Sequential Preparations Research Articles

Impact of a Mobile App on Paramedics' Perceived and Physiologic Stress Response During Simulated Prehospital Pediatric Cardiopulmonary Resuscitation: Study Nested Within a Multicenter Randomized Controlled Trial.

BackgroundOut-of-hospital cardiac arrests (OHCAs) are stressful, high-stake events that are associated with low survival rates. Acute stress experienced in this situation is associated with lower cardiopulmonary resuscitation performance in calculating drug dosages by emergency medical services. Children are particularly vulnerable to such errors. To date, no app has been validated to specifically support emergency drug preparation by paramedics through reducing the stress level of this procedure and medication errors.ObjectiveThis study aims to determine the effectiveness of an evidence-based mobile app compared with that of the conventional preparation methods in reducing acute stress in paramedics at the psychological and physiological levels while safely preparing emergency drugs during simulated pediatric OHCA scenarios.MethodsIn a parent, multicenter, randomized controlled trial of 14 emergency medical services, perceived and physiologic stress of advanced paramedics with drug preparation autonomy was assessed during a 20-minute, standardized, fully video-recorded, and highly realistic pediatric OHCA scenario in an 18-month-old child. The primary outcome was participants’ self-reported psychological stress perceived during sequential preparations of 4 intravenous emergency drugs (epinephrine, midazolam, 10% dextrose, and sodium bicarbonate) with the support of the PedAMINES (Pediatric Accurate Medication in Emergency Situations) app designed to help pediatric drug preparation (intervention) or conventional methods (control). The State-Trait Anxiety Inventory and Visual Analog Scale questionnaires were used to measure perceived stress. The secondary outcome was physiologic stress, measured by a single continuous measurement of the participants’ heart rate with optical photoplethysmography.ResultsFrom September 3, 2019, to January 21, 2020, 150 advanced paramedics underwent randomization. A total of 74 participants were assigned to the mobile app (intervention group), and 76 did not use the app (control group). A total of 600 drug doses were prepared. Higher State-Trait Anxiety Inventory–perceived stress increase from baseline was observed during the scenario using the conventional methods (mean 35.4, SD 8.2 to mean 49.8, SD 13.2; a 41.3%, 35.0 increase) than when using the app (mean 36.1, SD 8.1 to mean 39.0, SD 8.4; a 12.3%, 29.0 increase). This revealed a 30.1% (95% CI 20.5%-39.8%; P<.001) lower relative change in stress response in participants who used the app. On the Visual Analog Scale questionnaire, participants in the control group reported a higher increase in stress at the peak of the scenario (mean 7.1, SD 1.8 vs mean 6.4, SD 1.9; difference: −0.8, 95% CI −1.3 to −0.2; P=.005). Increase in heart rate during the scenario and over the 4 drugs was not different between the 2 groups.ConclusionsCompared with the conventional method, dedicated mobile apps can reduce acute perceived stress during the preparation of emergency drugs in the prehospital setting during critical situations. These findings can help advance the development and evaluation of mobile apps for OHCA management and should be encouraged.Trial RegistrationClinicalTrials.gov NCT03921346; https://clinicaltrials.gov/ct2/show/NCT03921346International Registered Report Identifier (IRRID)RR2-10.1186/s13063-019-3726-4

Effect of a Mobile App on Prehospital Medication Errors During Simulated Pediatric Resuscitation

