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Acta Diabetologica Aug 2015A variety of basal insulin preparations are used to treat patients with type 2 diabetes mellitus (T2DM). We aimed to summarize scientific evidence on relative efficacy... (Meta-Analysis)
Meta-Analysis Review
Systematic review and meta-analysis of randomized clinical trials comparing efficacy and safety outcomes of insulin glargine with NPH insulin, premixed insulin preparations or with insulin detemir in type 2 diabetes mellitus.
AIMS
A variety of basal insulin preparations are used to treat patients with type 2 diabetes mellitus (T2DM). We aimed to summarize scientific evidence on relative efficacy and safety of insulin glargine (IGlar) and other insulins in T2DM.
METHODS
A systematic review was carried out in major medical databases up to December 2012. Relevant studies compared efficacy and safety of IGlar, added to oral drugs (OAD) or/and in combination with bolus insulin, with protamine insulin (NPH) or premixed insulin (MIX) in the same regimen, as well as with insulin detemir (IDet), in T2DM. Target HbA1c level without hypoglycemic events was considered the primary endpoint.
RESULTS
Twenty eight RCTs involving 12,669 T2DM patients followed for 12-52 weeks were included in quantitative analysis. IGlar + OAD use was associated with higher probability of reaching target HbA1c level without hypoglycemia as compared to NPH + OAD (RR = 1.32 [1.09, 1.59]) or MIX without OAD (RR = 1.61 [1.22, 2.13]) and similar effect as IDet + OAD (RR = 1.07 [0.87, 1.33]) and MIX + OAD (RR = 1.09 [0.86, 1.38]). IGlar + OAD demonstrated significantly lower risk of symptomatic hypoglycemia as compared to NPH + OAD (RR = 0.89 [0.83, 0.96]), MIX + OAD (RR = 0.75 [0.68, 0.83]) and MIX without OAD(RR = 0.75 [0.68, 0.83]), but not with IDet + OAD (RR = 0.99 [0.90, 1.08]). In basal-bolus regimens, IGlar demonstrated similar proportion of T2DM patients achieving target HbA1c as compared to NPH (RR = 1.14 [0.91, 1.44]) but higher than MIX (RR = 1.26 [1.12, 1.42) or IDet (RR = 1.38 [1.11, 1.72]). The risk of severe hypoglycemia was lower in IGlar than in NPH (RR = 0.77 [0.63, 0.94]), with no differences in comparison with MIX (RR = 0.74 [0.46, 1.20]) and IDet (RR = 1.10 [0.54, 2.25]). IGlar + OAD has comparable safety profile to NPH, with less frequent adverse events leading to treatment discontinuation than MIX + OAD (RR = 0.41 [0.22, 0.76]) and IDet + OAD (RR = 0.40 [0.24, 0.69]). Also severe adverse reactions were less common for IGlar + OAD when compared to MIX + OAD (RR = 0.71 [0.52; 0.98]).
CONCLUSION
For the majority of examined efficacy and safety outcomes, IGlar use in T2DM patients was superior or non-inferior to the alternative insulin treatment options.
Topics: Diabetes Mellitus, Type 2; Drug Therapy, Combination; Glycated Hemoglobin; Humans; Hypoglycemia; Hypoglycemic Agents; Insulin; Insulin Detemir; Insulin Glargine; Insulin, Isophane; Insulin, Long-Acting; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 25585592
DOI: 10.1007/s00592-014-0698-4 -
BMJ Open Sep 2022Concepts of moral distress (MD) among physicians have evolved and extend beyond the notion of psychological distress caused by being in a situation in which one is...
BACKGROUND
Concepts of moral distress (MD) among physicians have evolved and extend beyond the notion of psychological distress caused by being in a situation in which one is constrained from acting on what one knows to be right. With many accounts involving complex personal, professional, legal, ethical and moral issues, we propose a review of current understanding of MD among physicians.
