Pelvic pain Archives - Revista Brasileira de Ginecologia e Obstetrícia
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2015;37(3):105-109
DOI 10.1590/SO100-720320150005201
To determine whether paraspinal block reduces pain scores compared to placebo in women with chronic pelvic pain refractory to drug therapy.
Subjects with chronic pelvic pain due to benign conditions and refractory to drug therapy were invited to participate in a randomized, double blind, superiority trial at a tertiary reference center. Subjects were randomly allocated to receive paraspinal anesthetic block with 1% lidocaine without epinephrine or placebo (control). Lidocaine was injected along the spinal process of the painful segment in the supra- and interspinal ligaments using a 25G X 2" needle. Placebo consisted of introduction of the needle in the same segment without injecting any substance. The main outcome measured was the pain score based on a visual analog scale at T0 (baseline), T1 (within 15 min after the procedure) and T2 (one week after the procedure). Data were statistically analyzed by ANOVA and the 95% confidence interval (95%CI).
Mean age was similar for both groups, i.e., 51.2 (paraspinal anesthetic block) and 51.8 years (control). A blind examiner measured the degree of pain according to the visual analog scale from 0 (no pain) to 10 (worst pain imaginable). Based on the visual analog scale, the mean pain scores of the paraspinal anesthetic block group at T0, T1 and T2 were 5.50 (SD=2.92; 95%CI 3.84-7.15), 2.72 (SD=2.10; 95%CI 1.53-3.90), and 4.36 (SD=2.37; 95%CI 1.89-6.82), respectively. The difference between T0 and T1 was statistically significant, with p=0.03.
Paraspinal anesthetic block had a small effect on visual analog scale pain score immediately after the injections, but no sustained benefit after one week. Further studies are needed to determine the efficacy of paraspinal anesthetic block with different lidocaine doses for the treatment of visceral pain of other causes.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2015;37(3):105-109
DOI 10.1590/SO100-720320150005201
To determine whether paraspinal block reduces pain scores compared to placebo in women with chronic pelvic pain refractory to drug therapy.
Subjects with chronic pelvic pain due to benign conditions and refractory to drug therapy were invited to participate in a randomized, double blind, superiority trial at a tertiary reference center. Subjects were randomly allocated to receive paraspinal anesthetic block with 1% lidocaine without epinephrine or placebo (control). Lidocaine was injected along the spinal process of the painful segment in the supra- and interspinal ligaments using a 25G X 2" needle. Placebo consisted of introduction of the needle in the same segment without injecting any substance. The main outcome measured was the pain score based on a visual analog scale at T0 (baseline), T1 (within 15 min after the procedure) and T2 (one week after the procedure). Data were statistically analyzed by ANOVA and the 95% confidence interval (95%CI).
Mean age was similar for both groups, i.e., 51.2 (paraspinal anesthetic block) and 51.8 years (control). A blind examiner measured the degree of pain according to the visual analog scale from 0 (no pain) to 10 (worst pain imaginable). Based on the visual analog scale, the mean pain scores of the paraspinal anesthetic block group at T0, T1 and T2 were 5.50 (SD=2.92; 95%CI 3.84-7.15), 2.72 (SD=2.10; 95%CI 1.53-3.90), and 4.36 (SD=2.37; 95%CI 1.89-6.82), respectively. The difference between T0 and T1 was statistically significant, with p=0.03.
Paraspinal anesthetic block had a small effect on visual analog scale pain score immediately after the injections, but no sustained benefit after one week. Further studies are needed to determine the efficacy of paraspinal anesthetic block with different lidocaine doses for the treatment of visceral pain of other causes.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2014;36(2):79-83
DOI 10.1590/S0100-72032014000200006
To investigate the presence of depressive symptoms in women with chronic pelvic
pain.
