RESUMO
Shoulder pain is a common musculoskeletal complaint, and rotator cuff (RC) pathologies are one of the main causes. The RC undergoes various tendinopathic and avascular changes during the aging process. Other degenerative changes affecting its healing potential make it an appealing target for biological agents. Platelet-rich plasma (PRP) has demonstrated the potential to deliver a high concentration of several growth factors and anti-inflammatory mediators, and its clinical use is mainly supported by experiments that demonstrated its positive effect on muscle, ligaments, and tendinous cells. This review aimed to specify the role of PRP and its future applications in RC tendinopathies based on the current clinical evidence. Due to the different characteristics and conflicting outcomes, clinicians should use PRP with moderate expectations until more consistent evidence is available. However, it is reasonable to consider PRP in patients with contraindications to corticosteroid injections or those with risk factors for inadequate healing. Its autologous origin makes it a safe treatment, and its characteristics make it a promising option for treating RC tendinopathy, but the efficacy has yet to be established.
RESUMO
INTRODUCTION: Biopredictive release tests are commonly used in the evaluation of oral medicines. They support decision-making in formulation development and allow predictions of the expected in-vivo performances. So far, there is limited experience in the application of these methodologies to injectable drug products. AREAS COVERED: Parenteral drug products cover a variety of dosage forms and administration sites, including subcutaneous, intramuscular, and intravenous injections. In this area, developing biopredictive and biorelevant methodologies often confronts us with unique challenges and knowledge gaps. Here, we provide a formulation-centric approach and explain the key considerations and workflow when designing biopredictive assays. Also, we outline the key role of computational methods in achieving clinical relevance and put all considerations into context using liposomal nanomedicines as an example. EXPERT OPINION: Biopredictive tools are the need of the hour to exploit the tremendous opportunities of injectable drug products. A growing number of biopharmaceuticals such as peptides, proteins, and nucleic acids require different strategies and a better understanding of the influences on drug absorption. Here, our design strategy must maintain the balance between robustness and complexity required for effective formulation development.
Assuntos
Biofarmácia , Modelos Biológicos , Administração Oral , Biofarmácia/métodos , Liberação Controlada de Fármacos , Injeções , Preparações Farmacêuticas , SolubilidadeRESUMO
BACKGROUND: Comprehensive patient assessment and planning are central to esthetic treatment with injectables. MD ASA™ (Multi-Dimensional Aesthetic Scan Assessment) is a novel tool developed for this purpose. AIMS: To describe the MD ASA technique and present its preliminary application. METHODS: MD ASA breaks down the face into five hierarchies (H1-H5). H1 shifts patients' focus from "distractions" (individual lines and folds) toward the overall messages their face portrays, based on eight Emotional Attributes: four negative (tired, sad, angry, and saggy); four positive (youthful, attractive, contoured, and feminine/masculine). Three priority Emotional Attributes are selected for each patient. This is followed by a process of narrowing down through facial thirds (H2), periorbital and perioral dynamics (H3), facial units (H4), and subunits (H5), to arrive at a final assessment. Based on the key facial signs identified, this can be translated into MD Codes equations and thus a treatment formula. A retrospective analysis was performed based on 12 female patients injected by expert clinicians at an educational event. All patients were selected for, and treated using, a single MD Codes formula derived from a common MD ASA work-up. RESULTS: There were substantial differences between patients and clinicians in their views of which anatomical areas needed treatment-but good alignment on priority Emotional Attributes. Patients were treated only for three negative Emotional Attributes, but improvements were observed across all eight attributes. CONCLUSIONS: MD ASA provides a practical method for translating facial messages into actionable injectable treatment plans and facilitates greater patient-clinician alignment. Prospective studies are warranted.
Assuntos
Técnicas Cosméticas , Estética , Feminino , Humanos , Estudos Prospectivos , Encaminhamento e Consulta , Estudos RetrospectivosRESUMO
BACKGROUND: Patients are looking for procedures which are minimally invasive and consequently incur minimal downtime. However, these procedures are not usually long lasting and have limited outcomes both esthetically and functionally. For these reasons, the number of patients seeking surgical rhinoplasty and who have previous nasally injected hyaluronic acid is increasing. METHODS: The aim of this article is to provide the surgeon with information for both the identification and surgical approach for those patients who seek nasal cosmetic surgery, and who have previously been treated with nasal injections of hyaluronic acid filler. RESULTS: We present cases that illustrate the use of this approach and suggest three possible patient management. CONCLUSIONS: There are three possible approaches: wait HA to be naturally reabsorbed; apply hyaluronidase before the surgery or proceed to rhinoplasty with no prior application of hyaluronidase. The physician must be aware of this progression and know how to manage each case to optimize the surgical outcome. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine Ratings, please refer to Table of Contents or online Instructions to Authors www.springer.com/00266 .
