population-by-environment interactions were all important predictors for seed oil in these wild populations. A complementary growth chamber experiment using C. sativa confirmed that growing conditions can dramatically affect both oil quantity and fatty acid composition in Camelina. CONCLUSIONS: Genetics, environmental conditions, and genotype-by-environment interactions all contribute to fatty acid variation in Camelina species. These insights suggest careful breeding may overcome the unfavorable FA compositions in oilseed crops that are predicted with warming climates.

Routine Assessment of Symptoms of Substance Use Disorders in Primary Care: Prevalence and Severity of Reported Symptoms.

BACKGROUND: Most patients with substance use disorders (SUDs) never receive treatment and SUDs are under-recognized in primary care (PC) where patients can be treated or linked to treatment. Asking PC patients to directly report SUD symptoms on questionnaires might help identify SUDs but to our knowledge, this approach is previously untested. OBJECTIVE: To describe the prevalence and severity of DSM-5 SUD symptoms reported by PC patients as part of routine care. DESIGN: Cross-sectional study using secondary data. PARTICIPANTS: A total of 241,265 adult patients who visited one of 25 PC sites in an integrated health system in Washington state and had alcohol, cannabis, or other drug use screening documented in their EHRs (March 2015-July 2018) were included in main analyses if they had a positive screen for high-risk substance use defined as AUDIT-C score 7-12 points, or report of past-year daily cannabis use or any other drug use. MAIN MEASURES: The main outcome was number of SUD symptoms based on Diagnostic and Statistical Manual, 5th edition (DSM-5), reported on Symptom Checklists (0-11) for alcohol or other drugs: 2-3 mild; 4-5 moderate; 6-11 severe. RESULTS: Of screened patients, 16,776 (5.7%) reported high-risk use of alcohol (2.4%), cannabis (3.9%), and/or other drugs (1.7%), and 65.0-69.9% of those completed Symptom Checklists. Of those with high-risk alcohol use, 52.5% (95% CI 50.9-54.0%) reported ≥ 2 symptoms consistent with mild-severe alcohol use disorders. Of those reporting daily cannabis use, 29.8% (28.6-30.9%) reported ≥ 2 symptoms consistent with mild-severe SUDs. Of those reporting any other drug use, 37.5% (35.7-39.3%) reported ≥ 2 symptoms consistent with mild-severe SUDs. CONCLUSIONS AND RELEVANCE: Many PC patients who screened positive for high-risk substance use reported symptoms consistent with DSM-5 SUDs on self-report Symptom Checklists. Use of SUD Symptom Checklists could support PC providers in making SUD diagnoses and initiating discussions of substance use.

Integration of screening, assessment, and treatment for cannabis and other drug use disorders in primary care: An evaluation in three pilot sites.

BACKGROUND: This pilot study evaluated whether use of evidence-based implementation strategies to integrate care for cannabis and other drug use into primary care (PC) as part of Behavioral Health Integration (BHI) increased diagnosis and treatment of substance use disorders (SUDs). METHODS: Patients who visited the three pilot PC sites were eligible. Implementation strategies included practice coaching, electronic health record decision support, and performance feedback (3/2015-4/2016). BHI introduced annual screening for past-year cannabis and other drug use, a Symptom Checklist for DSM-5 SUDs, and shared decision-making about treatment options. Main analyses tested whether the proportions of PC patients diagnosed with, and treated for, new cannabis or other drug use disorders (CUDs and DUDs, respectively), differed significantly pre- and post-implementation. RESULTS: Of 39,599 eligible patients, 57% and 59% were screened for cannabis and other drug use, respectively. Among PC patients reporting daily cannabis use (2%) or any drug use (1%), 51% and 37%, respectively, completed an SUD Symptom Checklist. The proportion of PC patients with newly diagnosed CUD increased significantly post-implementation (5 v 17 per 10,000 patients, p < 0.0001), but not other DUDs (10 vs 13 per 10,000, p = 0.24). The proportion treated for newly diagnosed CUDs did not increase post-implementation (1 vs 1 per 10,000, p = 0.80), but did for those treated for newly diagnosed other DUDs (1 vs 3 per 10,000, p = 0.038). CONCLUSIONS: A pilot implementation of BHI to increase routine screening and assessment for SUDs was associated with increased new CUD diagnoses and a small increase in treatment of new other DUDs.