METHODS
A systematic evidence-based approach guided systematic scoping review is proposed to map the current concepts of MD among physicians published in PubMed, Embase, PsycINFO, Web of Science, SCOPUS, ERIC and Google Scholar databases. Concurrent and independent thematic and direct content analysis (split approach) was conducted on included articles to enhance the reliability and transparency of the process. The themes and categories identified were combined using the jigsaw perspective to create domains that form the framework of the discussion that follows.
RESULTS
A total of 30 156 abstracts were identified, 2473 full-text articles were reviewed and 128 articles were included. The five domains identified were as follows: (1) current concepts, (2) risk factors, (3) impact, (4) tools and (5) interventions.
CONCLUSIONS
Initial reviews suggest that MD involves conflicts within a physician's personal beliefs, values and principles (personal constructs) caused by personal, ethical, moral, contextual, professional and sociocultural factors. How these experiences are processed and reflected on and then integrated into the physician's personal constructs impacts their self-concepts of personhood and identity and can result in MD. The ring theory of personhood facilitates an appreciation of how new experiences create dissonance and resonance within personal constructs. These insights allow the forwarding of a new broader concept of MD and a personalised approach to assessing and treating MD. While further studies are required to test these findings, they offer a personalised means of supporting a physician's MD and preventing burn-out.
Topics: Humans; Reproducibility of Results; Physicians; Morals
PubMed: 36691160
DOI: 10.1136/bmjopen-2022-064029 -
Current Hypertension Reports Apr 2022To perform a narrative systematic review on refractory hypertension (RfHT) with particular emphasis on prognosis.
PURPOSE OF REVIEW
To perform a narrative systematic review on refractory hypertension (RfHT) with particular emphasis on prognosis.
RECENT FINDINGS
There were 37 articles on RfHT, 13 non-systematic reviews, and 24 original studies. RfHT, a recently described extreme phenotype of anti-hypertensive treatment failure, shall be defined as uncontrolled out-of-office blood pressure (BP) levels despite the use of at least 5 anti-hypertensive drugs, including a long-acting diuretic and a mineraloreceptor antagonist. Its prevalence ranges from 0.5 to 4.3% of general treated hypertensives and between 3.6 and 51.4% of patients with resistant hypertension (RHT). RfHT is associated with younger age, African ancestry, obesity, hypertension-mediated organ damage and clinical cardiovascular diseases, and with some comorbidities, such as diabetes and obstructive sleep apnea. Its physiopathological mechanisms probably involve sympathetic overactivity and not volume overload. Patients with RfHT have a worse prognosis than non-refractory RHT individuals, with higher risks of adverse cardiovascular and renal outcomes and of mortality. RfHT represents a rare but true extreme phenotype of anti-hypertensive treatment failure distinct from RHT and with a significantly worse prognosis. Identifying such individuals is important to tailor specific interventions.
Topics: Antihypertensive Agents; Blood Pressure; Diuretics; Humans; Hypertension; Prognosis
PubMed: 35107787
DOI: 10.1007/s11906-022-01165-w -
The Cochrane Database of Systematic... Apr 2006Penfluridol, available since 1970, is an unusual long acting oral antipsychotic agent for the treatment of schizophrenia. It may be considered a depot medication as it... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Penfluridol, available since 1970, is an unusual long acting oral antipsychotic agent for the treatment of schizophrenia. It may be considered a depot medication as it is administered once a week.
OBJECTIVES
To review the effects of penfluridol for treatment of those with schizophrenia and schizophrenia-like illnesses in comparison to placebo, other antipsychotic medication or no intervention.
SEARCH STRATEGY
We undertook electronic searches of the Cochrane Schizophrenia Group's Register (2005), the Cochrane Central Register of Controlled Trials (2003-5) and LILACS (1982-2005). We hand searched references of all identified studies and sought citations of these studies in the Science Citation Index. We contacted the authors of trials and the manufacturer of penfluridol.
SELECTION CRITERIA
We reliably selected all randomised clinical trials comparing penfluridol to placebo or typical or atypical antipsychotic drugs for schizophrenia or serious mental illness.