Assuntos
Ácido Hialurônico , Rinoplastia , Humanos , Hialuronoglucosaminidase , Nariz/cirurgia , Resultado do TratamentoRESUMO
The plunging nasal tip is a challenging condition because, although it is predominantly a dynamic deformity which occurs during smiling, it also indicates a structural problem. When a person smiles, the paired depressor septi nasi muscles pull the tip caudally at the same time as the levator labii superioris alaeque nasi muscles pull the alar base and lateral lip cephalically. This movement causes straightening of the alar rim. Even though surgical rhinoplasty is the gold standard to restore nasal appearance, the procedure may fail to treat the dynamic cause of the drooping tip. This article outlines the anatomical concepts that lead to a drooping tip and presents a technique that can treat both the dynamic and structural causes of the drooping tip using hyaluronic acid filler. Cases are also presented that illustrate these concepts. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
Assuntos
Ácido Hialurônico , Rinoplastia , Músculos Faciais/cirurgia , Humanos , Nariz/cirurgia , Sorriso , Resultado do TratamentoRESUMO
Second-line injectable drugs (kanamycin, amikacin and capreomycin) have been an integral part of the multidrug-resistant tuberculosis (MDR-TB) treatment regimen for decades, despite their known association with renal failure and ototoxicity. Unfortunately, there are many countries that haven't included new or reused drugs in their treatment regimens for MDR-TB and still depend on second-line injectable drugs (SLIDs) in order to have a sufficient amount of effective drugs in their regimens. Our purpose is to show the frequency and severity of the ototoxicity associated with the use of SLIDs only detected initially by means of an audiometry. We conducted a retrospective analysis including all the patients who received treatment regimens with SLIDs from 2010 to 2017 in a tuberculosis clinic in Mexico. 47 patients who received SLIDs (amikacin, kanamycin, capreomycin) were included in the analysis. The mean age was 40.3 ± 16.4 years. Thirty one patients (63.3%) had previously received TB treatment in the past. The most commonly used SLID was amikacin in 33 cases (67.3%), followed by capreomycin in 14 cases (28.6%). Twenty seven patients (55.1%) developed significant hearing loss (> 40 dB), and 13 patients (26.5%) developed severe or profound hearing loss (> 70 dB). Severe hearing loss is a common, irreversible and now unnecessary complication of the MDR/RR-TB (multidrug- and rifampicin-resistant tuberculosis) treatment, since the SLIDs may and shall be substituted by new and reused, more effective and far less toxic drugs.
Assuntos
Terapêutica , TuberculoseRESUMO
Administration of local anesthetics is one of the most effective pain control techniques for postoperative analgesia. However, anesthetic agents easily diffuse into the injection site, limiting the time of anesthesia. One approach to prolong analgesia is to entrap local anesthetic agents in nanostructured carriers (e.g., liposomes). Here, we report that using an ammonium sulphate gradient was the best strategy to improve the encapsulation (62.6%) of dibucaine (DBC) into liposomes. Light scattering and nanotracking analyses were used to characterize vesicle properties, such as, size, polydispersity, zeta potentials, and number. In vitro kinetic experiments revealed the sustained release of DBC (50% in 7 h) from the liposomes. In addition, in vitro (3T3 cells in culture) and in vivo (zebrafish) toxicity assays revealed that ionic-gradient liposomes were able to reduce DBC cyto/cardiotoxicity and morphological changes in zebrafish larvae. Moreover, the anesthesia time attained after infiltrative administration in mice was longer with encapsulated DBC (27 h) than that with free DBC (11 h), at 320 µM (0.012%), confirming it as a promising long-acting liposome formulation for parenteral drug administration of DBC.
Assuntos
Anestésicos Locais/farmacocinética , Anestésicos Locais/toxicidade , Dibucaína/farmacocinética , Dibucaína/toxicidade , Atividade Motora/efeitos dos fármacos , Medição da Dor/efeitos dos fármacos , Animais , Células 3T3 BALB , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/fisiologia , Liberação Controlada de Fármacos , Lipossomos , Masculino , Camundongos , Atividade Motora/fisiologia , Medição da Dor/métodos , Fosfatidilcolinas/farmacocinética , Fosfatidilcolinas/toxicidade , Peixe-ZebraAssuntos
Anticoncepção/psicologia , Anticoncepcionais Orais Hormonais/uso terapêutico , Aceitação pelo Paciente de Cuidados de Saúde/psicologia , Grupos Populacionais/psicologia , Progestinas/uso terapêutico , Anticoncepção/métodos , Comportamento Contraceptivo/psicologia , Feminino , Humanos , México , Estudos RetrospectivosRESUMO
Ceftazidime is a broad spectrum antibiotic administered mainly by the parenteral route, and it is especially effective against Pseudomonas aeruginosa. The period of time in which serum levels exceed the Minimum Inhibitory Concentration (MIC) is an important pharmacodynamic parameter for its efficacy. One of the forms to extend this period is to administer the antibiotic by continuous infusion, after prior dilution in a Parenteral Solution (PS). The present work assessed the stability of ceftazidime in 5% glucose PS for 24 hours, combined or not with aminophylline, through High Performance Liquid Chromatography (HPLC). The physicochemical evaluation was accompanied by in vitro antimicrobial activity compared MIC test in the 24-hour period. Escherichia coli and Pseudomonas aeruginosa were the microorganisms chosen for the MIC comparison. The HPLC analysis confirmed ceftazidime and aminophylline individual stability on PS, while the MIC values were slightly higher than the mean described in the literature. When both drugs were associated in the same PS, the ceftazidime concentration by HPLC decreased 25% after 24 hours. Not only did the MIC values show high loss of antibiotic activity within the same period, but also altered MIC values immediately after the preparation, which was not detected by HPLC. Our results indicate that this drug combination is not compatible, even if used right away, and that PS might not be the best vehicle for ceftazidime, emphasizing the importance of the MIC evaluation for drug interactions.
