Category: 8. Health

Introduction

The advancement of medical technology and evolving healthcare concepts has led to the widespread adoption of day surgery, a new medical service model.¹ Anaesthetic techniques are the cornerstone of day surgery. Therefore, improving anaesthesia concepts and methods is essential to ensure safe and effective outcomes in this setting.

In clinical practice, drugs with complementary effects are often used together. The combination of sedatives and opioids is a standard practice for procedural sedation and general anaesthesia. For example, the combination of propofol with fentanyl, midazolam with fentanyl, and propofol with remifentanil improved efficacy, reducing the dosage of both drugs, and reducing adverse effects.^2–5 However, drug interactions can alter pharmacological outcomes,⁶ making it essential to understand the characteristics of these interactions. Remimazolam, a novel, ultrafast, and short-acting benzodiazepine, gained approval for use in both procedural sedation and general anaesthesia.^7–9 Alfentanil, a fentanyl derivative, is a short-acting μ-opioid analgesic widely used in various clinical settings, including endoscopy, abortion, and general anaesthesia.^10–13

Given the rapid onset and offset of remimazolam and alfentanil, their combination could be an ideal anaesthetic regimen for day surgeries. Despite this potential, only a few studies have explored the remimazolam-alfentanil interaction. Our hypothesis is that alfentanil may enhance the sedative effects of remimazolam during anaesthesia induction in patients undergoing urological day surgery.

Methods

Study Design and Participants

This study was a single-centre, single-blinded, randomised clinical trial. Ethical approval was granted by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (identifier: 2022-KY-E-302; Chairperson: Prof. Songqing He) on 13 September 2022 and was registered with the Chinese Clinical Trial Registry (https://www.chictr.org.cn; registration number: ChiCTR2200064130, principal investigator: Xuehai Guan; date of registration: 27 September 2022). Written informed consent was obtained from all patients before enrolment. This trial was performed at the First Affiliated Hospital of Guangxi Medical University in accordance with the Declaration of Helsinki and CONSORT guidelines.

A total of 114 patients, aged 18–65 years, with an American Society of Anaesthesiologists (ASA)physical status I–III, undergoing elective urological day surgery under general anaesthesia, were enrolled. Patients with a history of difficult airway (modified Mallampati class 3–4), asthma, severe hypertension (systolic blood pressure ≥ 180 mmHg or diastolic blood pressure ≥ 110 mmHg), pulmonary heart disease, pulmonary arterial hypertension, cardiac insufficiency, hyperthyroidism, epilepsy, or psychosis were excluded. Further exclusion criteria included allergic reactions to drugs, obesity (body mass index, BMI ≥ 30 kg.m⁻²), pregnancy, and analgesic abuse.

Randomisation and Masking

Enrolled patients were randomly assigned to either the RMZ-AF or AF-RMZ group using a computer-generated randomisation code (EpiCalc 2000 software) in a 1:1 ratio. Randomisation was performed by an independent anaesthesiologist who was only involved in patient assignment and drug preparation. Group assignments were concealed in sealed envelopes. Patients, surgeons, and data collectors were blinded to the group allocation throughout the process, with the allocation only revealed after data collection and analysis were completed.

Anaesthesia Management and Intervention

All patients fasted for 8 h before surgery, with no premedication administered. Upon arrival in the operating room, standard monitoring was initiated, including non-invasive blood pressure measurement, electrocardiography, capnography, pulse oximetry (SpO₂), and bispectral index (BIS). All patients inhaled 100% oxygen through a mask for 3 min before anaesthesia induction. In the RMZ-AF group, anaesthesia was induced using remimazolam tosilate (RMZ; Jiangsu Hengrui Medicine Co., Lianyungang, China; diluted with normal saline to 1 mg mL⁻¹), starting at 6 mg kg⁻¹ h⁻¹ until the BIS reached 40–60 and was maintained between 0.2–2 mg kg⁻¹ h⁻¹. When BIS was within 40–60, alfentanil (AF; 30 µg kg⁻¹ IV; Yichang Humanwell Pharmaceutical Co., Yichang, China) and rocuronium (0.6 mg kg⁻¹ IV; Sinopharm Chemical Reagent Co., Shanghai, China) were administered. In the AF-RMZ group, anaesthesia was induced by using alfentanil (30µg kg⁻¹ IV), followed by remimazolam tosilate, starting at 6 mg kg⁻¹ h⁻¹ until BIS reached 40–60 and was maintained between 0.2–2 mg kg⁻¹ h⁻¹. When BIS was within 40–60, rocuronium (0.6 mg kg⁻¹ IV) was administered. In both groups, a laryngeal mask airway (LMA) was inserted 1 min after rocuronium administration. Anaesthesia was maintained using a combination of remimazolam (0.2–2 mg kg⁻¹ h⁻¹) and alfentanil (1–2 µg kg⁻¹ min⁻¹), adjusted based on the clinical signs and symptoms, BIS values (maintained at a range of 40–60), and the patient’s overall condition. Rocuronium was administered as a repeated bolus dose of 0.1–0.2 mg kg⁻¹ when needed. All patients underwent mechanical ventilation (tidal volume, 8 mL kg⁻¹; respiratory rate: 8–12 breaths min⁻¹; oxygen concentration, 60%; and fresh gas flow, 2 L min⁻¹). All patients with hypotension (a 30% decrease in mean arterial blood pressure (MBP) compared with baseline) were treated with ephedrine at the discretion of the attending anaesthesiologist.

If signs of intraoperative awakening (BIS > 60) were detected, the remimazolam infusion rate was adjusted to 10 mg kg⁻¹ h ⁻¹ for up to 1 min. If awakening signs persisted, remimazolam was discontinued and replaced with propofol. All drugs were discontinued at the end of the surgery, and patients were transferred to the post-anaesthesia care unit (PACU) for recovery.

Outcomes

The primary outcome was the time from remimazolam administration to loss of consciousness (LOC) during anaesthesia induction. The consciousness was assessed by using Modified Observer`s Assessment Alertness/Sedation Scale (MOAA/S; 0, no response after painful trapezius squeeze, defined as LOC; 1, responds only after painful trapezius squeeze; 2, responds only after mild prodding or shaking; 3, response to name spoken loudly and/or repeatedly; 4, response to name spoken in normal tone; 5, response readily to name spoken in normal tone) with 10s interval during anaesthesia induction.

Secondary outcomes included anaesthetic and surgical characteristics, vital signs, and adverse events. The durations of surgery, anaesthesia, and PACU stay, as well as the time of eyes-opening and extubation, were recorded. We recorded the administration of remimazolam and alfentanil at the following time points: from administration to LOC, at BIS ≤ 60, and at the end of surgery. Total administration of rocuronium, ephedrine, and crystalloid infusion volumes were also recorded. Vital signs (mean arterial blood pressure [MBP], heart rate, SpO₂, and BIS) were recorded at the following time points: 5 min before anaesthesia (baseline), at LOC, at BIS ≤ 60, at intubation, at 1 and 5 min after intubation, at the beginning of surgery, at 5 min after surgery, at time of eyes-opening, at time of extubation, and at discharge from the PACU. Adverse events such as hypertension (≥ 30% increase in MBP from baseline), hypotension (≥ 30% decrease in MBP from baseline), bradycardia (<50 beats min⁻¹), tachycardia (>100 beats min⁻¹), injection pain, dysphoria, nausea/vomiting, awareness, delirium, and hiccups were also recorded.

Statistical Analyses

Statistical analyses were performed using GraphPad Prism 9.0 (Dotmatics, Boston, MA, USA). The normality and equality of variances for continuous variables were tested using the Kolmogorov–Smirnov and sphericity tests, respectively. Continuous values with normal distribution and equal variance are presented as means (SD) and were analysed using an unpaired t-test or repeated-measures two-way analysis of variance (ANOVA), followed by Bonferroni’s multiple comparison test. Continuous values with non-normal distribution and unequal variance are presented as medians (interquartile range [IQR]) and were analysed using the Mann–Whitney U-test. Categorical values are presented as numbers (%) and were analysed using Fisher’s exact test. A P-value of <0.05 was considered statistically significant.

