Estimating the Effect of Bariatric Surgery on Cardiovascular Events Using Observational Data?

BACKGROUND: Observational studies have reported strongly protective effects of bariatric surgery on cardiovascular disease, but with oversimplified definitions of the intervention, eligibility criteria, and follow-up, which deviate from those in a randomized trial. We describe an attempt to estimate the effect of bariatric surgery on cardiovascular disease without introducing these sources of bias, which may not be entirely possible with existing observational data. METHODS: We propose two target trials among persons with diabetes: (1) bariatric operation (vs. no operation) among individuals who have undergone preoperative preparation (lifestyle modifications and screening) and (2) preoperative preparation and a bariatric operation (vs. neither preoperative nor operative component). We emulated both target trials using observational data of US veterans. RESULTS: Comparing bariatric surgery with no surgery (target trial #1; 8,087 individuals), the 7-year cardiovascular risk was 18.0% (95% CI = 6.9, 32.7) in the surgery group and 18.9% (95% CI = 17.7, 20.1) in the no-surgery group (risk difference -0.9, 95% CI = -12.0, 14.0). Comparing preoperative components plus surgery vs. neither (target trial #2; 10,065 individuals), the 7-year cardiovascular risk was 17.4% (95% CI = 13.6, 22.0) in the surgery group and 18.8% (95% CI = 17.8, 19.9) in the no-surgery group (risk difference -1.4, 95% CI = -5.1, 3.2). Body mass index and hemoglobin A1c were reduced with bariatric interventions in both emulations. CONCLUSIONS: Within limitations of available observational data, our estimates do not provide evidence that bariatric surgery reduces cardiovascular disease and support equipoise for a randomized trial of bariatric surgery for cardiovascular disease prevention.

Video article: the subtemporal extradural approach to cavernous sinus tumour.

OBJECTIVE: Here we demonstrate via operative video the subtemporal extradural approach to a tumour in the cavernous sinus. METHODS: The extradural approach is performed here in a paediatric patient (a 15-year-old child) via a right extended pterional osteoplastic craniotomy with removal of the zygomatic arch. The operative microscope is introduced, and the dura is divided at the superior orbital fissure into endosteal and meningeal layers using a diamond knife. The middle cranial fossa floor is drilled flat to increase access, and the plane is further developed towards the cavernous sinus. The tumour is seen bulging from within the cavernous sinus, and the cavernous sinus is opened in the anteromedial triangle between cranial nerves Vi and Vii. After biopsy, the tumour is debulked with an ultrasonic aspirator. Doppler is used to identify the internal carotid artery and preserve it. The bone flap is replaced, and the wound is closed in layers in standard fashion. RESULTS: The patient recovered well and was discharged on post-operative day 3. Persistent sixth nerve palsy (present pre-operatively) was present; however, otherwise, there was good recovery from surgery. Good resection of tumour is demonstrated on post-operative MR imaging. CONCLUSIONS: This approach is uncommon but important as it enables extradural access to the cavernous sinus, minimising the complications associated with an intradural approach such as cortical injury. In this video, we also demonstrate the fundamental anatomy using annotation and cadaveric images to enhance understanding required for the neurosurgeon to successfully complete this approach. The patient consented to the procedure in the standard fashion.

Quantitative and functional visual field outcomes after endoscopic trans-sphenoidal pituitary adenectomy.

OBJECTIVE: Quantitative data on visual outcomes after trans-sphenoidal surgery is lacking in the literature. This study aims to address this by quantitatively assessing visual field outcomes after endoscopic trans-sphenoidal pituitary adenectomy using the capabilities of modern semi-automated kinetic perimetry. METHODS: Visual field area (deg2) calculated on perimetry performed before and after surgery was statistically analysed. Functional improvement was assessed against UK driving standards. RESULTS: Sixty-four patients (128 eyes) were analysed (May 2016-Nov 2019). I4e and I3e isopter area significantly increased after surgery (p < 0.0001). Of eyes with pre-operative deficits: 80.7% improved and 7.9% worsened; the median amount of improvement was 60% (IQR 6-246%). Median increase in I4e isopter was 2213deg2 (IQR 595-4271deg2) and in I3e isopter 1034 deg2 (IQR 180-2001 deg2). Thirteen out of fifteen (87%) patients with III4e data regained driving eligibility after surgery. Age and extent of resection (EOR) did not correlate with visual improvement. Better pre-operative visual field area correlated with a better post-operative area (p < 0.0001). However, the rate of improvement in the visual field area increased with poorer pre-operative vision (p < 0.0001). CONCLUSIONS: A median visual field improvement of 60% may be expected in over 80% of patients. Functionally, a significant proportion of patients can expect to regain driving eligibility. EOR did not impact on visual recovery. When the primary goal of surgery is alleviating visual impairment, optic apparatus decompression without the aim for gross total resection appears a valid strategy. Patients with the worst pre-operative visual field often experience the greatest improvement, and therefore, poor pre-operative vision alone should not preclude surgical intervention.