DATA COLLECTION AND ANALYSIS
We independently extracted and analysed data on an intention-to-treat basis. We calculated the relative risk (RR) and 95% confidence intervals (CI) of homogeneous dichotomous data using a random effects model, and where possible calculated the number needed to treat. We calculated weighted mean differences (WMD) for continuous data.
MAIN RESULTS
We included twenty-five studies with a total of 1024 participants. Most of these studies were undertaken in the 1970s when penfluridol was launched. Ten studies, with 365 patients, compared penfluridol to placebo. In the meta-analysis of medium-term lasting studies, penfluridol was superior to placebo in the main efficacy measures: 'improvement in global state' (n=159, 4 RCTs, RR 0.69 CI 0.6 to 0.8, NNT 3 CI 2 to 10) and 'needing additional antipsychotic' (n=138, 5 RCTs, RR 0.43 CI 0.2 to 0.8, NNT 3 CI 1.8 to 20).A total of 449 patients from eleven studies were randomised to penfluridol or oral typical antipsychotics. There were no particular differences between penfluridol versus chlorpromazine, fluphenazine, trifluoperazine, thioridazine, or thiothixene for the main outcome measures in medium-term trials: 'improvement on global state' (N=2 studies), 'leaving the study early' (N=6), 'needing additional antipsychotic' (N=3), needing antiparkinsonian medication (N=2), and side-effects. Six studies, with 274 patients, compared penfluridol to depot typical antipsychotics. In general, for the efficacy and safety measures, no differences were established, but penfluridol was superior in keeping the patients in treatment; 'leaving the study early' (n=218, 5RCTs, RR 0.55 CI 0.3 to 0.97, NNT 6 CI 3.4 to 50).
AUTHORS' CONCLUSIONS
Although there are shortcomings and gaps in the data, there appears to be enough overall consistency for different outcomes. The efficacy and adverse effects profile of penfluridol are similar to other typical antipsychotics; both oral and depot. Furthermore, penfluridol is shown to be an adequate treatment option for people with schizophrenia, especially those who do not respond to oral medication on a daily basis and do not adapt well to depot drugs. One of the results favouring penfluridol was a lower drop out rate in medium term when compared to depot medications. It is also an option for chronic sufferers of schizophrenia with residual psychotic symptoms who nevertheless need continuous use of antipsychotic medication. An additional benefit of penfluridol is that it is a low-cost intervention.
Topics: Antipsychotic Agents; Humans; Penfluridol; Randomized Controlled Trials as Topic; Schizophrenia
PubMed: 16625563
DOI: 10.1002/14651858.CD002923.pub2 -
Contraception Feb 2022The vaginal ring (ring) is a female-initiated, long-acting drug delivery system for different indications, including HIV prevention. Our aim was to provide evidence for... (Meta-Analysis)
Meta-Analysis
OBJECTIVE
The vaginal ring (ring) is a female-initiated, long-acting drug delivery system for different indications, including HIV prevention. Our aim was to provide evidence for acceptability of the vaginal ring across indications to support dapivirine and multipurpose prevention technology ring introduction and roll out.
STUDY DESIGN
This systematic review and meta-analysis followed PRISMA guidelines. We searched PubMed, Web of Science, Embase, and grey literature for publications reporting favorable ring acceptability and secondary outcomes involving actual ring use (comfort, ease of ring use, ring comfort during sex, expulsions, and vaginal symptoms) or hypothetical acceptability for any indication published January 1, 1970-June 15, 2021. We estimated random-effects pooled prevalence, assessing between-study variation using meta-regression.
