Bacteriology and treatment of malodorous lower reproductive tract in gynecologic cancer patients.

OBJECTIVE: To determine the bacteriology of lower genital tract cancers to direct potential treatment modalities and to determine the impact of treatment on quality of life. METHODS: Gram stain, saline preparations, tumor pH determinations, and anaerobic and aerobic tumor cultures were obtained from 13 consecutive patients with malodorous gynecologic cancers and 13 patients (controls) with nonmalodorous tumors. All patients with odor were treated with topical metronidazole for 7 days. Odor assessment questionnaires were administered daily in the treatment group. Quality-of-life evaluation was assessed using the Functional Assessment of Cancer Therapy questionnaire before and after treatment. RESULTS: Cancer of the cervix (n = 21) was the most common primary site and accounted for 81% (95% confidence interval 61%, 93%) of malodorous gynecologic cancers. Eight of 13 (62%) patients with malodorous tumors had bacterial vaginosis compared with four of 13 (31%) of those without odor (P =.11). Aerobic and anaerobic bacteria were isolated with equal frequency from malodorous gynecologic cancers. Results of odor assessment questionnaires showed a graded improvement with topical antibiotic therapy (P <.001). The Functional Assessment of Cancer Therapy questionnaire indicated improved quality of life after therapy (P =.02). CONCLUSION: Most patients with odor had bacterial vaginosis and had an improvement in odor with topical metronidazole. Therefore, this treatment might be useful for patients with malodorous pelvic tumors.

Fallopian tube prolapse after hysterectomy.

BACKGROUND: Fallopian tube prolapse is reported to most commonly occur after vaginal hysterectomy. Both diagnosis and management have varied, resulting in differing efficacies of treatment. METHODS: We reviewed the presentation, diagnosis, management, and outcomes of 18 cases of tubal prolapse in 17 women. RESULTS: Most cases (65%) occurred after abdominal hysterectomy. The post-hysterectomy course was complicated by cuff cellulitis in three women, an infected cuff hematoma in one, and post-extubation pulmonary edema in one; four were observed for elevated temperature only. At presentation, 44% complained of dyspareunia, 39% vaginal bleeding, 33% vaginal discharge, 28% abdominal pain, and 28% were asymptomatic. Seven women had vaginal excision (one requiring an additional abdominal procedure), three had laparotomy with salpingectomy, and seven (41%) had spontaneous disappearance of prolapsed fallopian tube without treatment. CONCLUSIONS: In our series, tubal prolapse most commonly occurred after abdominal hysterectomy. Moreover, women with tubal prolapse may be asymptomatic, and observation alone may lead to resolution.

Design of the PID Evaluation and Clinical Health (PEACH) Study.

This paper describes the PID Evaluation and Clinical Health Study (PEACH), a multicenter, randomized clinical trial designed to compare treatment with outpatient and inpatient antimicrobial regimens among women with pelvic inflammatory disease (PID). PEACH is the first trial to evaluate the effectiveness and cost-effectiveness of currently recommended antibiotic combinations in preventing infertility, ectopic pregnancy, chronic pelvic pain, recurrent PID, and other health outcomes. It is also the largest prospective study of PID ever conducted in North America. We describe the PEACH study's specific aims, study organization, patient selection criteria, conditions for exclusion, data collected upon entry, randomization and treatment, adherence measures, follow-up activities, quality-of-life measures, outcomes, and statistical analyses. In the first 11 months of enrollment (March 1996-January 1997), 312 women were randomized. Of eligible women, 59% consented to enroll. Participating women are primarily black (72%) and young (mean age 24 years). After a median of 5.5 months of follow-up, we were in contact with 95% of study participants. The PEACH study will provide a rationale for selecting between inpatient and outpatient antibiotic treatment, the two most common treatment strategies, for PID.

Tissue penetration of Meropenem in patients undergoing gynecologic surgery.

