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Australian Occupational Therapy Journal Jun 2019Paediatric occupational therapy seeks to improve children's engagement and participation in life roles. A wide variety of intervention approaches exist. Our aim was to...
INTRODUCTION
Paediatric occupational therapy seeks to improve children's engagement and participation in life roles. A wide variety of intervention approaches exist. Our aim was to summarise the best-available intervention evidence for children with disabilities, to assist families and therapists choose effective care.
METHODS
We conducted a systematic review (SR) using the Cochrane methodology, and reported findings according to PRISMA. CINAHL, Cochrane Library, MEDLINE, OTSeeker, PEDro, PsycINFO were searched. Two independent reviewers: (i) determined whether studies met inclusion: SR or randomised controlled trial (RCT); an occupational therapy intervention for children with a disability; (ii) categorised interventions based on name, core components and diagnostic population; (iii) rated quality of evidence and determined the strength of recommendation using GRADE criteria; and (iv) made recommendations using the Evidence Alert Traffic Light System.
RESULTS
129 articles met inclusion (n = 75 (58%) SRs; n = 54 (42%)) RCTs, measuring the effectiveness of 52 interventions, across 22 diagnoses, enabling analysis of 135 intervention indications. Thirty percent of the indications assessed (n = 40/135) were graded 'do it' (Green Go); 56% (75/135) 'probably do it' (Yellow Measure); 10% (n = 14/135) 'probably don't do it' (Yellow Measure); and 4% (n = 6/135) 'don't do it' (Red Stop). Green lights were: Behavioural Interventions; Bimanual; Coaching; Cognitive Cog-Fun & CAPS; CO-OP; CIMT; CIMT plus Bimanual; Context-Focused; Ditto; Early Intervention (ABA, Developmental Care); Family Centred Care; Feeding interventions; Goal Directed Training; Handwriting Task-Specific Practice; Home Programs; Joint Attention; Mental Health Interventions; occupational therapy after toxin; Kinesiotape; Pain Management; Parent Education; PECS; Positioning; Pressure Care; Social Skills Training; Treadmill Training and Weight Loss 'Mighty Moves'.
CONCLUSION
Evidence supports 40 intervention indications, with the greatest number at the activities-level of the International Classification of Function. Yellow light interventions should be accompanied by a sensitive outcome measure to monitor progress and red light interventions could be discontinued because effective alternatives existed.
Topics: Child; Child, Preschool; Humans; Disabled Children; Occupational Therapy; Randomized Controlled Trials as Topic
PubMed: 30968419
DOI: 10.1111/1440-1630.12573 -
The Cochrane Database of Systematic... Feb 2017Dementia is a collective name for different degenerative brain syndromes which, according to Alzheimer's Disease International, affects approximately 35.6 million people... (Review)
Review
BACKGROUND
Dementia is a collective name for different degenerative brain syndromes which, according to Alzheimer's Disease International, affects approximately 35.6 million people worldwide. The latest NICE guideline for dementia highlights the value of diverse treatment options for the different stages and symptoms of dementia including non-pharmacological treatments. Relevant literature also argues for the value of interventions that acknowledge the complexity of the condition and address the person as a whole, including their physical, emotional, social and cognitive processes. At the same time, there is growing literature that highlights the capacity of the arts and embodied practices to address this complexity. Dance movement therapy is an embodied psychological intervention that can address complexity and thus, may be useful for people with dementia, but its effectiveness remains unclear.
OBJECTIVES
To assess the effects of dance movement therapy on behavioural, social, cognitive and emotional symptoms of people with dementia in comparison to no treatment, standard care or any other treatment. Also, to compare different forms of dance movement therapy (e.g. Laban-based dance movement therapy, Chacian dance movement therapy or Authentic Movement).
SEARCH METHODS
Searches took place up to March 2016 through ALOIS, Cochrane Dementia and Cognitive Improvement's Specialized Register, which covers CENTRAL, a number of major healthcare databases and trial registers, and grey literature sources. We checked bibliographies of relevant studies and reviews, and contacted professional associations, educational programmes and experts from around the world.
SELECTION CRITERIA
We considered randomised controlled trials (RCTs) in any language, including cross-over design and cluster-RCTs for inclusion. Studies considered had to include people with dementia, in any age group and in any setting, with interventions delivered by a dance movement therapy practitioner who (i) had received formal training (ii) was a dance movement therapist in training or (iii) was otherwise recognised as a dance movement therapist in the country in which the study was conducted.
