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Biomedical subjects

L A Mattsson

Publications and source records attributed to L A Mattsson.

At least 19 recordsLinked to original sources

A low-dose start in hormone replacement therapy provides a beneficial bleeding profile and few side-effects: randomized comparison with a conventional-dose regimen.

OBJECTIVE: To compare bleeding control, efficacy and safety of two dose-ranging continuous combined hormone replacement therapy (HRT) regimens with those of a conventional continuous combined HRT. METHODS: An open, 2-year, multicenter study was conducted in 393 postmenopausal women recruited from 16 study sites. The women were randomized to three continuous combined HRT regimens. One group (n = 131) started with 1 mg of estradiol valerate (E2V) plus 2.5 mg of medroxyprogesterone acetate (MPA), the second group (n = 130) received 1 mg E2V + 5 mg MPA and the third (n = 132) 2 mg estradiol (E2) and 1 mg norethisterone acetate (NETA). In the two E2V/MPA groups the initial E2V dose of 1 mg was increased to 2 mg after six cycles (one cycle = 28 days) to evaluate the effect of dose increase on bleeding control. RESULTS: The E2V/MPA regimens with a lower estrogen dose induced less bleeding and other adverse effects during the first six cycles than did the E2/NETA regimen. Bleeding disturbances and breast tenderness resulted in significantly more discontinuations in the E2/NETA group. After the estrogen dose increase in the E2V/MPA regimens, all groups showed comparable bleeding patterns and adverse effect profiles. The lower E2V dose was as effective as standard-dose E2 in relieving climacteric symptoms. All regimens provided excellent endometrial safety. No hyperplasias were reported. CONCLUSIONS: Continuous combined HRT should be started, and continued, with the lowest effective doses. An increase of the estrogen dose is recommended only if the initial dose is not sufficient for symptom control.

Aged↗

A longitudinal population study of climacteric symptoms and their treatment in a random sample of Swedish women.

OBJECTIVES: To assess, first, the prevalence and severity of symptoms associated with the climacteric period and their treatment and, second, the prevalence of exercise, smoking and body weight in a population-based sample of Swedish women. MATERIAL AND METHODS: Prospective, longitudinal cohort study, initiated in 1992, in women aged 46, 50, 54, 58 and 62 years with a follow-up 6 years later. Information was obtained from the same women (n=3816) on both occasions using a postal questionnaire regarding sociodemographic variables, general and reproductive health, the occurrence of climacteric symptoms and their severity, and the use of hormone replacement therapy (HRT). RESULTS: The prevalences of climacteric symptoms were as follows (1992/1998): vasomotor symptoms, 52%/62%; depression/irritability, 57%/65%; sleeping disturbances, 51%/69%; muscle/joint pain, 55%/70%; and loss of libido, 38%/57%. HRT with medium-potency estrogens was currently being used by 34% (1992: 14%), and 12% (1992: 8%) were using low-potency estrogens. The maximum prevalence of HRT (medium-potency estrogens) use was found in the 56-year-old group, at 46% (1992: 25% in the 54-year-old group). Body mass for the whole group had increased from 66.3 to 68.9 kg. Exercise was more frequent in all age groups in 1998 compared to 1992. There was a decrease in current smokers from 32 to 26% between the two periods. Compared with 1992, the women in all five birth cohorts considered themselves to be less healthy and quality of life had decreased for the whole group. CONCLUSIONS: The prevalence of symptoms associated with the climacteric period and the use of HRT had increased markedly in this longitudinal study of the same women followed between 1992 and 1998. During the same period, smoking decreased, while body weight and exercise frequency increased.

Age Distribution↗

Low dose hormone replacement therapy: clinical efficacy.

The frequency of hormone replacement therapy (HRT) users has increased during the last 2 decades. A majority of women taking HRT prefer to use formulations that will not induce bleeding disturbances. Accordingly many women prefer continuous combined HRT to obtain amenorrhoea. Previously comparatively high doses of estrogens and progestogens were prescribed to women in the climacteric period. Low doses of estrogens such as estradiol 1 mg and conjugated equine estrogens 0.3 mg orally per day or transdermally applied estradiol 25 mug per 24 hours have been shown to be effective for the treatment of vasomotor symptoms and for prevention of bone loss. With low dose HRT in a continuous combined regimen amenorrhoea will be obtained in a majority of women after a few months of treatment. Low doses of progestogen especially if given on a continuous basis have been shown to protect the endometrium from hyperplasia. Favourable effects in lipid- and lipoprotein patterns have been reported. In addition, fewer side effects such as mastalgia have been found during treatment with low dose regimen compared to high doses. For women requesting HRT it might be a rational alternative to begin with low dose formulations since these doses are sufficient for the majority of women.