Retinoic acid elicits a coordinated expression of gut homing markers on T lymphocytes of Zambian men receiving oral Vivotif, but not Rotarix, Dukoral or OPVERO vaccines.

All-trans retinoic acid (ATRA) up-regulates, in laboratory animals, the expression of the gut homing markers α4ß7 integrin and CCR9 on lymphocytes, increasing their gut tropism. Here, we show that, in healthy adult volunteers, ATRA induced an increase of these gut homing markers on T cells in vivo in a time dependent manner. The coordinated increase of α4ß7 and CCR9 by ATRA was seen in 57% (12/21) of volunteers and only when given together with an oral Vivotif vaccine. When this coordinated response to ATRA and Vivotif vaccine was present, it was strongly correlated with the gut immunoglobulin A (IgA) specific response to vaccine LPS (ρ = 0.82; P = 0.02). Using RNA-Seq analysis of whole blood transcription, patients receiving ATRA and Vivotif in conjunction showed transcriptomic changes in immune-related pathways, particularly including interferon α/ß signaling pathway, membrane-ECM interactions and immune hubs. These results suggest that exogenous ATRA can be used to manipulate responses to a subclass of oral vaccines, so far limited to a live attenuated Vivotif vaccine.

Safety of Noninvasive Electrical Stimulation of Acupuncture Points During a Routine Neonatal Heel Stick.

BACKGROUND: Hospitalized infants may undergo frequent painful procedures with inadequate pain relief. Alternative pain relief interventions are needed. OBJECTIVE: The aim of this research was to determine the safety of noninvasive electrical stimulation of acupuncture points (NESAP) in neonates who were receiving routine heel sticks. DESIGN: This was a descriptive study performed to assess the safety of using a transcutaneous electrical nerve stimulation (TENS) unit to deliver NESAP to neonates. SETTING/SUBJECTS: The subjects were healthy newborn infants<3 days old before hospital discharge. INTERVENTION: The intervention was NESAP delivered via a TENS unit, administered before, during, and after heel stick. The electrodes of the TENS unit were applied at four acupuncture points. Settings were gradually increased: 6 infants received 1.0 mA, 2 Hz; the second 6 infants received 2.0 mA, 10 Hz; and the last 18 infants received 3.5 mA, 10 Hz. MAIN OUTCOME MEASURES: THREE MAIN MEASURES WERE USED: (1) skin assessment (2) vital signs; (3) pain scores using the Premature Infant Pain Profile (PIPP). RESULTS: There were no significant changes in vital signs during and after NESAP. There were no changes in PIPP scores in the first 12 infants after initiation of NESAP. A slight but nonsignificant increase in PIPP scores (from 2.65 to 3.5 on a scale of 0-18) occurred in the last 18 infants. There were no adverse events during or after NESAP. CONCLUSIONS: NESAP is safe for infants with low settings on a TENS unit.

Soy food supplementation, dietary fat reduction and peripheral blood gene expression in postmenopausal women--a randomized, controlled trial.

SCOPE: The effect of soy food supplementation or dietary fat reduction on gene expression is not well studied. METHODS AND RESULTS: We evaluated the potential of gene expression profiling in peripheral blood mononuclear cells (PBMCs) collected at baseline and at the completion of an 8-wk controlled dietary intervention. Healthy postmenopausal women were randomized to a very-low-fat diet (VLFD; 11% of energy as fat) (n=21), a Step 1 diet (25% energy as fat) supplemented with soy food (SFD; 50 mg isoflavones per day) (n=20), or a control Step 1 diet (CD; 27% energy as fat) with no SFD (n=18). All diets were prepared at the General Clinical Research Center of the University of Southern California. We did not observe any gene that showed variable response across the three dietary interventions. However, there were notable changes in gene expression associated with the intervention in the VLFD and SFD groups. Our findings suggest that the expression of nicotinamide phosphoribosyltransferase (NAMPT) and genes related to Fc γ R-mediated phagocytosis and cytokine interactions may be significantly altered in association with dietary fat reduction and soy supplementation. Gene expression changes in NAMPT were somewhat dampened with adjustment for weight but changes related to Fc γ R-mediated phagocytosis and cytokine interactions remained largely unchanged. CONCLUSION: PBMCs can reveal novel gene expression changes in association with controlled dietary intervention.

