Canagliflozin and Cardiovascular and Renal Outcomes in Type 2 Diabetes Mellitus and Chronic Kidney Disease in Primary and Secondary Cardiovascular Prevention Groups

Background: Canagliflozin reduces the risk of kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, but effects on specific cardiovascular outcomes are uncertain, as are effects in people without previous cardiovascular disease (primary prevention). Methods: In CREDENCE (Canagliflozin and Renal Events in Diabetes With Established Nephropathy Clinical Evaluation), 4401 participants with type 2 diabetes mellitus and chronic kidney disease were randomly assigned to canagliflozin or placebo on a background of optimized standard of care. Results: Primary prevention participants (n=2181, 49.6%) were younger (61 versus 65 years), were more often female (37% versus 31%), and had shorter duration of diabetes mellitus (15 years versus 16 years) compared with secondary prevention participants (n=2220, 50.4%). Canagliflozin reduced the risk of major cardiovascular events overall (hazard ratio [HR], 0.80 [95% CI, 0.67-0.95]; P=0.01), with consistent reductions in both the primary (HR, 0.68 [95% CI, 0.49-0.94]) and secondary (HR, 0.85 [95% CI, 0.69-1.06]) prevention groups (P for interaction=0.25). Effects were also similar for the components of the composite including cardiovascular death (HR, 0.78 [95% CI, 0.61-1.00]), nonfatal myocardial infarction (HR, 0.81 [95% CI, 0.59-1.10]), and nonfatal stroke (HR, 0.80 [95% CI, 0.56-1.15]). The risk of the primary composite renal outcome and the composite of cardiovascular death or hospitalization for heart failure were also consistently reduced in both the primary and secondary prevention groups (P for interaction >0.5 for each outcome). Conclusions: Canagliflozin significantly reduced major cardiovascular events and kidney failure in patients with type 2 diabetes mellitus and chronic kidney disease, including in participants who did not have previous cardiovascular disease

Canagliflozin and renal outcomes in type 2 diabetes and nephropathy

BACKGROUND Type 2 diabetes mellitus is the leading cause of kidney failure worldwide, but few effective long-term treatments are available. In cardiovascular trials of inhibitors of sodium–glucose cotransporter 2 (SGLT2), exploratory results have suggested that such drugs may improve renal outcomes in patients with type 2 diabetes. METHODS In this double-blind, randomized trial, we assigned patients with type 2 diabetes and albuminuric chronic kidney disease to receive canagliflozin, an oral SGLT2 inhibitor, at a dose of 100 mg daily or placebo. All the patients had an estimated glomerular filtration rate (GFR) of 30 to <90 ml per minute per 1.73 m2 of body-surface area and albuminuria (ratio of albumin [mg] to creatinine [g], >300 to 5000) and were treated with renin–angiotensin system blockade. The primary outcome was a composite of end-stage kidney disease (dialysis, transplantation, or a sustained estimated GFR of <15 ml per minute per 1.73 m2), a doubling of the serum creatinine level, or death from renal or cardiovascular causes. Prespecified secondary outcomes were tested hierarchically. RESULTS The trial was stopped early after a planned interim analysis on the recommendation of the data and safety monitoring committee. At that time, 4401 patients had undergone randomization, with a median follow-up of 2.62 years. The relative risk of the primary outcome was 30% lower in the canagliflozin group than in the placebo group, with event rates of 43.2 and 61.2 per 1000 patient-years, respectively (hazard ratio, 0.70; 95% confidence interval [CI], 0.59 to 0.82; P=0.00001). The relative risk of the renal-specific composite of end-stage kidney disease, a doubling of the creatinine level, or death from renal causes was lower by 34% (hazard ratio, 0.66; 95% CI, 0.53 to 0.81; P<0.001), and the relative risk of end-stage kidney disease was lower by 32% (hazard ratio, 0.68; 95% CI, 0.54 to 0.86; P=0.002). The canagliflozin group also had a lower risk of cardiovascular death, myocardial infarction, or stroke (hazard ratio, 0.80; 95% CI, 0.67 to 0.95; P=0.01) and hospitalization for heart failure (hazard ratio, 0.61; 95% CI, 0.47 to 0.80; P<0.001). There were no significant differences in rates of amputation or fracture. CONCLUSIONS In patients with type 2 diabetes and kidney disease, the risk of kidney failure and cardiovascular events was lower in the canagliflozin group than in the placebo group at a median follow-up of 2.62 years