The purpose of this study was to assess the tissue-penetrating ability of a new beta-lactam antibiotic, meropenem, in 64 patients undergoing elective gynecologic surgery. Patients received a single 500-mg dose intravenously before surgery. Plasma and tissue concentrations of meropenem were highest at approximately 1 hour, and good tissue penetration was seen in the variety of specimens evaluated. The median plasma concentration at approximately 1 hour was 13.3 micrograms/mL. The median fluid and tissue concentrations at approximately 1 hour were as follows: cervix, 8.5 micrograms/g; endometrium, 2.3 micrograms/g; fallopian tube, 1.9 micrograms/g; myometrium, 3.6 micrograms/g; ovary, 2.3 micrograms/g; and uterus, 2.3 micrograms/g. These tissue concentrations exceed the MICs of meropenem for 90% of typical pathogens associated with gynecologic infections. Meropenem readily penetrates gynecologic tissue. A single 500-mg dose provides adequate tissue concentrations for treatment of gynecologic infections caused by susceptible pathogens.

A multicenter study comparing intravenous meropenem with clindamycin plus gentamicin for the treatment of acute gynecologic and obstetric pelvic infections in hospitalized women.

We conducted a multicenter trial to compare the efficacy and safety of meropenem with the efficacy and safety of clindamycin plus gentamicin in the treatment of 515 hospitalized patients with acute gynecologic and obstetric pelvic infections. At the end of treatment, the rates of satisfactory clinical and bacteriologic response were high (88%) in both treatment groups: the rates of response were 90% for the meropenem group and 86% for the clindamycin/gentamicin group. No serious adverse events occurred. The most frequently reported drug-related adverse clinical events in the meropenem group were nausea and injection-site reactions (> 1% of patients), and the most common drug-related laboratory abnormality was thrombocythemia. Similar patterns of adverse events occurred in the clindamycin/gentamicin group; however, the incidence of diarrhea and eosinophilia was higher in this group. In summary, this trial demonstrated that meropenem is an effective and safe alternative to the combination of clindamycin plus gentamicin for the treatment of women with acute gynecologic and obstetric pelvic infections.

Infection after hysterectomy.

Antibiotic prophylaxis and advances in technology have reduced operative site infections after hysterectomy to a minimum. Pelvic infections are the most common infection type and respond promptly to a variety of parenteral single-agent and combination antibiotic regimens. Oral antibiotic regimens following parenteral therapy are unnecessary. Abdominal incision infections are less common than pelvic infections, less common than seromas or hematomas, and usually do not require antimicrobial therapy. Abscesses or infected hematomas require parenteral antimicrobial therapy, and drainage of those located above the cuff will predictably shorten therapy time. With early discharge from the hospital, many infections will not become evident until after the patient is home. For that reason, it is important that the patient's discharge instructions outline symptoms and signs associated with these infections so she can present for care at the earliest possible time.

Cefazolin is inferior to cefotetan as single-dose prophylaxis for women undergoing elective total abdominal hysterectomy.

The purpose of this prospective, randomized, double-blind clinical trial was to compare the efficacy of 1-g doses of intravenous cefazolin with that of 1-g doses of intravenous cefotetan in preventing major operative site infections after elective abdominal hysterectomy. A major operative site infection requiring parenteral antimicrobial therapy developed in 46 (9%) of 511 evaluable women: 30 (11.6%) of 258 women given cefazolin prophylaxis and 16 (6.3%) of 253 women given cefotetan prophylaxis (relative risk, 1.84; 95% confidence interval, 1.03 to 3.29; P < .05). Risk factors for major operative site infection were younger age, lower postoperative hemoglobin concentration, and a proliferative endometrium. Ten (3.9%) of 258 women given cefazolin prophylaxis had a postoperative pelvic abscess; two of these women required additional surgical procedures, compared with two (0.8%) of 253 women given cefotetan prophylaxis who had an abscess but did not require surgery (relative risk, 4.9; 95% confidence interval, 1.09 to 22.16; P = .04). A greater number of infections and more serious infections occurred following cefazolin prophylaxis; this treatment resulted in 234 additional hospital days for administration of parenteral antimicrobial therapy.

Prophylactic antibiotics for suction curettage in incomplete abortion.

