HELLP syndrome at <23 weeks' gestation: a systematic literature review.

OBJECTIVE: We performed a systematic review to evaluate the clinical presentation and maternal and fetal outcomes in pregnancies with early-onset HELLP (hemolysis, elevated liver enzymes, and low platelets) syndrome. DATA SOURCES: PubMed, Ovid MEDLINE, Scopus, CINAHL, Cochrane Library, and ClinicalTrials.gov were queried from inception through January 1, 2023 with the following terms: "HELLP syndrome," "HELLP," "hemolysis, elevated liver enzymes, low platelets," "hemolysis, elevated liver enzymes, low platelets syndrome," "pre-viable," "peri-viable," "previable," "periviable," "first trimester," "second trimester," "before 23 weeks," "<23 weeks," "<23 week gestation," and "before 23 weeks gestation." We also included an additional case from our institution. STUDY ELIGIBILITY CRITERIA: Abstracts, unpublished studies, and review articles were excluded, yielding 46 studies that met our inclusion criteria. METHODS: Two reviewers (N.S.I. and M.H.M.) performed the study selection and subsequent data extraction independently, after which the results were reviewed together. PRISMA guidelines were followed, and our study was registered at PROSPERO (CRD42021292692). RESULTS: A total of 55 patients had 58 pregnancies complicated by early-onset HELLP syndrome, including 3 with recurrent HELLP. The most common presenting signs/symptoms were abdominal pain (35/45; 78%), hypertension (32/49; 65%), nausea/vomiting (16/45; 36%), headache (13/45; 29%), and edema (8/45; 18%). Lactate dehydrogenase ≥600 IU/L was observed in 21 of 31 (68%) cases, whereas liver enzyme abnormalities and thrombocytopenia were reported in 48 of 51 (94%) and 50 of 54 (93%) cases, respectively. Maternal complications were encountered in 25 of 56 (45%) cases. The most common complications were hepatic (13/56; 23%), central nervous system-related (11/56; 20%), and respiratory (11/56; 20%). In 36 of 57 (63%) cases, pregnancy was terminated. Of the 21 continued pregnancies, early fetal death (at <20 weeks' gestation) was reported in 10 (48%), stillbirth in 6 (28%), and neonatal demise in 2 (10%). Living neonates were reported in 3 of 21 (14%) cases, all delivered at 23 weeks. The perinatal mortality rate was 73% (8/11). One case (2%) reported maternal death. Antiphospholipid syndrome was diagnosed in 14 of 29 (48%) cases. CONCLUSION: Early-onset HELLP syndrome presents with symptoms similar to those observed in later gestation. Maternal complications are life-threatening, with the most common complications being hepatic, central nervous system-related, and respiratory. Fetal outcomes are poor.

Ageism in healthcare technology: the older patients' aspirations for improved online accessibility.

Objective: To identify concerns, barriers and facilitators impacting the use of patient portals by older patients as well as desired features in future updates. Materials and Methods: This is a cross-sectional study consisting of 2 focus group discussions culminating in an anonymous survey administered to women who were 65 years and older receiving urogynecologic care in Northwest Ohio. Results: Of the 205 women surveyed (91% response rate), providers and healthcare systems play the primary 2 roles (73% and 69%, respectively) in facilitating patients' use of patient portal systems and telehealth applications. Barriers to use revolved around technical difficulties (50%), privacy concerns (45%), and cost of technology (24%). The most important features desired were the ability to modify the text size within the application (47%) and an intuitive, simple interface (46%). Additional assistance for navigating technical challenges was suggested, specifically set-up of accounts (36%), saving and sharing information with caregivers (35%), and sign-in and navigation of portals (32%). Conclusion: The paucity of age-aligned medical access software and products may lead to worsening of digital exclusion and disparities in healthcare. Portal application developers and healthcare systems must advance efforts that consider the needs of those who may be older when designing patient portals.

The Effect of Video Education on Skin-to-Skin Contact at the Time of Delivery: A Randomized Controlled Trial.