RESULTS
Of 2,234 records, we included 123 studies with 40,434 actual and hypothetical ring users. The primary outcome assessment included 50 studies with 60 ring subgroups totaling 19,271 ring users. The favorable acceptability pooled prevalence was 85.6% (95%CI 81.3, 89.0), while hypothetical acceptability among non-ring users was 27.6% (95%CI 17.5, 40.5). In meta-regression, acceptability was higher in menopause (95.4%; 95%CI 88.4, 98.2) compared to contraceptive rings (83.7%; 95%CI 75.6, 89.5). Acceptability was lower in pharmacokinetic studies (50%; 95%CI 22.1, 77.9) compared to RCTs (89.5%; 95%CI 85.8.92.4) and in studies assessing acceptability at ≥12 months (78.5%; 95%CI 66.5, 87.1) versus studies assessing acceptability at <3 months (91.9%; 95%CI 83.7, 96.1). European (90.6%; 95%CI 83.9, 94.7), Asian (97.1%; 95%CI 92.0, 99.0), and multi-region studies (93.5%; 95%CI 84.6, 97.4) reported more favorable acceptability compared to African studies (59.4%; 95%CI 38.3, 77.5). Secondary outcomes were similarly favorable, including ring comfort (92.9%; 95%CI 89.2, 95.4), ease of use (90.9%; 95%CI 86.5, 94.0), and comfort during sex (82.7%; 95%CI 76.4, 87.6). Limitations include inconsistent outcome definitions and unmeasured factors affecting acceptability.
CONCLUSIONS
Women who used vaginal rings reported they were acceptable across indications geographic regions and indications. Policy makers should consider the ring as an important option for pregnancy and HIV prevention drug development.
IMPLICATIONS
This review found favorable acceptability among vaginal ring users across indications and geographic areas, in contrast to low hypothetical acceptability among non-users. Vaginal rings are an important drug delivery system for pregnancy and HIV preventions, and scale-up should plan to address initial hesitancy among new users.
Topics: Contraceptive Devices, Female; Female; Humans; Pregnancy; Vagina
PubMed: 34644609
DOI: 10.1016/j.contraception.2021.10.001 -
Journal of Affective Disorders Mar 2017The aim of this review was to assess whether suicide prevention provided in the primary health care setting and delivered by GPs results in fewer suicide deaths,... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The aim of this review was to assess whether suicide prevention provided in the primary health care setting and delivered by GPs results in fewer suicide deaths, episodes of self-harm, attempts and lower frequency of thoughts about suicide.
METHODS
We conducted a systematic review and meta-analysis using PRIMSA guidelines. Eligible studies: 1) evaluated an intervention provided by GPs; 2) assessed suicide, self-harm, attempted suicide or suicide ideation as outcomes, and; 3) used a quasi-experimental observational or trial design. Study specific effect sizes were combined using the random effects meta-analysis, with effects transformed into relative risk (RR).
RESULTS
We extracted data from 14 studies for quantitative meta-analysis. The RR for suicide death in quasi-experimental observational studies comparing an intervention region against another region acting as a "control" was 1.26 (95% CI 0.58, 2.74). When suicide in the intervention region was compared before and after the GP program, the RR was 0.78 (95% CI 0.62, 0.97). There was no evidence of a treatment effect for GP training on rates of suicide death in one cRCT (RR 1.07, 95% CI 0.79, 1.45). There was no evidence of effect for the most other outcomes studied.
LIMITATIONS
All of the studies included in this review are likely to have a high level of bias. It is also possible that we excluded or missed relevant studies in our review process CONCLUSIONS: Interventions have produced equivocal results, which varied by study design and outcome. Given these results, we cannot recommend the roll out of GP suicide prevention initiatives.
Topics: Family Practice; Humans; Primary Prevention; Psychotherapy; Self-Injurious Behavior; Suicidal Ideation; Suicide, Attempted; Suicide Prevention
PubMed: 28068618
DOI: 10.1016/j.jad.2016.12.035 -
Journal of Affective Disorders Oct 2017Cognitive symptoms in Major Depressive Disorder (MDD) are persistent and commonly entail neurocognitive impairment and a decline in quality of life. This systematic... (Review)
Review
BACKGROUND
Cognitive symptoms in Major Depressive Disorder (MDD) are persistent and commonly entail neurocognitive impairment and a decline in quality of life. This systematic review gathers the current scientific evidence on therapeutic strategies for neuropsychological impairment in MDD.