Ceftazidima é um antimicrobiano administrado por via parenteral, que apresenta amplo espectro de ação, principalmente contra Pseudomonas aeruginosa. O tempo em que a concentração sérica de ceftazidima permanece acima da concentração mínima inibitória (MIC) é um importante parâmetro farmacodinâmico para a determinação da eficácia antimicrobiana e pode ser potencializado através da utilização de infusão contínua em soluções parenterais (PS). Este artigo visa a avaliar a estabilidade da ceftazidima em solução de glicose 5%, na presença e na ausência do fármaco aminofilina, através de cromatografia líquida de alta eficiência HPLC e MIC durante o período de 24 horas. Os microorganismos selecionados para a determinação do MIC foram Escherichia coli e Pseudomonas aeruginosa. Os ensaios em cromatógrafo líquido confirmaram a estabilidade dos fármacos ceftazidima e aminofilina quando são individualmente associados em PS, enquanto os valores de MIC ficaram maiores que os valores encontrados na literatura. Quando ambos os fármacos foram associados na mesma solução parenteral a concentração de ceftazidima obtida por HPLC diminuiu 25% depois de 24 horas. Os valores de MIC mostraram maior decaimento da atividade antimicrobiana neste mesmo período e também valores de MIC alterados nas soluções preparadas no tempo zero, decaimento este que não foi detectado em HPLC. Os resultados indicaram incompatibilidade na associação dos fármacos em PS, enfatizando a importância dos resultados de MIC para interações de fármacos.
Assuntos
Ceftazidima/análise , Aminofilina/análise , Preparações Farmacêuticas/análise , Testes de Sensibilidade Microbiana , Cromatografia Líquida de Alta Pressão , GlucoseRESUMO
Introdução: A toxina botulínica é opção importante para o tratamento das rugas faciais dinâmicas. A toxina botulínica Lanzhou tipo A (LBTX-A) foi introduzida na China no início da década de 1990 e aprovada no Brasil em 2003. Objetivo: Avaliar a efi cácia e a tolerabilidade de LBTX-A para tratamento estético de rugas dinâmicas na parte superior da face. Materiais e Métodos: Em um estudo multicêntrico prospectivo com rótulo aberto, 110 indivíduos dos dois gêneros (idades de 25 a 65 anos) foram tratados com um total de 53 U de LBTX-A cada, distribuídos em 15 locais nos músculos frontal, corrugador, prócero e lateral ocular da órbita. Os pacientes foram revisados sete vezes no intervalo de 180 dias. A efi cácia foi avaliada por eletromiografi a, análise fotográfi ca e pelas opiniões do investigador e do paciente. A tolerabilidade foi avaliada pela incidência de eventos adversos. Resultados: Duas semanas depois das injeções, 94% dos pacientes tratados consideraram o resultado bom ou excelente. Na maioria dos casos, os resultados se prolongaram por 90 dias. Depois da injeção, quase todos os pacientes informaram dor leve ou ausência de dor e efeitos colaterais mínimos e reversíveis, como edema facial (seis pacientes), sensação de entumescimento facial (três pacientes) e ptose palpebral (dois pacientes). Conclusões: LBTX-A é efi ciente e bem tolerado para tratamento das linhas faciais dinâmicas.
Introduction: The botulinum toxin is a valuable option for the treatment of dynamic facial wrinkles. The Lanzhou botulinum toxin type A (LBTX-A) was introduced in China in the early 90's and approved in Brazil in 2003. Objective: Evaluate the effi cacy and tolerability of LBTX-A for the cosmetic treatment of dynamic wrinkles of the upper face. Material and Methods: In a prospective, open-label, multicenter study, 110 subjects of both sexes (aged from 25 to 65 years) were treated with a total of 53 U of LBTX-A each, distributed in fi fteen sites in the frontal, corrugator, procerus, orbicular ocular lateral muscles. The patients were reviewed 7 times within 180 days. Effi cacy was assessed by electromyography, photographic analysis and the investigator's and patient's opinions. Tolerability was assessed by the incidence of adverse events. Results: Two weeks post-injection, 94% of the treated patients considered the result as good or excellent. Results lasted 90 days in most cases. After injection, most patients reported mild or no pain, and minimal and reversible side effects as facial edema (6 patients), stuffi ness feeling (3 patients) and eyelid ptosis (2 patients). Conclusions: We conclude that LBTX-A is effi cient and well tolerated for the treatment of dynamic facial lines.