DATA COLLECTION AND ANALYSIS
The two review authors independently reviewed studies on an abstract/title level and again after reading the full paper, and we independently evaluated methodological quality.
MAIN RESULTS
Of the 102 studies identified through electronic searches and personal communication, after de-duplication we screened 80 at title/abstract level. We then reviewed 19 full papers, none of which met the inclusion criteria. Although three studies mentioned dance movement therapy as their intervention, they were excluded because they were not delivered by a qualified dance movement therapy practitioner. As a result, no studies were included in this review.
AUTHORS' CONCLUSIONS
Trials of high methodological quality, large sample sizes and clarity in the way the intervention is put together and delivered are needed to assess whether dance movement therapy is an effective intervention for dementia.
Topics: Dance Therapy; Dancing; Dementia; Humans; Movement
PubMed: 28155990
DOI: 10.1002/14651858.CD011022.pub2 -
JAMA Oncology Jul 2019Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Programmed cell death (PD-1) and programmed cell death ligand 1 (PD-L1) inhibitors have been increasingly used in cancer therapy. Understanding the treatment-related adverse events of these drugs is critical for clinical practice.
OBJECTIVE
To evaluate the incidences of treatment-related adverse events of PD-1 and PD-L1 inhibitors and the differences between different drugs and cancer types.
DATA SOURCES
PubMed, Web of Science, Embase, and Scopus were searched from October 1, 2017, through December 15, 2018.
STUDY SELECTION
Published clinical trials on single-agent PD-1 and PD-L1 inhibitors with tabulated data on treatment-related adverse events were included.
DATA EXTRACTION AND SYNTHESIS
Trial name, phase, cancer type, PD-1 and PD-L1 inhibitor used, dose escalation, dosing schedule, number of patients, number of all adverse events, and criteria for adverse event reporting data were extracted from each included study, and bayesian multilevel regression models were applied for data analysis.
MAIN OUTCOMES AND MEASURES
Incidences of treatment-related adverse events and differences between different drugs and cancer types.
RESULTS
This systematic review and meta-analysis included 125 clinical trials involving 20 128 patients; 12 277 (66.0%) of 18 610 patients from 106 studies developed at least 1 adverse event of any grade (severity), and 2627 (14.0%) of 18 715 patients from 110 studies developed at least 1 adverse event of grade 3 or higher severity. The most common all-grade adverse events were fatigue (18.26%; 95% CI, 16.49%-20.11%), pruritus (10.61%; 95% CI, 9.46%-11.83%), and diarrhea (9.47%; 95% CI, 8.43%-10.58%). The most common grade 3 or higher adverse events were fatigue (0.89%; 95% CI, 0.69%-1.14%), anemia (0.78%; 95% CI, 0.59%-1.02%), and aspartate aminotransferase increase (0.75%; 95% CI, 0.56%-0.99%). Hypothyroidism (6.07%; 95% CI, 5.35%-6.85%) and hyperthyroidism (2.82%; 95% CI, 2.40%-3.29%) were the most frequent all-grade endocrine immune-related adverse events. Nivolumab was associated with higher mean incidences of all-grade adverse events compared with pembrolizumab (odds ratio [OR], 1.28; 95% CI, 0.97-1.79) and grade 3 or higher adverse events (OR, 1.30; 95% CI, 0.89-2.00). PD-1 inhibitors were associated with a higher mean incidence of grade 3 or higher adverse events compared with PD-L1 inhibitors (OR, 1.58; 95% CI, 1.00-2.54).
CONCLUSIONS AND RELEVANCE
Different PD-1 and PD-L1 inhibitors appear to have varying treatment-related adverse events; a comprehensive summary of the incidences of treatment-related adverse events in clinical trials provides an important guide for clinicians.