This study was designed as a superiority trial. PASS software (version 11.0; NCCS, Utah, USA) was used to calculate the sample size. Preliminary tests showed that the time from remimazolam administration to LOC (mean [SD]) was 106.0 (30.0) s and 123.0 (32) s in the AF-RMZ and RMZ-AF groups, respectively. We calculated that 54 patients per group were required to achieve 80% power at a two-sided alpha of 0.05 to detect a significant difference in the primary outcome. To account for a potential 5% dropout rate, we enrolled 57 patients in each group.

Results

Between September 2022 and December 2023, 171 patients were screened for eligibility. Of these, 30 did not meet the inclusion criteria, 27 declined to participate, while 114 were successfully recruited and randomised into either the RMZ-AF or AF-RMZ group (n=57 per group). A total of 114 patients were included in the analysis (Figure 1). Table 1 presents the patient demographic data. No statistically significant differences were observed between the groups.

Table 1 Baseline Characteristics of Patients

Figure 1 CONSORT diagram for the trial. CONSORT indicates Consolidated Standards for Reporting of Trials.

The time from remimazolam administration to LOC during anaesthesia induction was significantly shorter in the AF-RMZ group than in the RMZ-AF group (87.3 [25.7] s vs 132.3 [32.3] s, P<0.0001, Table 2). Similarly, the time from remimazolam administration to BIS ≤ 60 was significantly shorter in the AF-RMZ group than in the RMZ-AF group (168.2 [58.1] s vs 207.8 [61.6] s, P=0.0006, Table 2).

Table 2 Sedation Characteristics of Patients Receiving Remimazolam Combined with or Without Alfentanil for Anaesthesia Induction

No significant differences were found between groups in terms of anaesthesia duration, surgery duration, eyes-opening time, extubation time, or PACU stay (Table 2). The total administration of remimazolam did not differ significantly between groups (Table 3). However, remimazolam doses were more in the RMZ-AF group than in the AF-RMZ group at LOC (14.7 [12.3, 16.4] mg vs 9.9 [8.5, 11.0] mg, P<0.0001) and at BIS ≤ 60 (21.3 [17.5, 25.1] mg vs 18.4 [13.1, 22.6] mg, P=0.0058). No differences were found between the groups in terms of the total administration of alfentanil, ephedrine, rocuronium, or crystalloid infusion volume.

Table 3 Characteristics of Anaesthesia and Surgery in Patients Receiving Remimazolam Combined with or Without Alfentanil for Anaesthesia Induction

Table 4 presents the incidence of adverse events. Hypotension was the most common adverse event, but no difference was found between the RMZ-AF and AF-RMZ groups (28 [49.1%] vs 22 [38.6%], 95% CI: 1.3 [0.84–2.0], P=0.3454). The incidence of hypertension was 10.5% (n=6) in the RMZ-AF group and 15.8% (n=9) in the AF-RMZ group (95% CI: 1.5 [0.59–3.8], P=0.5808). Tachycardia occurred in 12.3% of patients in both groups. No patients in either group experienced bradycardia, injection pain, dysphoria, nausea/vomiting, awareness, delirium, or hiccups.

Table 4 Incidence of Adverse Event in Patients Receiving Remimazolam Combined with or Without Alfentanil for Anaesthesia Induction

No significant differences were observed in MBP, heart rate, SpO₂, or BIS values at any time point (Figure 2).

Figure 2 Changes in vital signs of patients receiving remimazolam combined with or without alfentanil for anaesthesia induction. Data are displayed as means (SD) (A–C) or medians (D). Data were compared using repeated-measures two-way analysis of variance (ANOVA) with Geisser-Greenhouse correction, followed by Bonferroni`s multiple comparisons test. (A) Drug: F (1, 112) = 0.8040, p=0.3718; Time: F (11, 1232) = 127.5, p<0.0001; Drug Ⅹ Time: F (11, 1232) = 1.597, p=0.0936; Subject: F (112.1232) = 8.416, p<0.0001. (B) Drug: F (1, 112) = 0.0362, p=0.8494; Time: F (11, 1232) = 11.92, p<0.0001; Drug Ⅹ Time: F (11, 1232) = 7.392, p<0.0001; Subject: F (112.1232) = 14.33, p<0.0001. (C) Drug: F (1, 112) = 1.045, p=0.3088; Time: F (11, 1232) = 11.43, p<0.0001; Drug Ⅹ Time: F (11, 1232) = 0.5367, p=0.8793; Subject: F (112.1232) = 4.385, p<0.0001. (D) Drug: F (1, 112) = 0.7292, p=0.3950; Time: F (8, 896) = 639.0, p<0.0001; Drug Ⅹ Time: F (8, 896) = 1.627, p=0.1131; Subject: F (112.896) = 3.800, p<0.0001. Abbreviations: RMZ, remimazolam; AF, alfentanil; MBP, mean arterial blood pressure; HR, heart rate; SpO2, pulse oximetry; LOC, loss of consciousness; BIS, bispectral index; PACU, post-anaesthesia care unit.

Discussion

This is the first reported randomised controlled trial investigating the interaction between remimazolam and alfentanil. The main finding of our results showed that the time to LOC and the doses of remimazolam required to reach LOC and BIS ≤ 60 during anaesthesia induction were shorter and lower, respectively, in the AF-RMZ group than in the RMZ-AF group. These results confirm our hypothesis that alfentanil enhances the sedative effects of remimazolam during anaesthesia induction in patients undergoing urological day surgery.

Drug interactions can be classified as synergism, additivity, or antagonism, regardless of whether one drug exerts an effect on its own.^14–17 During anaesthesia induction and maintenance, it is a common practice to use two or more drugs either successively or simultaneously. Combining sedatives and opioids has a synergistic effect, enhancing anaesthesia, reducing the dosage of both drugs, and minimising adverse events.¹⁸ For instance, the combination of propofol and alfentanil changed alfentanil’s pharmacokinetics by decreasing elimination clearance by 15%, rapid distribution clearance by 68%, slow distribution clearance by 51%, and lag time by 62%.⁶ Although we did not conduct pharmacokinetic assessments in this study, we speculate that pretreatment with alfentanil can also affect the pharmacokinetics of remimazolam by decreasing elimination clearance and slowing distribution clearance, thereby enhancing the sedative effect of remimazolam.

Drug interactions may occur through the modulation of the action site.¹⁹ Therefore, understanding the mechanisms underlying these interactions is critical. The combination of propofol and alfentanil produced synergistic antinociceptive effects²⁰ through the inhibition of phosphorylated extracellular signal-regulated kinase 1/2, c-Fos protein²¹ and the adenylyl cyclase pathway.²² Propofol exerts sedative effects by potentiating GABA responses and activating GABA type A receptors (GABAARs).²³ Similarly, remimazolam exerts sedative effects by also acting on GABAARs.⁷ Alfentanil exerts its analgesic effect by acting on mu-opioid receptors (MOR). Since both GABAARs and MOR are co-expressed in some primary afferent neurons, it is plausible that propofol–alfentanil and remimazolam-alfentanil administration may activate the same neural pathways, thereby enhancing their sedative effects.

Alfentanil has been used as a sedative regimen in intensive care without causing prolonged respiratory depression.²⁴ Given that the time to LOC or BIS ≤ 60 and the doses of remimazolam required were significantly shorter or lower, respectively, in the AF-RMZ group compared with the RMZ-AF group, we concluded that alfentanil enhances the sedative effect of remimazolam. The peak effect of a bolus injection of alfentanil occurs at approximately 3–4 min,²⁵ while remimazolam reaches a peak effect at 2–3 min. By administering alfentanil immediately before remimazolam, the peak effect of both drugs overlaps, maximising remimazolam’s sedative efficacy. As the exact nature of their interaction – whether synergistic or additive – remains unclear, further investigation is required to elucidate the underlying mechanisms.