RESUMO
A total of 1,904 women, aged 15-38, used an injectable contraceptive combination of 90 mg dihydroxyprogesterone acetophenide with 6 mg estradiol enanthate, given once during each menstrual cycle between the 7th and 10th day, and preferably on the 8th day of the cycle, for a total of 17,576 cycles. Of these 1,904 women, 1,197 completed 12 cycles of use of the injectable combination. One subject became pregnant during the trial, resulting in a cumulative pregnancy rate of 0.07%. Principal reasons for discontinuation were personal, non-medical reasons, such as lost to follow-up, no longer wished to continue, protocol violation, desire to change to another contraceptive method, moved away, or other personal reasons. Mean weight of 1,901 subjects at admission to the trial was 53.5 +/- 0.2 kg and this increased to 54.3 +/- 0.3 kg after 12 cycles of use. Approximately 50% of subjects experienced menstrual bleeding similar to normal throughout the study period. The most frequent menstrual abnormality was irregular bleeding, experienced by approximately one-third of subjects.
Assuntos
Acetofenida de Algestona/administração & dosagem , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/efeitos adversos , Estradiol/análogos & derivados , Adolescente , Adulto , Método Duplo-Cego , Estradiol/administração & dosagem , Feminino , Humanos , Injeções , Ciclo Menstrual , Satisfação do Paciente , Gravidez , Hemorragia Uterina/induzido quimicamenteRESUMO
A phase III clinical study was carried out among 534 fertile Latin American women to evaluate cycle control, side effects, and contraceptive efficacy of a once-a-month combined injectable, Mesigyna, consisting of 50 mg norethisterone enanthate and 5 mg estradiol valerate. The pregnancy rate at 1 year was 0 per 100 woman-years for a total experience of 4688 woman-months. The overall discontinuation rate at one year was 17.9%. Discontinuation rate for bleeding problems was 5.1%. The Colombian women had a significant increase (p <0.001) in bleeding problems compared to other countries. The discontinuation rate for amenorrhea was 1.1%. There were no significant differences between the groups regarding discontinuation for other medical or non-medical reasons. Mean weight gain after one year of use was 1.02 kg. Mesigyna is an appropiate once-a-month injectable contraceptive for Latin American women since it is highly effective and its perception of normal menstrual bleeding is of importance in the Latin American population.
Assuntos
Anticoncepcionais Femininos , Estradiol/análogos & derivados , Noretindrona/análogos & derivados , Adolescente , Adulto , Amenorreia/induzido quimicamente , Pressão Sanguínea , Anticoncepcionais Femininos/administração & dosagem , Anticoncepcionais Femininos/efeitos adversos , Combinação de Medicamentos , Feminino , Humanos , Injeções , América Latina , Gravidez , Hemorragia Uterina/induzido quimicamente , Aumento de PesoRESUMO
A prospective study was conducted with 430 new depot medroxyprogesterone acetate (DMPA) acceptors to estimate continuation rates and investigate factors associated with length of use. Data were collected on services received and sociodemographic characteristics of participants. Women were enrolled over the course of 1 year and were followed for up to 13 months. Failure to return to the same clinic within 104 days of the last injection was the outcome of interest. The 3-, 6-, 9-, and 12-month continuation rates were 68%, 67%, 55%, and 51%, respectively. In the bivariate analysis, women who were told to return to the clinic for side effects were more likely to continue using DMPA than those who were not given such advice (p <0.05). Likewise, women who received information on DMPA efficacy, side effects, and amenorrhea were more likely to continue using DMPA compared to those who did not receive such information (p <0.05). A proportional hazards regression model was constructed to estimate the simultaneous effect of various factors on length of use. In results consistent with the bivariate analysis, women who were told to return to the clinic were 2.7 times more likely to continue using DMPA compared to women who did not receive that advice. Likewise, women who were told about the possibility of amenorrhea were 2.5 times more likely to continue using DMPA compared to those who did not receive that information. The regression model also identified new factors such as number of children, attitude toward menstruation, lactating at admission, and spousal input on method choice. The findings suggest that providers play an important role in ensuring the highest possible continuation rates for DMPA.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Acetato de Medroxiprogesterona/administração & dosagem , Cooperação do Paciente/estatística & dados numéricos , Educação de Pacientes como Assunto/estatística & dados numéricos , Satisfação do Paciente/estatística & dados numéricos , Adolescente , Adulto , Bolívia , Anticoncepcionais Femininos/efeitos adversos , Escolaridade , Feminino , Humanos , Lactação , Masculino , Estado Civil , Acetato de Medroxiprogesterona/efeitos adversos , Distúrbios Menstruais , Estudos Multicêntricos como Assunto , Paridade , Cooperação do Paciente/psicologia , Modelos de Riscos Proporcionais , Estudos ProspectivosRESUMO