Topics: Antineoplastic Agents, Immunological; B7-H1 Antigen; Clinical Trials as Topic; Humans; Neoplasms; Programmed Cell Death 1 Receptor
PubMed: 31021376
DOI: 10.1001/jamaoncol.2019.0393 -
The Cochrane Database of Systematic... Nov 2016Mother-infant separation post birth is common. In standard hospital care, newborn infants are held wrapped or dressed in their mother's arms, placed in open cribs or... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Mother-infant separation post birth is common. In standard hospital care, newborn infants are held wrapped or dressed in their mother's arms, placed in open cribs or under radiant warmers. Skin-to-skin contact (SSC) begins ideally at birth and should last continually until the end of the first breastfeeding. SSC involves placing the dried, naked baby prone on the mother's bare chest, often covered with a warm blanket. According to mammalian neuroscience, the intimate contact inherent in this place (habitat) evokes neuro-behaviors ensuring fulfillment of basic biological needs. This time frame immediately post birth may represent a 'sensitive period' for programming future physiology and behavior.
OBJECTIVES
To assess the effects of immediate or early SSC for healthy newborn infants compared to standard contact on establishment and maintenance of breastfeeding and infant physiology.
SEARCH METHODS
We searched the Cochrane Pregnancy and Childbirth Group's Trials Register (17 December 2015), made personal contact with trialists, consulted the bibliography on kangaroo mother care (KMC) maintained by Dr Susan Ludington, and reviewed reference lists of retrieved studies.
SELECTION CRITERIA
Randomized controlled trials that compared immediate or early SSC with usual hospital care.
DATA COLLECTION AND ANALYSIS
Two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. Quality of the evidence was assessed using the GRADE approach.
MAIN RESULTS
We included 46 trials with 3850 women and their infants; 38 trials with 3472 women and infants contributed data to our analyses. Trials took place in 21 countries, and most recruited small samples (just 12 trials randomized more than 100 women). Eight trials included women who had SSC after cesarean birth. All infants recruited to trials were healthy, and the majority were full term. Six trials studied late preterm infants (greater than 35 weeks' gestation). No included trial met all criteria for good quality with respect to methodology and reporting; no trial was successfully blinded, and all analyses were imprecise due to small sample size. Many analyses had statistical heterogeneity due to considerable differences between SSC and standard care control groups. Results for womenSSC women were more likely than women with standard contact to be breastfeeding at one to four months post birth, though there was some uncertainty in this estimate due to risks of bias in included trials (average risk ratio (RR) 1.24, 95% confidence interval (CI) 1.07 to 1.43; participants = 887; studies = 14; I² = 41%; GRADE: moderate quality). SSC women also breast fed their infants longer, though data were limited (mean difference (MD) 64 days, 95% CI 37.96 to 89.50; participants = 264; studies = six; GRADE:low quality); this result was from a sensitivity analysis excluding one trial contributing all of the heterogeneity in the primary analysis. SSC women were probably more likely to exclusively breast feed from hospital discharge to one month post birth and from six weeks to six months post birth, though both analyses had substantial heterogeneity (from discharge average RR 1.30, 95% CI 1.12 to 1.49; participants = 711; studies = six; I² = 44%; GRADE: moderate quality; from six weeks average RR 1.50, 95% CI 1.18 to 1.90; participants = 640; studies = seven; I² = 62%; GRADE: moderate quality).Women in the SCC group had higher mean scores for breastfeeding effectiveness, with moderate heterogeneity (IBFAT (Infant Breastfeeding Assessment Tool) score MD 2.28, 95% CI 1.41 to 3.15; participants = 384; studies = four; I² = 41%). SSC infants were more likely to breast feed successfully during their first feed, with high heterogeneity (average RR 1.32, 95% CI 1.04 to 1.67; participants = 575; studies = five; I² = 85%). Results for infantsSSC infants had higher SCRIP (stability of the cardio-respiratory system) scores overall, suggesting better stabilization on three physiological parameters. However, there were few infants, and the clinical significance of the test was unclear because trialists reported averages of multiple time points (standardized mean difference (SMD) 1.24, 95% CI 0.76 to 1.72; participants = 81; studies = two; GRADE low quality). SSC infants had higher blood glucose levels (MD 10.49, 95% CI 8.39 to 12.59; participants = 144; studies = three; GRADE: low quality), but similar temperature to infants in standard care (MD 0.30 degree Celcius (°C) 95% CI 0.13 °C to 0.47 °C; participants = 558; studies = six; I² = 88%; GRADE: low quality). Women and infants after cesarean birthWomen practicing SSC after cesarean birth were probably more likely to breast feed one to four months post birth and to breast feed successfully (IBFAT score), but analyses were based on just two trials and few women. Evidence was insufficient to determine whether SSC could improve breastfeeding at other times after cesarean. Single trials contributed to infant respiratory rate, maternal pain and maternal state anxiety with no power to detect group differences. SubgroupsWe found no differences for any outcome when we compared times of initiation (immediate less than 10 minutes post birth versus early 10 minutes or more post birth) or lengths of contact time (60 minutes or less contact versus more than 60 minutes contact).