Medication errors are a leading cause of injury and avoidable harm, affecting millions of people worldwide each year. Children are particularly susceptible to medication errors, but innovative interventions for the prevention of these errors in prehospital emergency care are lacking. To assess the efficacy of an evidence-based mobile app in reducing the occurrence of medication errors compared with conventional preparation methods during simulated pediatric out-of-hospital cardiac arrest scenarios. This nationwide, open-label, multicenter, randomized clinical trial was conducted at 14 emergency medical services centers in Switzerland from September 3, 2019, to January 21, 2020. The participants were 150 advanced paramedics with drug preparation autonomy. Each participant was exposed to a 20-minute, standardized, fully video-recorded, realistic pediatric out-of-hospital cardiac arrest cardiopulmonary resuscitation scenario concerning an 18-month-old child. Participants were tested on sequential preparations of 4 intravenous emergency drugs of varying degrees of preparation difficulty (epinephrine, midazolam, 10% dextrose, and sodium bicarbonate). Participants were randomized (1:1 ratio) to the support of an app designed to assist with pediatric drug preparation (intervention; n = 74) or to follow conventional drug preparation methods without assistance (control; n = 76). The primary outcome was the rate of medication errors, defined as a failure in drug preparation according to predefined, expert consensus-based criteria. Logistic regression models with mixed effects were used to assess the effect of the app on binary outcomes. Secondary outcomes included times to drug preparation and delivery, assessed with linear regression models with mixed effects. In total, 150 advanced paramedics (mean [SD] age, 35.6 [7.2] years; 101 men [67.3%]; mean [SD] time since paramedic certification, 8.0 [6.2] years) participated in the study and completed 600 drug preparations. Of 304 preparations delivered using the conventional method, 191 (62.8%; 95% CI, 57.1%-68.3%) were associated with medication errors compared with 17 of 296 preparations delivered using the app (5.7%; 95% CI, 3.4%-9.0%). When accounting for repeated measures, with the app, the proportion of medication errors decreased in absolute terms by 66.5% (95% CI, 32.6%-83.8%; P < .001), the mean time to drug preparation decreased by 40 seconds (95% CI, 23-57 seconds; P < .001), and the mean time to drug delivery decreased by 47 seconds (95% CI, 27-66 seconds; P < .001). The risk of medication errors varied across drugs with conventional methods (19.7%-100%) when compared with the app (4.1%-6.8%). Compared with conventional methods, the use of a mobile app significantly decreased the rate of medication errors and time to drug delivery for emergency drug preparation in a prehospital setting. Dedicated mobile apps have the potential to improve medication safety and change practices in pediatric emergency medicine. ClinicalTrials.gov Identifier: NCT03921346.

Microencapsulation May Preserve the Viability of Probiotic Bacteria During a Baking Process and Digestion: A Case Study with Bifidobacterium animalis Subsp. lactis in Bread.

The high sensitivity of probiotic bacteria (PB) to many environmental factors limits the number of food products where they can be incorporated. This study aimed to examine the capability of a unique three-layered microcapsule structure to protect PB against extremely elevated temperatures and low pHs to allow their incorporation into bakery goods. The microcapsules were prepared first by granulation of a Bifidobacterium lactis (BL) strain, as a model PB, to form a core, and then coating the core with three consecutive protective layers. The physical features and the shape of the microcapsules obtained from three sequential preparations were characterized using various methods. A viable cell count was utilized to evaluate the efficiency of the microcapsule structure to protect the bacteria during a bread-baking process carried out at 180°C for 40min and also during the exposure to simulated gastric fluid (pH 1.2) for up to 1h. The results showed that whereas the free bacteria (unprotected BL) encountered a significant viability loss under these conditions, the microencapsulated BL presented superior resistance.