OBJECTIVE: To determine the timing of onset of contraceptive effectiveness after the first injection of 150 mg of depot medroxyprogesterone acetate (DMPA) administered between days 8 and 13 of the menstrual cycle. DESIGN: Descriptive, prospective study. SETTING: A tertiary university referral center. PATIENT(S): Thirty healthy women between 18 and 40 years of age. INTERVENTION: Volunteers were injected with DMPA between days 8 and 13 (5 women on each day) of the menstrual cycle. MAIN OUTCOME MEASURE(S): Ovarian function determined by serum levels of E2 and progesterone and follicular development evaluated by vaginal ultrasound. RESULT(S): In nine (30%) of 30 women studied, DMPA did not prevent ovulation. All ovulations occurred in women receiving DMPA between days 10 and 13 of the cycle. No woman who received injections on day 8 or 9 ovulated. Ovulation suppression was more effective in women with low ovarian activity. All ovulation occurred within 3 days after the injection. CONCLUSION: A back-up contraceptive method, used after the 7th day of the menstrual cycle, is recommended for up to 7 days after the first injection of DMPA.
PIP: To ensure ovulation does not occur, it is recommended that Depo-Provera injections be administered within the first 7 days of the menstrual cycle. In some settings, this requirement acts as a barrier to women's free access to injectable contraception. Thus, the present study investigated the timing of onset of contraceptive effectiveness when the first injection of depot medroxyprogesterone acetate is administered between days 8-13 of the menstrual cycle. 30 women 18-40 years of age attending a university referral center in Campinas, Brazil, in 1995-96, were enrolled. Ovulation, detected through serum progesterone and estradiol assays and confirmed by follicle rupture at vaginal ultrasound, occurred in 9 cases (30%). No ovulations occurred when injection was administered on day 8 (n = 5) or day 9 (n = 5) of the menstrual cycle; only 1 of the 5 women treated on day 10 ovulated. On the other hand, 4 of the 10 women treated on days 11 and 12 and 4 of the 5 injected on day 13 showed evidence of ovulation. All ovulation occurred within 3 days after injection. Ovulation occurred only among women who had serum estradiol levels of 100 pg/ml and above and a leading follicle diameter greater than 13 mm at the time of injection. Ovulation suppression was more effective in women with low ovarian activity. A back-up contraceptive method used for 4 days after Depo-Provera injection should provide sufficient protection when the method is administered after day 7 of the menstrual cycle. However, given the uncertainty of the assumption of short viability of the human oocyte, it is safer to recommend 1 week's use of a back-up method or abstinence.
Assuntos
Anticoncepcionais Femininos/uso terapêutico , Acetato de Medroxiprogesterona/uso terapêutico , Ciclo Menstrual , Ovário/efeitos dos fármacos , Adolescente , Adulto , Esquema de Medicação , Feminino , Humanos , Estudos Prospectivos , Resultado do TratamentoRESUMO
A large introductory study of Cyclofem, a once-a-month injectable contraceptive, was conducted in three Mexican provinces. A total of 3457 healthy women participated: 640 women from rural areas (community-based component) and 2817 women from urban and suburban areas (health center-based component). A total of 20,316 women-months of treatment experience were accumulated during a one year period. Cyclofem proved its use-effectiveness (pregnancy rate of 0.03%) and its safety under routine service conditions of family planning facilities in Mexico. The overall life table continuation rate at 1 year was 26.1%. Higher continuation rates were observed in the community-based component (36.6%) as compared to the health center component (23.7%). The most common reason for method discontinuation was change of address. Only 15% of the discontinuations were attributable to the injectable contraceptive method, with the overall 1 year discontinuation rate for bleeding problems (including amenorrhea) was < 11%. These observations underscore the importance of appropriate counseling and follow-up measures, providing convenient access to repeat injections, and other service delivery issues related to continuation of Cyclofem. The results of this trial have once again demonstrated that Cyclofem is a highly effective method with an acceptable side effect profile. In addition, the study provided the elements for its approval by local health authorities and its inclusion into the Ministry of Health Family Planning Program.