AUTHORS' CONCLUSIONS
Evidence supports the use of SSC to promote breastfeeding. Studies with larger sample sizes are necessary to confirm physiological benefit for infants during transition to extra-uterine life and to establish possible dose-response effects and optimal initiation time. Methodological quality of trials remains problematic, and small trials reporting different outcomes with different scales and limited data limit our confidence in the benefits of SSC for infants. Our review included only healthy infants, which limits the range of physiological parameters observed and makes their interpretation difficult.
Topics: Breast Feeding; Female; Humans; Infant; Infant, Newborn; Kangaroo-Mother Care Method; Mother-Child Relations; Mothers; Object Attachment; Randomized Controlled Trials as Topic; Skin Physiological Phenomena; Touch
PubMed: 27885658
DOI: 10.1002/14651858.CD003519.pub4 -
The Cochrane Database of Systematic... Jan 2015Terminally ill people experience a variety of symptoms in the last hours and days of life, including delirium, agitation, anxiety, terminal restlessness, dyspnoea, pain,... (Review)
Review
BACKGROUND
Terminally ill people experience a variety of symptoms in the last hours and days of life, including delirium, agitation, anxiety, terminal restlessness, dyspnoea, pain, vomiting, and psychological and physical distress. In the terminal phase of life, these symptoms may become refractory, and unable to be controlled by supportive and palliative therapies specifically targeted to these symptoms. Palliative sedation therapy is one potential solution to providing relief from these refractory symptoms. Sedation in terminally ill people is intended to provide relief from refractory symptoms that are not controlled by other methods. Sedative drugs such as benzodiazepines are titrated to achieve the desired level of sedation; the level of sedation can be easily maintained and the effect is reversible.
OBJECTIVES
To assess the evidence for the benefit of palliative pharmacological sedation on quality of life, survival, and specific refractory symptoms in terminally ill adults during their last few days of life.
SEARCH METHODS
We searched the Cochrane Central Register of Controlled Trials (CENTRAL; 2014, Issue 11), MEDLINE (1946 to November 2014), and EMBASE (1974 to December 2014), using search terms representing the sedative drug names and classes, disease stage, and study designs.
SELECTION CRITERIA
We included randomised controlled trials (RCTs), quasi-RCTs, non-RCTs, and observational studies (e.g. before-and-after, interrupted-time-series) with quantitative outcomes. We excluded studies with only qualitative outcomes or that had no comparison (i.e. no control group or no within-group comparison) (e.g. single arm case series).
DATA COLLECTION AND ANALYSIS
Two review authors independently screened titles and abstracts of citations, and full text of potentially eligible studies. Two review authors independently carried out data extraction using standard data extraction forms. A third review author acted as arbiter for both stages. We carried out no meta-analyses due to insufficient data for pooling on any outcome; therefore, we reported outcomes narratively.
MAIN RESULTS
The searches resulted in 14 included studies, involving 4167 adults, of whom 1137 received palliative sedation. More than 95% of people had cancer. No studies were randomised or quasi-randomised. All were consecutive case series, with only three having prospective data collection. Risk of bias was high, due to lack of randomisation. No studies measured quality of life or participant well-being, which was the primary outcome of the review. Five studies measured symptom control, using four different methods, so pooling was not possible. The results demonstrated that despite sedation, delirium and dyspnoea were still troublesome symptoms in these people in the last few days of life. Control of other symptoms appeared to be similar in sedated and non-sedated people. Only one study measured unintended adverse effects of sedative drugs and found no major events; however, four of 70 participants appeared to have drug-induced delirium. The study noticed no respiratory suppression. Thirteen of the 14 studies measured survival time from admission or referral to death, and all demonstrated no statistically significant difference between sedated and non-sedated groups.
AUTHORS' CONCLUSIONS
There was insufficient evidence about the efficacy of palliative sedation in terms of a person's quality of life or symptom control. There was evidence that palliative sedation did not hasten death, which has been a concern of physicians and families in prescribing this treatment. However, this evidence comes from low quality studies, so should be interpreted with caution. Further studies that specifically measure the efficacy and quality of life in sedated people, compared with non-sedated people, and quantify adverse effects are required.