METHOD
A systematic search on PubMed, PsycINFO and Clinicaltrials.gov was carried out on December 2016 according to PRISMA using Boolean terms to identify interventions for the treatment of cognitive dysfunction in MDD. Only English-written articles providing original data and focusing in adults with MDD were included with no time restrictions.
RESULTS
A total of 95 studies reporting data on 40 pharmacological and non-pharmacological interventions were included. Interventions were grouped into the following categories: 1) Pharmacological Therapies (antidepressants, stimulants, compounds acting on NMDA receptors, compounds acting on the cholinergic system, compounds showing anti-inflammatory or antioxidant properties, other mechanisms of action), 2) Physical Therapies and 3) Psychological Therapies, 4) Exercise. There are some promising compounds showing a positive impact on cognitive symptoms including vortioxetine, lisdexamfetamine or erythropoietin.
LIMITATIONS
The studies included showed significant methodological differences in heterogeneous samples. The lack of a standardized neuropsychological battery makes comparisons between studies difficult.
CONCLUSION
Current evidence is not sufficient to widely recommend the use of procognitive treatments in MDD although promising results are coming to light.
Topics: Cognitive Dysfunction; Depressive Disorder, Major; Humans; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 28651185
DOI: 10.1016/j.jad.2017.06.034 -
Journal of Child Health Care : For... Apr 2024Adolescents face issues regarding physical health, mental health, sexual health, drug and alcohol problems, stress, and peer pressure. Little is known about adolescents'... (Review)
Review
Adolescents face issues regarding physical health, mental health, sexual health, drug and alcohol problems, stress, and peer pressure. Little is known about adolescents' help-seeking behaviours in relation to health concerns. The general practitioner (GP) is usually the first point of contact for adolescents. The aim of this systematic review was to identify, describe, and summarize evidence on barriers and enablers experienced by adolescents when accessing GP-led primary care services. Systematic searches using four electronic databases (PsycINFO, MEDLINE, CINAHL, and SocINDEX) were conducted and the quality of the included studies was appraised. Six studies were included in this review. Findings indicate that barriers to GP access relate to trust, confidentiality, privacy, and communication. Adolescents also reported barriers such as transport, cost, and lack of information. Adolescents reported enablers being services that are sensitive to their needs, healthcare professionals who understand them, and services that are flexible regarding out of hours access. Listening to and acting on the voice of adolescents is important to developing youth-friendly services.
PubMed: 38629615
DOI: 10.1177/13674935241239837 -
Gesundheitswesen (Bundesverband Der... 2010The aim of this systematic review was to analyse the effects of gatekeeping where primary care physicians (PCP) control access to specialist care. (Review)
Review
AIM
The aim of this systematic review was to analyse the effects of gatekeeping where primary care physicians (PCP) control access to specialist care.
METHODS
Literature search in Medline, EMBASE, Cochrane Library, and a hand search were carried out.
INCLUSION CRITERIA
(1) intervention: gatekeeping by PCP compared to free access to specialist care; (2) outcomes: health outcomes, health related quality of life, quality of care, utilization of care, costs, satisfaction of patients and providers; (3) design: RCT, quasi-random. CT, CBA, cohort and case control studies, ITS. Data extraction and assessment was done by two independent reviewers according to Cochrane EPOC-Group and USTFCPS.
RESULTS
24 included studies (1989-2007) were as follows: 1 RCT, 2 quasi-randomised CT, 3 prospective, and 12 retrospective cohort studies, 4 CBA, and 2 ITS. 67% of the studies analysed data from the USA, the remaining from CH, UK, DK and NL. Studies had relevant limitations concerning the quality of execution and publication. Overall 13 of 24 studies reported a positive and two a negative effect of gatekeeping compared to open access models; nine showed no differences. The results varied according to outcome parameters.