1812: Russian Intelligence in Paris (According to French Archive Documents)1

ABSTRACTThis article is devoted to the intelligence activities of the Russian Embassy in Paris on the eve of and at the beginning of the war between Russia and France in 1812. The author has introduced into scholarly circulation a large set of unpublished documents stored in France’s National Archives and the Archive of the Ministry of Foreign Affairs and has come to the following conclusions. On the eve of and beginning of the War of 1812 the Russian Embassy in Paris, led by the ‘brilliant’ Prince A. B. Kurakin, played a very important role in the plan for Petersburg to obtain valuable information about the plans and operations of the adversary. Contrary to previous impressions, when the prince was depicted as a kind of ‘dummy’ or, in the best case, a ‘cover’ figure, convincing facts contained in French archive documents add a truly dramatic nuance to this historical personage. Possessing a political flair and extensive connections in Europe and the United States, Kurakin was able to quickly and precisely understand the true meaning of Napoleon’s actions and words and to inform Petersburg about this in a timely fashion. The Russian Embassy in Paris was the main center for the collection and analysis of varied information that attested to the French leadership’s sequential preparations for war against Russia. Despite the widespread opinion about the key role of Colonel A. I. Chernyshev in obtaining secret information about Napoleon’s war machine, the true ‘resident’ in Paris was, nevertheless, Kurakin. Moreover, Chernyshev’s ill-conceived and reckless actions threatened the embassy’s fulfillment of its intelligence functions. However, despite the emergence of serious problems associated with the disclosure of the ‘Chernyshev-Michel group’, Kurakin continued to actively collect intelligence about both Napoleon’s actions and plans and the domestic situation in France itself. Under conditions of the commencement of war between the two powers and his actually being a hostage, the prince did not cease his efforts to collect information and find methods for delivering it to the Russian leadership.

The determination of organic acids in urine with gas chromatography-mass spectrometry and its application in clinical diagnosis

Objectivo To analyze urine organic acids in the urine using gas chromatography-mass spectrometry(GC/MS)for diagnosis of inherited metabolic diseases,especially for organic acids metabolic disorders.Methods 195 clinical urine samples from the patients with suspected organic acids metabolic disorders and 5 normal urine from adults were collected.After mixing some urine with intemal standards according to the concentration creatinine and adding hydroxylamine hydrochloride to mixture,the organic acids with hydroxyl group were oximated to the ketobodies.Organic acids were extracted twice with ethyl acetate and ethyl ether and derivatized with BSTFA-TMCS.An the organic acids were determined with Agilent GC/MS 6890/5973i with scan model.the mass-to-charge ratio range is 50-550 m/z,all data were nalyzed with Agilent GCMSD ChemStationG1701DA.We also investigated the linearity, accurate,precision.recovery and Carry-over by determining the internal standards in normal samples and positive organic acids in spiked control samples.Results More than one hundred kinds of organic acids in urine samples can be analyzed with this method.According to the two internal standards in normal urine samples,the minimal detection limit MMA and 2.PA was 2.5-2.8 μmol/L.Intra-and interassay coefficient of variation for MMA and 2-PA are both less than 10%.Pre-processing Interassay coefficient by sequential preparations of the same sample was 14%.The recoveries of the spiked samples were 95%-105%.Carryover analysis was less than 1%.All the parameters meet the requirement for clinical diagnosis.12 samples demonstrated positive including 6 cases of methylmalonic acidemia,1 case of propionic acidemia,3 cases of tyrosinemia Ⅰ,1 case of maple syrup urine disease and 1 cases of ketosis.Conclusions The method for the determination of organic acids in urine by GC/MS has been successfully established.It can be used for clinical screening and diagnosis for inherited genetic metabolic diseases. Key words: Metabolism,inborn errors; Urinalysis; Organic acids; Mass fragmentography

Oral Contraceptives and the Risk of Breast Cancer

The overall literature suggests that women who use oral contraceptives (OCs), or have done so in the previous decade, have a slightly higher risk of breast cancer. Now that more women who took OCs early in their reproductive years are reaching a high-risk age for breast cancer, an interview study was carried out to assess OCs as a risk factor. A total of 4575 women 35 to 64 years of age were interviewed along with 4682 control women. Between 75% and 80% of women in both groups had used some type of OC. The risk of breast cancer in women who had used any type of OC at any time, compared with never-users, was 0.9. The figure ranged from 0.6 to 0.9 for current users or women who had previously used a single type of OC. Relatively less risk was associated with the use of multiphasic formulations compared with monophasic, sequential, and progestin-only preparations. More than 2500 women had begun using OCs before age 20, and their relative risk of breast cancer was similar to that for women who began OCs when older. Similar risk figures were obtained for high- and low-estrogen-dose preparations. Women 35 to 44 years of age had findings similar to those for women aged 45 to 64 years. Relative risk estimates did not correlate with the duration of OC use in older women who had ever used OCs. Analysis of the time since first use of an OC, age at last use, duration of use according to the estrogen dose, and use in relation to the first term pregnancy disclosed no significant associations. White and black women had comparable risk figures, and type of progestin was not a factor. The investigators believe that current or previous use of oral contraception by women 35 to 64 years of age did not significantly increase the risk of breast cancer in this study. There now is strong evidence that former OC use does not increase the breast cancer risk in later life when the disease is more prevalent.