Combining alfentanil and midazolam is recommended in different clinical practices. The combination of remimazolam with alfentanil for anaesthesia during endoscopic retrograde cholangiopancreatography (ERCP), colonoscopy, and gastroscopy procedures showed fewer respiratory depression events and haemodynamic advantages than the propofol-alfentanil combination.^26–28 Hypertension, hypotension, and tachycardia were the major adverse events among the two groups; however, no differences were found between the groups in our trial. The awakening time was slightly longer, and the incidence of adverse events (nausea, abdominal pain, fatigue, dizziness, and abdominal distension) were lower in remimazolam-alfentanil group than that in the propofol-alfentanil group during gastroscopy.²⁷ The postoperative 15-item quality of recovery questionnaire score was higher, and the abdominal pain was lower in the remimazolam-alfentanil group than in the propofol-alfentanil group during ERCP procedure.²⁶ Thus, combining remimazolam and alfentanil may be a safe option for anaesthesia.

Sedative-hypnotic drugs and opioids are risk factors for post-operative nausea and vomiting (PONV), which can prolong recovery. None of the patients developed PONV during our trial. Consistent with a previous report, alfentanil reduced the incidence of PONV than fentanyl.²⁹ The use of rapidly metabolic sedative-hypnotic drugs and opioids for anaesthesia is effective in reducing the risk of PONV.³⁰

None of the patients developed emergence delirium (ED) during our trial. Intranasal alfentanil, in addition to oral midazolam, did not decrease sevoflurane-induced ED.³¹ Intravenous alfentanil decreased the incidence of ED in the PACU.³² Compared with intravenous injection, the bioavailability of intranasal alfentanil was reduced to 64.7%.³³ We infer that the different bio-availabilities of alfentanil result in this discrepancy in preventing ED.

Hiccups are a troublesome adverse event associated with remimazolam. Although remimazolam-induced hiccups are generally self-limiting, they are associated with the risk of regurgitation and aspiration, particularly in patients with a full stomach. No patients developed hiccups during this trial. The incidence of hiccups depends on the bolus rate of remimazolam administered during sedation induction.³⁴ We believe that remimazolam administration at a rate of 6 mg kg⁻¹ h⁻¹ during anaesthesia induction would be appropriate. No patients in our trial experienced injection pain, dysphoria, or increased awareness.

Although there was no significant difference in the incidence of adverse events between the two groups in this study, which differed from those of other studies,^26,27 the reasons may be differences in the study population, differences in drug dosage and administration methods, and the study sample size.

This study had several limitations. First, the trial focused exclusively on patients undergoing urological day surgery, limiting the generalisability of the findings to other populations. Further studies are needed to validate these conclusions in other contexts. Second, this was a single-blinded trial. Although the patients, surgeons, and data collectors were blinded to the group assignment throughout the process, the possibility of bias cannot be entirely excluded. Third, all patients were drawn from a single centre, and genetic and racial factors may limit the applicability of our findings to other populations. Further multi-centre clinical trials are required to confirm this conclusion.

Conclusion

In conclusion, alfentanil enhances the sedative effects of remimazolam during anaesthesia induction in patients undergoing urological day surgery. The combination of remimazolam and alfentanil for general anaesthesia would improve efficacy, reducing the adverse effects and dosage of drug. But the potential mechanisms need further study.

Abbreviations

MBP, mean arterial blood pressure; CI, confidence interval; GABA_A, gamma-aminobutyric acid receptor subunit A; ASA, American Society of Anaesthesiologist; PACU, post-anaesthesia care unit; SpO₂, pulse oximetry; BIS, bispectral index; LOC, loss of consciousness; IQR, interquartile range; ASD, absolute standardized difference; ANOVA, analysis of variance; RMZ, remimazolam; AF, alfentanil.

Data Sharing Statement

The data generated during the current study are available from the corresponding author on reasonable request.

Ethic Approval

This study was approved by the Medical Ethics Committee of the First Affiliated Hospital of Guangxi Medical University (identifier: 2022-KY-E-302; Chairperson: Prof. Songqing He) on 13 September 2022 and was registered with the Chinese Clinical Trial Registry (https://www.chictr.org.cn; registration number: ChiCTR2200064130, principal investigator: Xuehai Guan; date of registration: 27 September 2022). Written informed consent was obtained from all patients before enrolment. This trial was performed at the First Affiliated Hospital of Guangxi Medical University in accordance with the Declaration of Helsinki and CONSORT guidelines.

Acknowledgments

This study was supported by the Natural Science Foundation of Guangxi Zhuang Autonomous Region (2022GXNSFAA035628, 2024GXNSFAA010222), the Clinical Research “Climbing” Program of the First Affiliated Hospital of Guangxi Medical University (YYZS2022005), the Guangxi Zhuang Autonomous Region Health Commission’s Self-Fund Research Project on Western Medicine (Z-A20230492), and the Guangxi Zhuang Autonomous Region Traditional Chinese Medicine Appropriate Technology Development and Promotion Project (GZSY22-59). The funder had no role in the concept, patient recruitment, data collection, analysis, interpretation, trial design, or making the decision to submit for publication.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Disclosure

The authors report no conflicts of interest in this work.

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Introduction

Coronary Heart Disease (CHD), as one of the leading causes of death and disability worldwide, has become a significant public health concern.¹ Advances in medical technology have significantly improved the survival rates of CHD patients, enabling an increasing number of individuals to live with the condition for extended periods and resume normal activities. However, quality of life issues during the rehabilitation process, especially sexual health issues, are increasingly attracting widespread attention. Research indicates that sexual dysfunction is prevalent among CHD patients² and can be attributed to multiple factors, including the disease itself, side effects of treatment, and psychological stress.³ There is a close internal link between heart health and sexual health, CHD may directly lead to sexual dysfunction by affecting blood vessel function and blood circulation, and sexual activity itself as a physical activity, will produce a certain load on heart function, thereby causing patients to worry about sexual safety.⁴ Therefore, comprehensive research on heart health and sexual health as a whole will not only help reveal the interaction mechanism between the two, but also provide patients with more comprehensive rehabilitation guidance.

Sexual health, as defined by the World Health Organization (WHO) is an integral component of overall well-being, encompassing physical, psychological, and social dimensions.⁵ For patients with CHD, the disease and its treatments, including surgery and medication, often negatively impact sexual activity, leading to issues such as erectile dysfunction, reduced libido, and decreased sexual satisfaction.⁶ In addition, psychological problems such as anxiety and depression after the illness further aggravate the problem of sexual health.^7,8 Sexual health issues not only affect the individual quality of life of patients, but can also have a negative impact on marital relationships and family harmony.⁹ However, due to cultural, social and doctor-patient relationship, sexual health issues are often ignored or avoided in clinical practice. Patients do not come forward because of shame or lack of trust in the doctor, and the doctor may fail to initiate such discussions because of limited time, lack of expertise, or fear of offending the patient.

The topic of sex is particularly sensitive within Chinese culture. Influenced by traditional beliefs, sexual issues are often considered taboo in many cases and rarely discussed openly even in medical settings.⁸ This cultural background makes CHD patients face more complex sexual health issues during recovery. Although some studies have pointed out that sexual counseling has an important role in helping patients resume sexual life,¹⁰ systematic and standardized sexual counseling services have not yet been formed in China. There is a significant gap between patients’ needs and the services they actually receive, affecting their full recovery. This gap not only hinders the full recovery of patients, but also highlights the urgency of in-depth exploratory counseling and its influencing factors.

The lack of patient perspective is also a shortcoming in the current study. The existing literature mainly focuses on the perspective of medical staff or the impact of disease, and pays less attention to patients’ own experiences and needs.^8,11,12 This lack is due to a number of reasons. First, cultural taboos prevent patients from speaking openly about sexual health problems, making it difficult for researchers to obtain first-hand information from patients.⁸ Second, in clinical practice, medical professionals often prioritize the acute symptoms of heart disease over the sexual health needs of patients, thus limiting the systematic exploration of patient perspectives.^13,14

Based on the Comprehensive Framework for Implementation Research (CFIR) and the Capability, Opportunity, Motivation-behavior model (COM-B), this study explores the facilitators and barriers to the implementation of sexual counseling through qualitative research methods. Heart health and sexual health, two key areas that affect patients’ quality of life, face the challenge of stigmatizing discussions in many cultures, especially in the context of China, where such traditional beliefs are deeply ingrained. Combining these two theories, this study provides a comprehensive understanding the implementation status of sexual counseling in CHD patients from the perspective of both the supply and demand of sexual counseling through in-depth interviews, provides theoretical support for the formulation of more effective intervention strategies, and provides specific recommendations for policy makers, healthcare administrators and front-line medical professionals in practice.