This descriptive cross-sectional study was performed with women aged 18 years or
older, diagnosed with chronic pelvic pain, with no pregnancy history in the
previous year, and with no cancer history. The sample was established by
calculating the representative sample, estimated as 50 women. All women were
undergoing treatment at a gynecology outpatient clinic, referred by the primary
health care network of the Brazilian national health system. Data collection was
performed from October2009 to May 2010. The women's sociodemographic, economic and
clinical characteristics were analyzed. Pain intensity was evaluated using a
visual analogue scale. The depressive symptoms were investigated using Beck's
Depression Inventory. Statistical analysis was performed using position measures
(mean, median), dispersion (standard deviation) and the χ2 test. Values
of p≤ .05 were considered statistically significant.
The participants' mean age was 41.6±9.4 years. The following features
predominated: secondary education level; pardo (brown) skin color; Catholic
religion; and living with a steady partner. Most (98%) were economically active
and worked with general domestic services. Regarding the participants' subjective
perception of pain, 52% reported experiencing intense pain, while 48% reported
experiencing moderate pain. Most women (52%) had been living with pain for five
years or less, and 30%, for over 11 years. The mean BDI score was 17.4 (±9.4). It
was observed that 58% of the women presented mild, moderate and severe depressive
symptoms according to the BDI. The most frequent depressive symptoms were
fatigability, loss of libido, irritability, difficulty to work, somatic
preoccupations, crying, dissatisfaction, sadness, and insomnia.
Depressive symptoms were frequent among these women suffering with chronic pelvic
pain.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2014;36(2):79-83
DOI 10.1590/S0100-72032014000200006
To investigate the presence of depressive symptoms in women with chronic pelvic
pain.
This descriptive cross-sectional study was performed with women aged 18 years or
older, diagnosed with chronic pelvic pain, with no pregnancy history in the
previous year, and with no cancer history. The sample was established by
calculating the representative sample, estimated as 50 women. All women were
undergoing treatment at a gynecology outpatient clinic, referred by the primary
health care network of the Brazilian national health system. Data collection was
performed from October2009 to May 2010. The women's sociodemographic, economic and
clinical characteristics were analyzed. Pain intensity was evaluated using a
visual analogue scale. The depressive symptoms were investigated using Beck's
Depression Inventory. Statistical analysis was performed using position measures
(mean, median), dispersion (standard deviation) and the χ2 test. Values
of p≤ .05 were considered statistically significant.
The participants' mean age was 41.6±9.4 years. The following features
predominated: secondary education level; pardo (brown) skin color; Catholic
religion; and living with a steady partner. Most (98%) were economically active
and worked with general domestic services. Regarding the participants' subjective
perception of pain, 52% reported experiencing intense pain, while 48% reported
experiencing moderate pain. Most women (52%) had been living with pain for five
years or less, and 30%, for over 11 years. The mean BDI score was 17.4 (±9.4). It
was observed that 58% of the women presented mild, moderate and severe depressive
symptoms according to the BDI. The most frequent depressive symptoms were
fatigability, loss of libido, irritability, difficulty to work, somatic
preoccupations, crying, dissatisfaction, sadness, and insomnia.
Depressive symptoms were frequent among these women suffering with chronic pelvic
pain.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2013;35(6):262-267
DOI 10.1590/S0100-72032013000600005
PURPOSE: To correlate preoperative serum cancer antigen 125 (Ca-125) levels and laparoscopic findings in women with pelvic pain symptoms suggestive of endometriosis. METHODS: A retrospective study was conducted including all women with pelvic pain symptoms suspected for endometriosis operated by laparoscopy from January 2010 to March 2013. Patients were divided into 2 groups according to preoperative Ca-125 level (<35 U/mL and >35 U/mL). Subsequently, patients with ovarian endometriomas were excluded and a further analysis was conducted again according to the preoperative Ca-125 level. The following parameters were compared between groups: presence of ovarian endometrioma, presence and number of deep infiltrating endometriosis (DIE) lesions and American Society for Reproductive Medicine score. The statistical analysis was performed with Statistica