HIV seroconversion and prevalence rates in heterosexual discordant couples in China: a systematic review and meta-analysis

This study aims to systematically review published literature on heterosexual transmission among HIV discordant couples in China. We conducted a systematic review and random-effects meta-analysis of 32 published articles in both Chinese and English. The summarized overall HIV seroconversion rate among discordant couples in China is 1.2 per 100 person-years (95% CI 0.9-1.7/100 PY). The overall estimate for HIV prevalence through heterosexual transmission in discordant couples is 11.5% (95% CI 8.2%-15.2%) in China. In a stratified meta-analysis by region, Henan province showed an HIV seroconversion rate of 0.9/100 PY (95% CI 0.6-1.2/100 PY) and an HIV prevalence rate of 3.9% (95% CI 2.5-5.7%). Yunnan province showed an HIV seroconversion rate of 1.7/100 PY (95% CI 1.2-2.3/100 PY) and an HIV prevalence rate of 17.0% (95% CI 13.7-20.6%). Other provinces collectively showed a HIV seroconversion rate of 3.9/100 PY (95% CI 1.0-8.7/100 PY) and an HIV prevalence rate of 21.5% (95% CI 9.6-36.5%). In a stratified meta-analysis by time, the subgroup from 1994 to 2004 had a seroconversion rate of 3.9/100 PY (95% CI 1.0-8.7/100 PY) and the subgroup from 2005 to 2011 had a seroconversion rate of 1.1/100 PY (95% CI 0.8-1.5/100 PY). These data show that China's free national HIV prevention and treatment program has been successful at limiting transmission in discordant couples. Because heterosexual transmission is now the dominant method of HIV transmission in China, it is important to understand seroconversion and prevalence rates in discordant couples to develop more effective prevention and treatment programs.     

Pregnancy and HIV transmission among HIV-discordant couples in a clinical trial in Kisumu, Kenya

Objectives

A large proportion of new HIV infections in sub‐Saharan Africa occur in stable HIV‐discordant partnerships. In some couples, the strong desire to conceive a child may lead to risky behaviour despite knowledge of discordant serostatus. Our objective was to compare HIV transmission between discordant couples who did and did not conceive during participation in a clinical trial.

Methods

Five hundred and thirty‐two HIV‐discordant couples were followed for up to 2 years in Kisumu, Kenya as part of the Partners in Prevention HSV/HIV Transmission Study. Quarterly HIV‐1 antibody and urine pregnancy test results were analysed.

Results

Forty‐one HIV‐1 seroconversions occurred over 888 person‐years of follow‐up, resulting in an annual incidence of 4.6/100 person‐years. Twenty seroconversions occurred among 186 HIV‐1‐uninfected individuals in partnerships in which pregnancy occurred (10.8% of HIV‐1‐negative partners in this group seroconverted), in comparison to 21 seroconversions among 353 uninfected individuals in partnerships in which pregnancy did not occur (5.9% of HIV‐1‐negative partners seroconverted), resulting in a relative risk of 1.8 [95% confidence interval (CI) 1.01–3.26; P<0.05].

Conclusions

Pregnancy was associated with an increased risk of HIV seroconversion in discordant couples. These data suggest that the intention to conceive among HIV discordant couples may be contributing to the epidemic.     

Determinants of physical and global functioning in adult HIV-positive heterosexual men

Little is known about the psychosocial factors that might impact the functioning ability of heterosexual men living with HIV. We examined positive and negative coping, social support, and HIV stigma as predictors of physical and global functioning in a cross-sectional sample of 317 HIV-infected adult heterosexual male patients recruited from clinical and social service agencies in New York City. Study participants were primarily minority and low income. Sixty-four percent were African-American, 55% were single, and 90% were 40 years of age or older. The majority had long-term HIV (LTHIV), with an average duration of 15 years since diagnosis. After controlling for participant characteristics, structural equation modeling analyses revealed that positive coping and social support had a significant positive direct effect on global functioning, while stigma had a significant negative direct effect on global functioning. The physical functioning model revealed that negative coping and HIV stigma had significant negative direct effects, whereas social support had a significant positive indirect effect. Age and duration of HIV diagnosis were not associated with physical and global functioning. In conclusion, we found that heterosexual men living with LTHIV who have ineffective coping, less social support, and greater stigma have reduced functioning ability. Study findings have implications for developing interventions aimed at increasing and retaining functioning ability with the end goal of improving successful aging in this population.     