CONCLUSIONS
International evidence on effects of gatekeeping is limited by the low internal validity of studies and applicability to other contexts. It suggests that gatekeeping by PCP decreases utilization of specialist care and health care costs. Based on very few studies health outcomes and patient quality of life in gatekeeping models might be comparable with those in open access models. Evidence is inconsistent or not available concerning the quality of care, patient or provider satisfaction.
Topics: Cost Control; Economics, Medical; Gatekeeping; Germany; Health Care Costs; Medicine; Outcome Assessment, Health Care; Physician's Role; Physicians, Primary Care
PubMed: 19795341
DOI: 10.1055/s-0029-1234126 -
Health Technology Assessment... Sep 2007To review the clinical effectiveness and cost-effectiveness of a new technology, the inhaled insulin, Exubera (Pfizer and Sanofi-Aventis, in collaboration with Nektar... (Review)
Review
OBJECTIVES
To review the clinical effectiveness and cost-effectiveness of a new technology, the inhaled insulin, Exubera (Pfizer and Sanofi-Aventis, in collaboration with Nektar Therapeutics), a short-acting insulin.
DATA SOURCES
Electronic databases were searched up to November 2005.
REVIEW METHODS
A systematic literature review was conducted and economic modelling carried out. An industry model was used for modelling.
RESULTS
Nine trials of inhaled insulins were found, but only seven used the Exubera form of inhaled insulin. The other two used inhaled insulins that have not yet been licensed. There were five trials in type 1 and two in type 2 diabetes. Inhaled insulin is clinically effective, and is as good as short-acting soluble insulin in controlling blood glucose, plus it works slightly more quickly. None of the published trials compared it with short-acting analogues. Most patients in the trials were on combinations of short-acting, and either long- or intermediate-acting insulin, and both were changed, making it more difficult to assess the effects of only the change from soluble to inhaled insulin. Patient preference was the only significant difference between inhaled and soluble insulin in the trials. Most patients preferred inhaled to injected short-acting insulin, and this has some effect on quality of life measures. However, the control groups mostly used syringes and needles, rather than pens. As pens are more convenient, their use might have narrowed the patient satisfaction difference. There were no trials of inhaled insulin against continuous subcutaneous insulin infusion (CSII). No serious adverse experiences of inhaled insulin in the lung have been seen to date, but it is too soon yet to judge long-term effects. The manufacturer's model appears to be a high-quality one, although the results depend more on the assumptions fed into the model than on the model itself. The key assumptions are the size of the gain in quality of life utility from inhaling rather than injecting insulin, the effect of having an inhaled option on the willingness to start insulin among people with poor diabetic control on oral drugs, and the effect on glycaemic control. We consider that these assumptions make the cost-effectiveness appear better than it really would be. The manufacturer's submission assumed utility gains of 0.036-0.075 in patients with type 1 diabetes, and 0.027-0.067 in those with type 2, based on an unpublished utility elicitation study sponsored by the manufacturer. We thought that these gains were optimistic and that gains of 0.02 or less were more likely, on average. However, patients with particular problems with injection sites might have more to gain, although they might also be a group with much to gain from CSII. A key factor is the cost of inhaled insulin. Much more insulin has to be given by inhaler than by injection, and so the cost of inhaled insulin is much higher than injected. The extra cost depends on dosage but ranges from around 600 pounds to over 1000 pounds per patient per year.
CONCLUSIONS
The inhaled insulin, Exubera, appears to be as effective, but no better than injected short-acting insulin. The additional cost is so much more that it is unlikely to be cost-effective. The long-term safety is uncertain. Additional research is recommended into the safety, efficacy and cost-effectiveness of inhaled insulin.
Topics: Administration, Inhalation; Clinical Trials as Topic; Cost-Benefit Analysis; Diabetes Mellitus, Type 2; Humans; Hypoglycemic Agents; Insulin; Patient Satisfaction
PubMed: 17767897
DOI: 10.3310/hta11330