Methods

Study Design and Participants

This study uses a describe qualitative research to assess the determinants influencing the implementation of sexual counselling. Purposive sampling method was used to select medical staff and patients from the cardiovascular department of the First Affiliated Hospital of Xinxiang Medical College, Henan Province in China from November 2023 to January 2024 as the study objects. Doctors and nurses who experience in treating or caring for patients in the cardiovascular department for more than 2 years are selected. Patients diagnosed with coronary heart disease, aged 18 years or older, had a stable sexual partner, maintained a normal sexual life before the disease, and had no communication disorders were selected. Patients with CHD combined with heart failure and mental illness were excluded.

Theoretical Framework

CFIR and COM-B model were used as theoretical guidance to guide data collection and analysis. CFIR is divided into five dimensions and 39 components, including intervention characteristics, inner setting, outer setting, participant characteristics and implementation process.¹⁵ The framework serves as a determinant framework that offering researchers a structured approach to analyzing and understanding the various factors that influence the successful implementation of a project, policy, or intervention.¹⁶ Based on CFIR, this study analyzed factors such as intervention characteristics, environment and participant characteristics in the implementation of sexual counseling from the perspective of medical staff. For example, “How do you think to conduct sexual counseling for patients with CHD (eg, way, method, content)?” explores intervention characteristics, “What do you think are the factors that sexual counseling does not conducted in patients with CHD?” examines the potential influence of external environment (eg, culture) and internal environment (eg, resources), and “Do you know anything about sexual counseling for cardiovascular patients?” assesses individual characteristics.

The COM-B model comprising capability, opportunity and motivation-behavior,¹⁷ This model examines the behavioral changes of people from three dimensions of ability, opportunity and motivation,¹⁸ which is used to guide the understanding of relevant behaviors, establish the behavioral goals, and lay the foundation for designing intervention measures.¹⁸ Based on the COM-B model, this study analyzed the determinants of sexual counseling seeking behavior from the perspective of patients. Such as “Do you know anything about having sexual life safely after illness?” assesses psychological ability, “Who do you want to get it from, and in what way (eg, telephone, brochure)?” explores physical opportunities, and “What do you think are the reasons for not seeking counseling?” reflects reflective motivation.

Research Team

Our team consisted of four researchers, a female professor responsible for the design and quality control of the study, two Ph.D. researchers (two females) involved in the collection and analysis of the data, and another female professor with extensive experience in qualitative research who was responsible for negotiating and determining the code.

Data Collection

Two researchers established good relationships with participants. Face-to-face semi-structured interviews were used in this study. An interview outline was developed for medical staff and patients based on CFIR and COM-B models. After the interview outline is drawn up, researchers familiar with the subject are invited to revise it. After the pre-experiment, the interview outline was modified again to form the final interview outline (Appendix 1). Each interview lasted 30 to 50 minutes. Before the interview, the demographic data of the participants were collected, the purpose of the interview was informed, and the interview was started with the consent of the participants. During the interview, two researchers participated in the interview and collected data simultaneously through notes and recordings. The interview was conducted in a quiet and undisturbed environment. After the interviews, the two researchers transcribed the interviews verbatim into text within 24 hours. A researcher used the notes taken during the interview to supplement and verify the interview text. Subsequently, the two researchers summarized the data and analyzed whether new topics appeared to determine the saturation of information. When the information reached saturation, the number of participants in the interview was the sample size of this study.

Data Analysis

After the interviews, NVivo11 software was used to encode the data. Data analysis followed the thematic analysis method proposed by Braun and Clarke.¹⁹ The analysis process included steps such as becoming familiar with the interview data, generating initial codes, summarizing themes, reviewing themes, and naming themes. First, two researchers read each transcript word for word and took preliminary notes to familiarize themselves with the data. Next, by reading the data line by line, the researcher marked the words and sentences related to the research questions and openly coded the data. Subsequently, similar or related codes were sorted together to form a preliminary coding framework. After the initial codes are generated, the researchers summarized and organized these codes, identified potential topics, and brought together all the codes and data fragments related to each potential theme to form a preliminary framework of themes. Finally, each theme was checked for consistency with the relevant codes and the entire data set, and individual themes were mapped into the CFIR and COM-B models.

Researcher Reflexivity

In this study, two researchers systematically reflected on the potential influence of their personal backgrounds, perspectives, and experiences on the research process through detailed reflective journals and regular team discussions. To enhance the reliability of the results, the study used data source triangulation (collecting data from both medical staff and patients’ perspectives) and researcher triangulation (two researchers independently coded, which was reviewed and agreed upon by a third researcher). In addition, methodological rigor and robustness of study findings were ensured by checking preliminary results with participants, confirming data saturation (new information no longer appears), and following the COREQ 32-item checklist.

Ethics

This study was approved by the Ethics Committee of the First Affiliated Hospital of Xinxiang Medical College (No. (Nọ): EC-022-005). The researchers adhered to the Declaration of Helsinki. The information collected in the study was strictly confidential and anonymous. Letters were used to replace the patients’ name in the study, “D” stands for doctor, “N” stands for nurse, “M” stands for male patient, and “F” stands for female patient. Participants were informed that they could withdraw from the study at any time and/or refuse to answer any questions.

Results

A total of 23 participants were included in this study, including 10 medical staff and 13 patients with CHD. The medical staff included 8 doctors and 2 nurses, 7 of whom were male and 3 were female (Table 1). Among the patients, there were 10 males and 3 females, aged mainly between 41 and 50 years old, accounting for 46.2%, most of the patients had a junior high school education (Table 2).

Table 1 Demographic Data with Medical Staff (n=10)

Table 2 Demographic Data with Patients (n=13)

Interview Results of Medical Staff

The themes and subthemes derived from the study are shown in Table 3.

Table 3 Facilitators and Barriers Themes with Medical Staff

Intervention Characteristics

Integrate into Daily Health Education

Medical staff recommend integrating sexual counseling into routine health education to reduce the embarrassment of patients and medical staff when discussing sexual health issues. By naturally embedding the content of sexual health education into routine health education, sexual counseling can become a part of routine care, thereby alleviating the psychological burden on patients when asking questions. This approach sends a clear message to patients that sexual health is part of a comprehensive health management process and that they can feel free to ask questions without feeling uncomfortable or shy.

D9: Incorporate knowledge about sexual life into daily health education so that it is not easy to cause discomfort to patients. There is no need to talk about it specifically. Just give patients a signal so that those who have questions can actively ask medical staff.

Use of Information Brochures

Medical staff recommend using detailed health education brochures that patients can read in private. This approach effectively protects patients’ privacy and enables them to obtain sexual health information in an undisturbed environment. At the same time, the brochures can provide guidance on how to obtain further sexual counseling, reminding patients to actively seek help when needed. This approach not only makes it easier for patients to access information, it also increases the likelihood that they will proactively contact their medical staff, thereby improving the overall effectiveness of care.

D8: You can provide patients with a health knowledge booklet and write the content in the booklet as detailed as possible. This can not only protect the patient’s privacy, but also send a signal to the patient, allowing the patient to ask medical staff if he has any questions.

Personalized Consultation Based on Patient Needs

Medical staff emphasize that sexual counseling must be tailored to the individual needs of patients to ensure that their specific circumstances and special requirements are met. Each patient’s background, medical condition, and focus on sexual health issues may be different, so sexual counseling cannot be a one-size-fits-all approach. Medical staff should fully understand the patient’s personal experience, cultural background and psychological state so as to provide targeted advice and support. Personalized sexual counseling can not only more accurately address patients’ specific problems, but also improve patient satisfaction and treatment outcomes.