Sex practice correlates of human immunodeficiency virus transmission and acquired immunodeficiency syndrome incidence in heterosexual partners and offspring of U.S. hemophilic men

We assessed the risk of human immunodeficiency virus (HIV) transmission from heterosexual seropositive hemophilic men to their female sex partners through an HIV serosurvey and questionnaire study conducted during 1984-1987. Five percent of 21 female partners of asymptomatic men and 11% of 35 partners of HIV-symptomatic (acquired immunodeficiency syndrome [AIDS], AIDS-related complex [ARC], peripheral generalized lymphadenopathy [PGL]) hemophilic men had been infected when first tested. One of 19 seronegative women tested about 1 year later reportedly seroconverted. Only 18% of a sample of the serosurvey women responding to sex practices questions said their partners used condoms "nearly always." Over 60% engaged in oral/genital sex in addition to vaginal intercourse. Only 12% of still-seronegative women followed the preventive strategy of consistent avoidance of oral/genital sex, together with consistent condom use by the male partner. Further evidence for heterosexual transmission comes from the CDC national AIDS surveillance reports showing 25 women who acquired HIV infection through heterosexual contact with U.S. hemophilic men (September 6, 1988). Seven (28%) were diagnosed and reported in the first 6 months of 1988. Their ages range from 20 years to more than 70 years. The dates of infection for the women are unknown but must have been at least 5 years before AIDS diagnosis for at least one. Only approximately 30% of their male partners had already manifested any HIV-associated illness. Through May 18, 1988, six cases of AIDS have occurred in children whose infection was acquired through exposure of the mother to a hemophilic partner. Four were diagnosed in latter 1987. The median age at diagnosis was 4.5 months. Four had died. None of their mothers is as yet diagnosed.     

Differences in testing,stigma, and perceived consequences of stigmatization among heterosexual men and women living with HIV in Bengaluru,India

Approximately 2.4 million people in India are living with HIV. Gender inequality affects HIV prevention, detection, and management. The purpose of this paper was to describe gender differences in the experience of living with HIV in Bengaluru, India. A subsample of n = 313 (159 men and 154 women) from a larger cohort was used for these analyses. Participants were recruited through AIDS service organizations. They completed an interviewer-administered survey assessing HIV testing experience, types of stigma, and perceived consequences of stigmatization. The majority of men (67%) reported getting HIV tested because of illness, while women were more likely to be tested after learning their spouse's HIV-positive status (42%). More men (59%) than women (45%, p<0.05) were tested in private care settings. Men reported significantly higher mean levels of internalized stigma (men: M=0.71, SD = 0.63; women: M=0.46, SD = 0.55; p<0.001), whereas the women reported significantly higher scores for enacted stigma (men: M=1.30, SD = 1.69; women: M=2.10, SD = 2.17; p<0.001). These differences remained significant after controlling for potential socio-demographic covariates. Following their diagnosis, more women reported moving out of their homes (men: 16%; women: 26%; p<0.05). More men (89%) than women (66%; p<0.001) reported to have modified their sexual behavior after being diagnosed. These findings suggest that the experience of living with HIV and HIV stigma varies by gender in this population. Suggestions for a gender-based approach to HIV prevention and stigma reduction are provided.     

Examining the health and health service utilization of heterosexual men with HIV: a community-informed scoping review

The prevalence of HIV infection among heterosexual men has increased. Consequently, the need for health and support services for this group is likely to increase. We conducted a scoping review of studies regarding the health and health service use of heterosexual men with HIV that was informed by research priorities identified by this community. We searched six databases from inception to August 2014. We included all English-language qualitative and quantitative studies examining the health and health service use of heterosexual men with HIV. Our search strategy yielded 2665 references, of which 70 were included in the scoping review. We summarized the research into the following domains identified by summit participants: treatment of HIV and its complications (n?=?9), health and social support services utilization (n?=?27), social determinants of health (n?=?20), prevention (n?=?11), family planning (n?=?4) and psychosocial research (n?=?33). Key findings from the review included poor mental health-related well-being, over-representation among “late presenters” to care and greater fear of disclosure of HIV status relative to men who have sex with men. In general, research conducted to date was not well aligned with the priorities identified by the community.     