Bone Density↗

Safety and tolerability of pulsed estrogen therapy: key factors for an improved compliance.

Hormone replacement therapy (HRT) is recognized as the 'gold standard' for the treatment of the short- and long-term consequences of estrogen deprivation. Compliance with HRT is poor, mainly due to side-effects and fear of cancer. Many women discontinue the treatment prematurely and will not derive its full benefit. This presentation summarizes the results of studies assessing the safety and tolerability of pulsed estrogen therapy (Aerodiol) versus conventional estrogen therapy. The mammary safety was assessed in well-recognized experimental models. In comparison with oral administration, pulsed therapy showed a significantly lower rate of tumor induction (p < 0.05) and reduced tumor growth. The endometrial safety of Aerodiol was assessed in a long-term study. After 1 year of treatment, 311 biopsies could be evaluated: 34% were atrophic, 16% proliferative, 39% secretory, 4% menstrual and 7% had no endometrial tissue. No cases of endometrial hyperplasia or cancer were detected. In a comparative study comprising 659 women, a lower frequency of irregular bleeding was reported with Aerodiol compared with orally administered estradiol. In two randomized studies, the frequency of mastalgia has been found to be significantly lower with Aerodiol compared with orally and transdermally administered estradiol. Aerodiol has been found to be well-tolerated, with better gynecological acceptability than conventional estrogen, and individualization of therapy might increase compliance. Intranasally administered estradiol is an attractive alternative for many women.

Administration, Cutaneous↗

Knowledge, attitudes and management strategies in Scandinavia concerning hormone replacement therapy: a comparison between gynecologists in Denmark, Norway and Sweden.

OBJECTIVES: To describe and compare attitudes, knowledge and management strategies concerning the prescription of hormone replacement therapy (HRT) between gynecologists from three Scandinavian countries. DESIGN AND METHODS: In a cross-sectional study gynecologists in Denmark (n=386), Norway (n=475) and Sweden (n=1323) were invited by letter to complete and return an enclosed questionnaire. Then 1653 of the 2184 (76%) contacted gynecologists completed and returned the questionnaire. RESULTS: of the 1653 Scandinavian gynecologists, 42% offered HRT to all women provided there was no contraindication, while 58% recommended HRT to selected women after considering the advantages and disadvantages of HRT. In Norway and Sweden, the proportion of gynecologists routinely prescribing HRT for women without contraindications increased with age and in the oldest age group of gynecologists (>55 years) 49 and 56%, respectively, recommended HRT to all women. The gynecologists were unanimous in their choice of the type of HRT for perimenopausal women as 94% preferred cyclical or sequential combined (estrogen/progestogen) treatment or estrogen monotherapy (orally or transdermally) for hysterectomized women (95%). For postmenopausal women, 75% of the gynecologists offered continuous combined HRT while cyclical combined therapy was chosen by 15% of the gynecologists. No significant differences were found between physicians in the three countries regarding indications and contraindications to HRT. CONCLUSIONS: Scandinavian gynecologists are generally well informed concerning HRT and liberally recommend HRT for women without contraindications.

Adult↗

A population based study of Swedish women's opinions about antenatal, delivery and postpartum care.