N7: When doing sexual counseling, you need to first understand the patient’s condition and educate the patient based on his or her needs.

Misconceptions About Specialists

Patients often mistakenly believe that cardiologists focus only on the treatment of heart disease. This misunderstanding stems from a narrow understanding of the role of the cardiovascular physician, which leads patients to view sexual health issues as a separate area unrelated to heart disease. As a result, they are unaware that cardiologists can provide valuable assistance, leading to a lack of trust in the physician’s overall abilities and limiting the willingness to proactively seek help.

D4: Some patients believe that specialists are responsible for their own treatments and are unaware that doctors have knowledge in this area. They mistakenly believe that cardiologists only treat heart problems.

Outer Setting

Benefit from External Learning

Healthcare professionals who have received sexual counseling training or have participated in sexual counseling practices have found these experiences to be very beneficial to their professional development and patient care. The training made them realize the importance of sexual health knowledge in practical work and improved their ability to identify and solve patients’ sexual health problems. Through systematic training, healthcare professionals can not only provide effective sexual counseling to help patients understand and manage disease-related sexual issues, but also significantly improve the overall quality of life of patients.

D10: I have learned relevant guidance when I was training in other hospitals. It clearly stated how long it takes to resume sexual intercourse after myocardial infarction or PCI surgery. The hospital also provided patients with rehabilitation and guidance in this aspect, which improved their quality of life.

Traditional Culture’s Barriers to Sexual Counseling

Medical staff believe that traditional culture has a significant impact on patients’ ability and willingness to discuss sexual health issues. In Chinese culture, sex is considered a private and taboo topic, which means that even if patients have concerns, they may choose to keep silent due to embarrassment and shame. Especially when communicating with medical staff of the opposite sex, patients’ resistance is more obvious. Traditional gender roles and privacy concepts further aggravate their shyness and anxiety.

D6: In China, sex is a very sensitive topic, and even if patients have sexual problems, they will avoid talking about it in most cases.

D10: Influenced by traditional culture, I am relatively conservative and embarrassed to ask. I also won’t take the initiative to tell patients these things because I don’t know whether they need it or not.

N7: When facing patients of the opposite sex, sometimes patients are reluctant to speak because they feel embarrassed. For example, male patients are embarrassed to speak to female doctors.

Inner Setting

Lack of Suitable Environment for Consultation

Lack of a privacy is one of the most important barriers to sexual counseling. The noise, high turnover and small space in the wards limit the possibility of private and sensitive discussions. In this environment, it is difficult for patients to open up about their sexual health concerns and needs. In addition, the presence of other patients and medical staff may make patients feel embarrassed and reluctant to ask sexual questions, causing them to feel ignored and affecting their acceptance of sexual counseling.

D10: Chinese culture are relatively conservative when discussing sexual topics, and sexual counseling must be conducted in a secret environment.

N3: The environment in the ward is quite noisy. It is not appropriate to conduct sexual counseling in the ward. It is better to have a private environment.

Characteristics of Individuals

Willingness to Learn and Implement Evidence-Based Practice

Many medical staff said that they would be willing to learn sexual counseling knowledge and apply it in clinical practice if evidence-based evidence and relevant training were available. Systematic training allows them to acquire best practices and the latest research, thereby enhancing the professionalism and effectiveness of their consultation. In summary, medical staff hope to improve their sexual health knowledge through scientific training in order to better meet the needs of patients.

D1: As long as I have evidence-based guidance on what to do, I am willing to give guidance to patients, and I am willing to learn and work on sexual counseling.

N7: Patients have this need and sexual life is very important to them, but they are unwilling to speak up. I think medical staff should actively carry out this work, and I am willing to join in this work.

Resistance to Sexual Counseling

Some medical staff are reluctant to provide sexual counseling, mainly due to lack of knowledge and interest in sexual health issues. On the one hand, many medical staff feel uncomfortable when providing sexual counseling due to lack of professional training and lack of knowledge. On the other hand, high workloads and tight schedules limit their ability to pay attention to and deal with patients’ sexual health issues.

D2: I have never thought about studying relevant literature. Compared with the disease itself, this is not important. Even if I know the relevant knowledge, I am still unwilling to carry out health education or consultation on sexual life.

D5: Doctors have limited energy and there are too many patients, they don’t have time to deal with these.

Patient Interview Results

The themes and subthemes derived from the study are shown in Table 4.

Table 4 Facilitators and Barriers Themes with Patients

Physical Capability

Physical Condition

Physical condition is an important barrier to sexual counseling for patients. Some patients tend to feel uneasy about changes in their physical condition, and even if they do not feel any discomfort in their daily activities, their anxiety and worry make them hesitant and unwilling to take the initiative to consult medical staff. Concerns about their physical condition limit their access to sexual health issues.

M1: I didn’t feel any discomfort and had no symptoms after light physical labor. Considering the illness, I started having sex after a while, and I didn’t have the awareness to ask for advice on when to start having sex.

Physiological Condition

Some patients believe that their sexual function declines with age, and even if they have sexual problems after becoming ill, they do not think it is necessary to seek professional consultation.

M9: After illness, I felt that the quality of my sexual life was not as good as before illness. However, as I got older, I had fewer sexual intercourses, so I was not willing to seek sexual counseling.

Psychological Capability

Misconception

Some patients have the wrong perception that sex is a completely personal issue, so they are ashamed to ask or discuss it with others. They do not seek sexual counseling not only because they are ashamed but also because they lack relevant knowledge and do not know where to get sexual counseling. In addition, due to the influence of sociocultural factors, they often have doubts about seeking professional support, which also exacerbates patients’ neglect of sexual health issues.

M13: I didn’t know that coronary heart disease affects sexual function, and I didn’t know that I could get sexual counseling from medical staff. Medical staff didn’t mention these things to me. Besides, sexual life is a personal matter, and I’m embarrassed to ask others.

Lack of Knowledge

Patients lack knowledge about sex. They often only realize the impact of disease on physical health, but do not realize that disease can also affect the quality of sexual life. Furthermore, because medical staff fail to offer patients with detailed information about sexual health during discharge instructions, patients were unable to obtain adequate sexual health knowledge.

F7: I did not know that coronary heart disease would affect sexual function. I just thought that after the operation, I was afraid to have sex. There was no medical staff to provide relevant education and guidance, and I did not know that I could seek sexual counseling from medical staff.

M5: I have not paid attention to whether coronary heart disease has any impact on my sexual life. When I was discharged from the hospital, the doctor informed me of the precautions I should take at home about the disease, but did not provide me with any knowledge about sexual life. Therefore, I had no awareness of seeking medical advice when I had sexual health problems.

Opportunity

Physical Opportunity

Social Environment

Social environment inhibits patients from discussing sexual health issues. People around them avoid talking about sexual health issues, and this atmosphere of silence makes them feel embarrassed to speak up and unable to take the initiative to talk about related topics or seek help.

M11: None of my friends talk about sex, and I am embarrassed to talk about it.

M10: I don’t know this knowledge either, and the people around me also lack this knowledge, so I can’t consult others.

Social Opportunity

Social Culture

Cultural norms and the perception that sexual topics are highly private prevent patients from discussing these sensitive topics with their healthcare providers. In Chinese culture, talking about sex is considered taboo, and even if patients realize they need help, they often remain silent due to cultural pressure.

M6: I am relatively conservative and think that sex is a private topic. I have never dared to ask other people. I have looked up relevant questions on the Internet and in books. I am embarrassed to consult medical staff.

M3: I think sexual topics are personal privacy and I am unwilling to mention them to outsiders. I have never asked anyone else and I don’t know that medical staff can provide relevant knowledge.

Motivation

Reflective Motivation

Self-Assessment

Patients often rely on self-assessment for sexual health issues, believe that they do not need sexual counseling if they do not have obvious symptoms, and lack the initiative to discuss sexual health issues with medical staff. This misconception causes them to ignore potential sexual health problems and weakens their willingness to seek professional guidance.

M1: I thought there was nothing wrong with my body, so I didn’t consult any medical staff and I didn’t know whether the disease had any impact on my sexual function.

