Face shape of unaffected parents with cleft affected offspring: combining three‐dimensional surface imaging and geometric morphometrics

Authors – Weinberg SM, Naidoo SD, Bardi KM, Brandon CA, Neiswanger K, Resick JM, Martin RA, Marazita ML Objective – Various lines of evidence suggest that face shape may be a predisposing factor for non‐syndromic cleft lip with or without cleft palate (CL/P). In the present study, 3D surface imaging and statistical shape analysis were used to evaluate face shape differences between the unaffected (non‐cleft) parents of individuals with CL / P and unrelated controls. Methods – Sixteen facial landmarks were collected from 3D captures of 80 unaffected parents and 80 matched controls. Prior to analysis, each unaffected parent was assigned to a subgroup on the basis of prior family history (positive or negative). A geometric morphometric approach was utilized to scale and superimpose the landmark coordinate data (Procrustes analysis), test for omnibus group differences in face shape, and uncover specific modes of shape variation capable of discriminating unaffected parents from controls. Results – Significant disparity in face shape was observed between unaffected parents and controls (p < 0.01). Notably, these changes were specific to parents with a positive family history of CL / P. Shape changes associated with CL / P predisposition included marked flattening of the facial profile (midface retrusion), reduced upper facial height, increased lower facial height, and excess interorbital width. Additionally, a sex‐specific pattern of parent‐control difference was evident in the transverse dimensions of the nasolabial complex. Conclusions – The faces of unaffected parents from multiplex cleft families displayed meaningful shape differences compared with the general population. Quantitative assessment of the facial phenotype in cleft families may enhance efforts to discover the root causes of CL /P.     

Appropriateness and complications of the use of spironolactone in patients treated in a heart failure clinic

Objectives

The widespread use of spironolactone in patients with congestive heart failure (CHF) has resulted in side effects and complications. We analyzed a cohort of patients treated by a dedicated CHF team, in order to examine the tolerability and safety of spironolactone in clinical practice.

Methods

We retrospectively evaluated data on 157 patients who were followed by the Heart Failure clinic of whom 100 patients on maximal treatment (all on β blockers, 99% on ACE inhibitors) received spironolactone. The complications following spironolactone use were defined as: hyperkalemia with serum K 5.2 mEq/l; creatinine 2.0 mg/dl; hyponatremia with serum Na 135 mEq/l, hypotension and side effects such as gynecomastia and abdominal pain.

Results

At 1 year follow-up 6 patients developed hyperkalemia (range 5.3-5.9), 4 of them had K > 5.5 mEq/l. Two patients developed hyponatremia. Six patients stopped spironolactone for: 1-gynecomastia, 2-worsening renal failure and hyperkalemia, 2-hyperkalemia (5.9 mEq/l) and 1 for bradycardia. There was an increase in mean creatinine level at 1 year (1.12 ± 0.35 vs. 1.21 ± 0.38 mg/dl, p = 0.02), however, no significant changes were found in GFR (99.9 ± 33.5 vs. 65.7 ± 27.7 ml min^− 1 1.73 m^− 2, p = ns) and potassium (4.5 ± 0.4 vs. 4.6 ± 0.5 mEq/l, p = ns). We found improvement of GFR by > 10% in 19 patients and worsening by > 10% in 38 patients. No patient was hospitalized or required urgent treatment for spironolactone-related side effects.

Conclusions

In patients with CHF on optimal therapy with ACE inhibitors and β blockers appropriate spironolactone use and close follow-up by a dedicated HF team can minimize the risk for adverse events and complications.     

A systematic review of the evidence for Canada's Physical Activity Guidelines for Adults

This systematic review examines critically the scientific basis for Canada's Physical Activity Guide for Healthy Active Living for adults. Particular reference is given to the dose-response relationship between physical activity and premature all-cause mortality and seven chronic diseases (cardiovascular disease, stroke, hypertension, colon cancer, breast cancer, type 2 diabetes (diabetes mellitus) and osteoporosis). The strength of the relationship between physical activity and specific health outcomes is evaluated critically. Literature was obtained through searching electronic databases (e.g., MEDLINE, EMBASE), cross-referencing, and through the authors' knowledge of the area. For inclusion in our systematic review articles must have at least 3 levels of physical activity and the concomitant risk for each chronic disease. The quality of included studies was appraised using a modified Downs and Black tool. Through this search we identified a total of 254 articles that met the eligibility criteria related to premature all-cause mortality (N = 70), cardiovascular disease (N = 49), stroke (N = 25), hypertension (N = 12), colon cancer (N = 33), breast cancer (N = 43), type 2 diabetes (N = 20), and osteoporosis (N = 2). Overall, the current literature supports clearly the dose-response relationship between physical activity and the seven chronic conditions identified. Moreover, higher levels of physical activity reduce the risk for premature all-cause mortality. The current Canadian guidelines appear to be appropriate to reduce the risk for the seven chronic conditions identified above and all-cause mortality.