Application and factor analysis of the menopause rating scale [MRS] in a post-marketing surveillance study of Climen®

Objectives: The menopause rating scale (MRS) has been developed as a modern tool for the assessment of menopausal complaints. It combines in practice excellent applicability and a good reliability, and there are normal values for the population available. For further practical evaluation, the MRS was applied in order to define the course of menopausal profiles in a large post-marketing surveillance study of a sequential oral hormone replacement therapy (HRT) preparation. Materials and methods: A total of 10 904 pre- and postmenopausal women (median age 49 years) with menopausal symptoms who so far had not used the sequential preparation (Climen®) were included in the study. Patients were admitted who were experienced with previous HRT (45.2%) or could be classified as never-users (54.8%). Users commonly switched over to Climen® due to signs of androgenisation, irregular bleeding, other adverse drug effects as well as inadequate efficiency. Demographic data and medical history were recorded together with a listing of body weight, blood pressure, waist and hip circumference and any skin lesions. Following 3 and 6 months of application, the observation parameters were rechecked and data on tolerability, cycle pattern and adverse drug effects were recorded. Efficacy, tolerability, and reasons for withdrawal were documented. A total of 1801 gynaecologists took part, recruiting an average of six patients in each practice. Pre- and postmenopausal cases with a median age of 49 years were represented with similar frequency. A factorial analysis known as the varimax method was used to define the ‘all-or-none’ structure of the loadings in order to determine the structure of the variables and their relationship to the menopausal factors. Results: The pre-treatment profile of the menopausal complaints by factor analysis splits up into four independent subscores of the MRS with the factors HOT FLUSHES, ATROPHY, psychological symptoms (PSYCHE), and somatic symptoms (SOMA). Current or ever-HRT did not alter the factorial profile of the MRS. Differences were observed in the intensity of the subscores with a tendency towards weaker symptoms following previous treatment with sequential preparations. SOMA appears to be related to increasing age, postmenopausal status, or co-morbidity requiring treatment. After six months of treatment, factorial loading of HOT FLUSHES, ATROPHY, PSYCHE and SOMA all dropped significantly. Conclusion: The MRS in its original ten-item profile suitably characterizes menopause-specific symptoms both with regard to profile and intensity of the symptoms. The MRS adequately monitors differentiated symptom variation with and without hormone replacement. Climen® confirmed a wide spectrum of activity in all aspects of the MRS. The subscore structure of the factors remained stable during treatment. Only slight modulations were seen with marked emphasis on psychic aspects and sexual complaints.

Changes in normal lipid profile of menopausal women with combined hormone replacement therapy: Comparative clinical trial of two hormonal combinations (conjugated estrogens/medroxyprogesterone acetate versus estradiol valerate/cyproterone acetate)