Objective The objective of this study was to measure the impact of video education at the time of admission for delivery on intent and participation in skin-to-skin contact (SSC) immediately after birth. Methods This study was a randomized controlled trial of educational intervention in women ( N = 240) of 18 years or older admitted in anticipation of normal spontaneous term delivery. Alternate patients were randomized into video ( N = 120) and no video ( N = 120) groups. Both groups received a survey about SSC. The video group watched an educational DVD and completed a postsurvey about SSC. Results During the preintervention survey, 89.2% of those in the video group compared with 83.3% of those in the no video group indicated that they planned to use SSC ( p = 0.396). After the video, 98.3% planned to do SSC after delivery ( p < 0.001). However, only 59.8% started SSC within 5 minutes of delivery in the video group and only 49.4% started SSC within 5 minutes of delivery in the no video group ( p = 0.17). Conclusion Video education alters the intention and trends toward participation in SSC within 5 minutes of delivery. Despite the plans for SSC, however, there was no significant difference in rates between the two groups. These findings support that obstacles, other than prenatal education, may affect early SSC. Key Points Significant obstacles impact skin-to-skin rate.Video education alters skin-to-skin intent.Video education can improve skin-to-skin rate.Education can happen at the time of delivery.Video education can impact mothers and infants.

Do medical student mental stress and burnout vary with virtual versus in-person residency interviews.

AIM: This study aimed to identify medical student stressors and mitigation methodologies based on interview modality. MATERIALS & METHODS: A survey was administered to obstetrics and gynecology applicants in in-person (IP) and virtual (VR) National Resident Matching Program cycles. This included demographics, the Mayo Clinic Medical Students Well-Being Index and stressor questions. RESULTS: A total of 137 of 151 surveys were completed (91% response rate). Subjective stress was significant in 76% of IP and 57% of VR applicants (p = 0.07). The objective Mayo Clinic Medical Students Well-Being Index values were higher in the IP (2.47 ± 1.75) compared with the VR group (2.00 ± 1.55; p = 0.10), suggesting lower stress with VR interviews. More IP (53%) compared with VR applicants (44%) were deemed 'at risk' (p < 0.01). CONCLUSION: VR interviews may mitigate select stressors during interviews.

Management of reproductive health after cardiac transplantation.

Pregnancy after cardiac transplantation poses immense challenges. Maternal risks include hypertensive disorders of pregnancy, rejection, and failure of the cardiac allograft that may lead to death. Fetal risks include potential teratogenic effects of immunosuppression and prematurity. Because of the high-risk nature of pregnancy in a heart transplant patient, management of reproductive health after cardiac transplantation should include preconception counseling to all women in the reproductive age group before and after cardiac transplantation. Reliable contraception is vital as nearly half of the pregnancies in this population are unintended. Despite the associated risks, successful pregnancies after cardiac transplantation have been reported. A multidisciplinary approach proposed in this review is essential for successful outcomes. A checklist for providers to guide management is provided.

Management of reproductive health in patients with pulmonary hypertension.

Pulmonary hypertension is characterized by elevated pulmonary artery pressure caused by several clinical conditions that affect pulmonary vasculature. Morbidity and death in this condition are related to the development of right ventricular failure. Normal physiologic changes that occur in pregnancy to support the growing fetus can pose hemodynamic challenges to the pregnant patient with pulmonary hypertension that results in increased morbidity and mortality rates. Current guidelines recommend that patients with known pulmonary hypertension be counseled against pregnancy. This review aims to provide clinicians with guidelines for preconception counseling, medication management, and delivery planning.

Maternal morbidity associated with skin incision type at cesarean delivery in obese patients: a systematic review.

AIM: To describe the relationship between cesarean skin incision type and postoperative wound complications (WCs) in obese pregnant patients. MATERIALS & METHODS: MEDLINE (PubMed and OVID), Embase, Scopus, Web of Science Core Collection, Cochrane Library and ClinicalTrials.gov databases were used for publication search. Selection criteria consisted of articles studying pregnant patients with BMI ≥30 kg/m2 undergoing cesarean delivery and assessing the effect of skin incision type on postoperative maternal outcomes. RESULTS: Ten publications met criteria for a systematic review of a total of 2946 patients. The transverse skin incision was associated with a lower rate of WC compared with the vertical skin incision. The pooled risk ratio for WCs was 0.47 (95% CI: 0.37-0.58; p < 0.00001). CONCLUSION: Transverse skin incision may be preferable to vertical skin incision at cesarean delivery in pregnant patients with obesity as it may be associated with a lower rate of WCs.PROSPERO registration ID: CRD42020151106.