Family Caregiver Perspectives on Caring for Ventilator-Assisted Individuals at Home

BACKGROUND: The trend of patients who are invasively ventilated to prefer home care is one that benefits both the patient and the health care system. However, this assumes a role for patients’ family members to become informal caregivers.OBJECTIVE: To explore the impact of caring for a ventilator-assisted individual on informal caregivers.METHODS: A descriptive design with semistructured caregiver interviews and the Caregiver Burden Inventory were used. Participants were informal caregivers of a family member with a progressive neuromuscular disease on invasive ventilation for at least six months. Transcript coding was performed and regularly reviewed, and recruitment continued until data saturation. Qualitative analysis was based on ‘thematic analysis’.RESULTS: A total of 21 caregivers were interviewed. Five themes developed: a sense of duty; restriction of day-to-day life; physical and emotional burden; training and education; and the need for more paid support. Caregivers described a sense of duty to take care of loved ones, but suffered a significant restriction of their own time with a negative impact on their physical and mental health. The initial transfer home was highlighted as the most stressful part of the process. The Caregiver Burden Inventory scores supported a high level of burden: median 49 (interquartile range 39.5 to 53.0) of a maximum 96.CONCLUSION: Homecare for ventilator-assisted individuals with progressive neuromuscular disease causes significant burden to informal care-givers. Approaches to lessen this burden, such as increased paid care, improved professional support and respite care, may enable home ventilation to be a more sustainable modality of care.Peer Reviewe

Long Term Follow-up of Ventilated Patients with Thoracic Restriction and Neuromuscular Disease

OBJECTIVE: To evaluate the long term effects of home mechanical ventilation (HMV) on pulmonary function, nighttime gas exchange, daytime arterial blood gases, sleep architecture and functional exercise capacity (6 min walk). Patients with respiratory failure attributable to thoracic restrictive disease (TRD) (kyphoscoliosis) or neuromuscular disease (NMD) were assessed, ventilated, trained and followed in a dedicated unit for the care of patients requiring long term ventilation.DESIGN: All patients admitted for home ventilation training since 1988 were reviewed. Measurements of lung function, gas exchange during wakefulness and sleep, as well as functional exercise capacity, were recorded before and immediately after the establishment of HMV. Measurements were repeated one to two years, five years and eight to 10 years later.PATIENTS: Seventy-four individuals with TRD or NMD who completed the home ventilation training program and continued with HMV during all or part of the day for at least one year were studied.RESULTS: Forty patients had TRD. The characteristics of these patients were (mean ± SE) as follows: age 58±2.4 years; vital capacity (VC) 27%±1.6% predicted, forced expiratory volume in 1 s (FEV1) 25%±1.5% predicted; FEV1/forced VC (FVC) 78%±1.8%. Thirty-four patients had NMD. The characteristics of these patients were as follows: age 44±3.1 years; VC 41%±4.9% predicted, FEV1 44±5.3% predicted; FEV1/FVC 83%±4.2%. There was a significant improvement in distance walked in 6 min (maximum change 51.2 m in patients with NMD and 93.0 m in patients with TRD), daytime partial pressure of arterial carbon dioxide (maximum change 12.9 mmHg in patients with NMD and 10.4 mmHg in patients with TRD) and nighttime partial pressure of arterial carbon dioxide (maximum change 11.7 mmHg in patients with NMD and 18.0 mmHg in patients with TRD) over time (P≤0.004). Ventilation resulted in an improvement in partial pressure of arterial oxygen in patients with TRD (68.1±2.8 mmHg to 80.1±3.5 mmHg) and in patients with NMD (52.9±1.7 mmHg to 65.3±2.1 mmHg), although the change was not statistically significant in patients with NMD (P=0.001 in patients with TRD; P=0.105 in patients with NMD). The improvement after ventilation was maintained over several years. Sleep efficiency (75%±18%, 79%±2.2%), the arousal index (13.4±13 events/h, 28.2±17 events/h) and the apnea-hypopnea index (10.1±11.3 events/h, 13.9±9.5 events/h) did not change with time in either patients with TRD or patients with NMD, respectively (P≥0.5).CONCLUSIONS: HMV was associated with sustained, long term improvements in nighttime and daytime gas exchange in patients with TRD and NMD. Function exercise capacity increased in patients with TRD and in a subgroup of ambulatory patients with NMD. In patients with TRD, these improvements were maintained for up to 10 years after HMV was established.Peer Reviewe

