但当我读完审稿者的意见后，会冒出有这样的感觉：“读过审稿者的意见，常常有一种要去跳楼的冲动”。
针对答复审稿者的意见，大家普遍感到很困难，这种情况下，我考虑也采用“实战”的方式，把我们组既往发表文章时，答复审稿者意见的原稿逐步发给大家，请大家对每篇都能详细去阅读，先反复看审稿者的问题，琢磨他们为什么要提出这样的问题，然后再看我们做的答复，有些答复很巧妙地避开审稿者故意“挖的坑”。希望能通过这种方式，使得大家在答复审稿者意见方面能逐渐得到提高。
按照我们上课时的顺序和发给大家的提纲，今天是第一篇：“精神分裂症吸烟的发病率和对临床症状和副作用的影响”
点评：这篇文章是纯临床的文章，走我们在课堂上说的“常规思路”：
1）是精神分裂症吸烟的发病（发生）率；
2）分析两组之间在临床一般资料、临床症状和副作用等方面的差异；
3）采用logistic 回归，分析与吸烟相关的因素。
下面是修改后的Cover Letter, 这部分是重点，可以先看，而且需要反复看：
Dear Academic Editor,
Thank you very much for sending me the valuable comments of the reviewer on our manuscript (PONE-D-11-17251: Cigarette smoking in male patients with chronic schizophrenia in a Chinese population: prevalence and relationship to clinical phenotypes), which is very helpful to improve the quality of our paper. A thoroughly revised vision of our manuscript has been made. The comments and the critiques of the reviewer have been addressed and itemized as follows:
Responses to the Reviewer:
Question 1: In an institutionalized setting, “fixed schedule” for smoking may affect the smoking patterns in the patients. More details on who funded the cigarettes – for e.g. did the patients have to buy it themselves? If the patients had to buy it themselves, where did they get their earnings? Was any other behavior reinforcement schedules used in this setting? For e.g. in older institutions, it was common to use cigarettes as part of token economy for treatment of negative symptoms. These points should be addressed as these can affect smoking rates/ patterns in a person.
Answer: These points are very excellent. We have addressed these points in the following paragraph: “The patients or their family members had to purchase the cigarettes, with occasional supplemented supplies from their friends or employers, but at very low prices for most cigarette brands. Thus, smoking was not economically limited, and for the assessment period of these baseline smoking behaviors no patients were engaged in any behavior reinforcement schedules using cigarettes”. Please read the Subjects, Materials and Methods section on Page 4.
Question 2: About the control group – although any axis 1 psychopathology was ruled out, there is no mention of any “axis 2” or a “family history of schizophrenia/ psychotic illness” in the control group. There is also no mention of “subsyndromal psychotic symptoms” in this population. These points are important as this is a cross sectional study – “today’s controls could be tomorrow’s cases” and the authors themselves quote Esterberg et al, who have shown that smoking was more common in first degree relatives of patients with schizophrenia with greater schizotypy. Further, it is not known if the control group had any sub-syndromal psychotic symptoms (that did not qualify for an axis one diagnosis). This issue is complicated by the fact that British psychiatric morbidity study (which the authors discuss) found that psychotic symptoms were 70% more likely in smokers in the general population. These points should be addressed in the discussion / limitations.
Answer: These are very good points, which are indeed important for our cross sectional study. We have addressed these points as follows: “Second, although any axis 1 psychopathology was ruled out in the control group, we did not evaluate any “axis 2” or a “family history of schizophrenia / psychotic illness” in this population. Since Esterberg et al (2007) reported that smoking was more common in schizotypic first degree relatives of schizophrenic patients, we may have had a small percentage of these persons as controls. Because the community rate of schizophrenia is about 1% and the rate of schizotypy is similarly low, the contribution of this potential confound to overestimating the smoking rate in our controls seems very small. Also, we did not evaluate “subsyndromal psychotic symptoms” in the control population, which is potentially important among younger controls who had not passed through the age of risk for developing schizophrenia. However, we had a relatively older sample (mean 46 years) and did not find that the smoking association was weakened among the older patients and controls”. Please read the first paragraph in the Limitations of the Study,Discussion section on Page 10.
Question 3: When comparing “ever smoker” rates between patients and controls, the authors mention that they conducted a logistic regression analysis in order to tackle the confounding variables including antipsychotic use and institutionalizing. Although this did not change any results, statistically “controlling” for these variables as covariates is inappropriate – because at least in the present study, they are inherently associated with the experimental (study) group. All “cases” in the study were institutionalized and were on antipsychotics – statistically co-varying for this is inappropriate. This however may be a moot point in this paper, because this did not change the results (Miller GA, Chapman JP. Misunderstanding analysis of covariance. J Abnorm Psychol 2001;110(1):40-8)
Answer: Indeed, although the results were not changed, “controlling” these variables including antipsychotic use and institutionalizing between patients and controls in statistic analysis, since these variables were not associated with control group. Hence anew statistical analysis has been performed and the results showed that “This difference remained significant after using logistic regression to control for the socio-demographic confounds, such as age, education, marital and socio-economic status, and alcohol use (X2=40.6, p<0.0001, adjusted odds ratio=2.17; 95% confidence interval, 1.42–2.98)”. Please read the last paragraph of theComparison of smoking between schizophrenia patients and controls, Resultssection on Page 6.
Question 4: The mean age at starting smoking was around 7 years before the onset of “clinical illness”. This study however does not take into consideration “prodromal phase” and the “duration of untreated psychosis”. Seven years may be long for “prodromal” or “duration of untreated psychosis”, however, it is possible that the rates of smoking have changed in this population over the “prodromal”, “untreated (undiagnosed) phase”, and the “diagnosed phase”. It is therefore very difficult to make any assumptions that “the association between smoking and schizophrenia cannot be explained by the illness, treatment or hospitalization”. This should be clarified in the discussion.
Answer: This is a good point, which has been clarified in the Discussion. Please read the Limitations of the Study, Discussion section on Page 10, showing as“Fifth, we did not take into consideration a “prodromal phase” or the “duration of untreated psychosis” in determining that the mean age at starting smoking was around 7 years before the onset of clinical illness. The “prodromal phase” is a complex syndrome that is very difficult to date in its onset and length, but seven years appears to be rather long for a “prodromal phase.” However, smoking may be associated with a prodromal period in some patients with schizophrenia”.
Question 5: In the results, the authors have shown a relationship between age and smoking status – dividing the age into “categorical” groups of 3. What was the rationale behind dividing the sample into these age groups? The relevance of this analysis is not clear is not addressed in the discussion section. This should be addressed in the discussion. The relationship between age, symptoms and smoking status could be explored.
Answer: Indeed, there is no rationale behind dividing the sample in these age groups. In order to avoid the concentration distraction of the readers, this section has been deleted from the Results section.
Question 6: A very small point which the authors may choose to address if seem fit, is the use of the term “schizophrenic” in the study. Some people may consider this inappropriate in an age of political correctness. A better non-controversial term would be “patients with schizophrenia”.
Answer: All the terms “schizophrenic” in this study have been changed to “patients with schizophrenia”
Hopefully, we have made an adequate revision based on the comments of the reviewer. If there is still something else we’ll need to do with the revision on our manuscript, please let me know. I’ll have them prepared as soon as possible.
Again, give our whole hearted thanks to you for your excellent job. Your kind assistance is greatly appreciated.
Yours sincerely,
Xiang Yang Zhang, MD, PhD