The Hudson Brace technique for emergency burr holes, an aide-memoire for the front-line military surgeon.

Traumatic brain injury is the leading cause of death in conflict and early surgical intervention achieves better outcomes. The British Army surgical kit includes a Hudson Brace and bit and Gigli saw for decompression of the cranial cavity. Here we demonstrate the Hudson Brace technique for non-neurosurgeons.

Rapid Growth of a Facet Joint Cyst Mimicking an Aggressive Tumor in the Lumbar Spine.

A 67-year-old patient with a history of fully treated bowel carcinoma presented with a short history of unilateral lumbosacral radiculopathy. No neurological deficit was found on examination. Magnetic resonance imaging (MRI) demonstrated initially L4/5 foraminal narrowing that was believed to be the cause for the patient's symptoms; however, a nerve root block led to no improvement in symptoms. MRI was repeated at 5 months and demonstrated a mass causing compression of the S1 nerve. However, the patient declined surgical decompression. MRI at 14 months subsequently showed rapid growth of the lesion suggestive of an aggressive process such as a metastatic lesion or even a nerve sheath tumor such as a Schwannoma. Open biopsy and decompression revealed the lesion to be a facet joint cyst and the patient recovered well and had satisfactory postoperative imaging at 3 months follow-up. There are no reports in the literature of facet joint cysts growing this quickly and thus mimicking other forms of lesion.

Direct Lateral Minimally Invasive Approach for Excision of a L1/L2 Neurofibroma-A Technical Note and Literature Review.

A case of resection of a large dumbbell-shaped nerve sheath tumor at L1/L2 via a direct lateral minimally invasive approach is described. The tumor was removed via a lateral, subdiaphragmatic, rib-sparing, retropleural, retroperitoneal approach. The thoracolumbar junction can be challenging via the lateral approach and to the best of our knowledge this is the first report of excision of a paravertebral tumor via this approach. We believe this provided the benefits of direct operative trajectory and exposure, excellent tumor access, and avoided the need for facetectomy and extended spinal instrumentation across the thoracolumbar junction. Complete tumor excision was achieved with preserved motor function and improvement in radicular pain and sensory neurological deficit.

Hypothetical Lifestyle Strategies in Middle-Aged Women and the Long-Term Risk of Stroke.

Background and Purpose- Long-term effect of lifestyle changes on stroke incidence has not been estimated in randomized trials. We used observational data to estimate the incidence of stroke under hypothetical lifestyle strategies in the NHS (Nurses' Health Study). Methods- We considered 3 nondietary strategies (smoking cessation, exercising ≥30 min/d, gradual body mass index reduction if overweight/obese) and several dietary strategies (eating ≥3 servings/wk of fish, ≤3 servings/wk of unprocessed red meat, no processed red meat, ≥1 servings/d of nuts, etc). We used the parametric g-formula to estimate the 26-year risk of stroke under these strategies. Results- In 59 727 women, mean age 52 years at baseline in 1986, the estimated 26-year risks under no lifestyle interventions were 4.7% for total stroke, 2.4% for ischemic stroke, and 0.7% for hemorrhagic stroke. Under the combined nondietary interventions, the estimated 26-year risk of total stroke was 3.5% (95% CI, 2.6%-4.3%) and ischemic stroke was 1.6% (95% CI, 1.1%-2.1%). Smaller reductions in total stroke risk were estimated under isolated dietary strategies of increased intake of fish and nuts and reduced intake of unprocessed red meat. Ischemic stroke risk was lower under reduced intake of unprocessed and processed red meat, and hemorrhagic stroke risk was lower under a strategy of increased fish consumption. Conclusions- In this population of middle-aged women, sustained, lifestyle modifications were estimated to reduce the 26-year risk of total stroke by 25% and ischemic stroke by 36%. Sustained dietary modifications were estimated to reduce the 26-year risk of total stroke by 23%.

Fronto-orbital advancement and reconstruction using reverse frontal bone graft without the use of orbital bar: a technical note.