Psychology

The patient’s psychological state has a negative impact on his or her physical health and the quality of his or her sexual life. When patients feel anxious or fearful about their illness or treatment outcomes, this emotional state can exacerbate their concerns about their sexual life, which can affect their sexual function and overall life satisfaction.

F8: After the operation, I have no symptoms after daily activities, but I am afraid of an acute attack of the disease and dare not have sex. I wonder if I can consult the medical staff of the cardiovascular department.

Automatic Motivation

Necessity of Things

Despite multiple barriers, some patients are eager to learn about the impact of the disease on their sexual health and believe that acquiring sexual health knowledge is crucial to improving their quality of life. These patients hope to obtain detailed sexual health knowledge and hope to get help from medical staff.

M6: Patients lack the knowledge about safe sex after the disease and are afraid to have sex. They hope to learn about this from medical staff and feel it is necessary to learn about it.

F4: Some patients are eager to learn relevant knowledge, hope that medical staff can provide relevant knowledge, and are willing to make changes.

Discussion

Based on the CFIR and COM-B models, this study systematically analyzed the determinants of sexual counseling for patients with CHD and found that there are many factors that affect sexual counseling, involving multiple levels such as medical staff, patients and their social environment. Most of the research results are consistent with previous studies.^11,12,20 Research shows that many medical staff believe that sexual counseling is difficult to implement directly. They suggest embedding sex-related knowledge into health education. This implicit intervention strategy can reduce patients’ embarrassment and discomfort, and patients may be more likely to accept it. This is consistent with a study, this study shows that due to the confidentiality of sexual topics, it is difficult for medical staff to provide sexual counseling. The study found that patients prefer to obtain sexual knowledge through indirect channels such as health education, WeChat and so on.⁷ However, this approach may also result in some patients being unaware of the availability of sexual counseling, thereby missing out on the opportunity to obtain targeted intervention. Therefore, future interventions should find a balance between implicit and explicit approaches to protect patient privacy while ensuring the effectiveness of information delivery.

The study found that some medical staff are resistant to sexual counseling, partly because they lack relevant knowledge and guidance. Many medical training programs do not pay enough attention to sexual health, and medical staff lack knowledge about the sexual health of patients with coronary heart disease.^13,14 This makes medical staff lack the confidence and ability to discuss such issues. Even if they recognize the importance of sexual health, they are often afraid to talk about it. On the other hand, high workload is an important factor that causes medical staff to ignore sexual health issues. Clinical medical staff face a large number of daily tasks and emergencies. Due to limitations of time and resources, they can only deal with patients’ disease treatment and lack the energy to pay attention to sexual health issues. In this case, patients’ sexual health issues become a secondary issue.¹³ Although sexual health is critical to a patient’s quality of life, it is often neglected due to time and resource constraints on medical staff.

Culture is an important factor affecting the implementation of counseling. In traditional Chinese culture, the moral constraints of Confucianism,²¹ the implicit expressions of Taoism, and the restraint concept of Buddhism²² have led Chinese to believe that sexual issues are private issues, or even taboo topics. This leads to patients often choosing to look up information on their own or not deal with it when they have sexual health problems.^23,24 This study also reached a similar conclusion. The perception and attitudes towards sexuality among Chinese people not only influence how patients approach sexual health issues but also affect how healthcare professionals address these concerns. Many medical staff are worried that discussing sexual issues will cause discomfort or embarrassment to patients, which leads them to avoid discussing them in actual work. This is consistent with the research views of Emily K. Hyde et al.¹¹ Cultural barriers lead to the neglect of sexual health issues in clinical practice. Compared with Western countries, patients in China are more reluctant to take the initiative to raise sexual health issues,¹⁴ resulting in medical staff not knowing how to intervene, which makes greater challenges to the promotion of sexual counseling in China. Therefore, future interventions need to gradually guide patients and health care professionals to discuss sexual issues more openly while respecting cultural backgrounds.

Despite the many obstacles, this study also found some factors that are conducive to the implementation of sexual counseling. For example, some medical staff said that they are willing to conduct sexual counseling if there is evidence-based guidance. This shows that by providing scientific evidence and practical operation guidelines, the enthusiasm of medical staff can be stimulated and the promotion of sexual counseling can be promoted. In addition, some patients expressed their desire to acquire sex-related knowledge and were willing to accept guidance from medical staff, which provided a good basis for the implementation of sexual counseling.

This study provides insights into the implementation of sexual counseling in the Chinese context and has certain implications for future research. By integrating CFIR and COM-B models to combine determinants from both supply and demand sides, this study transcends a single healthcare professional perspective, revealing the interplay between cultural taboos and environmental constraints and its implications for systemic interventions, offering valuable insights for countries with conservative cultural backgrounds. This study emphasizes the importance of patient education and suggests that implicit education (eg, manuals) is more suitable for sensitive environments. It also preliminarily identifies barriers and opportunities and suggests measures such as training, improving the consultation environment (eg, private space), and incorporating sexual health into cardiac rehabilitation guidelines to alleviate limitations in implementation. Meanwhile, future extension of these findings to multi-regional and multi-cultural studies is encouraged to verify their applicability.

Limitations

The study also has some limitations. First, the generalizability of the results may be affected by the limited sample size. Future studies should increase the sample size, especially by increasing the participation of patients and medical staff from different regions and cultural backgrounds. Secondly, the depth of qualitative research depends on participants’ willingness to express and the richness of interview data. Although this study ensures the adequacy of the subject through data saturation, some participants may not fully disclose their experience due to cultural taboos or personal reservations, which may limit the exploration of some potential problems. In addition, while the research team reduced subjective bias through reflection and triangulation, the researcher’s interpretation of the data may still be influenced by personal perspective. Therefore, future studies may consider combining quantitative studies to further verify the comprehensiveness of the results.

Conclusion

This study systematically analyzed the multiple factors that affect the implementation of sexual counseling for patients with CHD in China. The results showed that the implementation of sexual counseling was constrained by the knowledge and attitudes of medical staff, the counseling environment, the physical abilities and psychological barriers of patients, and the sociocultural background. Nevertheless, some medical staff and patients have a positive attitude towards sexual counseling, which provides a basis for promoting the implementation of sexual counseling. In the future, On the basis of respecting cultural background, we should explore in depth the effective intervention measures for the implementation of promotional counseling to comprehensively improve the quality of life of patients.

Data Sharing Statement

The data that support the findings of this study are available on request from the corresponding author. The data are not publicly available due to privacy or ethical restrictions.

Ethics Approval and Informed Consent

This study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the Ethics Committee of The First Affiliated Hospital of Xinxiang Medical University (No: EC-022-005).

Consent for Publication

All participants signed informed consent, including permission to publish anonymous responses and direct quotes.

Acknowledgments

We thank all the researchers and participants who participated in this study.

Author Contributions

All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.

Funding

The authors declare that no funds, grants, or other support were received during the preparation of this manuscript.

Disclosure

The authors have no relevant financial or non-financial interests to disclose for this work.

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22. Ruan FF. Sex in China: Studies in Sexology in Chinese Culture. Springer US; 1991. doi:10.1007/978-1-4899-0609-0

23. Kong X, Zhang H, Shen Y, Wu H, Chen R. The status quo of recovery of sex life in patients with coronary heart disease and the research progress of health education. Chin J Nurs. 2010;45(11):1039–1041.

24. Wang S, Li Y, Zhao D, Gao Y, Gao Y. A survey of knowledge and practice of cardiac rehabilitation staff on sexual health management of patients with coronary heart disease. Acad J Chin PLA Med Sch. 2012;33(10):1083–1084+1087.

A landmark 30-year study of over four million women in England has revealed that women with endometriosis-associated infertility are significantly more likely to become pregnant compared to those with infertility from other causes.

Presented today at the 41st Annual Meeting of the European Society of Human Reproduction and Embryology (ESHRE), the findings offer renewed optimism for millions of women living with endometriosis who are hoping to conceive. 

Endometriosis is a long-term condition in which tissue similar to the lining of the womb grows outside the womb, often causing severe pelvic pain and infertility. Globally, it is estimated to affect 190 million women and is recognised as a leading cause of infertility.