Topics: Adult; Conscious Sedation; Deep Sedation; Humans; Hypnotics and Sedatives; Palliative Care; Selection Bias; Terminal Care; Terminally Ill
PubMed: 25879099
DOI: 10.1002/14651858.CD010206.pub2 -
Journal of Geriatric Physical Therapy...A clinical practice guideline on physical therapist management of patients with suspected or confirmed osteoporosis was developed by a volunteer guideline development...
A clinical practice guideline on physical therapist management of patients with suspected or confirmed osteoporosis was developed by a volunteer guideline development group (GDG) that was appointed by the Academy of Geriatric Physical Therapy (APTA Geriatrics). The GDG consisted of an exercise physiologist and 6 physical therapists with clinical and methodological expertise. The guideline was based on a systematic review of existing clinical practice guidelines, followed by application of the ADAPTE methodological process described by Guidelines International Network for adapting guidelines for cultural and professional utility. The recommendations contained in this guideline are derived from the 2021 Scottish Intercollegiate Guideline Network (SIGN) document: Management of Osteoporosis and the Prevention of Fragility Fractures. These guidelines are intended to assist physical therapists practicing in the United States, and implementation in the context of the US health care system is discussed.
Topics: Aged; Exercise; Humans; Osteoporosis; Physical Therapists; Physical Therapy Modalities
PubMed: 35384943
DOI: 10.1519/JPT.0000000000000346 -
Journal of Bodywork and Movement... Jul 2023More than two-thirds of pregnant women experience low back pain during pregnancy. This condition increases with advancing pregnancy, interfering with work, daily... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
More than two-thirds of pregnant women experience low back pain during pregnancy. This condition increases with advancing pregnancy, interfering with work, daily activities and sleep.
OBJECTIVE
To assess the efficacy of the Pilates method in comparison to prenatal care on the control of lower back pain in pregnant women.
SEARCH METHODS
Electronic searches were carried out with no language or year of publication restriction in the databases Medline via Pubmed, Embase, CINAHL, LILACS, PEDro, and SPORTDiscus on 20 March 2021. The keywords "Pilates" and "Pregnancy" were applied and the search strategies, adapted to each databank.
SELECTION CRITERIA
Randomized clinical trials with pregnant women with muscle pain symptoms and Pilates as an intervention method in comparison to conventional prenatal care were considered.
DATA COLLECTION AND ANALYSIS
two review authors independently assessed trials for inclusion and risk of bias, extracted data and checked them for accuracy. The critical evaluation was done using the Risk of Bias tool assess the quality and GRADE to assess the certainty of evidence. We conducted a meta-analysis for the main outcome "pain".
RESULTS
through our searches, 687 papers were identified, but only two fulfilled the inclusion criteria and were included in this review. Only two studies compared Pilates with a control group without physical exercise for pain in the short term. In the meta-analysis, there was a significant difference for pain in the comparison between the Pilates group and the control group without exercise; the mean difference (MD) was -23.09 (95% CI), from -31.07 to -15.10, p = 0.001, for 65 individuals (33 in the Pilates group and 32 in the conventional group). Limitation found was the lack of blinding of therapists and participants and the small sample size of individual studies. In addition, no adverse effects were reported.
CONCLUSION
There is moderate-quality evidence that Pilates exercise may reduce pregnancy-related low-back pain more than usual prenatal or no exercise. Prospero registration number CRD42021223243.
Topics: Pregnancy; Female; Humans; Quality of Life; Low Back Pain; Exercise Therapy; Exercise Movement Techniques; Exercise
PubMed: 37330773
DOI: 10.1016/j.jbmt.2023.04.076 -
Childhood Obesity (Print) Mar 2020Childhood overweight and obesity are recognized as predictors of the risk of obesity in adulthood. The aim of this systematic literature review was to determine the...