INTRODUCTION: We describe our technique of using reverse frontal bone graft for FOAR for patients with metopic or coronal synostosis and present our complications using the Leeds classification system for complications in craniosynostosis surgery. METHODS: Since April 2015, seventeen patients have been operated using this technique. We perform a frontal bone graft that is then reversed, and supraorbital margins are drilled out. The orbital bar is then removed and drilled down to make bone dust and on-lay bone grafts which are then used to fill gaps on exposed dura and fill in around the temporal region. RESULTS: All 17 patients who underwent this technique have good cosmetic results. We report 5 (29%) complications and 8 (47%) blood transfusions (7 exposures, 1 cell salvage).

Weight Gain After Smoking Cessation and Lifestyle Strategies to Reduce it.

BACKGROUND: Weight gain following smoking cessation reduces the incentive to quit, especially among women. Exercise and diet interventions may reduce postcessation weight gain, but their long-term effect has not been estimated in randomized trials. METHODS: We estimated the long-term reduction in postcessation weight gain among women under smoking cessation alone or combined with (1) moderate-to-vigorous exercise (15, 30, 45, 60 minutes/day), and (2) exercise and diet modification (≤2 servings/week of unprocessed red meat; ≥5 servings/day of fruits and vegetables; minimal sugar-sweetened beverages, sweets and desserts, potato chips or fried potatoes, and processed red meat). RESULTS: Among 10,087 eligible smokers in the Nurses' Health Study and 9,271 in the Nurses' Health Study II, the estimated 10-year mean weights under smoking cessation were 75.0 (95% CI = 74.7, 75.5) kg and 79.0 (78.2, 79.6) kg, respectively. Pooling both cohorts, the estimated postcessation mean weight gain was 4.9 (7.3, 2.6) kg lower under a hypothetical strategy of exercising at least 30 minutes/day and diet modification, and 5.9 (8.0, 3.8) kg lower under exercising at least 60 minutes/day and diet modification, compared with smoking cessation without exercising. CONCLUSIONS: In this study, substantial weight gain occurred in women after smoking cessation, but we estimate that exercise and dietary modifications could have averted most of it.

The learning curve for endoscopic trans-sphenoidal resection of pituitary macroadenomas. A single institution experience, Leeds, UK.

BACKGROUND: The object of this study was to assess whether increasing operative experience results in greater endoscopic trans-sphenoidal resection of pituitary macroadenomas and lower complications. METHODS: A retrospective single institution cohort study was performed. Subjects underwent endoscopic trans-sphenoidal resection of pituitary macroadenoma between July 2009 and July 2016 by three neurosurgeons. Following data collection, statistical analysis compared percentage of tumor resection and length of hospital stay (LOS) with experience. Complications including CSF leak are reported. RESULTS: In total, 142 patients (87 male, 55 female) mean age 55.1 were included. Surgeon 1 performed 106 cases; surgeon 2 performed 23 cases; and surgeon 3 performed 13 cases. Mean pre-operative tumor volumes were 8.18 cm3, 6.52 cm3, and 3.47 cm3 and post-operative volumes were 2.21, 1.74, and 1.93 cm3 for surgeons 1, 2, and 3, respectively. Respective percentage resections were 74.3, 77.2, and 52.1%. Analysis demonstrated no difference in tumor resection with increasing experience for all three surgeons (p = 0.11, p = 0.17, and p = 0.26). Tumor consistency and cavernous sinus involvement did not appear to affect tumor resection. Mean LOS was 5 days, 4 days, and 3 days, respectively, with no significant correlation with experience for all three surgeons. Intraoperative CSF leak incidence was 19/106 (18%) for surgeon 1, 6/23(26%) for surgeon 2, and 2/13(15%) for surgeon 3. Primary closure rate was 96.3% and only three other complications occurred. CONCLUSIONS: This study demonstrates that in our institution there is no statistically significant learning curve for the endoscopic resection of pituitary macroadenoma. However, there is a trend of improvement in tumor resection with experience for one surgeon. These findings suggest that the surgeons in our institution were capable of performing this procedure effectively with a low complication rate since adoption of the endoscopic technique in 2009.

Smoking cessation and long-term weight gain in the Framingham Heart Study: an application of the parametric g-formula for a continuous outcome.

Weight gain after smoking cessation can lessen the health benefits of, and reduce the incentives for, quitting smoking. Randomized clinical trials of smoking cessation have estimated this weight gain only over short periods of follow-up. We provide an estimate of long-term post-cessation weight gain in the Framingham Heart Study, a prospective observational study. We identified 2001 smokers free of diabetes, cancer, and cardiovascular disease in 1952. Using the parametric g-formula we estimated mean weight in 1972 if all smokers had quit at baseline versus if all had continued smoking. Our estimates were adjusted for demographic, socio-economic, and clinical factors at baseline and during follow-up. The estimated mean weight (95 % CI) at 20 years if all smokers had quit smoking was 75.2 kg (73.5, 76.6), compared with 70.2 kg (68.7, 71.8) if they had smoked 20 cigarettes/day and 73.4 kg (71.9, 74.6) if they had smoked 5 cigarettes/day (i.e., an estimated mean weight gain of 5.1 kg (3.1, 6.6) and 1.8 kg (0.8, 2.8), respectively). Smokers who were overweight or obese at baseline had a greater post-cessation weight gain on average. Our estimates suggest that smoking cessation can result in increases in body weight over 20 years. While the benefits of smoking cessation outweigh the risks due to post-cessation weight gain, our results highlight the need for long-term weight management interventions in combination with smoking cessation.