This study was conducted as part of the EU FEMaLe (Finding Endometriosis through Machine Learning) consortium. Led by Dr. Lucky Saraswat from the Aberdeen Centre of Women’s Health Research, University of Aberdeen, together with researchers from the Centre for Reproductive Health at the University of Edinburgh, the research team carried out the largest and longest population-based study of its kind, analysing linked primary care, secondary care and maternity records for more than four million women in England who presented with infertility or symptoms related to endometriosis between 1991 and 2020.

Of the 4,041,770 women aged 13-50 years who attended primary care with infertility (n=245,994) or other symptoms of endometriosis, 111,197 had a surgically confirmed diagnosis of endometriosis via laparoscopy or laparotomy over the 30-year period. The overall population prevalence of female infertility across the population during the study period was 48.9 per 1,000 women, with highest rates observed among women aged 30 to 39.

Among those with infertility, 6.1% (14,904) had surgically confirmed endometriosis. Of these, 57.4% (8,556) experienced infertility before their diagnosis, underlining the ongoing delays in recognition and diagnosis of endometriosis.

The study reaffirmed a strong association between the condition and fertility challenges, showing that women with infertility were more than twice as likely to be diagnosed with endometriosis compared to women without infertility.

However, when examining pregnancy outcomes, women with endometriosis-associated infertility had a four times higher chance of conception compared to women with infertility from other causes, including ovulatory dysfunction, tubal factors, and unexplained infertility. In total, 40.5% of women with an endometriosis diagnosis (regardless of their infertility status) had at least one pregnancy during the study period. 

Reflecting on the potential explanations for this result, Dr. Saraswat said, “Endometriosis can vary in how it affects fertility. Women with milder forms may retain good reproductive potential, especially if the condition is diagnosed and managed early. There’s also moderate-quality evidence suggesting that laparoscopic surgery can improve pregnancy rates in some with endometriosis.”

She added that women with the condition may also be more likely to seek help earlier because of heightened awareness about the link between endometriosis and infertility. 

“While fertility remains multifactorial, with factors such as age playing a significant role, our findings offer robust, evidence-based data that can significantly enhance fertility counselling for women newly diagnosed with endometriosis – including information on the likelihood of infertility, overall pregnancy rates and outcomes, and how those outcomes compare to other causes of infertility.”

“These insights can empower women to make informed reproductive decisions“, she said. “They also provide a strong foundation for future research into how factors such as disease stage, site, surgical treatment and use of assisted reproduction influence pregnancy outcomes in women with endometriosis.” 

This study shows that women with endometriosis-related infertility are significantly more likely to conceive than those with other infertility causes. These findings provide valuable reassurance for patients and underscore the importance of early diagnosis and tailored treatment strategies.”

Professor Dr. Anis Feki, Chair-Elect of ESHRE

The study abstract will be published today in Human Reproduction, one of the world’s leading reproductive medicine journals.

Maintaining a healthy lifestyle-specifically, a diet rich in fibre but light on red/processed meat, regular exercise, not smoking, and sticking to a normal weight-is linked to a significantly lower risk of diverticulitis, finds a large long term study, published online in the journal Gut.

What’s more, these 5 components seem to offset the effects of inherited genes, the findings indicate.

Diverticulitis occurs when ‘pouches’ develop along the gut and become inflamed or infected in the wall of the large intestine (colon), explain the researchers. It’s a common cause of hospital admissions and a major reason for emergency colon surgery, they add.

Genetic and environmental factors, including lifestyle, contribute to the development of the condition, but it’s not clear exactly how these factors interact or the extent to which lifestyle might offset the genetic risk, they say.

To shed more light on this, the researchers derived an overall healthy lifestyle score (0-5) for diverticulitis from survey responses for 179,564 participants drawn from three prospective studies: the Nurses’ Health Study (NHS), NHSII, and the Health Professionals Follow-Up Study.

The score was based on 5 elements that have independently been associated with heightened risks of developing diverticulitis: smoking; weight (BMI); physical activity; fibre intake; and red/processed meat intake. 

The association between this score and incident diverticulitis was confirmed among 30,750 participants in the Southern Community Cohort Study (SCCS). 

Genetic risk was assessed using a polygenic risk score (PRS) in 36,077 people with available genotype information. 

During a monitoring period of 20 years, 10,299 new cases of diverticulitis were recorded. The 5 lifestyle factors were each significantly associated with the development of the condition. 

For example, compared with participants with a BMI below 25, those who were overweight were 32% more likely to develop diverticulitis, while those who were obese were 44% more likely to do so. 

Participants who had formerly or who were still smoking were, respectively, 17% and 13% more likely to be diagnosed with diverticulitis than those who had never smoked. And higher levels of physical activity were associated with a 16% reduced risk compared with lower levels. 

While higher fibre intake was associated with a 14% lower risk, higher red meat intake was associated with a 9% increased risk. 

And every 1-point increase in healthy lifestyle score was associated with a 12% lower risk of diverticulitis. Participants with a score of 5 were 50% less likely to be diagnosed with the condition than those with a score of 0.

The findings were consistently observed across all three studies and in different racial groups.

The association between healthy lifestyle score and incident diverticulitis was confirmed among 30,750 participants in the Southern Community Cohort Study (SCCS). 

Some 2183 new cases of diverticulitis were reported during an average monitoring period of nearly 12 years in this group. Those with a healthy lifestyle score of 3–5 had a substantially lower risk (31%) than those with a score of 0. 

Genetic risk was assessed using a polygenic (cumulative) risk score (PRS) in 36,077 people with available genotype information in the NHS, NHSII, and HPFS groups.

There were no notable differences in lifestyle factors across PRS categories, but PRS was significantly associated with incident diverticulitis. For each unit increase in PRS, the risk increased by 58%, and was particularly evident among those under the age of 60. 

And a healthy lifestyle seemed to offset genetic susceptibility to the condition. For example, those in the lowest PRS category and with a healthy lifestyle score of 4-5 were 37% less likely to develop diverticulitis compared to those with a score of 0.

Similarly, those with a medium PRS were 48% less likely to do so, while those in the highest PRS category were 50% less likely to do so. Further analysis showed that adopting a healthy lifestyle might prevent 23–42% of diverticulitis cases across PRS categories.

And when the effect of PRS and a healthy lifestyle score were combined, those in the highest PRS category with a healthy lifestyle score of 0 or 1 were 5 times more likely to develop diverticulitis than those in the lowest PRS category with a score of 4 or 5. 

The findings were further validated in the Mass General Brigham Biobank (MGBB).

This is an observational study, and as such, can’t establish cause. And the researchers acknowledge that ascertainment of diverticulitis was based on different approaches across the different studies.

Nevertheless, they conclude: “Our data provide consistent evidence from multiple data sets indicating that adherence to a healthy lifestyle is linked to a reduced risk of developing diverticulitis, irrespective of one’s genetic predisposition.”

A real-world, multicenter study of 67 evaluable patients treated with fecal microbiota, live-jslm (RBL), demonstrated a 77.6% treatment success rate at 8 weeks for preventing recurrent Clostridioides difficile infection (rCDI), with 87% maintaining remission at six months. These findings support RBL’s safety and efficacy beyond controlled clinical trials in an elderly, comorbid population frequently exposed to multiple rCDI risk factors.¹

What You Need To Know

RBL achieved a 77.6% treatment success rate at 8 weeks and 87% sustained remission at 6 months in a high-risk, elderly population.

The treatment was well tolerated, with minor adverse events reported in only 5 patients.

Advanced age and multiple CDI recurrences were common risk factors, emphasizing the need for effective microbiota-based preventive strategies in these patients.

