Improving PTSD Symptoms and Preventing Progression of Subclinical PTSD to an Overt Disorder by Treating Comorbid OSA With CPAP.

STUDY OBJECTIVES: Obstructive sleep apnea (OSA) and posttraumatic stress disorder (PTSD) are common in United States veterans. These conditions often coexist and symptoms overlap. Previous studies reported improvement in PTSD symptoms with continuous positive airway pressure (CPAP) therapy for comorbid OSA but its effect has not been assessed in a non-PTSD cohort. We have prospectively assessed the effect of CPAP therapy on clinical symptom improvement as a function of CPAP compliance levels among PTSD and non-PTSD veterans. METHODS: Veterans in whom OSA was newly diagnosed were enrolled in our study (n = 192). Assignment to PTSD and non-PTSD cohorts was determined by chart review. Each patient completed the military version of the PTSD Checklist (PCL), Epworth Sleepiness Scale (ESS), and reported nightmare frequency (NMF) at baseline and 6 months after CPAP therapy. CPAP adherence was objectively documented from machine compliance data. RESULTS: We had complete data for 177 veterans (PTSD n = 59, non-PTSD n = 118) for analysis. The mean ages were 51.24 years in the PTSD cohort and 52.36 years in the non-PTSD cohort (P = .30). In the PTSD cohort, the mean total PCL score (baseline = 66.06, post-CPAP = 61.27, P = .004, d = -0.34) and NMF (baseline = 4.61, post-CPAP = 1.49, P = .0001, d = -0.51) decreased after 6 months of CPAP treatment. Linear regression analysis showed that the CPAP compliance was the only significant predictor for these changes among veterans with PTSD (PCL score: P = .033, R2 = .65; NMF; P = .03, R2 = .61). Further analysis by CPAP compliance quartiles in this cohort (Q1 = 0% to 25%, Q2 = 26% to 50%, Q3 = 51% to 75%, Q4 > 75%) revealed that mean total PCL score declined in Q2 (change = -3.91, P = .045, d = 0.43), Q3 (change = -6.6, P = .002, d = 0.59), and Q4 (change = -7.94, P = .037, d = 0.49). In the non-PTSD cohort, the PCL score increased despite CPAP therapy in lower CPAP compliance quartiles Q1 (change = 8.71, P = .0001, d = 0.46) and Q2 (change = 4.51, P = .046, d = 0.27). With higher CPAP compliance (in Q3 and Q4) in this cohort, the mean total PCL scores slightly improved with CPAP but they were not statistically significant (P > .05). CONCLUSIONS: CPAP treatment reduces total PCL score and NMF in veterans with PTSD and OSA. Those with overt PTSD respond to even lower CPAP compliance, whereas non-PTSD patients require higher compliance to achieve any symptom improvement. Poor CPAP compliance results in increased PCL score in non-PTSD veterans and may lead to overt PTSD if the OSA remains undertreated. COMMENTARY: A commentary on this article appears in this issue on page 1121.

The effect of continuous positive air pressure (CPAP) on nightmares in patients with posttraumatic stress disorder (PTSD) and obstructive sleep apnea (OSA).

OBJECTIVES: Post-Traumatic Stress Disorder (PTSD) is increasingly prevalent among Veterans characterized by recurrent nightmare and disrupted sleep. Veterans with PTSD also have a high prevalence of obstructive sleep apnea (OSA) and untreated OSA worsens the sleep-related symptoms of PTSD. In our study, we hypothesized that among PTSD-afflicted Veterans with OSA, CPAP therapy may reduce the frequency of nightmares and a better CPAP compliance may be associated with increased symptom improvement. METHODS: We retrospectively reviewed medical records to identify OSA patients treated in a VA medical center who also carried a diagnosis of PTSD (n = 69). Data about patient characteristics and polysomnographic findings were extracted. Repeated-measures t-tests were performed, comparing mean nightmare frequency and Epworth sleepiness score (ESS) before and after CPAP treatment. Multiple linear regressions were done to identify factors predicting CPAP compliance. A logistic regression analysis was also done to estimate the odds of subjective improvement in PTSD symptoms with CPAP. RESULTS: CPAP therapy reduced the mean ESS from 14.62 to 8.52 (p < 0.001) and the mean number of nightmares per week from 10.32 to 5.26 (p < 0.01). Reduced nightmare frequency after CPAP treatment was best predicted by CPAP compliance (p < 0.001). Every 10% increase in CPAP compliance almost doubled the odds of benefitting by CPAP (odds ratio = 1.92, 95% CI = 1.47-2.5). CONCLUSIONS: In Veterans with PTSD and OSA, CPAP therapy reduces PTSD-associated nightmares and improves overall PTSD symptoms. We recommend that all PTSD patients should be screened clinically for symptoms of OSA and receive CPAP treatment whenever possible to improve PTSD symptoms.