Composite neonatal and maternal morbidities with small- versus appropriate- for gestational age among uncomplicated obese women undergoing repeat cesarean delivery.

PURPOSE: Our goal was to compare composite neonatal and maternal morbidities (composite neonatal morbidity (CNM), composite maternal morbidity (CMM)) among deliveries with small for age (SGA) versus appropriate for gestational age (AGA; birthweight 10-89%) among obese versus non-obese women undergoing repeat cesarean delivery (CD). STUDY DESIGN: This is a secondary analysis of a prospective observational study. Women who had elective CD ≥37 weeks were studied. We excluded multiple gestations, fetal anomalies, > 1 prior CD, and medical diseases. Patients were divided into BMI ≥30 versus <30 kg/m2. CNM included respiratory distress syndrome, necrotizing enterocolitis, severe intraventricular hemorrhage, seizure, or death; CMM included transfusion, hysterectomy, operative injury, coagulopathy, thromboembolism, pulmonary edema, or death. Multivariate logistic regression was used to control for confounding factors. RESULTS: Of 7561 women, we included 65% were obese and 35% were not. SGA rates differed significantly: 8 versus 12% (p < .001). Overall, CNM was significantly higher in patients with SGA versus AGA (adjusted odds ratio (aOR) 2.04, 95% CI 1.19-3.49). CMM of SGA in obese versus non-obese was statistically different (aOR 0.11, 95% CI 0.02-0.68). Among obese mothers, SGA neonates had significantly higher CNM compared with AGA ones (aOR 2.17, 95% CI 1.03-4.59). CONCLUSIONS: SGA occurred in 8% of low-risk obese women with prior CD. CNM of SGA babies in obese versus non-obese women were similar. Paradoxically, CMM was lower in obese cases, possibly reflecting the caution that obese patients receive preoperatively. Our findings may assist in counseling patients and designing trials.

The impact of time of delivery on gestations complicated by preterm premature rupture of membranes: daytime versus nighttime.

Background: Perinatal death, in particular intrapartum stillbirth and short-term neonatal death, as well as neonatal short-term and long-term morbidity have been associated with the time of day that the birth occurs. Indeed, evening and nighttime deliveries were associated with an increased risk of an adverse perinatal outcome when compared to similar daytime deliveries. Impact of shift change, as well as time of day delivery have been extensively studied in the context of maternal and neonatal complications of cesarean delivery, however, no studies were previously performed on timing of delivery and its effect on the outcome of pregnancies complicated by preterm premature rupture of membranes. Objective: Our objective was to compare obstetric, neonatal as well as long-term outcomes between women delivered in the daytime versus nighttime, in singleton gestations whose pregnancies were complicated by preterm premature rupture of membranes. Study design: This was a secondary analysis of a trial of the Eunice Kennedy Shriver National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network "A Randomized Clinical Trial of the Beneficial Effects of Antenatal Magnesium Sulfate for the Prevention of Cerebral Palsy." For this analysis, the time of delivery was divided into the daytime, from 07:01 to 19:00, and the nighttime, from 19:01 to 07:00. Epidemiological, obstetric characteristics as well as neonatal and long-term outcomes were compared between deliveries occurring during the daytime versus the nighttime periods. Inclusion criteria consisted of singleton gestations diagnosed with preterm premature rupture of membranes (PPROM). Multifetal gestations and pregnancies with preterm labor without preterm premature rupture of membranes were excluded. Results: A total of 1752 patients met inclusion criteria, 881 delivering during the daytime, while 871 during the nighttime. There were no differences in demographic maternal variables. There were no differences in the number of patients receiving steroids and the doses of steroids. Antibiotic prophylaxis was also equal in both groups. Postpartum endometritis, chorioamnionitis, and the latency to delivery were also equivalent between both the groups. Cesarean delivery for distress was the only different outcome, more prevalent in daytime deliveries (157 (44.7%) versus 108 (35.9%) of the nighttime ones p = .02). Neonatal adverse outcomes as well as long-term outcomes were similar between the two groups. Conclusions: In the setting of delivery at a tertiary care center, and in the era of universal use of steroids, and latency antibiotics for the management of preterm premature of membranes, there is no marked difference in pregnancy, neonatal as well as long-term outcomes for infants delivered in the daytime versus nighttime.