Long Term Follow-up of Ventilated Patients with Thoracic Restriction and Neuromuscular Disease

OBJECTIVE: To evaluate the long term effects of home mechanical ventilation (HMV) on pulmonary function, nighttime gas exchange, daytime arterial blood gases, sleep architecture and functional exercise capacity (6 min walk). Patients with respiratory failure attributable to thoracic restrictive disease (TRD) (kyphoscoliosis) or neuromuscular disease (NMD) were assessed, ventilated, trained and followed in a dedicated unit for the care of patients requiring long term ventilation

Institutional Care for Long-Term Mechanical Ventilation in Canada: A National Survey

INTRODUCTION: No national Canadian data define resource requirements and care delivery for ventilator-assisted individuals (VAIs) requiring long-term institutional care. Such data will assist in planning health care services to this population

Institutional Care for Long-Term Mechanical Ventilation in Canada: A National Survey

INTRODUCTION: No national Canadian data define resource requirements and care delivery for ventilator-assisted individuals (VAIs) requiring long-term institutional care. Such data will assist in planning health care services to this population.OBJECTIVE: To describe institutional and patient characteristics, prevalence, equipment used, care elements and admission barriers for VAIs requiring long-term institutional care.METHODS: Centres were identified from a national inventory and snowball referrals. The survey weblink was provided from December 2012 to April 2013. Weekly reminders were sent for six weeks.RESULTS: The response rate was 84% (54 of 64), with 44 adult and 10 pediatric centres providing data for 428 VAIs (301 invasive ventilation; 127 noninvasive ventilation [NIV]), equivalent to 1.3 VAIs per 100,000 population. An additional 106 VAIs were on wait lists in 18 centres. More VAIs with progressive neuromuscular disease received invasive ventilation than NIV (Pud_less_than0.001); more VAIs with chronic obstructive pulmonary disease (Pud_less_than0.001), obesity hypoventilation syndrome (Pud_less_than0.001) and central hypoventilation syndrome (P=0.02) required NIV. All centres used positive pressure ventilators, 21% diaphragmatic pacing, 15% negative pressure and 13% phrenic nerve stimulation. Most centres used lung volume recruitment (55%), manually (71%) and mechanically assisted cough (55%). Lack of beds and provincial funding were common admission barriers.CONCLUSIONS: Variable models and care practices exist for institutionalized care of Canadian VAIs. Patient prevalence was 1.3 per 100,000 Canadians.Peer Reviewe

Multidrug-Resistant Tuberculosis: Treatment and Outcomes of 93 Patients

BACKGROUND: Tuberculosis (TB) remains a leading cause of death worldwide and the emergence of multidrug-resistant TB (MDR TB) poses a threat to its control. There is scanty evidence regarding optimal management of MDR TB. The majority of Canadian cases of MDR TB are diagnosed in Ontario; most are managed by the Tuberculosis Service at West Park Healthcare Centre in Toronto. The authors reviewed 93 cases of MDR TB admitted from January 1, 2000 to December 31, 2011.RESULTS: Eighty-nine patients were foreign born. Fifty-six percent had a previous diagnosis of TB and most (70%) had only pulmonary involvement. Symptoms included productive cough, weight loss, fever and malaise. The average length of inpatient stay was 126 days. All patients had a peripherally inserted central catheter for the intensive treatment phase because medications were given intravenously. Treatment lasted for 24 months after bacteriologic conversion, and included a mean (± SD) of 5±1 drugs. A successful outcome at the end of treatment was observed in 84% of patients. Bacteriological conversion was achieved in 98% of patients with initial positive sputum cultures; conversion occurred by four months in 91%.CONCLUSIONS: MDR TB can be controlled with the available anti-TB drugs.Peer Reviewe