OBJECTIVE — To systematically review the incidence of posttransplantation diabetes (PTD), risk factors for its development, prognostic implications, and optimal management. RESEARCH DESIGN AND METHODS — We searched databases (MEDLINE, EMBASE, the Cochrane Library, and others) from inception to September 2000, reviewed bibliographies in reports retrieved, contacted transplantation experts, and reviewed specialty journals. Two reviewers independently determined report inclusion (original studies, in all languages, of PTD in adults with no history of diabetes before transplantation), assessed study methods, and extracted data using a standardized form. Meta-regression was used to explain between-study differences in incidence. RESULTS — Nineteen studies with 3,611 patients were included. The 12-month cumulative incidence of PTD is lower (10% in most studies) than it was 3 decades ago. The type of immunosuppression explained 74% of the variability in incidence (P 0.0004). Risk factors were patient age, nonwhite ethnicity, glucocorticoid treatment for rejection, and immunosuppression with high-dose cyclosporine and tacrolimus. PTD was associated with decreased graft and patient survival in earlier studies; later studies showed improved outcomes. Randomized trials of treatment regimens have not been conducted. CONCLUSIONS — Physicians should consider modification of immunosuppressive regimens to decrease the risk of PTD in high-risk transplant recipients. Randomized trials are needed to evaluate the use of oral glucose-lowering agents in transplant recipients, paying particular attention to interactions with immunosuppressive drugs. Diabetes Care 25:583–592, 2002

A systematic review of the literature

Objective: To systematically evaluate the published evidence regarding the characteristics and effectiveness of disease management programmes. Design: Meta-analysis. Data sources:Computerised databases for English language articles during 1987-2001. Study selection: 102 articles evaluating 118 disease management programmes. Main outcome measures: Pooled effect sizes calculated with a random effects model. Results: Patient education was the most commonly used intervention (92/118 programmes), followed by education of healthcare providers (47/118) and provider feedback (32/118). Most programmes (70/118) used more than one intervention. Provider education, feedback, and reminders were associated with significant improvements in provider adherence to guidelines (effect sizes (95% confidence intervals) 0.44 (0.19 to 0.68), 0.61 (0.28 to 0.93), and 0.52 (0.35 to 0.69) respectively) and with significant improvements in patient disease control (effect sizes 0.35 (0.19 to 0.51), 0.17 (0.10 to 0.25), and 0.22 (0.1 to 0.37) respectively). Patient education, reminders, and financial incentives were all associated with improvements in patient disease control (effect sizes 0.24 (0.07 to 0.40), 0.27 (0.17 to 0.36), and 0.40 (0.26 to 0.54) respectively). Conclusions: All studied interventions were associated with improvements in provider adherence to practice guidelines and disease control. The type and number of interventions varied greatly, and future studies should directly compare different types of intervention to find the most effective.

https://www.bmj.com/content/bmj/325/7370/925.full.pdf

Interventions used in disease management programmes for patients with chronic illness-which ones work? Meta-analysis of published reports.

Background
Patients with high blood pressure (hypertension) in the community frequently fail to meet treatment goals - a condition labelled as "uncontrolled" hypertension. The optimal way to organize and deliver care to hypertensive patients has not been clearly identified.

Objectives
To determine the effectiveness of interventions to improve control of blood pressure in patients with hypertension. To evaluate the effectiveness of reminders on improving the follow-up of patients with hypertension.

Search methods
All-language search of all articles (any year) in the Cochrane Controlled Trials Register (CCTR) and Medline; and Embase from January 1980.

Selection criteria
Randomized controlled trials (RCTs) of patients with hypertension that evaluated the following interventions: 
(1) self-monitoring 
(2) educational interventions directed to the patient 
(3) educational interventions directed to the health professional 
(4) health professional (nurse or pharmacist) led care 
(5) organisational interventions that aimed to improve the delivery of care 
(6) appointment reminder systems

Outcomes assessed were: 
(1) mean systolic and diastolic blood pressure 
(2) control of blood pressure 
(3) proportion of patients followed up at clinic

Data collection and analysis
Two authors extracted data independently and in duplicate and assessed each study according to the criteria outlined by the Cochrane Handbook.

