Integrated Care in Parkinson's Disease: A Systematic Review and Meta-Analysis.

BACKGROUND: Quality of life in Parkinson's disease (PD) is affected by motor and nonmotor symptoms, necessitating an integrated care approach. Existing care models vary considerably in numerous domains. The objectives of this study were to perform a systematic review and meta-analysis of PD integrated care models and develop recommendations for a representative model. METHODS: We conducted a systematic review of published integrated care models and a meta-analysis of randomized, controlled trials examining integrated care versus standard care. The primary outcome was health-related quality of life using a validated PD scale. We evaluated levels of care integration using the Rainbow Model of Integrated Care. RESULTS: Forty-eight publications were identified, including 8 randomized, controlled trials with health-related quality of life data (n = 1,149 total PD patients). Qualitative evaluation of individual care model integration guided by the Rainbow Model of Integrated Care revealed frequent clinical and professional integration, but infrequent organizational and population-based integration elements. Meta-analysis of randomized, controlled trials revealed significant heterogeneity (I2 = 90%, P < 0.0001). Subgroup analysis including only outpatient care models (n = 5) indicated homogeneity of effects (I2 = 0%, P = 0.52) and improved health-related quality of life favoring integrated care, with a small effect size (standardized mean difference [SMD], -0.17; 95% CI, -0.31 to -0.03; P = 0.02). CONCLUSIONS: Outpatient integrated PD care models may improve patient-reported health-related quality of life compared with standard care; however, because of variable methodological approaches and a high risk of bias related to inherent difficulties in study design (eg, blinding of participants and interventionists), generalizability of these results are difficult to establish. The Rainbow Model of Integrated Care is a promising method of evaluating elements and levels of integration from individual patient care to population health in a PD context. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, LLC. on behalf of International Parkinson and Movement Disorder Society.

Steroidal contraceptives: effect on bone fractures in women.

BACKGROUND: Steroidal contraceptive use has been associated with changes in bone mineral density in women. Whether such changes increase the risk of fractures later in life is not clear. Osteoporosis is a major public health concern. Age-related decline in bone mass increases the risk of fracture, especially of the spine, hip, and wrist. Concern about bone health influences the recommendation and use of these effective contraceptives globally. OBJECTIVES: Our aim was to evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women. SEARCH METHODS: Through April 2014, we searched for studies of fracture or bone health and hormonal contraceptives in MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS, as well as ClinicalTrials.gov and ICTRP. We examined reference lists of relevant articles for other trials. For the initial review, we wrote to investigators to find additional trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) were considered if they examined fractures, bone mineral density (BMD), or bone turnover markers in women with hormonal contraceptive use prior to menopause. Eligible interventions included comparisons of a hormonal contraceptive with a placebo or with another hormonal contraceptive that differed in terms of drug, dosage, or regimen. They also included providing a supplement to one group. DATA COLLECTION AND ANALYSIS: We assessed all titles and abstracts identified through the literature searches. Mean differences were computed using the inverse variance approach. For dichotomous outcomes, the Mantel-Haenszel odds ratio (OR) was calculated. Both included the 95% confidence interval (CI) and used a fixed-effect model. Due to differing interventions, no trials could be combined for meta-analysis. We applied principles from GRADE to assess the evidence quality and address confidence in the effect estimates. In addition, a sensitivity analysis included trials that provided sufficient data for this review and evidence of at least moderate quality. MAIN RESULTS: We found 19 RCTs that met our eligibility criteria. Eleven trials compared different combined oral contraceptives (COCs) or regimens of COCs; five examined an injectable versus another injectable, implant, or IUD; two studied implants, and one compared the transdermal patch versus the vaginal ring. No trial had fracture as an outcome. BMD was measured in 17 studies and 12 trials assessed biochemical markers of bone turnover. Depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density (BMD). The placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo supplement. COCs did not appear to negatively affect BMD, and some formulations had more positive effects than others. However, no COC trial was placebo-controlled. Where studies showed differences between groups in bone turnover markers, the results were generally consistent with those for BMD. For implants, the single-rod etonogestrel group showed a greater BMD decrease versus the two-rod levonorgestrel group but results were not consistent across all implant comparisons.The sensitivity analysis included 11 trials providing evidence of moderate or high quality. Four trials involving DMPA showed some positive effects of an estrogen supplement on BMD, a negative effect of DMPA-subcutaneous on lumbar spine BMD, and a negative effect of DMPA on a bone formation marker. Of the three COC trials, one had a BMD decrease for the group with gestodene plus EE 15 µg. Another indicated less bone resorption in the group with gestodene plus EE 30 µg versus EE 20 µg. AUTHORS' CONCLUSIONS: Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. The evidence quality was considered moderate overall, largely due to the trials of DMPA, implants, and the patch versus ring. The COC evidence varied in quality but was low overall. Many trials had small numbers of participants and some had large losses. Health care providers and women should consider the costs and benefits of these effective contraceptives. For example, injectable contraceptives and implants provide effective, long-term birth control yet do not involve a daily regimen. Progestin-only contraceptives are considered appropriate for women who should avoid estrogen due to medical conditions.