Using Big Data to Emulate a Target Trial When a Randomized Trial Is Not Available.

Ideally, questions about comparative effectiveness or safety would be answered using an appropriately designed and conducted randomized experiment. When we cannot conduct a randomized experiment, we analyze observational data. Causal inference from large observational databases (big data) can be viewed as an attempt to emulate a randomized experiment-the target experiment or target trial-that would answer the question of interest. When the goal is to guide decisions among several strategies, causal analyses of observational data need to be evaluated with respect to how well they emulate a particular target trial. We outline a framework for comparative effectiveness research using big data that makes the target trial explicit. This framework channels counterfactual theory for comparing the effects of sustained treatment strategies, organizes analytic approaches, provides a structured process for the criticism of observational studies, and helps avoid common methodologic pitfalls.

Methods to Estimate the Comparative Effectiveness of Clinical Strategies that Administer the Same Intervention at Different Times.

Clinical guidelines that rely on observational data due to the absence of data from randomized trials benefit when the observational data or its analysis emulates trial data or its analysis. In this paper, we review a methodology for emulating trials that compare the effects of different timing strategies, that is, strategies that vary the frequency of delivery of a medical intervention or procedure. We review trial emulation for comparing (i) single applications of the procedure at different times, (ii) fixed schedules of application, and (iii) schedules adapted to the evolving clinical characteristics of the patients. For illustration, we describe an application in which we estimate the effect of surveillance colonoscopies in patients who had an adenoma detected during the Norwegian Colorectal Cancer Prevention (NORCCAP) trial.

Endoscopic removal of a dermoid cyst via scalp incision.

Nasal dermoid sinus cysts are the most common congenital midline nasal lesions. We describe a novel technique for the excision of a nasal dermoid cyst in a 2-year-old boy using a four hand endoscopic approach via a small scalp incision behind the hairline. The technique, although somewhat challenging, avoids a facial scar.

Estimating absolute risks in the presence of nonadherence: an application to a follow-up study with baseline randomization.

The intention-to-treat (ITT) analysis provides a valid test of the null hypothesis and naturally results in both absolute and relative measures of risk. However, this analytic approach may miss the occurrence of serious adverse effects that would have been detected under full adherence to the assigned treatment. Inverse probability weighting of marginal structural models has been used to adjust for nonadherence, but most studies have provided only relative measures of risk. In this study, we used inverse probability weighting to estimate both absolute and relative measures of risk of invasive breast cancer under full adherence to the assigned treatment in the Women's Health Initiative estrogen-plus-progestin trial. In contrast to an ITT hazard ratio (HR) of 1.25 (95% confidence interval [CI] = 1.01 to 1.54), the HR for 8-year continuous estrogen-plus-progestin use versus no use was 1.68 (1.24 to 2.28). The estimated risk difference (cases/100 women) at year 8 was 0.83 (-0.03 to 1.69) in the ITT analysis, compared with 1.44 (0.52 to 2.37) in the adherence-adjusted analysis. Results were robust across various dose-response models. We also compared the dynamic treatment regimen "take hormone therapy until certain adverse events become apparent, then stop taking hormone therapy" with no use (HR = 1.64; 95% CI = 1.24 to 2.18). The methods described here are also applicable to observational studies with time-varying treatments.

Intervening on risk factors for coronary heart disease: an application of the parametric g-formula.

Estimating the population risk of disease under hypothetical interventions--such as the population risk of coronary heart disease (CHD) were everyone to quit smoking and start exercising or to start exercising if diagnosed with diabetes--may not be possible using standard analytic techniques. The parametric g-formula, which appropriately adjusts for time-varying confounders affected by prior exposures, is especially well suited to estimating effects when the intervention involves multiple factors (joint interventions) or when the intervention involves decisions that depend on the value of evolving time-dependent factors (dynamic interventions). We describe the parametric g-formula, and use it to estimate the effect of various hypothetical lifestyle interventions on the risk of CHD using data from the Nurses' Health Study. Over the period 1982-2002, the 20-year risk of CHD in this cohort was 3.50%. Under a joint intervention of no smoking, increased exercise, improved diet, moderate alcohol consumption and reduced body mass index, the estimated risk was 1.89% (95% confidence interval: 1.46-2.41). We discuss whether the assumptions required for the validity of the parametric g-formula hold in the Nurses' Health Study data. This work represents the first large-scale application of the parametric g-formula in an epidemiologic cohort study.