Childhood overweight and obesity are recognized as predictors of the risk of obesity in adulthood. The aim of this systematic literature review was to determine the association between dietary pattern and obesity risk among children. Articles were selected from databases (Cochrane Library, Lilacs, Eric, Livivo, and PubMed/Medline), without limitations regarding language or date. Database-specific search terms included the key words "obesity," "diet," "dietary pattern," "childhood," "children," "adolescents," and relevant synonyms. The review included studies that reported the assessment of the dietary pattern in childhood and that correlated eating patterns with the obesity risk through cluster analysis (CA) and/or factor analysis and/or principal component analysis and presented odds ratios (ORs). The methodology of the selected studies was evaluated using the JBI Critical Appraisal Checklist for Analytical Cross-Sectional Studies. Owing to the heterogeneity among the assessments of the association of dietary patterns and obesity, the results are described narratively. Using a selection process in two phases, 16 articles were included. Fifteen studies used a cross-sectional design, and one case-control study. The included studies showed variation in sample size (range = 232 to 10,187 children/adolescents) and age (range = 1-19 years old). The studies reported between two and five dietary patterns each. The OR for the relationship between the dietary pattern and the risk of childhood obesity ranged from OR = 1.02; confidence interval (95% CI) (0.91-1.15) to OR = 3.55; 95% CI (1.80-7.03). In this study, the dietary patterns identified by the studies were given different names. The food intake patterns identified could, in most factor or CA studies, be categorized as (1) potentially obesogenic foods that increased risk of becoming overweight (including fatty cheeses, sugary drinks, processed foods, fast food, candies, snacks, cakes, animal products, whole milk, and refined grains) or (2) food classified as healthy with the weakest association with the risk of becoming overweight or obese (including low levels of sugar and fat and high levels of fruits, vegetables, whole grains, fish, nuts, legumes, and yogurt). Overall, the results indicated from most studies that a diet with a lower percentage of obesogenic foods should be effective in reducing the risk of developing obesity.
Topics: Adolescent; Child; Diet; Feeding Behavior; Humans; Pediatric Obesity; Risk Factors
PubMed: 31742427
DOI: 10.1089/chi.2019.0059 -
The Cochrane Database of Systematic... May 2018Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18... (Review)
Review
BACKGROUND
Persistent infection with high-risk human papillomaviruses (hrHPV) types is causally linked with the development of cervical precancer and cancer. HPV types 16 and 18 cause approximately 70% of cervical cancers worldwide.
OBJECTIVES
To evaluate the harms and protection of prophylactic human papillomaviruses (HPV) vaccines against cervical precancer and HPV16/18 infection in adolescent girls and women.
SEARCH METHODS
We searched MEDLINE, Cochrane Central Register of Controlled Trials (CENTRAL) and Embase (June 2017) for reports on effects from trials. We searched trial registries and company results' registers to identify unpublished data for mortality and serious adverse events.
SELECTION CRITERIA
Randomised controlled trials comparing efficacy and safety in females offered HPV vaccines with placebo (vaccine adjuvants or another control vaccine).
DATA COLLECTION AND ANALYSIS
We used Cochrane methodology and GRADE to rate the certainty of evidence for protection against cervical precancer (cervical intraepithelial neoplasia grade 2 and above [CIN2+], CIN grade 3 and above [CIN3+], and adenocarcinoma-in-situ [AIS]), and for harms. We distinguished between the effects of vaccines by participants' baseline HPV DNA status. The outcomes were precancer associated with vaccine HPV types and precancer irrespective of HPV type. Results are presented as risks in control and vaccination groups and risk ratios (RR) with 95% confidence intervals in brackets.