Immediate start of hormonal contraceptives for contraception.

BACKGROUND: Health care providers often tell women to wait until the next menses to begin hormonal contraception. The intent is to avoid contraceptive use during an undetected pregnancy. An alternative is to start hormonal contraception immediately with back-up birth control for the first seven days. Immediate initiation was introduced with combined oral contraceptives (COCs), and has expanded to other hormonal contraceptives. At the time of the initial review, how immediate start compared to conventional menses-dependent start was unclear regarding effectiveness, continuation, and acceptability. The immediate-start approach may improve women's access to, and continuation of, hormonal contraception. OBJECTIVES: This review examined randomized controlled trials (RCTs) of immediate-start hormonal contraception for differences in effectiveness, continuation, and acceptability. SEARCH METHODS: In August 2012, we searched MEDLINE, CENTRAL, POPLINE, LILACS, ClinicalTrials.gov, and ICTRP for trials of immediate-start hormonal contraceptives. We contacted researchers to find other studies. Earlier searches also included EMBASE. SELECTION CRITERIA: We included RCTs that compared immediate start to conventional start of hormonal contraception. Also included were trials that compared immediate start of different hormonal contraceptive methods with each other. DATA COLLECTION AND ANALYSIS: Data were abstracted by two authors and entered into RevMan. The Peto odds ratio (OR) with 95% confidence interval (CI) was calculated. MAIN RESULTS: Five studies were included. No new eligible studies have been found since the review was initially conducted. Method discontinuation was similar between groups in all trials. Bleeding patterns and side effects were similar in trials that compared immediate with conventional start. In a study of depot medroxyprogesterone acetate (DMPA), immediate start of DMPA showed fewer pregnancies than a 'bridge' method before DMPA (OR 0.36; 95% CI 0.16 to 0.84). Further, more women in the immediate-DMPA group were very satisfied versus those with a 'bridge' method (OR 1.99; 95% CI 1.05 to 3.77). A trial of two immediate-start methods showed the vaginal ring group had less prolonged bleeding (OR 0.42; 95% CI 0.20 to 0.89) and less frequent bleeding (OR 0.23; 95% CI 0.05 to 1.03) than COC users. The ring group also reported fewer side effects. Also, more immediate ring users were very satisfied than immediate COC users (OR 2.88; 95% CI 1.59 to 5.22). AUTHORS' CONCLUSIONS: We found limited evidence that immediate start of hormonal contraception reduces unintended pregnancies or increases method continuation. However, the pregnancy rate was lower with immediate start of DMPA versus another method. Some differences were associated with contraceptive type rather than initiation method, i.e., immediate ring versus immediate COC. More studies are needed of immediate versus conventional start of the same hormonal contraceptive.