Objectives: To compare the effect on plasma lipids of conjugated estrogens/medroxyprogesterone acetate (CE/MPA) and estradiol valerate/cyproterone acetate (EV/CPA) in healthy peri and postmenopausal women during 1 year. Methods: Multicentric, controlled, single blinded Phase III clinical trial. Women were randomized to two treatment groups: Group A ( n=49 women): CE 0.625 mg/day for 21 days and MPA 5 mg from day 12 to 21. Group B ( n=55 women): EV 2 mg/day for 21 days and CPA 1 mg from day 12 to 21. Total cholesterol (TC), high density cholesterol (HDL-C), low density cholesterol (LDL-C), triglycerides, aminotransferases and alkaline phosphatase were measured before starting therapy, and after 3, 6, 9 and 12 months of hormone replacement therapy (HRT). TC/HDL-C and LDL-C/HDL-C ratios were determined. Results: There were no changes in TC levels. HDL-C increased and LDL-C decreased significantly, with no differences between groups but within each group. Triglycerides increased significantly but remained within normal values, with no differences between groups. TC/HDL-C ratio showed a slight and steady decrease in both groups. LDL-C/HDL-C ratio decreased in both treatment groups. Conclusion: Both cyclic sequential preparations used in HRT showed a favorable effect on plasma lipids in healthy peri and postmenopausal women, with an increase in HDL-C and a decrease in LDL-C levels, as well as in the LDL-C/HDL-C and TC/HDL-C ratios. Our study confirms the positive effect of estrogens on lipids, which does not seem to be adversely affected by the addition of progestogens derived from pregnanes.

Frequency of curettage in middle-aged women treated with sequential preparations versus untreated women

Over a 2-month period a register was kept of all dilatation and curettage procedures performed in Frederiksborg County, Denmark, involving women aged 40–59 years. The total recorded was 284. In the same period, questionnaires were sent out to 1200 women in the county who fell within the same, randomly selected age group, to establish the number of women treated with sequential oestrogen/progestogen and those who had been hysterectomized. Based on the results and the total female population in the county, it was calculated that the frequency of the procedure in sequentially-treated women as compared with untreated women was 3.1 times higher in the 55–59 age group. In the 40–54 age group no difference in the incidence of curettage in the sequentially-treated women could be demonstrated.

Ovulationshemmer: Die Bedeutung der Östrogendosis

The large prospective studies on adverse effects of oral contraceptives have unanimously revealed an increased risk of thromboembolic diseases, which seem to be associated with the dose of ethinylestradiol (EE). According to the recommendations of several medical committees, the dose of EE has, therefore, been more and more reduced; in some countries there are now ovulation inhibitors containing 20 micrograms EE. Since serious reactions, which have a relatively low incidence, are highly underreported (less than 10%), it is difficult to prove dose-dependent differences in the rates of cardiovascular diseases. There is, however, virtually no doubt that not only the incidence of thromboembolic diseases and stroke, but also that of benign liver tumours and gall bladder diseases is increased in relation to the EE-dose. A series of metabolic serum parameters, e.g. serum binding proteins, coagulation and fibrinolysis factors, angiotensinogen, is changed by EE in a dose-dependent manner which is, however, limited when the effects are receptor-mediated. Higher doses of EE have been shown to facilitate fibrin deposits on vascular subendothelium. The pharmacological effects of EE are to a large extent dependent on the dose, e.g. the irreversible reactions of EE and other ethinylated steroids with hepatic enzymes which are involved in the metabolism of steroids, drugs and toxic compounds. After long-term treatment with combinations containing 50 micrograms EE, in half of the women, abnormal liver function tests with pathological morphological alterations have been found. As combinations with low EE doses and a sufficiently effective progestogen component do not differ from higher dosed oral contraceptives in their contraceptive safety and cycle control, there are no indications for pills containing 50 micrograms EE, except the normophasic sequential preparations for women with sustained irregular bleedings when taking low dose combinations.

The effect of various regimens of hormone therapy on serum cholesterol and triglyceride concentrations in postmenopausal women.

The serum cholesterol and triglyceride concentrations of 84 postmenopausal women both before and after 2, 6 and 12 months therapy with various regimens of hormone therapy were measured. There was little alteration in mean serum cholesterol concentration with cyclical oestrogens but both sequential mestranol and norethisterone and sequential oestradiol valerate and norgestrel significantly reduced the mean serum cholesterol concentration to a level similar to that found in age-matched premenopausal women. There was a small and sometimes significant rise in serum triglyceride concentration with cyclical oestrogens. Sequential mestranol and norethisterone significantly elevated serum triglyceride levels, but sequential oestradiol valerate and norgestrel significantly depressed them. The results suggest that the progestogenic agent norgestrel has an important role to play in reducing both serum cholesterol and triglyceride levels, and that the sequential preparations, by virtue of their greater cholesterol lowering effect, should perhaps be preferred to cyclical oestrogens.