OBJECTIVE: To investigate the views and experiences of Swedish women regarding antenatal, delivery and postpartum care. STUDY DESIGN: A random sample of women from the birth cohorts 1955, 1959, 1963, 1967 and 1971 resident in the city of Göteborg (n=2880) was invited by letter to complete a questionnaire regarding antenatal, delivery and postpartum care. RESULTS: The overall response rate was 73% and 1130 (54%) of the 2109 responders had given birth to at least one child. Eighty-one percent of parous women answered that checking blood and urine samples, fetal heart rate, and the measurement of fundal height were the most important procedures in antenatal care. A majority had a positive attitude towards the use of electronic fetal heart rate monitoring (parous 85%; nulliparous 84%). Sixty percent of parous women were aware that ultrasound examination was voluntary and a majority (90%) had a positive attitude towards ultrasound scanning. Forty-three percent of parous women wanted antenatal clinics to be open until 8.00 p.m. A minority of both parous (4%) and nulliparous (4%) women were interested in home delivery. There were more parous (33%) than nulliparous (12%) women who expressed no anxiety at all about the next delivery. Seventy-nine percent of the parous women reported that they would like to have a planned visit with a delivery ward midwife before the next delivery. About 80% reported that they would feel very safe if their partners were present at the delivery (nulliparous 79%; parous 84%). Eighty-five percent preferred a single room or a room together with only one other woman in the postnatal ward. Seventy-two percent of the women wanted to stay 72 hours or less in the postpartum ward and 24% thought there had been too many visitors during the postnatal period. Over 80% were very positive towards breast-feeding. Approximately 80% of all women considered regular contractions up to twelve hours to be acceptable before delivery. CONCLUSIONS: This study has provided some useful information about women's opinion regarding antenatal, delivery and postpartum care which may be taken into account when instigating changes in the maternity care system.

Analysis of Variance↗

Clinical equivalence of intranasal and oral 17beta-estradiol for postmenopausal symptoms.

OBJECTIVE: The aim of this study was to demonstrate clinical equivalence between a novel intranasal estradiol formulation and a reference oral drug. STUDY DESIGN: In this multinational, double-blind, parallel-group study 659 postmenopausal women with moderate to severe postmenopausal symptoms were randomly assigned to receive either 300 microg/d intranasal 17beta-estradiol (S21400) or 2 mg/d oral micronized estradiol, plus the appropriate placebo, for 24 weeks. All patients also received 10 mg/d dydrogesterone for 14 days per 28-day cycle. Adjustment of intranasal dosage was permitted from week 14 on. The primary efficacy criterion was the Kupperman index at week 14, with a predefined limit of equivalence of 4. RESULTS: Kupperman index scores improved similarly in the 2 groups, from 28.4 +/- 6.2 to 10.0 +/- 8.6 (mean +/- SD) for S21400 and from 28.1 +/- 6.0 to 8.9 +/- 8.0 for oral therapy, with a difference between groups at week 14 of 1.1 +/- 0.6 (90% confidence interval, 0. 0 to 2.2). This was below the predefined equivalence limit of +4 for statistical noninferiority (P <.001). The daily number and intensity of hot flushes decreased similarly in the two treatment groups. Withdrawal bleeding was 20% less frequent with intranasal therapy (90% confidence interval, 12.5 to 27.6). Severe mastalgia was less frequent in the S21400 group (1.0%) than in the group with oral therapy (5.2%; P <.01). Triglyceride and angiotensinogen levels increased significantly with oral therapy but not with S21400. The same number of patients required dose adaptation in the 2 groups (approximately 20%). CONCLUSION: Intranasal administration of 300 microg/d estradiol was at least as effective as oral administration of 2 mg/d estradiol in alleviating postmenopausal symptoms, with less frequent mastalgia and uterine bleeding and without the metabolic consequences of the first-pass effect.

Administration, Intranasal↗

Prevalence and risk factors for prelabor rupture of the membranes (PROM) at or near-term in an urban Swedish population.

AIMS: To determine the prevalence, recurrence rate and to identify risk factors for prelabor rupture of the membranes (PROM) after 34 completed weeks in an urban Swedish population. METHODS: In a retrospective cohort study a sample of 2880 women aged 25-41 years, resident in the city of Göteborg, was randomly selected from the population register. According to information from the national Medical Birth Register (MBR), 1507 of these 2880 women had given birth 2736 times. 2270 of these deliveries had occurred in hospitals in the city of Göteborg and case records for 2242 of these deliveries were found. The case records were systematically analyzed for the occurrence of PROM and potential risk factors for PROM. 2208 of these deliveries occurred after 34 weeks of gestation. The further analyses were based on these 2208 deliveries. RESULTS: The prevalence of PROM after 34 week of gestation in this urban Swedish population was 12.9% and about 20% of the women in the population had experienced PROM at least once. In the multiple stepwise regression analysis, risk factors for PROM were primiparity, premature contractions, PROM in a previous pregnancy and bleeding in the first trimester. CONCLUSIONS: PROM is a common complication at or near term. The risk factors for PROM found in this representative study are difficult to influence and thus provide no guidance about how pregnancies should be managed to reduce the occurrence of PROM in the future.