Steroidal contraceptives: effect on bone fractures in women.

BACKGROUND: Steroidal contraceptive use has been associated with changes in bone mineral density in women. Whether such changes increase the risk of fractures later in life is not clear. Osteoporosis is a major public health concern. Age-related decline in bone mass increases the risk of fracture, especially of the spine, hip, and wrist. Concern about bone health influences the recommendation and use of these effective contraceptives globally. OBJECTIVES: To evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women SEARCH STRATEGY: We searched for studies of fracture or bone health and hormonal contraceptives in MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS, as well as ClinicalTrials.gov and ICTRP. We wrote to investigators to find additional trials. SELECTION CRITERIA: Randomized controlled trials (RCTs) were considered if they examined fractures, bone mineral density (BMD), or bone turnover in women with hormonal contraceptive use prior to menopause. Interventions could include comparing a hormonal contraceptive with a placebo or another hormonal contraceptive or could compare providing a supplement versus a placebo. DATA COLLECTION AND ANALYSIS: We assessed all titles and abstracts identified through the literature searches. Mean differences were computed using the inverse variance approach. For dichotomous outcomes, the Mantel-Haenszel odds ratio (OR) was calculated. Both included the 95% confidence interval (CI) and used a fixed-effect model. Due to different interventions, no trials could be combined for meta-analysis. MAIN RESULTS: Of the 16 RCTs we found, 2 used a placebo and 1 used a non-hormonal method as the comparison, while 13 compared two hormonal contraceptives. No trial had fracture as an outcome. Most measured BMD and several assessed bone turnover. Depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density. The placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo. Combination contraceptives did not appear to negatively affect bone health, but none were placebo-controlled. For implants, the single-rod etonogestrel group showed a greater BMD decrease versus the two-rod levonorgestrel group. However, results were not consistent across all implant comparisons. AUTHORS' CONCLUSIONS: Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. Many trials had small numbers of participants and some had large losses to follow up. Health care providers and women should consider the costs and benefits of these effective contraceptives. For example, injectable contraceptives and implants provide effective, long-term birth control yet do not involve a daily regimen. Progestin-only contraceptives are considered appropriate for women who should avoid estrogen due to medical conditions.

Nonspecific side effects of oral contraceptives: nocebo or noise?

Side effects of combined oral contraceptives are the most common reason why women discontinue them. Over the past half century, an elaborate mythology about these ill effects has evolved, fueled by rumor, gossip and poor-quality research. In contrast, placebo-controlled randomized trials document that nonspecific side effects are not significantly more common with combined oral contraceptives than with inert pills. These reported nonspecific side effects may reflect the nocebo phenomenon (the inverse of a placebo): if women are told to expect noxious side effects, these complaints occur because of the power of suggestion. Alternatively, nonspecific complaints may simply reflect their background prevalence in the population. Because Level I evidence documents no important increase in nonspecific side effects with oral contraceptives, counseling about these side effects or including them in package labeling is unwarranted and probably unethical. When in doubt, clinicians should err on the side of optimism.

Steroidal contraceptives: effect on bone fractures in women.