Vitamin D deficiency and the risk of preeclampsia and eclampsia in Bangladesh.

Maternal vitamin D deficiency has been proposed as a risk factor for preeclampsia, but no significant studies have been conducted to evaluate its relationship with eclampsia. Our goal in this study was to assess the prevalence and potential risk of vitamin D deficiency for both preeclampsia and eclampsia in Bangladesh. Using a case-control design, we measured serum 25(OH)D levels in pregnant women receiving care at the Dhaka Medical College Hospital with preeclampsia (n=33), eclampsia (n=79), and normal pregnancy (controls, n=76). Odds of developing preeclampsia and eclampsia with vitamin D deficiency were calculated using logistic regression analysis. The prevalence of vitamin D insufficiency was very high with more than 3 quarters (78%) of all subjects having a serum 25(OH)D level<30 ng/ml. The mean serum 25(OH)D level was 24.86 ng/ml in controls, 23.96 ng/ml in pre-eclamptic women, and 21.56 ng/ml in eclampsia patients. Comparing to those who had a serum 25(OH)D level of ≥30 ng/ml, the odds ratio (95% CI) of developing preeclampsia and eclampsia in mothers with vitamin D insufficiency were 3.9 (95% CI=1.18-12.87) and 5.14 (95% CI=1.98-13.37), respectively (adjusting for age, BMI and duration of pregnancy). The odds of developing preeclampsia and eclampsia may increase by up to 5-fold in women with vitamin D insufficiency. Since preeclampsia and eclampsia can lead to serious complications for both mother and the offspring, vitamin D may be supplemented during pregnancy in high risk populations to decrease these adverse consequences.

Testosterone deficiency as a risk factor for cardiovascular disease.

Testosterone deficiency (TD) has become a frequently diagnosed condition in our current society with an obesity epidemic. Men diagnosed with TD often have co-morbidities including metabolic syndrome. Challenging aspects in diagnosing and treating patients with TD include intra-individual variation of symptoms combined with lack of its correlation with serum levels of testosterone. Apart from sexual aspects including libido and erectile function, replacement therapy with testosterone might have beneficial metabolic effects, whereas untreated TD might increase cardiometabolic risk and disease. In this article, we review the cardiovascular and metabolic risks associated with TD, as well as risks and benefits of testosterone replacement therapy. We also provide insights into potential mechanisms of the association between cardiometabolic risks with TD (treated and untreated) and propose an individual treatment algorithm.

How many blows really make an FEV1, FVC, or PEFR?

We have collected peak expiratory flow rates, one-second forced expiratory volumes, and forced vital capacities in sets of 10 or 20 values at one-minute intervals from 30 normal, 49 asthmatic, and 26 bronchitic subjects. Analysis shows that the derivatives are compatible with a normal distribution of the values in the sets, so that the true value is best represented by the arithmetic mean of all valid attempts. One-third of all subjects showed skewness in one or more indices but these were equally divided between positive and negative directions. There is no sign of the dominant negative skewness that would result if the true value was indeed a maximum, which could be approached or equalled but never exceeded. There is no sign that repetition worsens performance. Seventy-two subjects showed no regression in any index and those of the remainder who deteriorated were balanced by equal numbers in all categories who improved. There is a significant tendency for both the highest and the lowest values to occur in the earlier part of any series. Probability theory suggests that this is a statistical phenomenon. The best estimate of the true value of these indices is probably the mean of as many observations as can be conveniently obtained and the data can be treated statistically as if they were a sample from a normally distributed population.

Influence of age on response to ipratropium and salbutamol in asthma.

We studied the differential response to inhaled salbutamol and ipratropium of 29 asthmatic patients, 18 intrinsic, 11 extrinsic, using peak expiratory flow rate (PEFR), forced expiratory volume in one second (FEV1), and forced vital capacity (FVC). Thirty minutes after a theoretically maximally bronchodilating dose of salbutamol (400 microgram) or ipratropium (80 microgram), second doses frequently caused further bronchodilatation. We suspect that second doses may reach bronchi untouched by the first inhalation. Analysis of variance showed a powerful intrinsic versus extrinsic effect, and there were clearly differences between patients in their response to treatment (patient versus drug interaction) but these differences were not removed by dividing the patients into intrinsic and extrinsic groups. Results for the group as a whole favoured salbutamol, but examination of individual results by a pattern-recognition technique showed ipratropium equally effective in eight patients and more effective in three. All patients with a definite predominant salbutamol response were less than 40 years old. The response to salbutamol declined significantly with age, whereas that to ipratropium did not. In general in patients aged less than 40 years salbutamol is the drug of choice. With advancing age, and the apparent decline of beta-adrenergic responsiveness, the initially comparatively small response to ipratropium becomes relatively more important and may predominate. In older patients ipratropium, or continued therapy with both drugs, may be preferable.