Unintended benefits: leadership skills and behavioral change among Guatemalan fieldworkers employed in a longitudinal household air pollution study.

The RESPIRE and CRECER studies measured the effects of reduced household air pollution (HAP) from wood-fired cookstoves on respiratory health in rural highland Guatemala. This article examines behavior change and leadership skill development in local community members who were hired as fieldworkers to assist with research. Fieldworkers administered household questionnaires, shared functions similar to community health workers, and bridged health resources to communities. A mixed-methods design for data collection (in-depth interviews, focus groups, impact drawings, knowledge questionnaire, and retrospective pre-test) was used. Purposive sampling included 10 fieldworkers and 13 local service providers. Fieldworkers showed an increase in knowledge, positive attitudes, and practices around HAP. They developed new technical, interpersonal, and leadership skills. Fieldworkers played a crucial role in building confianza (trust) with the community, bridging resources, and improving outside researchers' relationships with locals. Recommendations for future researchers include inclusion of additional training courses and adoption of community participatory approaches.

Disciplinary discourses: rates of cesarean section explained by medicine, midwifery, and feminism.

In the context of international concern about increasing rates of cesarean sections, we used discourse analysis to examine explanations arising from feminism and the disciplines of medicine and midwifery, and found that each was positioned differently in relation to the rising rates. Medical discourses asserted that doctors are authorities on birth and that, although cesareans are sometimes medically necessary, women recklessly choose unnecessary cesareans against medical advice. Midwifery discourses portrayed medicine as paternalistic toward both women and midwifery, and feminist discourses situated birth and women's bodies in the context of a patriarchally structured society. The findings illustrate the complex ways in which this intervention in birth is discursively constructed, and demonstrate its significance as a site of disciplinary conflict.

Ca2+-binding proteins tune Ca2+-feedback to Cav1.3 channels in mouse auditory hair cells.

Sound coding at the auditory inner hair cell synapse requires graded changes in neurotransmitter release, triggered by sustained activation of presynaptic Ca(v)1.3 voltage-gated Ca(2+) channels. Central to their role in this regard, Ca(v)1.3 channels in inner hair cells show little Ca(2+)-dependent inactivation, a fast negative feedback regulation by incoming Ca(2+) ions, which depends on calmodulin association with the Ca(2+) channel alpha(1) subunit. Ca(2+)-dependent inactivation characterizes nearly all voltage-gated Ca(2+) channels including Ca(v)1.3 in other excitable cells. The mechanism underlying the limited autoregulation of Ca(v)1.3 in inner hair cells remains a mystery. Previously, we established calmodulin-like Ca(2+)-binding proteins in the brain and retina (CaBPs) as essential modulators of voltage-gated Ca(2+) channels. Here, we demonstrate that CaBPs differentially modify Ca(2+) feedback to Ca(v)1.3 channels in transfected cells and explore their significance for Ca(v)1.3 regulation in inner hair cells. Of multiple CaBPs detected in inner hair cells (CaBP1, CaBP2, CaBP4 and CaBP5), CaBP1 most efficiently blunts Ca(2+)-dependent inactivation of Ca(v)1.3. CaBP1 and CaBP4 both interact with calmodulin-binding sequences in Ca(v)1.3, but CaBP4 more weakly inhibits Ca(2+)-dependent inactivation than CaBP1. Ca(2+)-dependent inactivation is marginally greater in inner hair cells from CaBP4(-/-) than from wild-type mice, yet CaBP4(-/-) mice are not hearing-impaired. In contrast to CaBP4, CaBP1 is strongly localized at the presynaptic ribbon synapse of adult inner hair cells both in wild-type and CaBP4(-/-) mice and therefore is positioned to modulate native Ca(v)1.3 channels. Our results reveal unexpected diversity in the strengths of CaBPs as Ca(2+) channel modulators, and implicate CaBP1 rather than CaBP4 in conferring the anomalous slow inactivation of Ca(v)1.3 Ca(2+) currents required for auditory transmission.