Main results
72 RCTs met our inclusion criteria. The methodological quality of included studies varied. An organized system of regular review allied to vigorous antihypertensive drug therapy was shown to reduce systolic blood pressure (weighted mean difference (WMD) -8.0 mmHg, 95% CI: -8.8 to -7.2 mmHg) and diastolic blood pressure (WMD -4.3 mmHg, 95% CI: -4.7 to -3.9 mmHg) for three strata of entry blood pressure, and all-cause mortality at five years follow-up (6.4% versus 7.8%, difference 1.4%) in a single large RCT- the Hypertension Detection and Follow-Up study. Other interventions had variable effects. Self-monitoring was associated with moderate net reduction in systolic blood pressure (WMD -2.5 mmHg, 95% CI: -3.7 to -1.3 mmHg) and diastolic blood pressure (WMD -1.8 mmHg, 95% CI: -2.4 to -1.2 mmHg). RCTs of educational interventions directed at patients or health professionals were heterogeneous but appeared unlikely to be associated with large net reductions in blood pressure by themselves. Nurse or pharmacist led care may be a promising way forward, with the majority of RCTs being associated with improved blood pressure control and mean SBP and DBP but these interventions require further evaluation. Appointment reminder systems also require further evaluation due to heterogeneity and small trial numbers, but the majority of trials increased the proportion of individuals who attended for follow-up (odds ratio 0.41, 95% CI 0.32 to 0.51) and in two small trials also led to improved blood pressure control, odds ratio favouring intervention 0.54 (95% CI 0.41 to 0.73).

Authors' conclusions
Family practices and community-based clinics need to have an organized system of regular follow-up and review of their hypertensive patients. Antihypertensive drug therapy should be implemented by means of a vigorous stepped care approach when patients do not reach target blood pressure levels. Self-monitoring and appointment reminders may be useful adjuncts to the above strategies to improve blood pressure control but require further evaluation.

Interventions used to improve control of blood pressure in patients with hypertension.

Background Suboptimum medication adherence is common in the United States and leads to serious negative health consequences but may respond to intervention. Purpose To assess the comparative effectiveness of patient, provider, systems, and policy interventions that aim to improve medication adherence for chronic health conditions in the United States. Data sources Eligible peer-reviewed publications from MEDLINE and the Cochrane Library indexed through 4 June 2012 and additional studies from reference lists and technical experts. Study selection Randomized, controlled trials of patient, provider, or systems interventions to improve adherence to long-term medications and nonrandomized studies of policy interventions to improve medication adherence. Data extraction Two investigators independently selected, extracted data from, and rated the risk of bias of relevant studies. Data synthesis The evidence was synthesized separately for each clinical condition; within each condition, the type of intervention was synthesized. Two reviewers graded the strength of evidence by using established criteria. From 4124 eligible abstracts, 62 trials of patient-, provider-, or systems-level interventions evaluated 18 types of interventions; another 4 observational studies and 1 trial of policy interventions evaluated the effect of reduced medication copayments or improved prescription drug coverage. Clinical conditions amenable to multiple approaches to improving adherence include hypertension, heart failure, depression, and asthma. Interventions that improve adherence across multiple clinical conditions include policy interventions to reduce copayments or improve prescription drug coverage, systems interventions to offer case management, and patient-level educational interventions with behavioral support. Limitations Studies were limited to adults with chronic conditions (excluding HIV, AIDS, severe mental illness, and substance abuse) in the United States. Clinical and methodological heterogeneity hindered quantitative data pooling. Conclusion Reduced out-of-pocket expenses, case management, and patient education with behavioral support all improved medication adherence for more than 1 condition. Evidence is limited on whether these approaches are broadly applicable or affect longterm medication adherence and health outcomes. Primary funding source Agency for Healthcare Research and Quality.

Interventions to improve adherence to self-administered medications for chronic diseases in the United States: a systematic review

Background
Self management interventions help patients with chronic obstructive pulmonary disease (COPD) acquire and practise the skills they need to carry out disease-specific medical regimens, guide changes in health behaviour and provide emotional support to enable patients to control their disease. Since the first update of this review in 2007, several studies have been published. The results of the second update are reported here.

Objectives
1. To evaluate whether self management interventions in COPD lead to improved health outcomes.

2. To evaluate whether self management interventions in COPD lead to reduced healthcare utilisation.

Search methods
We searched the Cochrane Airways Group Specialised Register of trials (current to August 2011).