OBJECTIVE: The purpose of this study was to investigate the efficacy of 200 mg of prophylactic doxycycline in preventing pelvic infection after curettage for spontaneous (incomplete) abortion. METHODS: A randomized, prospective, double-blinded study was carried out involving 300 women with an incomplete abortion who were given either placebo or 200 mg of doxycycline orally 30-60 min prior to curettage. A hematocrit, WBC count, pregnancy test, syphilis serology, Neisseria gonorrhoeae culture, and Micro Trak (monoclonal antibody test, Syba, San Jose, CA) for Chlamydia trachomatis were performed. The patients were scheduled for follow-up 2 weeks later. Antibiotic administration for any reason as well as the postoperative infection rate in these women was assessed. RESULTS: Eleven women were excluded from analysis, leaving 289 evaluable. N. gonorrhoeae was isolated from 6 (2%) women and C. trachomatis from 8 (3%) women, and the syphilis serology was serofast in 4 (1%) women. Endometritis complicated the procedure in 4 women who received placebo and in 1 woman who received doxycycline (P = 0.22). CONCLUSION: Prophylactic doxycycline is not effective in preventing pelvic infection after curettage for spontaneous (incomplete) abortion.

Comparison of three regimens recommended by the Centers for Disease Control and Prevention for the treatment of women hospitalized with acute pelvic inflammatory disease.

This six-center, prospective, open-label clinical trial compared the efficacy and safety of three regimens recommended by the Centers for Disease Control and Prevention (CDC) for the treatment of women hospitalized for acute pelvic inflammatory disease (PID). The study focused on the response to inpatient therapy, not on long-term prevention of sequelae. A severity score was used for objective comparison of the degree of illness before and after therapy. Women were randomly assigned (in a 1:1:1 ratio) to treatment with cefoxitin plus doxycycline, clindamycin plus gentamicin, or cefotetan plus doxycycline. Two hundred seventy-five (94.2%) of 292 evaluable women required no alteration in therapeutic regimen. The three regimens produced almost identical cure rates. No serious adverse clinical or laboratory events were observed. In short, the three regimens recommended by the CDC for inpatient therapy of acute PID were similarly effective and safe.

Results of a double-blind, placebo-controlled clinical trial program of single-dose ceftizoxime versus multiple-dose cefoxitin as prophylaxis for patients undergoing vaginal and abdominal hysterectomy.

In a series of three double-blind, controlled, clinical studies, the efficacy and safety of a single 1 gram dose of ceftizoxime were compared with those of a standard regimen, three 2 gram doses of cefoxitin, for prophylaxis of perioperative infection in women undergoing abdominal or vaginal hysterectomy. Two hundred and twenty-seven patients received ceftizoxime prophylaxis and 234 patients received cefoxitin prophylaxis. Study 1 entered 110 patients in Dallas, Texas and Los Angeles, California. Study 2 entered 242 patients in Canada. Study 3 entered 109 patients in Denver, Colorado. Within studies, the distribution of surgical procedures was comparable between antibiotic groups. The groups were similar for demographic and medical factors at each center and overall. Analyses were performed within and across studies, applying consistent criteria to the selection of evaluable patients and to the definitions of prophylactic success and primary and secondary prophylactic failure. Three hundred and sixteen patients were evaluable, 160 who received ceftizoxime and 156 who received cefoxitin. Overall, complete prophylactic success occurred in 138 of 160 evaluable patients (86.3 percent) receiving ceftizoxime and 128 of 156 evaluable patients (82.1 percent) receiving cefoxitin. Prophylactic success rates differed by study as well as by type of hysterectomy. In studies 1 and 2, prophylactic success rates for ceftizoxime were 95.1 and 87.6 percent, respectively, versus 93.1 and 87.8 percent for cefoxitin. In study 3, success rates were lowest, 70.0 percent for ceftizoxime and 59.5 percent for cefoxitin. Among evaluable patients overall, prophylactic success rates after vaginal hysterectomy were 91.0 percent for those receiving ceftizoxime and 85.1 percent for those receiving cefoxitin. After abdominal hysterectomy, success rates were 78.3 percent for both groups. Febrile morbidity rates and duration of hospitalization were comparable for both groups across all studies and within individual studies. Ceftizoxime and cefoxitin were safe and well tolerated. The results of these controlled studies indicate that single-dose ceftizoxime is as effective and safe as multiple-dose cefoxitin when used as adjunctive chemoprophylaxis in patients at risk of postoperative infection after vaginal or abdominal hysterectomy.

Randomized comparative study of cefepime and cefotaxime in the treatment of acute obstetric and gynaecological infections.