Observational studies analyzed like randomized experiments: an application to postmenopausal hormone therapy and coronary heart disease.

BACKGROUND: The Women's Health Initiative randomized trial found greater coronary heart disease (CHD) risk in women assigned to estrogen/progestin therapy than in those assigned to placebo. Observational studies had previously suggested reduced CHD risk in hormone users. METHODS: Using data from the observational Nurses' Health Study, we emulated the design and intention-to-treat (ITT) analysis of the randomized trial. The observational study was conceptualized as a sequence of "trials," in which eligible women were classified as initiators or noninitiators of estrogen/progestin therapy. RESULTS: The ITT hazard ratios (HRs) (95% confidence intervals) of CHD for initiators versus noninitiators were 1.42 (0.92-2.20) for the first 2 years, and 0.96 (0.78-1.18) for the entire follow-up. The ITT HRs were 0.84 (0.61-1.14) in women within 10 years of menopause, and 1.12 (0.84-1.48) in the others (P value for interaction = 0.08). These ITT estimates are similar to those from the Women's Health Initiative. Because the ITT approach causes severe treatment misclassification, we also estimated adherence-adjusted effects by inverse probability weighting. The HRs were 1.61 (0.97-2.66) for the first 2 years, and 0.98 (0.66-1.49) for the entire follow-up. The HRs were 0.54 (0.19-1.51) in women within 10 years after menopause, and 1.20 (0.78-1.84) in others (P value for interaction = 0.01). We also present comparisons between these estimates and previously reported Nurses' Health Study estimates. CONCLUSIONS: Our findings suggest that the discrepancies between the Women's Health Initiative and Nurses' Health Study ITT estimates could be largely explained by differences in the distribution of time since menopause and length of follow-up.

Second look at the spread of epidemics on networks.

In an important paper, Newman [Phys. Rev. E66, 016128 (2002)] claimed that a general network-based stochastic Susceptible-Infectious-Removed (SIR) epidemic model is isomorphic to a bond percolation model, where the bonds are the edges of the contact network and the bond occupation probability is equal to the marginal probability of transmission from an infected node to a susceptible neighbor. In this paper, we show that this isomorphism is incorrect and define a semidirected random network we call the epidemic percolation network that is exactly isomorphic to the SIR epidemic model in any finite population. In the limit of a large population, (i) the distribution of (self-limited) outbreak sizes is identical to the size distribution of (small) out-components, (ii) the epidemic threshold corresponds to the phase transition where a giant strongly connected component appears, (iii) the probability of a large epidemic is equal to the probability that an initial infection occurs in the giant in-component, and (iv) the relative final size of an epidemic is equal to the proportion of the network contained in the giant out-component. For the SIR model considered by Newman, we show that the epidemic percolation network predicts the same mean outbreak size below the epidemic threshold, the same epidemic threshold, and the same final size of an epidemic as the bond percolation model. However, the bond percolation model fails to predict the correct outbreak size distribution and probability of an epidemic when there is a nondegenerate infectious period distribution. We confirm our findings by comparing predictions from percolation networks and bond percolation models to the results of simulations. In the Appendix, we show that an isomorphism to an epidemic percolation network can be defined for any time-homogeneous stochastic SIR model.

On the efficacy of screening for breast cancer.

BACKGROUND: 'Mammography' (screening for breast cancer by X-ray examination) came to be widely-although not universally-accepted in the 1980s when a number of clinical trials demonstrated a substantial reduction in risk. Early detection, before the disease spread, permitted therapy that was simultaneously less invasive and more effective. Questions that remained were largely about efficacy for younger women and optimal frequency for older women. The consensus was challenged in a series of papers by two researchers at the Nordic branch of the Cochrane collaboration, Gøtzsche and Olsen, who concluded that mammography does not save lives: instead, it exposes women to unnecessary surgical procedures. METHODS: Qualitative review. RESULTS: The basis for the Gøtzsche-Olsen critique turns out to be simple. Studies that found a benefit from mammography were discounted as being of poor quality; remaining negative studies were combined by meta-analysis. The critique therefore rests on judgements of study quality, but these judgements are based on misreadings of the data and the literature. CONCLUSION: The prior consensus on mammography was correct.