version 8.0, using the Fisher exact test, Student's t-test and Mann-Whitney test, when needed. A p value of <0.05 was considered to be statistically significant. RESULTS: During the study period, a total of 350 women were submitted to laparoscopic treatment of endometriosis. One hundred thirty patients (37.1%) had Ca-125>35 U/mL and 220 (62.9%) had Ca-12<35 U/mL. The presence of ovarian endometriomas (47.7 versus 15.9%), DIE lesions (99.6 versus 78.6%) and intestinal DIE lesions (60 versus 30.9%) was more frequent, and the AFSr score was higher (34 versus 6) in the former group. In the second analysis, excluding the patients with ovarian endometriomas (>35 U/mL=68 patients and <35 U/mL=185 patients), similar results were obtained. The presence of DIE lesions (91.2 versus 76.2%), intestinal DIE lesions (63.2 versus 25.4%), bladder DIE lesions (20.6 versus 4.8%) and ureteral DIE lesions (7.3 versus 1.6%) was more frequent, and the AFSr score was higher (10 versus 6) in the Ca-125 >35 U/mL group. CONCLUSIONS: Investigation for DIE is mandatory in women with pelvic pain symptoms suggestive of endometriosis with a preoperative Ca-125 level >35 U/mL, especially when an ovarian endometrioma is not present.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2013;35(6):262-267
DOI 10.1590/S0100-72032013000600005
PURPOSE: To correlate preoperative serum cancer antigen 125 (Ca-125) levels and laparoscopic findings in women with pelvic pain symptoms suggestive of endometriosis. METHODS: A retrospective study was conducted including all women with pelvic pain symptoms suspected for endometriosis operated by laparoscopy from January 2010 to March 2013. Patients were divided into 2 groups according to preoperative Ca-125 level (<35 U/mL and >35 U/mL). Subsequently, patients with ovarian endometriomas were excluded and a further analysis was conducted again according to the preoperative Ca-125 level. The following parameters were compared between groups: presence of ovarian endometrioma, presence and number of deep infiltrating endometriosis (DIE) lesions and American Society for Reproductive Medicine score. The statistical analysis was performed with Statistica version 8.0, using the Fisher exact test, Student's t-test and Mann-Whitney test, when needed. A p value of <0.05 was considered to be statistically significant. RESULTS: During the study period, a total of 350 women were submitted to laparoscopic treatment of endometriosis. One hundred thirty patients (37.1%) had Ca-125>35 U/mL and 220 (62.9%) had Ca-12<35 U/mL. The presence of ovarian endometriomas (47.7 versus 15.9%), DIE lesions (99.6 versus 78.6%) and intestinal DIE lesions (60 versus 30.9%) was more frequent, and the AFSr score was higher (34 versus 6) in the former group. In the second analysis, excluding the patients with ovarian endometriomas (>35 U/mL=68 patients and <35 U/mL=185 patients), similar results were obtained. The presence of DIE lesions (91.2 versus 76.2%), intestinal DIE lesions (63.2 versus 25.4%), bladder DIE lesions (20.6 versus 4.8%) and ureteral DIE lesions (7.3 versus 1.6%) was more frequent, and the AFSr score was higher (10 versus 6) in the Ca-125 >35 U/mL group. CONCLUSIONS: Investigation for DIE is mandatory in women with pelvic pain symptoms suggestive of endometriosis with a preoperative Ca-125 level >35 U/mL, especially when an ovarian endometrioma is not present.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2013;35(2):84-89
DOI 10.1590/S0100-72032013000200008
PURPOSES: To determine the prevalence of irritable bowel syndrome (IBS) in women with chronic pelvic pain (CPP) and its associated features; to determine whether IBS and CPP constitute the same syndrome. METHODS: Cross-sectional population survey with systematic sequential sampling according to census districts in which 1470 women were interviewed with respect to the sample calculation. The participants resided in their own homes, were at least 14 years of age, experienced menarche and presented CPP according to the American College of Obstetrics and Gynaecology. The dependent variable was IBS based on Rome III criteria in women with CPP, and the following independent variables were possibly associated with IBS: age, schooling, duration of pain, sedentary lifestyle, migraine, depression, insomnia, back pain, dysmenorrhea, dyspareunia, depression, history of violence, and intestinal symptoms. The sample was subdivided into groups with and without IBS. After the descriptive analysis of the variables was performed, the respective frequencies were evaluated using GraphPad Prism 5 software. To evaluate the association between the dependent variable and the independent variables, the χ² test was used with a significance level of 5%. RESULTS: The prevalence of IBS in women with CPP was 19,5%. Pain duration (p=0.03), back pain (p=0.002), history of physical or sexual abuse (p=0.002), and intestinal complaints were more prevalent in the group with IBS and CPP. There was no difference between the groups regarding other criteria. CONCLUSION: The data confirmed the literature, identified several aspects that were shared between the pathologies and supported the hypothesis that both pathologies can constitute the same syndrome.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2013;35(2):84-89