Low uptake of HIV testing among male clients of female sex workers in China

Male client of female sex workers (MCFSW) is a sizable population transmitting HIV from high-risk population to female general population in China. This study was to investigate the prevalence of taking up any forms of HIV testing in lifetime and in the past year among MCFSW in Hong Kong. Factors associated with uptake of any forms HIV testing in the past year were also investigated. A cross-sectional survey was conducted. Participants were Hong Kong Chinese males aged ≥18 years, and self-reported had patronized at least one female sex workers (FSW) in the last six months. A total of 303 MCFSW recruited online (n?=?160) or from venues (n?=?143) completed the self-administered questionnaire. Logistic regression was used for data analysis. The prevalence of taking up any forms of HIV testing in lifetime and last year was 49.2% and 23.8%, respectively. Adjusting for these background variables, scale scores representing perceived severity of HIV infection (AOR: 1.17), perceived benefits of HIV testing (AOR: 1.18) and perceived self-efficacy in taking up HIV testing (AOR: 1.36) were significantly and positively associated with uptake of any forms of HIV testing in the last year, while negative associations were found for the Perceived Psychological Barrier Scale (AOR=?0.88) and the Perceived Logistical Barrier Scale (AOR: 0.78). MCFSW in Hong Kong reported low uptake of HIV testing. Health promotion is urgently needed. Modifying perceptions related to the Health Belief Model are potential useful strategies. The potential of using HIV self-testing to increase HIV testing coverage among MCFSW should also be considered.     

Attitudes towards couples HIV testing and counseling among Latino men who have sex with men in the Seattle area

Men who have sex with men (MSM) remain the most severely affected risk group in the US HIV/AIDS epidemic. One-third to two-thirds of HIV transmissions among MSM are estimated to come from primary sex partners. Couples HIV testing and counseling (CHTC), in which two individuals receive pre-test counseling, HIV testing and post-test prevention planning together, has been adapted for male couples in the USA, and is now available in more than 30 cities. Previous studies have demonstrated high levels of willingness to use CHTC among MSM, but to date no studies have explored this among Latino MSM (LMSM). To examine the willingness to use CHTC among and further cultural adaptation needed for LMSM, focus group discussions were held with men who self-identified as Latino, were in a relationship with another man, and resided in Seattle. Willingness to use CHTC was high. Participants reported that CHTC could strengthen and validate their relationships, help mitigate stigma, and provide a forum for support, protection, and information sharing. Barriers to CHTC use included fears of rejection, loneliness, and relationship dissolution, and concerns around deportation and financial burden. The high levels of reported willingness to use CHTC among this sample of LMSM point to the potential for CHTC to be further adapted to provide dyadic HIV testing services for LMSM.     

Risk factors for HIV transmission among heterosexual discordant couples in South India*

Objective

To assess the risk factors associated with heterosexual HIV transmission among South Indian discordant couples enrolled in clinical care.

Methods

A nested matched case–control study of serodiscordant couples in which the HIV‐infected partner (index case) was enrolled in care. Demographic and clinical characteristics, sexual behaviours, CD4 cell count and plasma HIV‐1 RNA loads were measured at enrolment and longitudinally over 12 months of follow‐up. The study included 70 cases who seroconverted during study follow‐up and 167 matched controls who remained persistently serodiscordant.

Results

The incidence of HIV infection among the initially seronegative partners was 6.52 per 100 person‐years. Persistently discordant patients were more likely to have initiated highly active antiretroviral therapy (HAART) than patients in seroconverting relationships (62.9%vs. 42.9%) (P=0.001). Patients in seroconverting relationships had significantly higher plasma viral loads (PVLs) than patients in discordant relationships at enrolment, at 6 months and at 12 months (P<0.05). Patients in seroconverting relationships were less likely to use condoms with their primary partners than patients in discordant relationships (P<0.05). Patients in relationships that seroconverted between 6 and 12 months were diagnosed more often with genital Herpes simplex than patients in discordant relationships (P=0.001). In the univariate and multivariate logistic regression, the following variables were associated with seroconversion: PVL >100 000 [odds ratio (OR): 1.82; 95% confidence interval (CI): 1.1–2.8], non‐disclosure of HIV status (OR: 5.5; 95% CI: 4.3–6.2) and not using condoms (OR: 2.8; 95% CI: 2.4–3.6).