MAIN RESULTS
We included 26 trials (73,428 participants). Ten trials, with follow-up of 1.3 to 8 years, addressed protection against CIN/AIS. Vaccine safety was evaluated over a period of 6 months to 7 years in 23 studies. Studies were not large enough or of sufficient duration to evaluate cervical cancer outcomes. All but one of the trials was funded by the vaccine manufacturers. We judged most included trials to be at low risk of bias. Studies involved monovalent (N = 1), bivalent (N = 18), and quadrivalent vaccines (N = 7). Most women were under 26 years of age. Three trials recruited women aged 25 and over. We summarize the effects of vaccines in participants who had at least one immunisation.Efficacy endpoints by initial HPV DNA statushrHPV negativeHPV vaccines reduce CIN2+, CIN3+, AIS associated with HPV16/18 compared with placebo in adolescent girls and women aged 15 to 26. There is high-certainty evidence that vaccines lower CIN2+ from 164 to 2/10,000 (RR 0.01 (0 to 0.05)) and CIN3+ from 70 to 0/10,000 (RR 0.01 (0.00 to 0.10). There is moderate-certainty evidence that vaccines reduce the risk of AIS from 9 to 0/10,000 (RR 0.10 (0.01 to 0.82).HPV vaccines reduce the risk of any CIN2+ from 287 to 106/10,000 (RR 0.37 (0.25 to 0.55), high certainty) and probably reduce any AIS lesions from 10 to 0/10,000 (RR 0.1 (0.01 to 0.76), moderate certainty). The size of reduction in CIN3+ with vaccines differed between bivalent and quadrivalent vaccines (bivalent: RR 0.08 (0.03 to 0.23), high certainty; quadrivalent: RR 0.54 (0.36 to 0.82), moderate certainty). Data in older women were not available for this comparison.HPV16/18 negativeIn those aged 15 to 26 years, vaccines reduce CIN2+ associated with HPV16/18 from 113 to 6 /10,000 (RR 0.05 (0.03 to 0.10). In women 24 years or older the absolute and relative reduction in the risk of these lesions is smaller (from 45 to 14/10,000, (RR 0.30 (0.11 to 0.81), moderate certainty). HPV vaccines reduce the risk of CIN3+ and AIS associated with HPV16/18 in younger women (RR 0.05 (0.02 to 0.14), high certainty and RR 0.09 (0.01 to 0.72), moderate certainty, respectively). No trials in older women have measured these outcomes.Vaccines reduce any CIN2+ from 231 to 95/10,000, (RR 0.41 (0.32 to 0.52)) in younger women. No data are reported for more severe lesions.Regardless of HPV DNA statusIn younger women HPV vaccines reduce the risk of CIN2+ associated with HPV16/18 from 341 to 157/10,000 (RR 0.46 (0.37 to 0.57), high certainty). Similar reductions in risk were observed for CIN3+ associated with HPV16/18 (high certainty). The number of women with AIS associated with HPV16/18 is reduced from 14 to 5/10,000 with HPV vaccines (high certainty).HPV vaccines reduce any CIN2+ from 559 to 391/10,000 (RR 0.70 (0.58 to 0.85, high certainty) and any AIS from 17 to 5/10,000 (RR 0.32 (0.15 to 0.67), high certainty). The reduction in any CIN3+ differed by vaccine type (bivalent vaccine: RR 0.55 (0.43 to 0.71) and quadrivalent vaccine: RR 0.81 (0.69 to 0.96)).In women vaccinated at 24 to 45 years of age, there is moderate-certainty evidence that the risks of CIN2+ associated with HPV16/18 and any CIN2+ are similar between vaccinated and unvaccinated women (RR 0.74 (0.52 to 1.05) and RR 1.04 (0.83 to 1.30) respectively). No data are reported in this age group for CIN3+ or AIS.Adverse effectsThe risk of serious adverse events is similar between control and HPV vaccines in women of all ages (669 versus 656/10,000, RR 0.98 (0.92 to 1.05), high certainty). Mortality was 11/10,000 in control groups compared with 14/10,000 (9 to 22) with HPV vaccine (RR 1.29 [0.85 to 1.98]; low certainty). The number of deaths was low overall but there is a higher number of deaths in older women. No pattern in the cause or timing of death has been established.Pregnancy outcomesAmong those who became pregnant during the studies, we did not find an increased risk of miscarriage (1618 versus 1424/10,000, RR 0.88 (0.68 to 1.14), high certainty) or termination (931 versus 838/10,000 RR 0.90 (0.80 to 1.02), high certainty). The effects on congenital abnormalities and stillbirths are uncertain (RR 1.22 (0.88 to 1.69), moderate certainty and (RR 1.12 (0.68 to 1.83), moderate certainty, respectively).
AUTHORS' CONCLUSIONS
There is high-certainty evidence that HPV vaccines protect against cervical precancer in adolescent girls and young women aged 15 to 26. The effect is higher for lesions associated with HPV16/18 than for lesions irrespective of HPV type. The effect is greater in those who are negative for hrHPV or HPV16/18 DNA at enrolment than those unselected for HPV DNA status. There is moderate-certainty evidence that HPV vaccines reduce CIN2+ in older women who are HPV16/18 negative, but not when they are unselected by HPV DNA status.We did not find an increased risk of serious adverse effects. Although the number of deaths is low overall, there were more deaths among women older than 25 years who received the vaccine. The deaths reported in the studies have been judged not to be related to the vaccine. Increased risk of adverse pregnancy outcomes after HPV vaccination cannot be excluded, although the risk of miscarriage and termination are similar between trial arms. Long-term of follow-up is needed to monitor the impact on cervical cancer, occurrence of rare harms and pregnancy outcomes.