PIP: The effectiveness and continuation rates associated with the once-a-month injectable contraceptive Cyclofem were investigated in an introductory trial conducted in three Mexican provinces (Sinaloa, Guanajuato, and Veracruz). Cyclofem contains 25 mg of medroxyprogesterone acetate and 5 mg of estradiol cypionate. A total of 3457 women (640 women from rural communities and 2817 from urban and suburban family planning centers) were enrolled and 20,316 woman-months of treatment experience were accumulated during the 12-month study period. The mean age of study participants was 23.6 years; 70% had previously used at least one contraceptive method. There was only one pregnancy (rate, 0.03%). The overall life-table continuation rate at 1 year was 26.1%, but this rate was higher in the community-based group (36.9%) than in the health center group (22.4%). This discrepancy is presumed to reflect the greater access of clinic clients to other contraception options. Continuation was highest among women 30-34 years of age, those with low levels of education, women with five or more children, and those who did not want more children. Only 14% of discontinuations were method-related. The 1-year discontinuation rate for bleeding problems, including amenorrhea, was 10.2%. These findings indicate Cyclofem is a safe, effective method appropriate for inclusion in Mexico's Ministry of Health Family Planning Program.
Assuntos
Anticoncepcionais Femininos , Estradiol/análogos & derivados , Acetato de Medroxiprogesterona/administração & dosagem , Adolescente , Adulto , Anticoncepcionais Orais Combinados/administração & dosagem , Anticoncepcionais Orais Combinados/efeitos adversos , Combinação de Medicamentos , Escolaridade , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Feminino , Humanos , Injeções Intramusculares , Acetato de Medroxiprogesterona/efeitos adversos , México , Satisfação do Paciente , Estudos ProspectivosRESUMO
OBJECTIVE: To evaluate the changes in cervical mucus within the first hours or days after depot medroxyprogesterone acetate (MPA) injection so as to estimate the time at which cervical mucus becomes hostile enough to prevent pregnancy. DESIGN: Multicenter, clinical descriptive study. SETTING: Family planning clinic. PATIENT(S): Thirty women who were between days 8 and 13 of their menstrual cycle and who had requested Depo-Provera were enrolled in the study. INTERVENTION(S): Cervical mucus and blood samples were obtained; transvaginal ultrasonography was performed. MAIN OUTCOME MEASURE(S): Cervical mucus scores, sperm penetration distances, ovarian follicular size, and serum levels of progesterone and estradiol. RESULT(S): From 6 to 24 hours after injection, there was a sharp decline in the cervical mucus score for most of the subjects. All subjects exhibited poor mucus on day 3 after injection, and by day 7, all subjects had zero scores, with the exception of two outliers on each day. Sperm penetration, as measured by the vanguard sperm distance, was already poor (< 1 cm) in 7 of the 30 subjects at the time of injection and was reduced progressively up to 24 hours after injection, when only four subjects had a sperm penetration of > 1 cm. A rapid decline in the estimated number of sperm was observed at 12 hours and more so at 24 hours in the majority of subjects. CONCLUSION(S): The data presented in this report confirmed that depot MPA causes profound changes in cervical mucus after injection. Although very little change was seen at 6 hours, alterations were observed subsequently, with 90% of the subjects showing a poor cervical mucus score 24 hours after administration of the progestin. No reliable clinical marker is available to identify in which women depot MPA might exert its effect on cervical mucus within 3 days. Thus, we believe that at present, women should be informed of this uncertainty and should use a backup method of contraception for 7 days when the first injection of depot MPA is provided after the seventh day of the menstrual cycle.
PIP: More accurate knowledge of the time of onset of cervical mucus changes after Depo-Provera injection would enable family planning providers to counsel new acceptors to use a backup method only for the amount of time it is really needed. To obtain such data, 30 women from a family planning clinic in Campinas, Brazil, who requested Depo-Provera in 1995-96 were recruited. At baseline, 11 women had a poor cervical mucus score (0-4), 12 had a fair score (3-8), and 7 scored in the good range (9-12). Between 6 and 24 hours after injection, a sharp decline occurred in the cervical mucus score in all but 3 patients (each of whom had a "good" score at baseline). On day 3, 29 women had "poor" mucus and the remaining woman had a cervical mucus score in the fair range. By day 7, 29 women had zero mucus scores; the score in the last woman was 1. 24 hours after injection, sperm penetration (measured by vanguard sperm distance) had decreased to under 1 cm in all but 4 women. At day 3, 1 of the 2 women with good penetration at 24 hours maintained a vanguard sperm distance of 2.5 cm and an estimated sperm count of 15,363. By day 7, sperm penetration was zero in all but 1 woman (0.5 cm). These findings confirm that depot medroxyprogesterone acetate causes profound changes in cervical mucus after injection. The lack of a more complete hostility to sperm penetration at day 3 was unexpected, however. Given the nonavailability of a reliable clinical marker to verify a contraceptive effect at 3 days, it seems prudent to advise new Depo-Provera acceptors to use a backup method for the first 7 days.