Conclusions

Couples‐based intervention models are crucial in preventing HIV transmission to seronegative spouses. Providing early treatment for sexually transmitted infections, HAART and enhancing condom use and disclosure could potentially decrease the risk of HIV transmission within Indian married couples.

     

Factors associated with uptake of home-based HIV counselling and testing and HIV care services among identified HIV-positive persons in Masaka,Uganda

We investigated uptake of home-based HIV counselling and testing (HBHCT) and HIV care services post-HBHCT in order to inform the design of future HBHCT programmes. We used data from an open-label cluster-randomised controlled trial which had demonstrated the effectiveness of a post-HBHCT counselling intervention in increasing linkage to HIV care. HBHCT was offered to adults (≥18 years) from 28 rural communities in Masaka, Uganda; consenting HIV-positive care naïve individuals were enrolled and referred for care. The trial's primary outcome was linkage to HIV care (clinic-verified registration for care) six months post-HBHCT. Random effects logistic regression was used to investigate factors associated with HBHCT uptake, linkage to care, CD4 count receipt, and antiretroviral therapy (ART) initiation; all analyses of uptake of post-HBHCT services were adjusted for trial arm allocation. Of 13,455 adults offered HBHCT, 12,100 (89.9%) accepted. HBHCT uptake was higher among men [adjusted odds ratio (aOR) 1.20, 95% confidence interval (CI)?=?1.07–1.36] than women, and decreased with increasing age. Of 551 (4.6%) persons who tested HIV-positive, 205 (37.2%) were in care. Of those not in care, 302 (87.3%) were enrolled in the trial and of these, 42.1% linked to care, 35.4% received CD4 counts, and 29.8% initiated ART at 6 months post-HBHCT. None of the investigated factors was associated with linkage to care. CD4 count receipt was lower in individuals who lived ≥30?min from an HIV clinic (aOR 0.60, 95%CI?=?0.34–1.06) versus those who lived closer. ART initiation was higher in older individuals (≥45 years versus <25 years, aOR 2.14, 95% CI?=?0.98–4.65), and lower in single (aOR 0.60, 95% CI?=?0.28–1.31) or divorced/separated/widowed (aOR 0.47, 95% CI?=?0.23–0.93) individuals versus those married/cohabiting. HBHCT was highly acceptable but uptake of post-HBHCT care was low. Other than post-HBHCT counselling, this study did not identify specific issues that require addressing to further improve linkage to care.     

Poor-quality health services and lack of programme support leads to low uptake of HIV testing in rural Mozambique

Mozambique has one of the world's highest burdens of HIV infection. Despite the increase in HIV-testing services throughout the country, the uptake has been low. To identify barriers to HIV testing we conducted a study in six rural districts in Zambézia Province. We recruited a total of 124 men and women from the community through purposeful sampling to participate in gender-specific focus group discussions about barriers to HIV testing. The participants noted three main barriers to HIV testing: 1) poor conduct by clinicians, including intentional disclosure of patients’ HIV status to other community members; 2) unintentional disclosure of patients’ HIV status through clinical practices; and, 3) a widespread fatalistic belief that HIV infection will result in death, particularly given poor access to adequate food. Improving quality and confidentiality within clinical service delivery, coupled with the introduction of food-supplement programmes should increase people's willingness to test and remain in care for HIV disease.     

HIV testing preferences among pregnant women attending antenatal care and their male partners: a discrete choice experiment in Uganda

HIV testing rates remain stubbornly low among men – a crucial target population for reaching the ambitious global and regional goals of the HIV programme. In an era of declining donor funding, identifying cost-effective strategies to increase testing rates amongst men remains paramount. Antenatal care is an effective entry-point for the delivery of HIV testing services for women, and partner testing presents an important opportunity to reach their male partners. We present the results of a discrete choice experiment in Uganda, examining preferences among 824 pregnant women and 896 male partners regarding service delivery characteristics of HIV testing. Both men and women preferred nurse administered testing to self-testing (OR = 0.835; p < 0.001), oral testing over a finger-prick test (OR = 1.176; p < 0.001) and testing with a partner over testing alone (OR = 1.230; p < 0.001). Men had a preference for testing at home compared to testing at a clinic (OR = 1.099; p = 0.024), but women were indifferent regarding the testing location. The cost of testing had the biggest effect on preferences. Free testing was preferred over a cost of US$2.90 (OR = 0.781; p < 0.001) or US$2.00 (OR = 0.670; p < 0.001). Offering an incentive of US$3.40 increased men’s preferences compared to a free test (OR = 1.168; p < 0.001), although this did not affect women’s preferences. Partner testing linked to antenatal care is a potential strategy to increase testing coverage among men, particularly given the preference for partner testing – provided costs to clients remain low. Future cost-effectiveness evaluations should investigate the economic impact of reaching men using these strategies.     