Topics: Adolescent; Adult; Female; Human papillomavirus 16; Human papillomavirus 18; Humans; Middle Aged; Papillomavirus Infections; Papillomavirus Vaccines; Precancerous Conditions; Pregnancy; Pregnancy Outcome; Randomized Controlled Trials as Topic; Uterine Cervical Neoplasms; Vaccination; Young Adult; Uterine Cervical Dysplasia
PubMed: 29740819
DOI: 10.1002/14651858.CD009069.pub3 -
BMC Psychiatry May 2021While clinical trial evidence has firmly established the efficacy of several atypical antipsychotics (AAPs) for treating bipolar depression, no randomized controlled... (Meta-Analysis)
Meta-Analysis
BACKGROUND
While clinical trial evidence has firmly established the efficacy of several atypical antipsychotics (AAPs) for treating bipolar depression, no randomized controlled trials (RCT's) comparing AAPs have been conducted. This Bayesian network meta-analysis (NMA) compared the relative efficacy and tolerability of AAP monotherapy in adults with bipolar depression.
METHODS
Efficacy measures included change in Montgomery Åsberg Depression Rating Scale (MADRS), Clinical Global Improvement - Bipolar Disorder (CGI-BP), response, and remission. Multiple tolerability outcomes were examined. Results from random effects models were reported as difference in change from baseline for continuous variables or odds ratios for dichotomous variables. Treatments were ranked using the surface under the curve cumulative ranking probabilities. Number needed to treat (NNT) and harm (NNH) were calculated.
RESULTS
Eighteen RCT's met inclusion criteria of the systematic literature review. On change in MADRS, lurasidone (- 4.71 [95% Crl - 6.98, - 2.41]), quetiapine (- 4.80 [- 5.93, - 3.72]), olanzapine (- 4.57 [- 5.92, - 3.20]), and cariprazine (- 2.29 [- 3.47, - 1.09]) were more efficacious than placebo. Lurasidone was associated with a significantly greater odds of response (≥50% improvement in MADRS) compared to cariprazine (1.78 [95% Crl 1.08, 2.77]), aripiprazole (2.38 [1.38, 3.85]), and ziprasidone (2.47 [1.41, 3.98]), but was similar to olanzapine (1.68 [0.99,2.65]) and quetiapine (1.25 [0.78, 1.90]). For change in CGI-BP-S-overall score, lurasidone was significantly better than cariprazine (- 0.38 [95% Crl - 0.66,-0.10]) and ziprasidone (- 0.58 [- 0.91,-0.26]), but similar to quetiapine (- 0.08 [- 0.36, 0.19])and olanzapine (- 0.04 [- 1.41, 1.46]). Lurasidone (0.34 kg [95% Crl - 0.22, 0.89]) and aripiprazole (0.20 kg [- 0.59, 1.00]) had a similar weight change compared to placebo, but olanzapine (2.88 kg [2.40, 3.36]), quetiapine (1.17 kg [0.84, 1.49]), and cariprazine (0.65 kg [0.34, 0.96]) were associated with greater weight gain. The NNT for response was the lowest for lurasidone (NNT = 5) followed by quetiapine (NNT = 6), olanzapine (NNT = 10) and cariprazine (NNT = 12).
CONCLUSIONS
In this NMA in adults with bipolar depression, which evaluated change in depressive symptoms (assessed by MADRS) across short-term trials, the largest improvement versus placebo was observed for lurasidone, olanzapine and quetiapine with cariprazine, showing a smaller treatment effect. Aripiprazole and ziprasidone were ineffective for the treatment of bipolar depression. Improvement in CGI-BP-S score for lurasidone was larger than cariprazine and ziprasidone but similar to quetiapine and olanzapine. Based on short term studies lurasidone and aripiprazole had similar weight gain compared to placebo.
Topics: Adult; Antipsychotic Agents; Bayes Theorem; Bipolar Disorder; Depression; Humans; Network Meta-Analysis; Quetiapine Fumarate; Treatment Outcome
PubMed: 33975574
DOI: 10.1186/s12888-021-03220-3