Caesarean Delivery Surgical Site Infection: What are Expected Rates and Potentially Modifiable Risk Factors?

OBJECTIVE: This study sought to determine baseline Caesarean delivery (CD) surgical site infection (SSI) rates in various patient subgroups and to identify potentially modifiable and non-modifiable risk factors for SSI. METHODS: This is a secondary analysis of a multicentre CD registry. Women who underwent CD were divided into SSI versus no SSI. SSI was defined as an infection that occurred in the part of the body where the surgery took place, within 30 days of surgery. Clinical characteristics and potential risk factors were compared between groups. RESULTS: Of 57 182 women, 3696 (6.5%) had SSI. SSI rates were higher in primary versus repeat CD (9.7% vs. 4.2%; P <0.001), and in CD after labour vs. no labour (9.5% vs. 3.8%; P <0.001). After adjustment for confounding factors, low transverse CD (adjusted OR [aOR] 0.7 [0.6-0.9]), CD performed between 7 pm and 7 am (aOR 0.9 [0.83-0.98]), primary CD (aOR 0.5 [0.5-0.6]), and intrapartum antibiotics (aOR 0.3 [0.1-0.4]) were associated with a decreased in the rate of SSI. Black race (aOR 1.9 [1.7-2.1]), tobacco use (aOR 1.4 [1.2-1.6]), increasing American Society of Anesthesiologists category (aOR 1.3 [1.1-1.6]), vertical skin incision (aOR 1.2 [1.1-1.3], emergency CD (aOR 1.3 [1.1-1.5]), and postpartum transfusion (aOR 2.7 [2.1-3.6]) were associated with an increase in the rate of SSI. CONCLUSION: This study estimates the CD SSI rates in different subgroups and serves as a baseline for future trials designed to develop preventive guidelines and protocols.

Adverse pregnancy outcomes in deliveries prior to, at and beyond 39 weeks; low- and high-risk women.

BACKGROUND: Hypertensive disorders are associated with maternal and neonatal complications. Though they are more common in women with history of prior preeclampsia, they can occur in uncomplicated pregnancies. OBJECTIVE: To determine the proportion of adverse pregnancy outcomes in deliveries prior to or at ≥39 weeks, in uncomplicated singleton nulliparous women (low-risk), as well as women with history of preeclampsia in a prior gestation (high-risk). STUDY DESIGN: This was a secondary analysis from the multicenter trials of low dose aspirin for preeclampsia prevention in low and high-risk pregnancies. The proportion of adverse pregnancy outcomes including hypertensive disorders in pregnancy, small for gestational age, placental abruption, neonatal intensive critical unit admission, and respiratory distress syndrome were evaluated in the two groups. Adverse pregnancy outcomes were stratified by gestational age at delivery (<39 weeks and ≥39 weeks). Descriptive statistics were performed, and results reported as percentages. RESULTS: Three thousand twenty-one pregnancies were included in the low risk group, and 600 in the high risk one. In the low risk group 362 (12%) had hypertensive disorders, with 58% occurring at ≥39 weeks. In the low risk group, the rate of small for gestational age was of 5.9%, placental abruption 0.4%, neonatal intensive care unit admission 9%, and respiratory distress syndrome 3.5%. Sixty percent of all small for gestational age, 31% of all placenta abruptions, 44% of all neonatal intensive care unit admissions and 33% of respiratory distress syndrome cases, occurred at ≥39 weeks in the low risk group. In contrast in the high risk group, 197 (33%) patients developed a hypertensive disorder, with 35.5% occurring at ≥39 weeks. The overall rate of small for gestational age was 9.2%, abruption 2%, neonatal intensive care unit admission 15.5%, and respiratory distress syndrome 5%. In this group, 24% of all small for gestational age, 8.3% of all placental abruptions, 16% of all neonatal intensive care unit admissions and 3% of respiratory distress syndrome cases, were at ≥39 weeks. CONCLUSIONS: We found that in low-risk women, the majority of hypertensive disorders occur at ≥39 weeks, whereas in women with prior preeclampsia the majority develops at <39 weeks. Moreover, a third of all placental abruption occurred at or beyond 39 weeks in the low risk group. Our findings suggest that in low-risk women, a policy of delivery at 39 weeks may prevent most of the adverse outcome that occurs beyond that gestational age cutoff.