St. John's wort (Hypericum perforatum) and breastfeeding: plasma and breast milk concentrations of hyperforin for 5 mothers and 2 infants.

BACKGROUND: Herbal preparations for depression, such as St. John's wort, are often preferred over pharmaceutical preparations by mothers and midwives after childbirth because these preparations are available to patients as over-the-counter "natural" treatments and are popularly assumed to be safe. The only existing report on St. John's wort excretion into human milk showed that only 1 active component (hyperforin) was detectable in breast milk, but was not detectable in the infants' plasma. Another report found more cases of minor problems in infants breast-fed by women taking St. John's wort. However, significance was reached only in comparison with disease-matched women (p<.01), not healthy controls (p=.20). METHOD: Five mothers who were taking 300 mg of St. John's wort 3 times daily (LI 160 [Jarsin], Lichtwer Pharma GmbH; Berlin, Germany) and their breastfed infants were assessed. Thirty-six breast milk samples (foremilk and hindmilk collected during an 18-hour period) and 5 mothers' and 2 infants' plasma samples were analyzed for hyperforin levels by tandem mass spectrometry (LC/MS/MS; limit of quantification=0.1 ng/mL). Data were gathered from January 2001 to February 2002. RESULTS: Hyperforin is excreted into breast milk at low levels. However, the compound was at the limit of quantification in the 2 infants' plasma samples (0.1 ng/mL). Milk/plasma ratios ranged from 0.04 to 0.13. The relative infant doses of 0.9% to 2.5% indicate that infant exposure to hyperforin through milk is comparable to levels reported in most studies assessing anti-depressants or neuroleptics. No side effects were seen in the mothers or infants. CONCLUSION: These results add to the evidence of the relative safety of St. John's wort while breast-feeding found in previous observational studies.

Endogenous and exogenous Ca2+ buffers differentially modulate Ca2+-dependent inactivation of Ca(v)2.1 Ca2+ channels.

Voltage-gated Ca2+ channels undergo a negative feedback regulation by Ca2+ ions, Ca2+-dependent inactivation, which is important for restricting Ca2+ signals in nerve and muscle. Although the molecular details underlying Ca2+-dependent inactivation have been characterized, little is known about how this process might be modulated in excitable cells. Based on previous findings that Ca2+-dependent inactivation of Ca(v)2.1 (P/Q-type) Ca2+ channels is suppressed by strong cytoplasmic Ca2+ buffering, we investigated how factors that regulate cellular Ca2+ levels affect inactivation of Ca(v)2.1 Ca2+ currents in transfected 293T cells. We found that inactivation of Ca(v)2.1 Ca2+ currents increased exponentially with current amplitude with low intracellular concentrations of the slow buffer EGTA (0.5 mm), but not with high concentrations of the fast Ca2+ buffer BAPTA (10 mm). However, when the concentration of BAPTA was reduced to 0.5 mm, inactivation of Ca2+ currents was significantly greater than with an equivalent concentration of EGTA, indicating the importance of buffer kinetics in modulating Ca2+-dependent inactivation of Ca(v)2.1. Cotransfection of Ca(v)2.1 with the EF-hand Ca2+-binding proteins, parvalbumin and calbindin, significantly altered the relationship between Ca2+ current amplitude and inactivation in ways that were unexpected from behavior as passive Ca2+ buffers. We conclude that Ca2+-dependent inactivation of Ca(v)2.1 depends on a subplasmalemmal Ca2+ microdomain that is affected by the amplitude of the Ca2+ current and differentially modulated by distinct Ca2+ buffers.

Endoplasmic reticulum stress induction of the Grp78/BiP promoter: activating mechanisms mediated by YY1 and its interactive chromatin modifiers.