Incidence of endometrial cancer in relation to the use of oral contraceptives.

Female residents of King and Ierce Counties in the state of Washington in whom endometrial cancer was diagnosed during 1975--77 were interviewed concerning prior use of oral contraceptives. Their responses were compared with those of a random sample of women from the same population. Women who had taken Oracon (0.1 mg of ethinyl estradiol and 25 mg of dimethisterone) were estimated to have a risk of endometrial cancer 7.3 times that of other women (P = 0.007). This elevation in risk was not seen in users of other sequential preparations. Women who had used combined oral contraceptives had only 50 per cent of the incidence of endometrial cancer of nonusers (P = 0.05), although the protective effect was not evident among those who subsequently took menopausal estrogens for more than two years. These associations suggest that development of neoplasia in the endometrium can be extremely sensitive to hormonal factors: if an oral contraceptive, like Oracon, emphasizes the estrogenic component, promotion of cancer can result; if like combined preparations, the contraceptive emphasizes the progestational component, protection against cancer can result.

Use of an alkali-soluble water-soluble extract of Blastomyces dermatitidis yeast-phase cell walls and isoelectrically focused components in peripheral lymphocyte transformations.

An alkali-soluble water-soluble extract of Blastomyces dermatitidis yeast-phase cell walls was tested for its ability to elicit a response in lymphocytes isolated from the peripheral blood of Blastomyces-infected guinea pigs. Sequential preparations of the antigen were reproducible and specific in the in vitro lymphocyte transformation assay. Cross-reactivity of the antigen was not evident in lymphocyte transformation assays on lymphocytes obtained from Histoplasma-infected guinea pigs or from animals sensitized with complete Freund adjuvant. Fractionation of the antigen was accomplished on an isoelectric-focusing column, using a sucrose density gradient support. Components were assayed for activity in skin testing and lymphocyte transformation. Comparison of column fractions to the whole antigen showed greater response to the whole antigen in in vivo and in vitro assays.

EFFECT OF HORMONE REPLACEMENT THERAPY ON GLUCOSE TOLERANCE IN POSTMENOPAUSAL WOMEN

Oral glucose tolerance tests were performed on 50 symptomatic postmenopausal women before and after three months of hormone replacement therapy. All patients were randomly allocated to one of five groups treated with various synthetic or so-called naturally occurring oestrogens. Therapy produced a significant deterioration of carbohydrate tolerance with sequential preparations containing 100 microgram of ethinyl oestradiol or graduated doses of mestranol up to 50 microgram. The conjugated equine oestrogen (1.25 mg daily) and oestrogen valerate (2 mg daily) treated groups did not show abnormal glucose tolerance. The decreased glucose tolerance may be due as much to dosage levels as to any metabolic characteristics of the various oestrogens prescribed.

Prevention of Endometrial Cancer

There seems little question that the cause of some endometrial cancer is some carcinogenic agent that may reach the endometrial surface initially as a "chance phenomenon." About 10 years needs to elapse before the earliest morphologic change eventuates in cancer. The question is what chance does an endometrium have of developing malignant neoplasms if it is periodically shed, albeit incompletely, as in normal ovulatory cycles. The occurrence of such an event is very rare. The importance of shedding in the prevention of endometrial cancer is not a new concept. Lipsett indicates that there is a consensus that progestational stimulation of the endometrium with subsequent withdrawal bleeding protects against endometrial cancer. If periodic shedding is important in the prevention of cancer, the important question is whether young women on oral contraceptives (OCs) shed their endometrium when they are bleeding. Studies of the effects of OCs on the endometrium in the 1960s showed that the combined pills produced "marked predecidual changes" but the sequential preparations did not. Predecidual changes are required to render the endometrium deciduous. It might be predicted that the sequentials would predispose to cancer after years of use because shedding probably did not occur. The new question is whether the low dosage OCs (with probable absence of shedding) predispose young women to endometrial cancer. The use of estrogens only with postmenopausal women preserves the unshed endometrium for the requisite number of years to allow a carcinogenic agent to exert its effect.