BACKGROUND: Steroidal contraceptive use has been associated with changes in bone mineral density in women. Whether such changes increase the risk of fractures later in life is not clear. However, osteoporosis is a major public health concern. Age-related decline in bone mass increases the risk of fracture, especially of the spine, hip, and wrist. Concern about bone health influences the recommendation and use of these effective contraceptives globally. OBJECTIVES: To evaluate the effect of using hormonal contraceptives before menopause on the risk of fracture in women SEARCH STRATEGY: We searched for studies of fracture or bone health and hormonal contraceptives in MEDLINE, POPLINE, CENTRAL, EMBASE, and LILACS, as well as in clinical trials databases (ClinicalTrials.gov and ICTRP). We wrote to investigators to find additional trials. SELECTION CRITERIA: Randomized controlled trials were considered if they examined fractures, bone mineral density (BMD), or bone turnover in women with hormonal contraceptive use prior to menopause. Studies were excluded if hormones were provided for treatment of a specific condition rather than for contraception. Interventions could include comparisons of a hormonal contraceptive with a placebo or with another hormonal contraceptive. Interventions could also include the provision of a supplement versus a placebo. DATA COLLECTION AND ANALYSIS: We assessed for inclusion all titles and abstracts identified through the literature searches with no language limitation. The mean difference was computed with 95% confidence interval (CI) using a fixed-effect model. MAIN RESULTS: We found 13 RCTs, 2 of which used a placebo. No trial had fracture as an outcome but most measured BMD. Combination contraceptives did not appear to affect bone health. Of progestin-only methods, depot medroxyprogesterone acetate (DMPA) was associated with decreased bone mineral density, while results were inconsistent for implants. The two placebo-controlled trials showed BMD increases for DMPA plus estrogen supplement and decreases for DMPA plus placebo. AUTHORS' CONCLUSIONS: Whether steroidal contraceptives influence fracture risk cannot be determined from existing information. Due to different interventions, no trials could be combined for meta-analysis. Many trials had small numbers of participants and some had large losses to follow up. Health care providers and women should consider the costs and benefits of these effective contraceptives. For example, injectable contraceptives and implants provide effective, long-term birth control yet do not involve a daily regimen. Progestin-only contraceptives are considered appropriate for women who should avoid estrogen due to medical conditions.

Nonhormonal drugs for contraception in men: a systematic review.

UNLABELLED: Nonhormonal drugs for contraception in men may have advantages over hormonal methods. The nonhormonal methods can have more rapid onset and less interference with androgen-dependent functions. This systematic review summarizes the clinical studies evaluating nonhormonal drugs administered to men for contraception. Relevant clinical results were found for gossypol, which is derived from the cotton plant, and for extracts of Tripterygium, a plant used in Chinese traditional medicine. Randomized, controlled trials were available on the efficacy of gossypol and on the effect of gossypol on potassium levels. Gossypol had problems with low efficacy and toxicity. For Tripterygium, 2 observational studies described men who were treated for rheumatoid arthritis. Although sperm density was lower among those taking Tripterygium, later reports indicated some toxicity. Nonclinical research continues on isolates of Tripterygium. No clinical studies for contraception in men were found for nonhormonal vaccines or neem, which is also a plant used for medicinal purposes. Clinical trials studied injecting styrene maleic anhydride into the vas deferens, but no comparative data were provided. At this time, no safe and effective nonhormonal drug is available for contraception in men. TARGET AUDIENCE: Obstetricians & Gynecologists, Family Physicians. LEARNING OBJECTIVES: After completion of this article, the reader should be able to state that the number of studies concerning the use of nonhormonal drugs for male contraception are very limited, point out that the two nonhormonal drugs used to a small degree have varying results and serious side effects, and recall that there are limited clinical studies on use of vas deferens injections and vaccines in humans.

Noncontraceptive health benefits of intrauterine devices: a systematic review.

Most women and their clinicians are unaware that IUDs confer important noncontraceptive health benefits. This review summarizes the evidence from published articles on this topic. We conducted a series of systematic literature searches to identify articles on the noncontraceptive health benefits of IUD use. We reviewed the potentially pertinent ones for content, grouped them according to type of IUD, and evaluated them using the U.S. Preventive Services Task Force rating system. Over 500 titles were identified and several hundred abstracts were reviewed. Use of nonhormonal IUDs (plastic and copper) was associated with a decrease in endometrial cancer. The levonorgestrel intrauterine system can treat a variety of gynecological disorders, including menorrhagia and anemia. The levonorgestrel system has also been used successfully as part of hormone replacement therapy, as adjuvant therapy with tamoxifen, and as an alternative to hysterectomy for women with bleeding problems. Like oral contraceptives, intrauterine contraceptives confer important noncontraceptive health benefits.