Patients with presumed acute gynaecological infections were randomized (2:1) to receive cefepime 2 g every 12 h (n = 159) or cefotaxime 2 g every 8 h (n = 72), both im or by a 30-min i.v. infusion. For evaluation of efficacy, patients were required to have a bacteriologically documented infection, with at least one pathogen isolated susceptible to both drugs. Duration of treatment was 2-8 days in the 95 cefepime-treated patients and 3-10 days in the 36 cefotaxime-treated patients with evaluable infections; approximately three-quarters of the patients in each group were treated for 4-5 days. Clinical response was satisfactory in 81/95 (85%) of the evaluable cefepime recipients and 30/36 (83%) of the evaluable cefotaxime recipients (P = 0.802). In total, 211 (85%) of the 247 pathogens isolated from evaluable cefepime recipients were eradicated, compared with 98 (90%) of 109 pathogens isolated from evaluable cefotaxime recipients. All pathogens were eradicated in 77 (81%) cefepime-treated patients and in 31 (86%) cefotaxime-treated patients (P = 0.379). Overall response to treatment, calculated by combining clinical response and individual patient bacteriological response, was considered effective, partially effective or ineffective in 77%, 13% and 11% of cefepime-treated patients respectively and in 75%, 19% and 6% of cefotaxime-treated patients respectively (P = 0.932 for effective response). Adverse clinical events were reported by 68 (43%) of 159 cefepime recipients and by 26 (36%) of 72 cefotaxime recipients (P = 0.342); adverse events were deemed drug-related in 6% of cefepime recipients (diarrhoea, rash and headache) and in 1% of cefotaxime recipients (diarrhoea, pruritus and rash). Treatment was discontinued prematurely due to adverse events in five cefepime-treated patients and in one cefotaxime-treated patient (P = 0.476). Local intolerance was reported by 33 (21%) of the 159 cefepime-treated patients and by 14 (19%) of the 72 cefotaxime-treated patients receiving drug via the iv route alone; none of the patients discontinued treatment because of local intolerance. Laboratory test abnormalities were observed in a small number of patients in each group (1-8%), but none warranted discontinuation of treatment. Cefepime 2 g bd appears to have efficacy and safety comparable to that of cefotaxime 2 g tid in the treatment of acute obstetric and gynaecological infections.

HIV and blood-borne diseases in relation to gynecologic surgery.

The advent of the AIDS epidemic coupled with enhanced recognition of the morbidity and mortality associated with occupationally acquired hepatitis B virus infection has resulted in a great interest in the epidemiologic characteristics of contact of surgical personnel with patient's blood and other bodily fluids in assessing and identifying risks of such contact, and in developing preventive interventions. The Centers for Disease control have made recommendations designed to decrease the transmission of blood-borne pathogens and have been given the force of law by the Occupational Safety and Health Administration. Despite prospective data documenting contamination rates and effect preventive measures, for unknown reasons many physicians and other health care workers continue to ignore preventive practices.

Inpatient treatment for uncomplicated and complicated acute pelvic inflammatory disease: ampicillin/sulbactam vs. Cefoxitin.

OBJECTIVE: Ampicillin plus sulbactam, an irreversible beta-lactamase inhibitor, was compared to cefoxitin in the treatment of women with acute pelvic inflammatory disease (PID) with and without inflammatory mass(es). METHODS: Participation in an open, prospective, randomized clinical trial was offered to all women given the clinical diagnosis of acute PID who required inpatient therapy. Neisseria gonorrhoeae and Chlamydia trachomatis were sought in cervical and endometrial samples and aerobic and anaerobic species were sought in endometrial samples prior to treatment initiation. Treatment was given on at least 4 days and until women were afebrile for at least 48 h. Daily examinations were performed to assess response to therapy and safety. Only women in whom C. trachomatis was identified were discharged from the hospital on oral doxycycline to be taken for 10-14 days. RESULTS: One hundred twenty-four women were evaluated for safety; 117 (94%) were evaluated for efficacy. Demographic characteristics were similar for women in each treatment group. N. gonorrhoeae was recovered from 59% and C. trachomatis was recovered from 42% of study subjects. Inflammatory masses were identified in 35/76 (46%) women given ampicillin/sulbactam and 17/41 (41%) women given cefoxitin. Ampicillin/sulbactam cured 75 ,of 76 women (98.7%) [95% confidence interval (CI) 92.9-100.0%] and cefoxitin cured 37 of,41,omen (90.2%) (95% CI 76.9-97.3%) in that treatment regimen. CONCLUSIONS: Overall ampicillin/sulbactam was more effective (P = 0.05) than cefoxitin, due to superior efficacy in infection complicated by inflammatory mass(es).35/35 vs. 12/17 cured; P = 0.007).