DOI 10.1590/S0100-72032013000200008
PURPOSES: To determine the prevalence of irritable bowel syndrome (IBS) in women with chronic pelvic pain (CPP) and its associated features; to determine whether IBS and CPP constitute the same syndrome. METHODS: Cross-sectional population survey with systematic sequential sampling according to census districts in which 1470 women were interviewed with respect to the sample calculation. The participants resided in their own homes, were at least 14 years of age, experienced menarche and presented CPP according to the American College of Obstetrics and Gynaecology. The dependent variable was IBS based on Rome III criteria in women with CPP, and the following independent variables were possibly associated with IBS: age, schooling, duration of pain, sedentary lifestyle, migraine, depression, insomnia, back pain, dysmenorrhea, dyspareunia, depression, history of violence, and intestinal symptoms. The sample was subdivided into groups with and without IBS. After the descriptive analysis of the variables was performed, the respective frequencies were evaluated using GraphPad Prism 5 software. To evaluate the association between the dependent variable and the independent variables, the χ² test was used with a significance level of 5%. RESULTS: The prevalence of IBS in women with CPP was 19,5%. Pain duration (p=0.03), back pain (p=0.002), history of physical or sexual abuse (p=0.002), and intestinal complaints were more prevalent in the group with IBS and CPP. There was no difference between the groups regarding other criteria. CONCLUSION: The data confirmed the literature, identified several aspects that were shared between the pathologies and supported the hypothesis that both pathologies can constitute the same syndrome.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2010;32(5):247-253
DOI 10.1590/S0100-72032010000500008
PURPOSE: to compare the quality of life (QL) of women with and without chronic pelvic pain (CPP) and to investigate the factors associated with QL in women with CPP. METHODS: a cross-sectional study was conducted on 30 women with CPP and 20 women without CPP. Sociodemographic and clinical characteristics were evaluated. QL was investigated by applying the SF-36 questionnaire, which contains eight domains: functional capacity, physical aspects, pain, general health status, vitality, social aspects, emotional aspects, and mental health. These domains can be summarized into two groups: physical component summary (PCS) and mental component summary (MCS). Pain intensity was investigated by applying the visual analogue scale. Linear regression analysis was used to compare QL scores between women with and without CPP and to identify factors associated with the QL of women with CPP. RESULTS: the mean age of women with and without CPP was 35.2±7.5 and 36±9.3 years (p=0.77), respectively. Women with CPP had a lower monthly family income (p=0.04) and a higher prevalence of dysmenorrhea (87 versus 40%; p<0.01) and depression (30 versus 5%; p=0.04) compared to women without CPP. Adjusted analysis for potential confounding variables revealed that women with CPP had lower QL scores in the pain (p<0.01) and social aspects (p<0.01) domains. Depression was negatively associated with the emotional aspects domain (p=0.05) and with the MCS (p=0.03), while pain intensity was negatively related to the pain domain (p<0.01) of the QL of women with CPP. CONCLUSIONS: women with CPP presented a worse QL compared to women without CPP. Depression and pain intensity were negatively related to the QL of women with CPP. Thus, the evaluation and treatment of pain and depressive symptoms must be among the priorities that aim to improve the QL of women with CPP.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2010;32(5):247-253
DOI 10.1590/S0100-72032010000500008