Insulin and proinsulin secretion under contraceptive steroid administration (author's transl)

An ivestigation has been performed in 49 women about the influence exerted on the glucose-tolerance, insulin and proinsulin secretion by hormonal contraceptives of different types and compositions. A disturbed dynamics of the insulin secretion with elevated values in the OGTT at two and three hours has been proven at a nearly equal degree using combined preparations (Anacyclin, Eugynon, Neogynon, Mikrogynon) or sequential preparations (Kombiquens, Ovanon). Though there has been interference with the glucose tolerance, the serum proinsulin in the OGTT showed increased levels too. When a combined preparation was applied, the proinsulin values were significantyl higher compared to a sequential type contraceptive. The observed disturbance of the insulin and proinsulin secretion is explained by a decreased sensitivity to insulin in the peripheral fat tissue. The actual dose of the estrogen-gestagen components has no influence on the described changes. Elevated insulin levels are demonstrable already during the first treatment cycle. The degree of the disturbance is independent of the duration of the medicamentous application during the first 6 contraceptive months. After withdrawal of the respective contraceptive steroid the insulin secretion showed nearly normal dynamics during the subseqeunt menstrual cycle.

Oral contraceptives and carbohydrate metabolism

Oral contraceptives and carbohydrate metabolism

A case control study into the possible effects of birth control pills on pre-clinical carcinoma of the cervix.

SummaryThis paper reports a study of the possible relationship between oral contraceptives and preclinical squamous carcinoma of the cervix in women in their third decade in the Province of British Columbia. A total of 310 cases of preclinical carcinoma of the cervix and 682 matched controls were evaluated. The mean interval between first use of contraceptives and entry into the study was 5·3 years for the 25‐29‐year‐old patients with preclinical carcinoma of the cervix, while the interval for the 20‐24‐year‐old patients was 2·9 years. No significant difference in the pattern or duration of contraceptive usage was found between the case and control groups. The use of the different contraceptive methods in the screened population of the entire province of British Columbia paralleled that of the selected case control study group with the exception of a less frequently reported use of sequential preparations. In terms of the social data, however, there did appear to be a significantly greater number of pregnancies and of atypical marital situations among the women with preclinical carcinoma of the cervix. This suggested a different pattern of social behaviour in the two groups.

PREGNANCIES DURING ORAL CONTRACEPTIVE TREATMENT

Investigation was undertaken to determine the difference in safety between combined and sequential preparations of oral contraceptives. 90 pregnancies in 1968 (73 women used sequential types and 17 used combined types) were recorded while using the pill. Using Pearls formula the pregnancy rate for combined preparations was .005 and .0467 for sequential preparations. The results showed 100 times greater risk of pregnancy when taking a sequential treatment. The data revealed that sequential treatment failed considerably more often because of method failure than patient failure. The protection rate of sequential preparation was found to be much better than all other non-oral contraceptives.

The discriminating use of combination and sequential preparations in the hormonal inhibition of ovulation

It appears that the biologic activity of oral-contraceptive components is more important than dosage. The incidence of side effects apparently depends less on the dosage of steroid given per cycle than on the potencies of the estrogen and progestin. Therefore, an attempt should be made to minimize the daily intake of estrogen to the lowest effective amount that does not cause bleeding abnormalities. Along with a properly selected progestin, such low doses of estrogen will provide dependable contraception. The potency of the components can be used as a guideline to minimizing side effects. Similarly, potency can help determine the cause of a particular side effect should it appear, and dosage can be adjusted accordingly. Also, consideration of the patient's hormone profile — whether she is estrogen dominant, progestin dominant, or a balance of the two — in prescribing oral contraceptives can help reduce expected side effects.