使用互联网交友的MSM最近1年HIV检测情况和抗病毒治疗意愿初步调查

目的初步了解使用互联网交友的男男性行为人群（MSM）最近1年HIV检测现况和抗病毒治疗意愿。方法于2011年11月,通过MSM交友网站招募MSM进行在线问卷调查,并采用SAS 9.2进行卡方检验和Lo-gistic回归分析。结果共有393名MSM完成问卷调查,319人年龄在30岁以下;322人学历在大专及以上;342人未婚;310人性取向为同性恋。381名MSM被问及若检测出HIV抗体阳性会怎样做时,有55.6%（212/381）表示会尽快开始抗病毒治疗。最近1年HIV检测率为32.8%（129/393）。在做过检测的129名MSM中,53.5%（69人）因担心自己有感染HIV的风险而去做检测,62.0%（80人）的检测地点在疾病预防控制中心。60.0%（77人）表明结果阳性时愿意接受抗病毒治疗。最近1年未做过检测的264名MSM中,53.4%（141人）认为自己没有感染HIV的风险而未去做检测,其中51.1%（135人）表明若检测结果阳性愿意接受抗病毒治疗。Logistic多因素回归分析显示,＂是否认为自己有感染风险＂可能是检测的影响因素[比值比（OR）=0.14,95%可信区间（CI）：0.08～0.25）]。结论本次调查的互联网交友的MSM,最近1年HIV检测率不高,＂是否意识到自己有感染HIV的风险＂可能是其影响因素,超过一半的MSM对抗病毒治疗态度较为积极     

Perceptions of door-to-door HIV counselling and testing in Botswana

Prevalence of HIV infection in Botswana is among the highest in the world, at 23.9% of 15 – 49-year-olds. Most HIV testing is conducted in voluntary counselling and testing centres or medical settings. Improved access to testing is urgently needed. This qualitative study assessed and documented community perceptions about the concept of door-to-door HIV counselling and rapid testing in two of the highest-prevalence districts of Botswana.

Community members associated many positive benefits with home-based, door-to-door HIV testing, including convenience, confidentiality, capacity to increase the number of people tested, and opportunities to increase knowledge of HIV transmission, prevention and care through provision of correct information to households. Community members also saw the intervention as increasing opportunities to engage and influence family members and to role model positive behaviours. Participants also perceived social risks and dangers associated with home-based testing including the potential for conflict, coercion, stigma, and psychological distress within households. Community members emphasised the need for individual and community preparation, including procedures to protect confidentiality, provisions for psychological and social support, and links to appropriate services for HIV-positive persons.     

The impact of HIV couple testing and counseling on social support among pregnant women and their partners in Lilongwe,Malawi: an observational study

Couples HIV testing and counseling (couple counseling) promotes safer sexual behaviors, increases communication between couples, and decreases HIV transmission. However, the impact of couple counseling on social support, critical for persons living with HIV, has not been examined. Ninety couples with a recently tested HIV-positive pregnant woman (female-positive couples) and 47 couples with a recently tested HIV-negative pregnant woman (female-negative couples) were enrolled in an observational study at an antenatal clinic in Malawi. Each couple member was assessed immediately before and one month after couple counseling for partner, family, and peer social support using the Multidimensional Scale of Perceived Social Support. Before couple counseling, social support was lower among women than men in both female-positive couples (β?=??10.00, p?<?.01) and female-negative couples (β?=??8.43, p??<?.01). After couple counseling, social support increased for women in female-positive couples (β?=?4.01, p?<?.01) and female-negative couples (β?=?4.69, p?<?.01) but not for men in either type of couple. Couple counseling could be an effective strategy to increase social support for women, including those with recent HIV diagnoses.     