Removal notice to The relationship between primary cesarean delivery skin incision type and wound complications in women with morbid obesity: Am J Obstet Gynecol 2014;210:319.e1-4.

This article has been removed: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been removed at the request of the Editors-in-Chief and Authors. The original publication reported that univariate analysis showed that a vertical skin incision in obese women undergoing Cesarean delivery was associated with a higher odds ratio for wound complications than a transverse skin incision. Multivariable analyses showed a reversal of the association (i.e. the odds of wound complications were lower in women with a vertical skin incision). However, there was an error in the way the variable was entered in the logistic analysis. Re-analysis with the correct coding of the variable indicates that a transverse skin incision is associated with decreased odds of wound complication compared to a vertical skin incision.

Effect of partial compliance on the prevention of recurrent preterm birth in women receiving weekly 17 alpha-hydroxyprogesterone caproate injections.

PURPOSE: To analyze the effect of partial compliance on preterm birth (PTB) prevention among women with previous PTB and receiving 17 alpha-hydroxyprogesterone caproate (17-OHPC). STUDY DESIGN: This is a secondary analysis of a multicenter trial for the prevention of recurrent PTB. Women with prior PTB were randomly assigned between 15 0/7 and 20 3/7 weeks to weekly injections of either 17-OHPC or placebo. Full 100% compliance (group 1) was compared to 40-80% (group 2). Recurrent PTB rates and odds ratios were calculated. Student's t, Chi-square, Wilcoxon Rank-Sum, multivariate logistic regression and Breslow-Day tests were used. RESULTS: Group 1 included 370 women versus 35 in group 2. In each group, the PTB rate was significantly reduced in pregnancies receiving 17-OHPC compared to placebo. The adjusted odds ratio for PTB rate in group 1 was 0.48 (95% CI 0.31-0.75) versus 0.18 (95% CI 0.04-0.92) in group 2. Comparing the homogeneity of both odds ratios, the rates of recurrent PTB prevention in both groups were not statistically different (Breslow-Day test; p= .15). CONCLUSION: A compliance rate of 40-80% did not significantly reduce 17-OHPC's efficacy. If confirmed, our findings could lead to a dramatic decrease in costs related to prevention of recurrent PTB.

Pregnancy Outcomes in Women with Preeclampsia Superimposed on Chronic Hypertension with and without Severe Features.

Objective The American Congress of Obstetricians and Gynecologists (ACOG) task force on hypertension in pregnancy introduced a new definition of superimposed preeclampsia (SIP) adding severe features (SF) as new criteria to define severe disease. They also recommended that those with SIP be delivered ≥ 37 weeks, whereas those with SF be delivered ≤ 34 weeks. Our aim was to investigate the validity of this new definition by comparing adverse pregnancy outcomes in SIP with (SIP-SF) and without SF (SIP). Study Design Women with chronic hypertension (CHTN) enrolled in a multicenter trial were studied. SIP was reclassified according to the new definition to SIP and SIP-SF (persistent systolic blood pressure [BP] > 160 or diastolic BP > 110, platelets < 100 K, liver function tests > 70, creatinine > 1.1, or persistent central nervous system/abdominal symptoms). Composite adverse outcomes including rates of indicated preterm birth, abruptio placentae, postpartum hemorrhage, and maternal death were compared by chi-square. Adjustment was done with a multivariate logistic-regression analysis and all statistical tests were two-sided. Results A total of 216 women (28%) out of 774 with CHTN developed SIP, 87 (11%) had SIP-SF, and 129 (17%) didn't have SF. Baseline characteristics including maternal age, baseline BP, and assignment to low-dose aspirin were similar between groups. Using univariate analysis, the composite adverse outcome was higher among the SIP-SF group (p = 0.04), as well as indicated preterm birth (p = 0.02), cesarean section (p = 0.02), and SGA (p = 0.02). After adjustment, composite adverse outcomes were not significantly different between groups. The rate of SGA, however, was higher among SIP-SF (adjusted odds ratio: 3.12, p = 0.02). Conclusion The rate of SIP-SF in this study was 11% of all women with CHTN. Surprisingly, pregnancy outcomes were not significantly different in those with and without SF. We suggest a prospective observational study to determine the optimal timing for delivery in those with SIP using new ACOG diagnostic criteria.