PURPOSE: to compare the quality of life (QL) of women with and without chronic pelvic pain (CPP) and to investigate the factors associated with QL in women with CPP. METHODS: a cross-sectional study was conducted on 30 women with CPP and 20 women without CPP. Sociodemographic and clinical characteristics were evaluated. QL was investigated by applying the SF-36 questionnaire, which contains eight domains: functional capacity, physical aspects, pain, general health status, vitality, social aspects, emotional aspects, and mental health. These domains can be summarized into two groups: physical component summary (PCS) and mental component summary (MCS). Pain intensity was investigated by applying the visual analogue scale. Linear regression analysis was used to compare QL scores between women with and without CPP and to identify factors associated with the QL of women with CPP. RESULTS: the mean age of women with and without CPP was 35.2±7.5 and 36±9.3 years (p=0.77), respectively. Women with CPP had a lower monthly family income (p=0.04) and a higher prevalence of dysmenorrhea (87 versus 40%; p<0.01) and depression (30 versus 5%; p=0.04) compared to women without CPP. Adjusted analysis for potential confounding variables revealed that women with CPP had lower QL scores in the pain (p<0.01) and social aspects (p<0.01) domains. Depression was negatively associated with the emotional aspects domain (p=0.05) and with the MCS (p=0.03), while pain intensity was negatively related to the pain domain (p<0.01) of the QL of women with CPP. CONCLUSIONS: women with CPP presented a worse QL compared to women without CPP. Depression and pain intensity were negatively related to the QL of women with CPP. Thus, the evaluation and treatment of pain and depressive symptoms must be among the priorities that aim to improve the QL of women with CPP.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2010;32(6):298-307
DOI 10.1590/S0100-72032010000600008
Endometriosis is characterized by the presence of endometrial tissue, localized outside the uterine cavity, such as peritoneal surface, ovaries, and rectum-vaginal septum. The prevalence is about 6 to 10%. Concerning the etiopathogenesis, the retrograde menstruation theory is accepted, although disruption in endometrial molecular biology seems to be fundamental to the development of endometriosis ectopic focuses. Women with endometriosis may be asymptomatic or may present complaints of dysmenorrhea, dispareunia, chronic pelvic pain and/or infertility. Although the definitive diagnosis of endometriosis needs a surgical intervention, mainly by laparoscopy, many findings obtained by physicalexamination and imaging and laboratory tests can predict, with a high degree of reliability, that the patient has endometriosis. The most common current treatments include surgery, ovarian suppression therapy or both. Pharmacological treatments that do not inhibit ovarian function are under investigation.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2010;32(6):298-307
DOI 10.1590/S0100-72032010000600008
Endometriosis is characterized by the presence of endometrial tissue, localized outside the uterine cavity, such as peritoneal surface, ovaries, and rectum-vaginal septum. The prevalence is about 6 to 10%. Concerning the etiopathogenesis, the retrograde menstruation theory is accepted, although disruption in endometrial molecular biology seems to be fundamental to the development of endometriosis ectopic focuses. Women with endometriosis may be asymptomatic or may present complaints of dysmenorrhea, dispareunia, chronic pelvic pain and/or infertility. Although the definitive diagnosis of endometriosis needs a surgical intervention, mainly by laparoscopy, many findings obtained by physicalexamination and imaging and laboratory tests can predict, with a high degree of reliability, that the patient has endometriosis. The most common current treatments include surgery, ovarian suppression therapy or both. Pharmacological treatments that do not inhibit ovarian function are under investigation.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2009;31(7):353-360
DOI 10.1590/S0100-72032009000700006
OBJECTIVE: to evaluate by photogrammetry, postural changes in women with chronic pelvic pain. METHODS: thirty women with complaint of chronic pelvic pain and 37 without it, in a total of 67 women, were evaluated. The evaluation was realized through anamnesis, fixed markers in defined anatomical sites, and frontal, posterior, left and right lateral photographies. Photo analysis has been done by the software CorelDraw®, version 11.0. Quantitative values for postural analysis of the ankle, the knee in the saggittal plan, pelvis, lumbar lordosis, thoracic kyphosis, adducted/abducted scapula, shoulders, head and third finger on the floor test were obtained. The qualitative variables studied were the knee (varus, valgus or normal), the presence or not of winged scapula and leveling of shoulders. The Statistical Package for Social Sciences, version 16.0 was used for the statistical analyses. Fisher's exact test and Monte-Carlo method were used to compare the qualitative variables, and for the quantitative data, t or Mann-Whitney test was used. The comparisons among continuous data, corrected for possible confusion variables were realized by the univariate covariance analysis. Significance level was established at 0.05 or 5%. RESULTS: there were significant differences between cases and controls for protruded head (47.5 and 52.0º, respectively; p<0.0001) and for protruded shoulders (1.9 and 1.6 cm, respectively; p=0.03). The other variables did not show significant differences. CONCLUSIONS: based on these results, attention to head and shoulder posture, to antalgic postures and to the emotional factor is recommended. Women with chronic pelvic pain should be treated, taking into consideration individual muscle-skeletal changes, and social and emotional conditions.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2009;31(7):353-360