The unfolded protein response is an evolutionarily conserved mechanism whereby cells respond to stress conditions that target the endoplasmic reticulum (ER). The transcriptional activation of the promoter of GRP78/BiP, a prosurvival ER chaperone, has been used extensively as an indicator of the onset of the UPR. YY1, a constitutively expressed multifunctional transcription factor, activates the Grp78 promoter only under ER stress conditions. Previously, in vivo footprinting analysis revealed that the YY1 binding site of the ER stress response element of the Grp78 promoter exhibits ER stress-induced changes in occupancy. Toward understanding the underlying mechanisms of these unique phenomena, we performed chromatin immunoprecipitation analyses, revealing that YY1 only occupies the Grp78 promoter upon ER stress and is mediated in part by the nuclear form of ATF6. We show that YY1 is an essential coactivator of ATF6 and uncover their specific interactive domains. Using small interfering RNA against YY1 and insertional mutation of the gene encoding ATF6alpha, we provide direct evidence that YY1 and ATF6 are required for optimal stress induction of Grp78. We also discovered enhancement of the ER-stressed induction of the Grp78 promoter through the interaction of YY1 with the arginine methyltransferase PRMT1 and evidence of its action through methylation of the arginine 3 residue on histone H4. Furthermore, we detected ER stress-induced binding of the histone acetyltransferase p300 to the Grp78 promoter and histone H4 acetylation. A model for the ER stress-mediated transcription factor binding and chromatin modifications at the Grp78 promoter leading to its activation is proposed.

Essential role of Ca2+-binding protein 4, a Cav1.4 channel regulator, in photoreceptor synaptic function.

CaBP1-8 are neuronal Ca(2+)-binding proteins with similarity to calmodulin (CaM). Here we show that CaBP4 is specifically expressed in photoreceptors, where it is localized to synaptic terminals. The outer plexiform layer, which contains the photoreceptor synapses with secondary neurons, was thinner in the Cabp4(-/-) mice than in control mice. Cabp4(-/-) retinas also had ectopic synapses originating from rod bipolar and horizontal cells tha HJt extended into the outer nuclear layer. Responses of Cabp4(-/-) rod bipolars were reduced in sensitivity about 100-fold. Electroretinograms (ERGs) indicated a reduction in cone and rod synaptic function. The phenotype of Cabp4(-/-) mice shares similarities with that of incomplete congenital stationary night blindness (CSNB2) patients. CaBP4 directly associated with the C-terminal domain of the Ca(v)1.4 alpha(1)-subunit and shifted the activation of Ca(v)1.4 to hyperpolarized voltages in transfected cells. These observations indicate that CaBP4 is important for normal synaptic function, probably through regulation of Ca(2+) influx and neurotransmitter release in photoreceptor synaptic terminals.

The safety of St. John's wort (Hypericum perforatum) during breastfeeding.

BACKGROUND: We examined the safety of St. John's wort to nursing mothers and their infants. METHOD: A prospective, observational, cohort study was conducted. Thirty-three breastfeeding women receiving St. John's wort (Group 1) who contacted our teratogen/toxicant counseling service regarding the safety of St. John's wort during breastfeeding were followed up between May 1999 and April 2001. These women were compared with 101 disease-matched (Group 2) and 33 age- and parity-matched nondisease controls (Group 3). Information collected included maternal and neonatal demographics, breastfeeding duration, use of St. John's wort, maternal and infant adverse events, infant weight over the first year of life, and whether or not the mother experienced a decrease in lactation. RESULTS: There were no statistically significant differences found in maternal or infant demographics or maternal adverse events. Whereas only 1 infant each in Groups 2 and 3 was reported to be colicky, there were 2 cases of "colic," 2 of "drowsiness," and 1 of "lethargy" in Group 1 (p <.01; Group 1 vs. Group 2, p <.01; Group 1 vs. Group 3, p =.20). Although 3 of these women in Group 1 consulted their doctor, specific medical treatment was not required. No significant difference was observed in the frequency of maternal report of decreased milk production among the groups, nor was a difference found in infant weight over the first year of life. CONCLUSION: These results provide a framework for the management of breastfeeding women receiving St. John's wort.