Fetal origins of autism spectrum disorders: the non-associated maternal factors.

AIM: Several population-based studies have been conducted to determine whether maternal exposures are involved in the pathophysiology of autism spectrum disorder (ASD). We review these studies and describe the factors not associated with increased risk for ASD development. METHODS: We identified studies describing associations between maternal exposures and ASD development. These studies include the Childhood Autism Risks from Genetics and the Environment, Nurses' Health Study II, and the Swedish population registry. RESULTS: Factors not associated with ASD development include Type 2 and gestational diabetes, chronic hypertension, fever treated with antipyretic medication, autoimmune disease and short interpregnancy intervals. CONCLUSION: There is increasing evidence that maternal exposures are involved in the pathophysiology of ASD in the developing fetus.

Folic acid supplementation: what is new? Fetal, obstetric, long-term benefits and risks.

The association between folic acid supplementation, prior to conception and/or during pregnancy and pregnancy outcomes, has been the subject of numerous studies. The worldwide recommendation of folic acid is at least 0.4 mg daily for all women of reproductive age, and 4-5 mg in high-risk women. In addition, evidence shows that folic acid supplementation could modulate other adverse pregnancy outcomes, specifically, in pregnancies complicated by seizure disorders, preeclampsia, anemia, fetal growth restriction and autism. This review summarizes the available national and international guidelines, concerning the indications and dosage of folic acid supplementation during pregnancy. In addition, it describes the potential preventive benefits of folic acid supplementation on multiple maternal and fetal outcomes, as well as potential risks.

Obesity epidemic: impact from preconception to postpartum.

The obesity epidemic is on the rise throughout the USA and the world. Not only does it affect the general population but it also specifically poses unique threats to a woman's life in the antepartum, peripartum and postpartum periods. An increased BMI is associated with worse perinatal outcomes, including higher rates of preeclampsia (and other hypertensive disorders), macrosomia, other neonatal morbidities and gestational diabetes. Isolated maternal obesity and additional maternal diabetes predispose the infant to potential adult disease through fetal programming. This review of the literature examines the effects of obesity on a woman's life, outlining complications beginning with preconception through the postpartum period.

Treatment options for hypertension in pregnancy and puerperium.

INTRODUCTION: Hypertensive disorders have become increasingly prevalent and complicate an increasing number of pregnancies. Therefore it is essential that the medications used to treat these disorders be well understood. Furthermore the management is complicated by special consideration needed for the physiologic changes of pregnancy as well as the consideration for possible adverse fetal effects. Areas covered: We performed a review of the scientific literature of medications used to treat hypertensive disorders in pregnancy. We reviewed the guidelines used by different societies all over the world. We also discussed the pharmacodynamics, pharmacokinetics and possible adverse effects relating to the antihypertensive medications. Finally, we discussed the long-term maternal implications of these diseases. Expert opinion: Overall, we encourage a step-wise approach to treating hypertensive disorders of pregnancy. While making sure to max out the use of one medications prior to shifting to another. Also, it is imperative not to be aggressive with treatment due to risk of compromising utero-placental blood flow. There is research currently involving biomarkers, nano-medicine and the placenta project with hopes of developing new targeted medications with a good fetal safety profile.

Successful Management of a Periviable Pregnancy with Morbidly Adherent Placenta after Uterine Rupture.

BACKGROUND: Although rare, trauma in pregnancy can cause uterine rupture. In a periviable pregnancy, uterine rupture can lead to premature delivery and significant morbidity. CASE: A 29-year-old woman with four prior CSs presented with uterine rupture and a protruding morbidly adherent placenta at 23+4 weeks of gestation. Since the pregnancy was highly desired, the defect was repaired and the decision made to continue with the pregnancy. The patient presented at 29+3 weeks of gestation with preterm labour and subsequently delivered a healthy male infant of 1130 grams. CONCLUSION: Expectant management followed by CS can be beneficial in certain cases of uterine rupture with morbidly adherent placenta following trauma. This is especially the case in a periviable pregnancy, since prolonging the pregnancy will improve neonatal outcomes. We recommend individualized management based on clinical presentation, imaging findings, and the patient's wishes.