Assuntos
Muco do Colo Uterino/efeitos dos fármacos , Anticoncepcionais Femininos/farmacologia , Acetato de Medroxiprogesterona/farmacologia , Espermatozoides/efeitos dos fármacos , Adulto , Muco do Colo Uterino/fisiologia , Anticoncepcionais Femininos/administração & dosagem , Feminino , Seguimentos , Humanos , Masculino , Acetato de Medroxiprogesterona/administração & dosagem , Espermatozoides/fisiologia , Fatores de TempoRESUMO
The bone density (BD) of 72 women using depot-medroxyprogesterone acetate (DMPA) for at least 1 year was compared with that of 64 women who were not users of hormonal contraceptives. The BD of lumbar spine, femoral neck, Ward's triangle, and trochanter was measured by dual energy X-ray absorptiometry (DEXA-LUNAR DPX). Estradiol (E2) concentrations were measured by radioimmunoassay (RIA). The mean age of DMPA users and nonusers was 31.8 and 31.1 years, respectively. Mean E, was 55.7 pg/mL for users and 149.9 pg/mL for controls (p < 0.001). The BD was significantly lower for DMPA users than for controls in all sites (p < 0.01). In addition, young adult T-scores in the lumbar spine were significantly lower among DMPA users than in controls (p < 0.01). Differences were maintained in a subsample of 47 women per group paired by age and body mass index (BMI). Multiple regression analysis showed that older age, lower BMI, and longer amenorrhea were associated with lower BD in the femoral neck, whereas lower BMI and use of DMPA were associated with lower BD in the lumbar spine.
PIP: Family planning programs that offer depot medroxyprogesterone acetate (DMPA) cannot be indifferent to the risk of lowered bone density. A study conducted at the Family Planning Clinic of the State University of Campinas (Sao Paulo, Brazil) compared bone densities in 72 women who had been using DMPA for at least 1 year (mean duration, 42 months) and 64 regularly menstruating nonusers. Mean age was 31 years in both groups; there were no significant differences between the 2 groups in terms of ethnicity, body mass index (BMI), or smoking. Mean serum estradiol concentrations were 55.7 +or- 40.5 pg/ml for DMPA users and 149.9 +or- 88.2 pg/ml for nonusers (p 0.001). The mean length of amenorrhea was 26.5 +or- 23.8 months among DMPA users. The mean bone density in DMPA users was significantly lower than that of controls at all sites evaluated (i.e., lumbar spine, femoral neck, Ward's triangle, and trochanter). 38 DMPA users, compared with only 17 controls, had a T-score in the lumbar spine lower than -1 standard deviation (p = 0.014). Multiple regression analysis identified BMI and DMPA use as variables significantly associated with bone density in the lumbar spine; in the femoral neck, these variables were BMI, age, and length of amenorrhea. Periodic bone densitometry should be considered for women over 40 years of age with low BMI who have more than 2 years of continuous amenorrhea.
Assuntos
Densidade Óssea/efeitos dos fármacos , Anticoncepcionais Femininos/farmacologia , Acetato de Medroxiprogesterona/farmacologia , Congêneres da Progesterona/farmacologia , Absorciometria de Fóton , Adulto , Estudos Transversais , Estradiol/sangue , Feminino , Humanos , Radioimunoensaio , Análise de Regressão , Fatores de TempoRESUMO
The objective of this study was to evaluate the return of fertility in women who used Cyclofem as a contraceptive method during the introductory studies conducted in Brazil, Chile, Colombia, and Peru. From these four cohorts, 101 women were eligible for the study. Thirty-one were not included in the study either because they refused to be interviewed, had initiated another contraceptive method the month after discontinuation, or were unable to be contacted. A total of 70 women were included in the study. Our results showed that the return to fertility rate after the discontinuation of Cyclofem was 1.4 per 100 women at the end of the first month and reached 82.9 at one year. More than 50% were pregnant at 6 months. Fifty-one (94.4%) pregnancies ended in a live birth, two were spontaneous first trimester abortions, and one was a hydatidiform mole. Return of fertility was not related to the woman's age at the time of discontinuation, her weight, or the number of Cyclofem injections. In conclusion, fertility is restored by 1 month following Cyclofem discontinuation. Users and potential users should be counseled regarding the rapid return of fertility after discontinuing this method of contraception.
PIP: Cyclofem, a monthly injectable contraceptive containing 5 mg estradiol cypionate and 25 mg medroxyprogesterone acetate, has been registered in several Latin American countries; however, the return to fertility after method discontinuation has not been investigated. To address this issue, 70 women were followed who had participated in introductory studies in Brazil, Chile, Colombia, and Peru during 1992-94 and who then discontinued injectable use to achieve pregnancy. The mean number of Cyclofem injections was 7.1 (range, 1-19). The fertility rate was 1.4 at the end of the first month after Cyclofem discontinuation, 52.9 after 6 months, and 82.9 at 12 months. 55 pregnancies (94.8%) ended in live-term births, with no congenital malformations; there were 2 spontaneous abortions in the first trimester. The number of months required to become pregnant was not significantly associated with maternal age, body weight, number of injections, or country site. The return to fertility for this method is comparable to that following discontinuation of copper IUDs, barrier methods, and oral contraceptives. Since information on return to fertility is essential to informed choice, these findings should be incorporated into educational and counseling materials for providers and potential acceptors of this new contraceptive method.