DOI 10.1590/S0100-72032009000700006
OBJECTIVE: to evaluate by photogrammetry, postural changes in women with chronic pelvic pain. METHODS: thirty women with complaint of chronic pelvic pain and 37 without it, in a total of 67 women, were evaluated. The evaluation was realized through anamnesis, fixed markers in defined anatomical sites, and frontal, posterior, left and right lateral photographies. Photo analysis has been done by the software CorelDraw®, version 11.0. Quantitative values for postural analysis of the ankle, the knee in the saggittal plan, pelvis, lumbar lordosis, thoracic kyphosis, adducted/abducted scapula, shoulders, head and third finger on the floor test were obtained. The qualitative variables studied were the knee (varus, valgus or normal), the presence or not of winged scapula and leveling of shoulders. The Statistical Package for Social Sciences, version 16.0 was used for the statistical analyses. Fisher's exact test and Monte-Carlo method were used to compare the qualitative variables, and for the quantitative data, t or Mann-Whitney test was used. The comparisons among continuous data, corrected for possible confusion variables were realized by the univariate covariance analysis. Significance level was established at 0.05 or 5%. RESULTS: there were significant differences between cases and controls for protruded head (47.5 and 52.0º, respectively; p<0.0001) and for protruded shoulders (1.9 and 1.6 cm, respectively; p=0.03). The other variables did not show significant differences. CONCLUSIONS: based on these results, attention to head and shoulder posture, to antalgic postures and to the emotional factor is recommended. Women with chronic pelvic pain should be treated, taking into consideration individual muscle-skeletal changes, and social and emotional conditions.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2006;28(12):733-740
DOI 10.1590/S0100-72032006001200008
Chronic pelvic pain is a debilitating and highly prevalent disease with a major impact on quality of life and work productivity, beyond significant costs to health services. The dilemma of managing patients with chronic pelvic pain continues to frustrate physicians confronted with these complaints, in part because its pathophysiology is poorly understood. Consequently, its treatment is often unsatisfactory and limited to temporary symptom relief. In the present revision, we discuss the adequate management of chronic pelvic pain. We point out that a comprehensive medical history and physical examination should include special attention to gastrointestinal, urological, gynecological, muscle-skeletal, neurological, psychiatric, and endocrine systems. Thus, a multidisciplinary approach is recommended. Additionally, we emphasize that, although useful, specific surgical procedures, such as laparoscopy, should be indicated only to selected patients, mainly after excluding irritable bowel syndrome and pain of myofascial origin.
Summary
Revista Brasileira de Ginecologia e Obstetrícia. 2006;28(12):733-740
DOI 10.1590/S0100-72032006001200008
Chronic pelvic pain is a debilitating and highly prevalent disease with a major impact on quality of life and work productivity, beyond significant costs to health services. The dilemma of managing patients with chronic pelvic pain continues to frustrate physicians confronted with these complaints, in part because its pathophysiology is poorly understood. Consequently, its treatment is often unsatisfactory and limited to temporary symptom relief. In the present revision, we discuss the adequate management of chronic pelvic pain. We point out that a comprehensive medical history and physical examination should include special attention to gastrointestinal, urological, gynecological, muscle-skeletal, neurological, psychiatric, and endocrine systems. Thus, a multidisciplinary approach is recommended. Additionally, we emphasize that, although useful, specific surgical procedures, such as laparoscopy, should be indicated only to selected patients, mainly after excluding irritable bowel syndrome and pain of myofascial origin.