Adult↗

Factors associated with climacteric symptoms and the use of hormone replacement therapy.

BACKGROUND: To investigate factors associated with climacteric symptoms and the use of hormone replacement therapy (HRT). METHODS: A random sample of women aged 46, 50, 54, 58 and 62 years resident in Goteborg, Sweden (n=5,990) were invited by letter to complete a postal questionnaire concerning the menopause and HRT use. RESULTS: The response rate was 76% (n=4,504). Women with a higher education, who exercised regularly and who had regular spare-time activities felt better and had fewer climacteric complaints (p<0.001) compared to lower educated women, women who exercised infrequently and women who had no spare-time activities. Climacteric symptoms were associated with dryness symptoms (dry eyes, skin, hair and mouth), bilateral salpingo-oophorectomy (SOE), use of psychotropical drugs and use of alternative remedies, previous hysterectomy and full-time occupation. Stepwise multiple regression analysis showed significant correlations between vasomotor symptoms and various dryness symptoms, no menstrual periods and use of alternative remedies. Current HRT-users (13%) had used estrogens for 4.0 years and past users (14%) for 4.3 years. A correlation (p<0.005) was found between HRT use and previous use of contraceptive pills, use of alternative remedies and hysterectomy. Education, occupation and the frequency of exercise did not influence the prevalence of HRT use. CONCLUSIONS: This study has shown that the experience of climacteric symptoms and well-being is associated with many different factors. Women with a higher education and those who exercised regularly were more often symptom-free. HRT use was associated with previous use of contraceptive pills, use of alternative remedies and hysterectomy.

Climacteric↗

Bioavailability of norethisterone acetate alone and in combination with estradiol administered in single or multiple oral doses to postmenopausal women.

OBJECTIVES: Twenty-four postmenopausal women were randomly allocated to a cross-over trial for an investigation of the pharmacokinetics of norethisterone acetate (NETA; 0.5 mg), administered alone or in combination with estradiol (E2; 1 mg), both after a single oral dose. In a second trial, the above combination of 0.5 mg NETA with 1 mg E2 was administered daily for 28 days. METHODS: Plasma levels of NET, E2, estrone (E1) and estrone sulphate fraction containing an admixture of estrone glucuronide (E1S/E1G) were measured by radioimmunoassay at various intervals up to 72 h in the first trial and at the same intervals after the 28th day in the second trial. RESULTS: In the first, single-dose trial, pharmacokinetic parameters of NET were similar for NETA administered alone and its combination with E2. There was no statistically significant difference in the area under curve values AUC0-24 and AUC0-infinity and no apparent major differences were observed for other pharmacokinetic parameters. No carry-over effects due to the cross-over design were seen. The multiple dosage in the second trial did not cause any major changes in the pharmacokinetic parameters of NET, except for the AUC0-24 and AUC0-infinity values which were significantly higher than those seen in the first trial. The levels of E2 exhibited, shortly after the intake of E2, a rapid burst. The levels gradually decreased to a nadir followed by an increase to the main peak and by the subsequent elimination phase. The difference between the peak and nadir levels was significant (P < 0.05) in the second, multiple-dose trial. This bimodal pattern was not observed in earlier studies. The main metabolite of E2 was E1S/E1G, followed by E1, as could be seen from the AUC0-infinity values. These were, in both trials, approximately 300 and 7-times higher for the E1S/E1G and E1, respectively, than those for E2. For all analytes, the AUC0-24 values were significantly higher in the second trial than those found in the first trial, indicating accumulation upon repeated administration. Pharmacokinetics of all analytes remained linear in the second trial, as follows from the statistically established equality of AUC0-24 found in the second, multiple-dose trial with AUC0-infinity in the first, single-dose trial. The absorption half-life and t-max values of E1S/E1G appeared to be considerably shorter than those of E1 in both trials. CONCLUSIONS: The bioavailability of NET was not influenced by its combination with 1 mg E2. The most abundant metabolite of E2 was the E1S/E1G fraction, which may have served as the main source of E2 and other estrogens due to metabolic interconversions during the absorption and elimination phases.