Assuntos
Anticoncepcionais Femininos/administração & dosagem , Estradiol/análogos & derivados , Fertilidade , Acetato de Medroxiprogesterona/administração & dosagem , Adulto , Estudos de Coortes , Anticoncepcionais Orais Combinados/administração & dosagem , Combinação de Medicamentos , Estradiol/administração & dosagem , Feminino , Humanos , Injeções , Gravidez , Fatores de TempoRESUMO
Healthy, regularly menstruating women, aged 14-38 years, were enrolled in a comparative, double-blind, phase III, clinical trial to evaluate the contraceptive efficacy and acceptability of a combination of 90 mg dihydroxyprogesterone acetophenide with 6 mg estradiol enanthate compared to the commercially available contraceptive combination of 150 mg dihydroxyprogesterone acetophenide with 10 mg estradiol enanthate. Subjects received the contraceptive combination intramuscularly, between the 7th and 10th day of each menstrual cycle, during 12 consecutive menstrual cycles. Approximately 60% of the subjects in both groups completed the study. Principal reasons for discontinuation were personal, nonmedical reasons. Principal medical reasons for discontinuation were menstrual-related, irregular bleeding being the most frequent. Differences in menstrual patterns between the two groups did not lead to differences in discontinuation rates. Three contraceptive failures occurred during the trial, one in Group A (90/6 mg) and two in Group B (150/10 mg), indicating that the lower dose formulation is at least as efficient as the higher dose.
Assuntos
Acetofenida de Algestona/efeitos adversos , Anticoncepcionais/efeitos adversos , Estradiol/análogos & derivados , Menstruação/efeitos dos fármacos , Congêneres da Progesterona/efeitos adversos , Hemorragia Uterina/induzido quimicamente , Adolescente , Adulto , Acetofenida de Algestona/administração & dosagem , Peso Corporal , Brasil , Estudos de Coortes , Anticoncepcionais/administração & dosagem , Relação Dose-Resposta a Droga , Método Duplo-Cego , Estradiol/administração & dosagem , Estradiol/efeitos adversos , Feminino , Humanos , Incidência , Menstruação/fisiologia , Aceitação pelo Paciente de Cuidados de Saúde , Pacientes Desistentes do Tratamento/estatística & dados numéricos , Congêneres da Progesterona/administração & dosagem , Hemorragia Uterina/epidemiologiaRESUMO
The objective of this study was to evaluate women's acceptance of and ability to self-administrate the injectable contraceptive Cyclofem using prefilled UniJect devices. A total of 102 women were invited to participate in the study. Fourteen women (13.7%) refused to participate. Of the remaining 88 women, 32 women (31.4%) consented to participate and were trained using oranges but were still afraid of the procedure and ultimately refused to self-administer the injections. Only 56 women (55%) ultimately self-injected Cyclofem with UniJect. They performed a total of 144 injections, all of them on the ventral side of the thigh. When nurses evaluated women's ability to activate the devices, they found that more than 80% were successful in both the group of women that later self-administered the injections and the group that did not. The evaluation of the self-administered injection technique showed that more than 90% of the women correctly self-administered the contraceptive using UniJect. With respect to the opinion of the women about the self-administration of the contraceptive, more than 50% (32 of 56) of women who self-injected preferred to self-administer the injection and said that they wished to continue with the self-administration, one-third (17) reported that they were afraid, and seven women (12.5%) expressed the opinion that the injection in the thigh was more painful than the administration in the buttocks or arm. In conclusion, our study showed that women can be trained to successfully self-administer the monthly injectable contraceptive Cyclofem and generally respond positively to UniJect.
PIP: Women's capability to self-administer the monthly injectable contraceptive, Cyclofem, through use of prefilled UniJect devices was evaluated in 88 volunteers recruited from three Brazilian health clinics. After training in self-injection in which oranges were used for practice, only 56 of these women (55%) elected to continue with the study. They performed a total of 144 injections on the ventral side of the thigh. When nurses evaluated women's ability to activate the UniJect device, they found more than 80% of women trained in the method and 93% of those who actually performed self-injection used the technique correctly in an angle of 90 degrees. 32 (57.1%) of the 56 women who self-injected indicated they preferred this method and wished to continue to self-inject at home, another 17 (30.4%) reported they liked the method but were afraid to perform it on their own, and seven (12.5%) complained of pain associated with injection in the thigh compared with the buttocks or arm. Self-administration of injectable contraception, a popular method in Latin American countries, has the potential to increase contraceptive coverage as well as reduce costs associated with transportation to a source of contraception. If women are to perform self-injection at home rather than at a clinic, they will require reminders about the dates of reinjection and the importance of aseptic procedures and proper disposal of injecting equipment.