Abdominal wound problems after hysterectomy with electrocautery vs. scalpel subcutaneous incision.

The purpose of this study was to evaluate the relationship between postoperative abdominal incision problems and opening subcutaneous tissues with electrocautery or scalpel. Women scheduled for elective abdominal hysterectomy who gave informed consent were randomly assigned to subcutaneous abdominal wall tissue incision by electrocautery or scalpel. Postoperative abdominal wound problem diagnoses included seroma, hematoma, infection, or dehiscence without identifiable etiology. Fifteen of 380 women (3.9%) developed a wound problem; six had scalpel and nine had electrosurgical subcutaneous incisions (P = 0.4). Thicker subcutaneous tissues (P = 0.04) and concurrent pelvic infection (P < 0.001) were significant risk factors for postoperative wound problems. Only two women (0.5%) developed an infection. We conclude that the method of subcutaneous tissue incision was unrelated to the development of postoperative abdominal incision problems in 380 women undergoing elective abdominal hysterectomy.

Evaluation of new anti-infective drugs for the treatment of intraabdominal infections. Infectious Diseases Society of America and the Food and Drug Administration.

These guidelines deal with the evaluation of anti-infective drugs for the treatment of intraabdominal infections. The clinical entities consist of infections arising from any part of the gastrointestinal tract, from the distal esophagus to the colon. These include surgical infections of the bowel, biliary tree, liver, spleen, and pancreas. Virtually all intraabdominal infections are due to multiple microorganisms resident in the gastrointestinal tract; these include aerobes and facultative and obligate anaerobes. Infections are classified as complicated (requiring an operative procedure), uncomplicated (managed medically), and postoperative wound (the operative procedure should be curative, but anti-infective drugs are used to prevent further infection at the site). Clinical criteria are paramount for entry into a study and for evaluation of efficacy. For complicated infections an adequate operation is an important determinant of outcome and needs assessment. Cultures of purulent intraabdominal fluid or abscess material are the only valid microbiologic indicators of infection. The acute physiology and chronic health evaluation score is useful in defining the severity of acute illness. The control regimen should consist of effective, established drugs and surgical procedures for the condition. Duration of therapy for complicated infections is usually 5-14 days; for uncomplicated infections, 3-7 days; and for postoperative wound infection, 2-5 days. Periodic assessment of safety and efficacy must be conducted during therapy. The outcome at final assessment is cure, failure, or indeterminate.

Evaluation of new anti-infective drugs for the treatment of acute pelvic infections in hospitalized women. Infectious Diseases Society of America and the Food and Drug Administration.

This set of guidelines deals with evaluation of anti-infective drugs for treatment of acute pelvic infections in hospitalized women. The clinical entities include infectious complications of cesarean section; elective hysterectomy; and septic, incomplete abortion. Conditions including endomyometritis, cuff cellulitis, pelvic cellulitis, parametritis, phlegmon, and pelvic abscesses may arise due to a variety of bacterial species, both aerobic and anaerobic, that comprise the endogenous flora of the lower reproductive tract. Anaerobic bacteria have assumed particular importance, and therapy should be directed against such organisms. The roles of enterococci, chlamydiae, and mycoplasmas remain uncertain. Culture samples must be obtained under conditions assuring minimal vaginal contamination. Before a new drug may be used for treatment of human pelvic infections, considerable information is necessary about its antimicrobial spectrum as well as its safety and efficacy. Placebo-controlled trials are considered unethical. Historical controls may be used, but concurrent active control comparative trials are preferred. Parenteral administration is recommended for at least the initial 4 days of therapy, but orally administered drugs may be evaluated for completion of longer courses. The expected cure rate is approximately 90%. Uncomplicated infections should be treated for at least 4 days; more complicated infections may require prolonged therapy. Although clinical cure is paramount, microbiologic response must also be taken into account. In the final assessment, outcome will be classified as cure, failure, or indeterminate.

Evaluation of new anti-infective drugs for the treatment of acute pelvic inflammatory disease. Infectious Diseases Society of America and the Food and Drug Administration.