Administration, Oral↗

Adipose tissue distribution in postmenopausal women with adenomatous hyperplasia of the endometrium.

OBJECTIVE: To investigate body fat distribution in postmenopausal women with adenomatous and atypical hyperplasia of the endometrium. METHODS: A prospective population-based case control study was performed in a health care county in Sweden. General obesity, as reflected by body mass index (BMI), and adipose tissue distribution, expressed as waist to hip circumference ratio (WHR), were evaluated in a cohort of 367 postmenopausal women who underwent dilatation and curettage because of uterine bleeding. The study group consisted of 29 women with adenomatous or atypical hyperplasia of the endometrium. The controls consisted of 49 age-matched postmenopausal women randomly selected from the computerized population register of the same region. RESULTS: The frequency of endometrial adenomatous and atypical hyperplasia in postmenopausal women with bleeding was 7.2%. In the total population of postmenopausal women the incidence of these endometrial lesions was 44 per 100,000 per year. Body weight (P = 0.039), BMI (P = 0.007), and WHR (P = 0.022) were higher in postmenopausal women with endometrial adenomatous and atypical hyperplasia than in controls. In multivariate analysis only BMI remained statistically associated with adenomatous hyperplasia (P = 0.012). CONCLUSIONS: General obesity, but neither upper nor lower body fat distribution, was characteristic of postmenopausal women with adenomatous and atypical hyperplasia of the endometrium. Overall obesity is a risk factor for these endometrial precancerous lesions, as it is also claimed to be for endometrial cancer.

Adipose Tissue↗

Continuous, combined hormone replacement: randomized comparison of transdermal and oral preparations.

OBJECTIVE: To compare two new transdermal, continuous, combined formulations and an oral regimen of hormone replacement therapy (HRT) with respect to endometrial hyperplasia, bleeding patterns, and climacteric symptoms in postmenopausal women. METHODS: This was a randomized, open, parallel-group trial during 1 year in 441 postmenopausal women who received either a 10-cm2 patch of 0.025 mg estradiol (E2) and 0.125 mg norethisterone acetate, a 20-cm2 patch of 0.05 mg E2 and 0.25 mg norethisterone acetate twice weekly, or tablets of 2 mg E2 and 1 mg norethisterone acetate once daily. The efficacy variables were frequency of endometrial hyperplasia after 1 year of treatment, number of bleeding and spotting days from the fourth to sixth treatment months, relief of climacteric symptoms, and tolerability. RESULTS: The frequency of endometrial hyperplasia was no more than 2% after 1 year of treatment in all groups. One case of simple hyperplasia was detected among the women treated with 10-cm2 patches and two among those treated with oral HRT. From the fourth to sixth treatment months, amenorrhea occurred in 73%, 47%, and 66% of the women in the 10-cm2, 20-cm2, and oral HRT groups, respectively. The 10-cm2 patches and oral treatment were associated with fewer bleeding days than were the 20-cm2 patches (P<.001). During the last 3 months of the treatment year, amenorrhea was found in 100 subjects (86%) for 10-cm2 patches, 61 (65%) for 20-cm2 patches, and in 85 (79%) for oral HRT. All treatments alleviated the climacteric symptoms to a comparable extent. CONCLUSION: In postmenopausal women, 10-cm2 patches relieved climacteric symptoms and prevented endometrial hyperplasia at least as effectively as oral HRT. Amenorrhea was induced early in a high percentage of women using 10-cm2 patches and oral HRT, and these therapies seemed to be convenient, effective, and safe for estrogen deficiency symptoms in postmenopausal women.

Administration, Cutaneous↗

The effects of oestrogen replacement therapy on haemostatic variables in postmenopausal women with non-insulin-dependent diabetes mellitus.