Selection criteria
Controlled trials (randomised and non-randomised) published after 1994, assessing the efficacy of self management interventions for individuals with COPD, were included. Interventions with fewer than two contact moments between study participants and healthcare providers were excluded.

Data collection and analysis
Two review authors independently assessed trial quality and extracted data. Investigators were contacted to ask for additional information. When appropriate, study results were pooled using a random-effects model. The primary outcomes of the review were health-related quality of life (HRQoL) and number of hospital admissions.

Main results
Twenty-nine studies were included. Twenty-three studies on 3189 participants compared self management versus usual care; six studies on 499 participants compared different components of self management on a head-to-head basis. Although we included non-randomised controlled clinical trials as well as RCTs in this review, we restricted the primary analysis to RCTs only and reported these trials in the abstract.

In the 23 studies with a usual care control group, follow-up time ranged from two to 24 months. The content of the interventions was diverse. A statistically relevant effect of self management on HRQoL was found (St George's Respiratory Questionnaire (SGRQ) total score, mean difference (MD) -3.51, 95% confidence interval (CI) -5.37 to -1.65, 10 studies, 1413 participants, moderate-quality evidence). Self management also led to a lower probability of respiratory-related hospitalisations (odds ratio (OR) 0.57, 95% CI 0.43 to 0.75, nine studies, 1749 participants, moderate-quality evidence) and all cause hospitalisations (OR 0.60; 95% CI 0.40 to 0.89, 6 studies, 1365 participants, moderate-quality evidence). Over one year of follow-up, eight (95% CI 5 to 14) participants with a high baseline risk of respiratory-related hospital admission needed to be treated to prevent one participant with at least one hospital admission, and 20 (95% CI 15 to 35) participants with a low baseline risk of hospitalisation needed to be treated to prevent one participant with at least one respiratory-related hospital admission.

No statistically significant effect of self management on mortality (OR 0.79, 95% CI 0.58 to 1.07, 8 studies, 2134 participants, very low-quality evidence) was detected. Also, dyspnoea measured by the (modified) Medical Research Council Scale ((m)MRC) was reduced in individuals who participated in self management (MD -0.83, 95% CI -1.36 to -0.30, 3 studies, 119 participants, low-quality evidence). The difference in exercise capacity as measured by the six-minute walking test was not statistically significant (MD 33.69 m, 95% CI -9.12 to 76.50, 6 studies, 570 participants, very low-quality evidence). Subgroup analyses depending on the use of an exercise programme as part of the intervention revealed no statistically significant differences between studies with and without exercise programmes in our primary outcomes of HRQoL and respiratory-related hospital admissions.

We were unable to pool head-to-head trials because of heterogeneity among interventions and controls; thus results are presented narratively within the review.

Authors' conclusions
Self management interventions in patients with COPD are associated with improved health-related quality of life as measured by the SGRQ, a reduction in respiratory-related and all cause hospital admissions, and improvement in dyspnoea as measured by the (m)MRC. No statistically significant differences were found in other outcome parameters. However, heterogeneity among interventions, study populations, follow-up time and outcome measures makes it difficult to formulate clear recommendations regarding the most effective form and content of self management in COPD.

Self management for patients with chronic obstructive pulmonary disease

Objective To evaluate the impact of pharmaceutical care on selected clinical and economic outcomes in patients with hypertension chronic obstructive pulmonary disease (COPD) in ambulatory care settings. Design Clinic patients with hypertension or COPD were radomly assigned to a treatment group (pharmaceutical care) or a control group (traditional pharmacy care) over a six·month period. Clircal pharmacists and pharmacy residents conducted the protocols. There were 133 evaluable patients (63 treatment and 70 control) in the hypertension study arm and 98 evaluable patients (43 treatment and 55 control) in the COPD study arm. Setting 10 Departments of Veerans Affairs medical centers and 1 academic medical center. Interventions Patient-centered pharmaceutical care model (employing stadardized care) implemented by clinical pharmacy residents. Main Outcome Measures Patient knowledge, medication compliance, and health resource use. Results The hypertension treatment group had a significantly greater reduction in systolic blood pressure from visit 1 to visit 5 than did the control group. In the COPD study arm, trends were positive in the treatment group for patient ratings of symptom interference with activities and dyspnea measures. There was a significant difference between the hypertension treatment and control group for compliance. There were no significant changes in compliance scores in the COPD study arm. Mean number of hospitalization and other health care provider visits was higher for the hypertension control group. For patients with COPD, hospitalizations increased in the control group, and the number of other health care provider visits was higher in the control group. Conclusion Pharmacists' participation in a pharmaceutical care program resulted in disease state improvement in ambulatory patients with hypertension and COPD.