Pelvic inflammatory disease (PID) is a syndrome unrelated to pregnancy or surgery and characterized by lower abdominal pain and tenderness, cervical motion tenderness, and adnexal tenderness. Fever, leukocytosis, and the results of laboratory tests are used to support the diagnosis. Participants in clinical trials should be stratified into two groups: those with and those without tubo-ovarian abscess--i.e., those with complicated and those with uncomplicated PID. Diagnostic studies and treatment should be directed at four major groups of pathogens: Neisseria gonorrhoeae, Chlamydia trachomatis, anaerobic bacteria, and facultative bacteria such as Escherichia coli. Women requiring hospitalization should generally be treated as inpatients for at least 4-7 days; outpatient therapy should then be instituted to complete a 14- to 21-day course. Clinical and laboratory evaluations should be conducted daily during hospitalization and both 2-4 days and 2-4 weeks after the completion of therapy.

Prophylactic antibiotics in gynecologic and obstetric surgery.

Preventing infections at operative sites has long been a goal of gynecologic and obstetric surgeons. These infections constitute the leading cause of morbidity after both elective and emergent surgical procedures. Serious sequelae such as bacteremia, septic shock, phlegmon, pelvic abscess, septic pelvic thrombophlebitis, wound abscess, and fascial dehiscence may complicate primary infections, with devastating results. Early attempts to prevent postoperative infections concentrated on aseptic techniques and the modification of surgical skills. Soon after the introduction of antibiotics into clinical medicine, surgeons began to administer these drugs to clinically uninfected women to prevent operative-site infection; that practice has been documented and assessed in a large volume of literature. This article reviews the chronologic development of prospective data in the areas of benign gynecology, obstetrics, gynecologic oncology, and infertility and makes recommendations regarding antibiotic prophylaxis of infections associated with surgical procedures.

Sexual assault in pregnancy.

Little is known about the acute effects of sexual assault on pregnant victims and the outcome of their gestations. A retrospective review of sexual assault victims in Dallas County from 1983-1988 revealed that 114 of 5734 (2%) were pregnant. There were 0.55 and 0.75 gravid sexual assault victims per 1000 deliveries for Dallas County and Parkland Memorial Hospital, respectively. The purposes of this study were to examine patient demographics, forensic evidence and patterns of injury in pregnant victims compared with 114 matched nonpregnant sexual assault victims, and to compare pregnancy outcome with that of the Parkland Memorial Hospital obstetric population. The typical victim was a black, parous gravida in her twenties at a mean gestational age of 15 weeks, without previous prenatal care. Vulvar (95%), oral (27%), and anal (6%) penetration were reported with similar frequency in both groups. The detection of whole and motile sperm from the vaginal specimens was similar in pregnant and nonpregnant women. Physical trauma was more common in nonpregnant victims (63 versus 43%; P less than .004), especially genital trauma (21 versus 5%; P less than .001). Injury was more common to the head and neck or extremities than to the abdomen, chest, or back in both groups. There was no difference in the pattern of trauma by gestational age, but there were no truncal injuries in women at 20 weeks' gestation or greater. There were no spontaneous abortions or deliveries within 4 weeks of the assault, but low birth weight delivery (24%) and preterm delivery (16%) were common.(ABSTRACT TRUNCATED AT 250 WORDS)

Cefazolin for hysterectomy prophylaxis.

Efficacy data for single-dose cefazolin prophylaxis at hysterectomy are meager, and there are none evaluating the impact of route of administration on efficacy. For these reasons, 772 women undergoing elective abdominal or vaginal hysterectomy for benign diseases were given 1 g cefazolin either intramuscularly or intravenously in a randomized clinical trial. Preoperative diagnoses and clinical, surgical, and outcome variables were similar by route of administration for each surgical approach. Risk factors for infection after abdominal hysterectomy included younger age, lower postoperative hemoglobin concentration, and pelvic hematoma; women who developed infection after vaginal hysterectomy were heavier than those who remained uninfected and were more likely to have a pelvic hematoma. The overall incidence of major operative site infection requiring parenteral antimicrobial therapy in evaluable women was 7.2%: 7.6% for 539 women undergoing abdominal hysterectomy and 6.3% for 207 women undergoing vaginal hysterectomy. Postoperative infection was unrelated to route of cefazolin administration.