Women with diabetes mellitus have an increased risk of developing coronary heart disease which may be related at least partially to unfavourable changes in haemostasis. The effect of oestrogen replacement therapy on haemostasis has not been studied systematically in women with non-insulin-dependent diabetes mellitus (NIDDM) and therefore this study was performed for that purpose. Twenty-five postmenopausal women with NIDDM were treated with 2 mg of 17-beta-oestradiol orally for 3 months in a double-blind, crossover, placebo-controlled trial. During the last 16 days of active treatment, 1 mg of norethisterone acetate was added for 10 days for endometrial protection. Blood samples were taken at baseline and after 68 days of active or placebo treatment. Treatment with oestradiol was followed by a marked decrease in the activity of plasminogen activator inhibitor, compared with placebo. The activity of tissue plasminogen activator increased significantly. Levels of antithrombin decreased during treatment with oestradiol, whereas no changes were seen in levels of fibrinogen, von Willebrand factor, prothrombin fragment 1+2, protein S, protein C or resistance to activated protein C. In conclusion, oestrogen replacement therapy in postmenopausal women with NIDDM improved the fibrinolytic activity, while only clinically insignificant alterations in the clotting system were seen. These changes in haemostasis may have a favourable impact on the risk for coronary heart disease in diabetic women.

Aged↗

Transvaginal ultrasonography and endometrial histology in peri- and postmenopausal women on hormone replacement therapy.

OBJECTIVE: To determine the association between endometrial thickness and endometrial histology in a large sample of women using HRT. DESIGN: Results from three multi-centre studies were combined. PARTICIPANTS: Five hundred and sixty-four climacteric women were treated with either sequential, continuous combined or long-cycle therapy. MAIN OUTCOME MEASURES: The women underwent 717 examinations with both transvaginal ultrasonography and histological examination of the endometrium. Endometrial thickness was measured and associated with the histological findings. RESULTS: Eight cases of endometrial hyperplasia were diagnosed. All the hyperplasias were simple without atypia. Two cases had an endometrial thickness < 4 mm and two a thickness > 8 mm. The > 4 mm threshold for abnormal endometrium had a sensitivity of 75%, a specificity of 47%, a positive predictive value of 2% and a negative predictive value of 99%. CONCLUSION: No association could be found between the endometrial thickness measured by transvaginal ultrasonography and endometrial pathology. In six out of eight women with simple hyperplasia the endometrium measured > 4 mm.

Administration, Cutaneous↗

Estrogen-progestogen therapy for low bone mineral density in primary biliary cirrhosis.

AIMS/BACKGROUND: Patients with primary biliary cirrhosis (PBC) often have osteoporosis of the high-turnover type, suggesting that estrogen could have a beneficial effect. However, the cholestatic potential of estrogen could imply a risk of increased cholestasis in a disease characterized by cholestasis. The aim of the present study was to test whether hormone replacement therapy (HRT) could be used to increase bone mineral density (BMD) in PBC patients with osteoporosis, without causing deterioration of the liver function. METHODS: Nine female PBC patients with osteoporosis and one with osteopenia were offered HRT for two years. The change in BMD was compared to the change in ten age-matched female PBC patients who had less severe or no osteopenia and who did not receive HRT. Liver function tests were checked at six-month intervals. RESULTS: HRT patients showed a statistically significant increase in lumbar spine BMD and total body BMD whereas control patients showed a significant decrease in lumbar and total body BMD. In contrast to the controls, HRT patients also showed a decrease in truncal fat (-3.8%). Neither of the groups showed any statistically significant changes in the liver function tests. CONCLUSIONS: HRT is safe and effective in female PBC patients with osteoporosis.

Absorptiometry, Photon↗

European Community multi-Center Trial "Fetal ECG Analysis During Labor": ST plus CTG analysis.

This report form part of the European Community Multi-Center Trial "Fetal ECG Analysis during Labor". Aim of this prospective trial was to identify changes in the fetal ECG waveform with cases of verified fetal hypoxia. In this paper we also report on the use of a newly developed automatic system for identification of ST waveform changes (ST Log). All ECG were recorded with the STAN recorder (Neoventa Medical AB, Gothenburg, Sweden). The ECG information was not displayed during labor in order not to influence the clinical management. This report includes data from 320 cases and include six cases of fetal intrapartum hypoxia. Twenty seven cases showed changes in ST waveform. All five cases with the most marked ST change (a rise in T/QRS of > 0.10 units and lasting more then 10 minutes) had signs of ongoing intrapartum hypoxia. Six out of six cases with evidence of intrapartum asphyxia, showed ST changes. On the basis of our multi-center trial it appears that the combined analysis of CTG and ST waveform changes provides an accurate way to identify adverse events during labor. The work is continuing with a new STAN recorder developed by Neoventa Medical in Göteborg and currently being tested in a Swedish randomized, controlled multi-center trial.

Acid-Base Equilibrium↗