Multi-ethnic perspective of uptake of HIV testing and HIV-related stigma: A cross-sectional population-based study

The objective of this study was to identify demographic characteristics and correlates of the uptake of HIV testing, willingness to be tested and perceived HIV-related stigma of Malaysian lay public. A cross-sectional computer-assisted telephone interview survey of a representative sample of multiracial Malaysians aged 18 years and above was conducted between December and July 2011. The survey collected information on demographics, knowledge about HIV transmission and religious beliefs on attitudes to HIV/AIDS. A total of 2271 households were successfully interviewed. The response rate was 48.65%. The HIV transmission knowledge score ranged from 0 to 15 (mean =10.56; SD±2.42). Three of the most common misconceptions about HIV transmission were mosquito bite (42.8%), eating in a restaurant where the cook is HIV positive (20.4%) and using a public toilet (20.1%). Only 20.6% reported ever having been tested for HIV, 49.1% reported a willingness to be tested for HIV and 30.3% had no intention of getting an HIV test. Low-risk perception (63.7%) constitutes a major barrier to HIV testing. Being Malay and Chinese (relative to Indian) were the strongest predictors of low-risk perception. Other significant predictors of low-risk perception were being male, being married and living in an urban locality. Perceived self-stigma if tested positive for HIV was prevalent (78.8%). Multivariate findings showed that being female, Malay, low income, living in rural localities and public stigma were significant correlates of self-stigma. These findings warrant interventions to reduce the disproportionate HIV transmission misconception, barriers to HIV testing and stigma and discriminative attitudes to involve considerations of sociocultural economic and demographic characteristics.     

Gender differences in HIV disclosure,stigma, and perceptions of health

HIV disclosure is a gateway to HIV prevention – particularly among couples living in regions severely affected by the HIV epidemic. This cross-sectional study utilizes data collected from 862 people living with HIV across three countries (Ethiopia, Mozambique, and Uganda) in 2011 to determine the role of partner disclosure on self-reported health perceptions and changes in sexual risk behavior. The study's secondary aims are to understand whether or not internalized stigma mediates this relationship and if there is a different pattern of results by gender. The multivariate analysis reveals that the three key HIV-related independent variables, belonging to a support group, doing volunteer work, and disclosing to one's spouse or partner, were significantly associated with lower levels of internalized stigma. Internalized stigma was associated with self-perceptions of poorer health for both women and men, with women reporting higher levels of internalized stigma than men. Disclosure to spouse was positively associated with perceptions of better health for women but not for men. For men, doing HIV-related volunteer work and disclosing their status to their spouse were positively associated with self-reported changes in sexual risk behavior, although stigma was not found to mediate this relationship. Findings from this study suggest that disclosure and stigma have gender-specific effects on individual well-being and changes in sexual risk behaviors. As such, programs must address gender inequity in disclosure patterns and stigma to enhance prevention efforts.     

Low HIV testing uptake following diagnosis of a sexually transmitted infection in Spain: implications for the implementation of efficient strategies to reduce the undiagnosed HIV epidemic

Sexually transmitted infections (STIs) are recognized as one of the conditions in which HIV testing is most clearly indicated. We analyse whether people diagnosed with an STI are being tested for HIV according to the experience of participants in an outreach rapid testing programme in Spain. Between 2008 and 2010, 6293 individuals underwent rapid testing and completed a self-administered questionnaire. We calculated the percentage of individuals that were diagnosed with an STI in the last 5 years and identified the setting where the last episode occurred. We then determined the percentage not receiving an HIV test after the last STI diagnosis and estimated the associated factors. Overall, 17.3% (N?=?959) of participants reported an STI diagnosis in the last 5 years, of which 81.5% occurred in general medical settings. Sixty-one percent reported not undergoing HIV testing after their last STI diagnosis, 2.2% of whom reported they had refused the test. Not receiving an HIV test after the last STI diagnosis was independently associated with not being a man who has sex with men (MSM), having had fewer sexual partners, being diagnosed in general medical settings and having received a diagnosis other than syphilis. An unacceptably large percentage of people diagnosed with STI are not being tested for HIV because healthcare providers frequently fail to offer the test. Offering routine HIV testing at general medical settings, regardless of the type of STI diagnosed and population group, should be a high priority and is probably a more efficient strategy than universal screening in general healthcare settings.