RBL, FDA-approved in November 2022 as the first microbiota-based product for rCDI prevention in adults, is administered rectally after standard-of-care antibiotics. The study population had a median age of 74 years and a median Charlson comorbidity score of 4, with over half having three or more prior CDI recurrences. Risk factors were prevalent, including advanced age (72%), gastric acid suppressant use (55%), immunocompromise (24%), and recent non-CDI antibiotic exposure (21%).¹

All patients received prior antibiotics, most commonly fidaxomicin (58%), before RBL administration. Adverse events were minimal, limited to minor leakage in 5 patients. Age ≥65 was significantly associated with higher recurrence risk. Among patients experiencing recurrence within 8 weeks, median time to relapse was 28 days. Of 30 patients with 6-month follow-up data, 26 (87%) sustained treatment response.¹

These data provide important evidence for clinicians managing complex rCDI cases, highlighting RBL as a valuable and well-tolerated intervention to reduce recurrence risk in routine practice.¹

In relation to RBL, in a recent interview with Paul Feuerstadt, MD, FACG, AGAF, he emphasized that beyond effectively reducing recurrent Clostridioides difficile infections, the treatment plays a crucial role in improving patients’ overall quality of life. Feuerstadt described how recurrent CDI often leads to significant anxiety, fear, and social isolation, likening the emotional burden to post-traumatic stress. He noted that RBL not only targets the infection but also helps restore patients’ mental, physical, and social well-being, allowing them to regain confidence and normalcy in their daily lives.²

Reference

1.Seo S, Hengel R, Krishnan S, et al. Real-World Experience with Fecal Microbiota Treatment (live-jslm) for the Prevention of Recurrent Clostridioides difficile Infection. Abstract 85 E. MAD-ID Meeting. May 28–31, 2025. Orlando, FL.

2.Improved Symptoms and Health-Related Quality of Life in Adults with Recurrent Clostridioides Difficile Infection after Fecal Microbiota, Live-jslm (RBL) Administration by Colonoscopy. Abstract presented at DDW 2025, May 3-6, 2025. Accessed July 1, 2025.

This study investigates the effectiveness of a vitamin D3-loaded nanoemulsion in improving the core symptoms of autism spectrum disorder (ASD) in children. Children with ASD often have low vitamin D3 levels, which are linked to delays in language development, adaptive behavior, and fine motor skills. While traditional vitamin D3 supplementation has shown mixed results in past studies, this research evaluates whether a nanoemulsion form-engineered to enhance absorption and bioavailability-might produce better outcomes.

Eighty children between the ages of 3 and 6 with diagnosed ASD were randomly assigned into two groups: one receiving the vitamin D3 nanoemulsion, and the other receiving a standard marketed vitamin D3 product, both for a duration of 6 months. Their vitamin D3 levels, adaptive behaviors, and language abilities were assessed before and after supplementation using standardized tools such as the Childhood Autism Rating Scale (CARS), Vineland Adaptive Behavior Scale, and Preschool Language Scale. Only the nanoemulsion group showed statistically significant improvements in vitamin D3 levels, autism severity, social IQ, and both receptive and expressive language performance. The conventional supplement, despite raising blood vitamin D3 levels, did not lead to meaningful improvements in behavioral outcomes.

The study concludes that the nanoemulsion form of vitamin D3 is superior to the conventional oral form in terms of increasing vitamin bioavailability and producing clinically relevant improvements in children with ASD. The authors suggest that nanoemulsion technology could offer a valuable strategy for enhancing the effectiveness of nutritional interventions in neurodevelopmental disorders. However, they acknowledge that further studies with larger sample sizes and long-term follow-up are needed to confirm these findings and explore potential gender-related differences in response.

A new study published in Allergy from researchers at Sweden’s Karolinska Institutet reveals that biologic therapies mepolizumab and dupilumab—while clinically effective in reducing exacerbations and improving asthma control—do not fully eliminate type 2 inflammatory lymphocytes in individuals with severe asthma. Paradoxically, treatment is associated with increased frequencies of circulating type 2 innate lymphoid cells (ILC2), type 2 helper T cells (Th2), and cytotoxic T cells (Tc2), alongside phenotypic shifts that may alter their tissue homing and functional properties.

These findings suggest that persistent immune activation may continue under the surface, raising questions about the feasibility of biologic-free remission in some patients.

“We were surprised to find that blood levels of inflammatory cells increased rather than decreased,” Lorenz Wirth, doctoral student at Karolinska Institutet’s Department of Medicine in Huddinge, Sweden, said in a statement. “This could explain why inflammation of the airways often returns when the treatment is tapered or discontinued. It is important that we understand the long-term immunological effects of these drugs.”

The study addresses a critical gap in understanding how these targeted therapies influence immune cell dynamics beyond blood eosinophils. While biologics targeting interleukin (IL)-5 (eg, mepolizumab) or the IL-4 receptor alpha chain (eg, dupilumab) are now standard therapy for individuals with severe, eosinophilic, or Th2–high asthma, little is known about their impact on circulating type 2 lymphocytes—cells central to asthma pathogenesis. Given that some patients remain symptomatic despite treatment and that long-term remission is an emerging goal, researchers sought to characterize whether these cells persist or resolve with therapy.

Researchers analyzed peripheral blood samples from 40 participants with severe asthma enrolled in the longitudinal BIOCROSS study. All participants had uncontrolled asthma despite guideline-directed therapy and were treated with mepolizumab (n=33) or dupilumab (n=7). The research team collected blood samples at baseline, 4 months, and 12 months. Flow cytometry, single-cell RNA sequencing, and ex vivo stimulation assays were used to characterize type 2 lymphocyte populations and their transcriptional and functional changes over time.

FINDINGS

Clinically, both therapies led to significant improvements. Mepolizumab-treated participants showed reduced annual exacerbation rates (from 3.79 to 0.64; P <.001), decreased oral corticosteroid use, and improved Asthma Control Questionnaire (ACQ-6) and Asthma Quality of Life Questionnaire (AQLQ) scores. Participants treated with dupilumab also improved across similar measures, though the small sample size limited statistical comparisons, authors noted.

Yasinka and colleagues were surprised that, despite these gains, both treatments were associated with increased frequencies of circulating ILC2s. Mepolizumab also increased Th2 and Tc2 cells—particularly those with a central memory phenotype. These lymphocytes exhibited reduced expression of homing receptors, suggesting the potential for decreased airway trafficking, the researchers said. Notably, CD117^low ILC2s—associated with more active Th2 inflammation—were enriched in circulation, expressing elevated levels of CD62L and KLRG1.

Transcriptional analyses further revealed that mepolizumab-treated patients had increased expression of activator protein-1 (AP-1) family genes across type 2 lymphocyte subsets; the AP-1 family mediates biologic processes including proliferation and differentiation, authors explained. Functional assays supported these findings: after 1 year of treatment, type 2 lymphocytes produced more IL-5 and IL-13 in response to stimulation, indicating preserved or even enhanced pro-inflammatory potential despite biologic therapy.

The data put the paradox in context: while biologics reduce clinical symptoms and eosinophilic inflammation, they do not eliminate, and may even enrich, a population of functionally active type 2 lymphocytes with altered trafficking patterns. The authors hypothesize that mepolizumab, in particular, may redirect these cells away from inflamed airways into circulation—a mechanism that reduces local inflammation but does not equate to immune resolution.

Wirth et al acknowledge several limitations with the study, including the small size of the dupilumab subgroup and the absence of airway tissue samples. Findings are also limited to peripheral blood, which may not fully reflect activity in lung tissue, they wrote.

The authors conclude that long-term disease control in asthma may not equate to immunologic remission. Persistent inflammatory cell populations could represent a latent risk for disease flare or may influence decisions about tapering biologics, they advised. Further research should investigate whether specific biomarkers can identify patients likely to achieve durable, treatment-free remission or whether additional strategies are needed to suppress the full spectrum of type 2 inflammation.

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References

Wirth L, Weigel W, Stamper CT, et al. High-dimensional analysis of type 2 lymphocyte dynamics during mepolizumab or dupilumab treatment in severe asthma. Allergy. 2025;0:1–16 doi:10.1111/all.16633

Inflammatory cells remain in the blood after treatment of severe asthma. News release. Karolinska Institutet. June 26, 2025. Accessed July 2, 2025. https://news.ki.se/inflammatory-cells-remain-in-the-blood-after-treatment-of-severe-asthma

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