Part 2. Clinical and Economic Outcomes in the Hypertension and COPD Arms of a Multicenter Outcomes Study

Objective To evaluate the effects of pharmaceutical care on selected humanistic outcomes in patients with hypertension or chronic obstructive pulmonary disease (COPD). Design Clinic patients with hypertension or COPD were randomly assigned to a treatment group (pharmaceutical care) or a control group (traditional pharmacy care) over a six-month period. Clinical pharmacists and pharmacy residents conducted the protocols. There were 133 evaluable patients (63 treatment, 70 control) in the hypertension study arm and 98 evaluable patients (43 treatment, 55 control) in the COPD study arm. The Pharmaceutical Care Questionnaire evaluated patient satisfaction with care. Tests specific to the disease states assessed disease and disease management knowledge. Quality of life (QOL) was evaluated using the Health Status Questionnaire 2.0 (HSQ 2.0) in the COPD arm; in the hypertension arm, the Hypertension/Lipid TyPE Specification Form 5.1 was used. Setting Ambulatory care centers of 10 Department of Veterans Affairs (DVA) medical centers and 1 university medical center. Interventions Patient-centered pharmaceutical care model (employing standardized care) implemented by clinical pharmacy residents. Main Outcome Measures Satisfaction with pharmaceutical care, disease and disease management knowledge, and QOL. Results Statistically significant differences in most satisfaction items were found, with treatment patients expressing greater satisfaction. Treatment groups in both arms strongly agreed that pharmacists helped them with confidence in use of their medication and understanding of their illness, gave complete explanations about their medications, made them feel that their care was a priority, and followed up on their questions and concerns. In the hypertension arm, treatment patients demonstrated significant increases in knowledge scores. Trends in QOL were positive for both hypertension groups, with a significant decrease found in number of treatment patients reporting problems with sexual function. In the COPD arm, improvement trends were significantly stronger for treatment patients. Conclusion Although patients were not dissatisfied with traditional pharmacy care, they were more satisfied overall with the pharmaceutical care model.

Part 3. Humanistic Outcomes in the Hypertension and COPD Arms of a Multicenter Outcomes Study

Objectives To: (1) develop a pharmaceutical care multicenter outcomes research project using clinical pharmacy residents and preceptors; (2) develop two research protocols to document pharmacists' impact on clinical, economic, and humanistic outcomes of therapy; (3) develop and implement a data collection process and methodology for outcomes research; (4) evaluate the effectiveness of the multicenter outcomes research process; and (5) prepare clinical pharmacy preceptors and residents to conduct outcomes research. Design and Setting Two research protocols were developed, each a randomized, parallel, open-label evaluation of patients at 10 Department of Veterans Affairs and 1 university medical center. One protocol focused on patients with chronic obstructive pulmonary disease (COPD) and the other on patients with hypertension. The study evaluated pharmacists' management of these two patient groups. Patients and Other Participants 133 patients with hypertension and 98 patients with COPD; 33 pharmacy directors and preceptors; 45 pharmacy residents. Main Outcome Measures Clinical, economic, and humanistic outcomes of pharmacists' interventions. The processes of developing a multicenter outcomes study were evaluated, including the data collection process. Results The two study protocols and an educational program for study participants were developed. A data collection process was developed and implemented, with the paper process being successful and the computer data collection process not implemented due to time constraints. Overall, the multicenter outcomes research process was successful. Conclusion The study provides a framework of processes and sites for the future development of other outcomes research studies. Clinical, economic, and humanistic outcomes are reported in Parts 2 and 3.

James M. Holt

Papers

Part 2. Clinical and Economic Outcomes in the Hypertension and COPD Arms of a Multicenter Outcomes Study

Part 3. Humanistic Outcomes in the Hypertension and COPD Arms of a Multicenter Outcomes Study

Part 1. Development, Implementation, and Evaluation of a Multicenter Pharmaceutical Care Outcomes Study